[Corpus Hermeticum in history].
The originator and founder of hermetism was the mythical Hermes Trismegistos, a deity of the syncretic Hellenistic religion that came into being through the identification of the Greek god Hermes with the Egyptian god Thot. In later Hellenistsic times various hermetic writers considered Hermes Trismegistos to have been a historical personage, a king, prophet and philosopher (physician), as well as author of many widely disseminated writings that made up the so-called Corpus Hermeticum (eighteen separate treatises from the 2nd-4th centuries AD) and the so-called Emerald Table (Tabula Smaragdina). The Corpus Hermeticum is a collection of treatises of a philosophical, religious, theological as well as theosophical nature. The collection played an important role in the development of the philosophy of alchemy and hermetism, and formed the basis for an alchemist philosophy of nature. There are currently two views among scholars on the origins of hermetism. According to one, hermetism derived directly from Egypt, while according to the other it orginated in Greece. In the years 1945-46 a number of hermetic texts forming part of the now famous gnostic "library" were discovered in Nag-Hammadi (Chenosboskion) in Upper Egypt. The Coptic texts from Nag-Hammadi date from the middle of the 4th century AD, and according to experts are translations from the Greek. Some authors (R. Reitzenstein and T. Zieliński) have suggested that along with the appearance in Egypt of the Hermetic Books, attributed to Hermes Trismegistos, there also appeared a new god in Egypt, Poimandres, and a new religion was established, hermetism, which competed for influence with Christianity. The present article discusses the main of the hermetic treatises, including Poimandres, which contains an account of the creation of the world. The article also discusses the reasons for the decline of hermetism as a religion and stresses that in spite of this decline the doctrine managed to survive in the form of alchemic hermetism, which played an important role in the culture of the Renaissance. The article also cites the voluminous work by W. Scott and A. S. Ferguson (1924-1936), and A. D. Nock and A. -J. Festugiére (1945-1964), which contains contemporary, English and French, commentaries on and translations of the Corpus Hermeticum texts.


Inclusion of pyridoxine to flaxseed cake in poultry feed improves productivity of omega-3 enriched eggs.
Flaxseed cake produced during flax oil production is rich in protein, and could be utilized in the production of omega-3 enriched eggs or value added eggs. But the presence of anti-nutrients in flaxseed cake adversely affects the bird and egg characteristics. Supplementation of pyridoxine may prove beneficial as noted by earlier research. In our study, we divided 30 layer birds into three groups and supplemented them with different combination feeds containing: (A) control ration, (B) fresh flax seed cake with pyridoxine and (C) fresh flax seed cake without pyridoxine. Crushed 2% flaxseed was also added to the flaxseed cake groups for deposition of sufficient omega-3 fatty acids into the eggs. Supplementation was given for a period of 4 weeks and egg as well as bird characteristics observed. Birds fed pyridoxine showed better incorporation of omega-3 fatty acids into the egg yolk. Supplementation of flaxseed cake with pyridoxine resulted in better yields of omega-3 eggs as well as improved health of layer birds.


Anatomo-proteomic characterization of human basal ganglia: focus on striatum and globus pallidus.
The basal ganglia (BG) are a complex network of subcortical nuclei involved in the coordination and integration of the motor activity. Although these independent anatomical structures are functionally related, the proteome present in each isolated nucleus remains largely unexplored. In order to analyse the BG proteome in a large-scale format, we used a multi-dimensional fractionation approach which combines isolation of anatomically-defined nuclei, and protein/peptide chromatographic fractionation strategies coupled to mass spectrometry. Using this workflow, we have obtained a proteomic expression profile across striatum and globus pallidus structures among which 1681 proteins were located in caudate nucleus (CN), 1329 in putamen, 1419 in medial globus pallidus (GPi), and 1480 in lateral globus pallidus (GPe), establishing a BG reference proteome to a depth of 2979 unique proteins. Protein interactome mapping highlighted significant clustering of common proteins in striatal and pallidal structures, contributing to oxidative phosphorylation, protein degradation and neurotrophin signalling pathways. In silico analyses emphasized specific pathways represented in striatal and pallidal structures highlighting 5-hydroxytryptamine degradation, synaptic vesicle trafficking, and dopamine, metabotropic glutamate and muscarinic acetylcholine receptor pathways. Additional bioinformatic analyses also revealed that: i) nearly 4% of identified proteins have been previously associated to neurodegenerative syndromes, ii) 11% of protein set tends to localize to synaptic terminal, and iii) 20% of identified proteins were also localized in cerebrospinal fluid (CSF). Overall, the anatomo-proteomic profiling of BG complements the anatomical atlas of the human brain transcriptome, increasing our knowledge about the molecular basis of the BG and the etiology of the movement disorders.


[DENGUE FEVER IN RUSSIA: PROBLEMS OF DIAGNOSTICS].
The authors report clinical and laboratory data concerning a case of hemorrhagic dengue fever introduced to Ul'yanovsk by a tourist who had spent holiday in Vietnam. The clinical picture of the disease is described along with results of clinical and laboratory analyses. The approaches to the evaluation of the patient's health status during the period of primary examination and medical care as well as the problems that arose after the final diagnosis was established are discussed.


Quantifying the Elasticity Properties of the Median Nerve during the Upper Limb Neurodynamic Test 1.
The upper limb neurodynamic test 1 (ULNT1) consists of a series of movements that are thought to detect an increase in neuromechanical sensitivity. In vivo, no trail was made to quantify the association between the nerve elasticity and different limb postures during ULNT1. (1) To investigate the relationship between nerve elasticity and limb postures during ULNT1 and (2) to investigate the intra- and interoperator reliabilities of shear wave elastography (SWE) in quantifying the elasticity of median nerve. Twenty healthy subjects (mean age: 19.9 ± 1.4 years old) participated in this study. The median nerve was imaged during elbow extension in the following postures: (1) with neutral posture, (2) with wrist extension (WE), (3) with contralateral cervical flexion (CCF), and (4) with both WE and CCF. The intra- and interoperator reliabilities measured by two operators at NP and CCF+WE and intraclass correlation coefficients (ICCs) were calculated. The intraoperator (ICC = 0.72-0.75) and interoperator (ICC = 0.89-0.94) reliabilities for measuring the elasticity of the median nerve ranged from good to excellent. The mean shear modulus of the median nerve increased by 53.68% from NP to WE+CCF. SWE is a reliable tool to quantify the elasticity of the median nerve. There was acute modulation in the elasticity of the median nerve during the ULNT1 when healthy participants reported substantial discomfort. Further studies need to focus on the elasticity properties of the median nerve in patients with peripheral neuropathic pain.


Incidence and risk factors of preoperative isolated calf deep venous thrombosis following hip fractures.
There is still a lack of data on isolated calf deep vein thrombosis (ICDVT) following hip fractures surgery. The study aimed to determine the incidence of preoperative ICDVT and the associated risk factors in patients with hip fractures requiring surgery.The 289 patients who required hip surgery were included, duplex ultrasonography was routinely used to make a definite diagnosis of preoperative ICDVT located in unilateral or bilateral calf. Data on demographics and laboratory-associated blood biomarkers results were included. Univariate analyses were used to analyse the data of demographics, comorbidities, personal history operation related indexes and laboratory biomarkers, then the multivariate logistic regression analysis was employed to identify the independent risk factors associated with ICDVT.Sixty-eight (23.5%) patients were diagnosed with preoperative ICDVTs. The univariate analyses showed significant differences regarding ICDVT were age, current smoking, alcohol consumption, time from injury to operation, albumin, white blood cells, lymphocyte, red blood cells, hemoglobin, hematocrit, and activated partial thromboplastin time level among the 44 factors. The multivariable model confirmed 3 risk factors were significantly independent in association with preoperative ICDVTs, including current smoking, time delay from injury to operation and activated partial thromboplastin time ( < 28seconds).The incidence of preoperative ICDVT in hip fracture was 23.5%, and patients with associated risk factors are prone to form ICDVTs, identification of these factors may help to reduce the incidence of ICDVT with hip fractures by taking early prevention measures.


Disability and health-related quality of life in patients undergoing spinal fusion: a comparison with a general population sample.
The aim of the present study was to compare one-year-follow-up data on disability and health-related quality of life (HRQoL) between spinal fusion patients and age- and sex-matched general population. The data on fusion patients were collected prospectively using a spinal fusion data base in two Finnish hospitals. A general population sample matched for age, sex and residential area was drawn from the Finnish Population Register. All participants completed a questionnaire and the main outcome measures were the Oswestry Disability Index (ODI) and the Short Form-36 questionnaire (SF-36). Altogether 252 (69% females) fusion patients and 682 (67% females) population sample subjects participated in the study. In general population the mean ODI was 15 (SD 17) in females and 9 (SD 13) in males. The corresponding preoperative ODI values were 47 (SD16) and 40 (SD 15) and one year follow-up values 22 (SD 17) and 23 (SD 20). In both sexes the ODI decreased significantly after surgery but remained higher than in the general population, p < 0.001. The physical component summary score (PCS) of the SF-36 was lower in the patients than general population sample both preoperatively and at one-year follow-up (p < 0.001). The mental component summary score (MCS) was lower preoperatively (p < 0.001), but reached the general population level after one year in both men (p = 0.42) and women (p = 0.61). Disability and HRQoL improved significantly after spinal fusion surgery during a one- year follow-up. However, the patients did not reach the level of the general population in the ODI or in the physical component of HRQoL at that time, although in the mental component the difference disappeared.


[The Law of 19 Ventôse, year 21 (10 March 1803): fundamental text and provisional expedient].
During the last years of the Ancien Régime, Fourcroy established the link between Vicq d'Azyr and Colombier who both wore themselves out in order to reform the medical profession, fallen into a state of turmoil. But both died, and henceforth everything was handled by Fourcroy. On 10 March 1803 (19 Ventose an XI) he arranged for the passage of a fundamental law--today is its bi-centennial--reorganising the profession. Henceforth no one could exercise that profession without having been received as a doctor, except in underdeveloped regions where "health officers" (less qualified practitioners) would be accepted.


Novel oral anticoagulants for stroke prevention in atrial fibrillation: focus on apixaban.
Stroke prevention in atrial fibrillation (AF) has been challenging over decades, mostly due to a number of difficulties associated with oral vitamin K antagonists (VKAs), which have been the most effective stroke prevention treatment for a long time. The oral direct thrombin inhibitors (e.g., dabigatran) and oral direct inhibitors of factor Xa (e.g., rivaroxaban, apixaban) have emerged recently as an alternative to VKAs for stroke prevention in AF. These drugs act rapidly, and have a predictable and stable dose-related anticoagulant effect with a few clinically relevant drug-drug interactions. The novel oral anticoagulants are used in fixed doses with no need for regular laboratory monitoring of anticoagulation intensity. However, each of these drugs has distinct pharmacological properties that could influence optimal use in clinical practice. The following phase 3 randomized trials with novel oral anticoagulants versus warfarin for stroke prevention in AF have been completed: the Randomized Evaluation of Long-term Anticoagulant therapy (RE-LY) trial with dabigatran, the Rivaroxaban Once daily oral direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) trial with rivaroxaban, and the Apixaban for Reduction of Stroke and Other Thromboembolism Events in Atrial Fibrillation (ARISTOTLE) trial with apixaban. Moreover, the Apixaban Versus Acetylsalicylic Acid to prevent Strokes (AVERROES) trial included patients with AF who have failed or were unsuitable for warfarin, and compared apixaban versus aspirin for stroke prevention in AF. Overall, apixaban has two large trials for stroke prevention in AF showing benefits not only over warfarin, but also over aspirin among those patients who have failed or refused warfarin. In the ARISTOTLE trial, apixaban was superior to warfarin in the reduction of stroke or systemic embolism, major bleeding, intracranial hemorrhage, and all-cause mortality, with a similar reduction in the rate of ischemic stroke and better tolerability. When compared with aspirin in the AVERROES trial, apixaban was associated with more effective reduction of stroke, a similar risk of major bleeding, and better tolerability. In this review article, the authors summarize the current knowledge on novel oral anticoagulants and discuss the clinical aspects of their use for stroke prevention in AF, with particular emphasis on apixaban.


Study of the efficacy and safety of the combination ramipril 2.5 mg plus hydrochlorothiazide 12.5 mg in patients with mild-to-moderate hypertension. ATHES Study Group.
In a double-blind, parallel-group multicentre study, the efficacy and safety of a fixed low-dose combination of ramipril 2.5 mg and hydrochlorothiazide (HCT) 12.5 mg was compared with each of the component drugs when given as monotherapy. After a four-week placebo run-in, patients were randomized to receive either ramipril 2.5 mg (n = 218) or HCT 12.5 mg (n = 220), or the fixed-dose combination of ramipril 2.5 mg and HCT 12.5 mg (n = 222), for a period of eight weeks. At the end of the study, in which 624 patients had completed treatment, it was found that the decrease in supine diastolic blood pressure (the main efficacy parameter) was greater in the ramipril-HCT combination group than in either the ramipril or the HCT monotherapy groups, the difference being statistically significant when compared with the HCT group (-14.3, -13.1 and -12.4 mm Hg, respectively). Reductions in standing DBP and supine and standing systolic blood pressure (SBP) were also greatest in the combination group. The incidence of adverse events was lower in the combination group than in either of the monotherapy groups, and there were no serious clinically significant laboratory abnormalities in the combination group.


The mechanism of visible light-induced C-C cross-coupling by Csp3-H bond activation.
Csp3-C cross-coupling by activating Csp3-H bonds is a dream reaction for the chemical community, and visible light-induced transition metal-catalysis under mild reaction conditions is considered a powerful tool to achieve it. Advancement of this research area is still in its infancy because of the chemical and technical complexity of this catalysis. Mechanistic studies illuminating the operative reaction pathways can rationalize the increasing amount of experimental catalysis data and provide the knowledge allowing faster and rational advances in the field. This goal requires complementary experimental and theoretical mechanistic studies, as each of them is unfit to clarify the operative mechanisms alone. In this tutorial review we summarize representative experimental and computational mechanistic studies, highlighting weaknesses, strengths, and synergies between the two approaches.


Fasting decreases plasma FGF21 in obese subjects and the expression of FGF21 receptors in adipose tissue in both lean and obese subjects
Fibroblast growth factor 21 (FGF21) is a metabolic regulator of energy and lipid metabolism. FGF21 is highly expressed in liver while FGF21 receptors (beta-klotho (KLB) and FGFR1c) are highly expressed in white adipose tissues (WATs). Plasma FGF21 has been shown to be increased after 7–10 days of fasting but oppositely plasma FGF21 is also increased in obesity. The aim of this study was to measure the effect of 60 h of fasting on plasma FGF21 levels in obese and lean subjects and to determine the gene expression of KLB and FGFR1c in the subcutaneous WAT before, during and after 60 h of fasting. Eight obese (BMI >30 kg/m2) and seven lean subjects (BMI <25 kg/m2) were fasted for 60 h and blood samples were taken at time 0 and after 12, 36 and 60 h of fasting. A biopsy from the subcutaneous WAT was taken at time 0, 12 and 60 h of fasting. FGF21 was measured in plasma by an ELISA and mRNA expression of KLB and FGFR1c was measured in WAT by quantitative PCR (qPCR). The fast significantly decreased plasma FGF21 in obese subjects while no change in plasma FGF21 was observed in lean subjects. Interestingly, KLB was significantly decreased in WAT in response to fasting in both lean and obese subjects indicating a potential important adaptive regulation of KLB in response to fasting.


Nephrotoxic effects of aminoglycoside treatment on renal protein reabsorption and accumulation.
To quantify the effects of gentamicin, kanamycin and netilmicin on renal protein reabsorption and accumulation, these drugs were administered to rats intraperitoneally (30 mg/kg/day) for 7, 14 or 21 days. Scanning electron microscopy of the glomerular endothelia, urinary measurements of sodium, potassium, endogenous lysozyme, N-acetyl-beta-D-glucosaminidase (NAG) as well as clearance and accumulation experiments after i.v. administration of egg-white lysozyme and measurements of inulin clearance (GFR) were done in each treatment group. Gentamicin administration decreased diameter, density and shape of endothelial fenestrae. Kanamycin and netilmicin appeared to have no effect at the dose used. All three aminoglycosides decreased GFR and increased urinary excretion of sodium and potassium. While gentamicin and kanamycin decreased the percentage reabsorption and accumulation of lysozyme after i.v. administration of egg-white lysozyme netilmicin had no effect. Daily excretion of total protein, endogenous lysozyme and NAG increased only after treatment with kanamycin and gentamicin. Thus, aminoglycosides may act as nephrotoxicants at glomerular and/or tubular level inducing impairment of renal reabsorption and accumulation of proteins.


Firearm ownership and storage practices, U.S. households, 1992-2002. A systematic review.
Because the presence and improper storage of household firearms are risk factors for injury, it is important to understand the prevalence of ownership and storage practices within households to help guide intervention development. This systematic review of published articles (1992 to 2002) provides prevalence estimates of firearm ownership and storage practices in U.S. households. A search of bibliographic databases (MedLine, CINAHL, PsycInfo, Sociological Abstracts) was completed in January 2003. Although all were cross-sectional, the 42 articles included in this review varied in type; there were seven national and five state prevalence studies, as well as studies using clinic-based convenience samples (n =14) and samples of professionals (n =10). Published studies indicate that firearms are present in about one third of U.S. households. Handguns in particular are present in more than half of U.S. households with firearms, or about 19% of all U.S. households. The prevalence of firearms and handguns in households with young people was similar to the prevalence overall. Firearm ownership was highest in the South. Although the methodologic rigor of published articles varies substantially, the literature clearly establishes that firearms are common in U.S. households, even in the homes of medical professionals and those with children.


Technical Note: Initial characterization of the new EBT-XD Gafchromic film.
To assess the dosimetric accuracy and energy dependence of the new EBT-eXtended Dose (XD) Gafchromic film and to compare the lateral response artifact (LRA) between EBT-XD and EBT3 film. EBT3 and EBT-XD calibration curves were created by exposing films to known doses from 0 to 3000 cGy using a 6 MV beam. To assess the accuracy and dynamic range of EBT-XD, a 60° enhanced dynamic wedge (EDW) was used to deliver a dose range of approximately 200-2900 cGy. Comparison to treatment planning system (TPS) calculation was made using a gamma analysis with 2%/2 mm passing criteria. To assess and compare the LRA between EBT3 and EBT-XD, 21 × 21 cm(2) open fields delivered doses of 1000, 2000, and 3000 cGy to both types of film. Films were placed at the center of the scanner, and ratios of measured to TPS predicted doses were calculated at 50 and 80 mm lateral from the scanner center in order to quantitatively assess the LRA. To evaluate the energy dependence of EBT-XD film, seven known doses ranging from 400 to 3000 cGy were delivered using both 6 and 18 MV beams and the resulting optical densities (ODs) compared. The gamma passing rate was 99.1% for the 6 MV EDW delivery. EBT-XD film exhibited minimal LRA (<1%) up to 3000 cGy. In contrast, EBT3 demonstrated an under-response of 11.3% and 22.7% at lateral positions of 50 and 80 mm, respectively, for the 3000 cGy exposure. Differences between ODs of the EBT-XD films exposed to known doses from 6 to 18 MV beams were <0.8% suggesting minimal energy dependence throughout this energy range. The LRA of EBT-XD is greatly reduced when compared to EBT3. This in combination with its accuracy from 0 to 3000 cGy and minimal energy dependence from 6 to 18 MV makes EBT-XD film well suited for dosimetric measurements in high dose SRS/SBRT applications.


Competency assessment of the operating room staff and some related factors: A multi-center cross-sectional study.
Operating Rooms (ORs) are complicated environments that necessitate the improvement of OR staff's knowledge and skills to remain clinically competent and secure patient safety. The aim of this study was to assess clinical competence of OR staff in accordance with some related factors. This descriptive analytical cross-sectional study was conducted on 227 OR staff in nine academic hospitals. Sampling was performed from the beginning to the end of May 2019 and the samples were selected by quota sampling. Data were collected using a researcher-made questionnaire encompassing six dimensions of competency including general knowledge, specialized knowledge, general practical skills, specific practical skills, personality, and motivation. Data analysis was performed using descriptive and interpretive statistics. The mean (SD) total score of competence was 80.99, which was optimal (11.28). The lowest score was related to the dimension of general practical skills with the mean (SD) score of 53.32 (10.26). The mean score of specialized practical skills was significantly higher in single-specialty ORs (F = 21.53, p < 0.001). Based on multiple linear regression test, it was possible to predict clinical competency through the age and work experience (R-squared = 0.96, beta = 0.31, p = 0.022). Specialized training has overshadowed the general practical skills that are related to the observation of basic principles of patient safety apart from surgical specialization. Strengthening of competence in general practical skills need to be prioritized in empowerment programs. We need a fixed and permanent space for the continuation of educational programs designed to promote perioperative general practical skills.


Luspatercept for β-thalassemia: beyond red blood cell transfusions.
Red blood cell transfusions and iron chelation therapy are the cornerstone of treatment for β-thalassemia, with allogeneic hematopoietic stem cell transplantation and gene therapy offering further disease-management options for eligible patients. With up to 90% of severe cases of β-thalassemia occurring in resource-constrained countries, and estimates indicating that 22,500 deaths occur annually as a direct consequence of undertransfusion, provision of adequate treatment remains a major issue. In this review, we provide an overview of luspatercept, a first-in-class erythroid maturation agent, and present the available clinical data related to the treatment of β-thalassemia. The recent approval of luspatercept offers a new, long-term therapeutic option for adult patients with transfusion-dependent β-thalassemia to reduce red blood cell transfusion burden, anemia, and iron overload.


Localized Molecular Orbital-Based Embedding Scheme for Correlated Methods.
Embedding strategies currently provide the best compromise between accuracy and computational cost in modeling chemical properties and processes of large and complex systems. In this framework, different methods have been proposed all over the years, from the very popular QM/MM approaches to the more recent and very promising density matrix and density functional embedding techniques. Here, we present a further development of the quantum mechanics/extremely localized molecular orbital technique (QM/ELMO) method, a recently proposed multiscale embedding strategy in which the chemically active region of the investigated system is treated at a fully quantum mechanical level, while the rest is described by frozen extremely localized molecular orbitals previously transferred from proper libraries or tailor-made model molecules. In particular, in this work we discuss and assess in detail the extension of the QM/ELMO approach to density functional theory and post-Hartree-Fock techniques by evaluating its performances when it is used to describe chemical reactions, bond dissociations, and intermolecular interactions. The preliminary test calculations have shown that, in the investigated cases, the new embedding strategy enables the results of the corresponding fully quantum mechanical computations to be reproduced within chemical accuracy in almost all the cases but with a significantly reduced computational cost, especially when correlated post-Hartree-Fock strategies are used to describe the quantum mechanical subsystem. In light of the obtained results, we already envisage the future application of the new correlated QM/ELMO techniques to the investigation of more challenging problems, such as the modeling of enzyme catalysis, the study of excited states of biomolecules, and the refinement of macromolecular X-ray crystal structures.


Effect of maillard reaction on allergenicity of scallop tropomyosin.
Scallop tropomyosin (TM), the major allergen of shellfish, was prepared from adductor muscles and reacted with four reducing sugars to investigate the effect of the Maillard reaction on the allergenicity of TM. The IgE-binding ability of TM increased significantly with the progress of the reaction with glucose, ribose, and maltose, but not with maltotriose. The allergenicity was enhanced at the early stage of the Maillard reaction, and the trend of the effect depended on the type of reducing sugar used. 2,4,6-Trinitrobenzenesulfonic acid treatment of the lysine residues in TM showed that the protein surface charge resulting from the Maillard reaction had no effect on the enhancement of the allergenicity. Thus, the change in the allergenicity would be closely related to the structural change caused by the Maillard reaction.


A novel GJA8 mutation (p.V44A) causing autosomal dominant congenital cataract.
To examine the mechanism by which a novel connexin 50 (Cx50) mutation, Cx50 V44A, in a Chinese family causes suture-sparing autosomal dominant congenital nuclear cataracts. Family history and clinical data were recorded and direct gene sequencing was used to identify the disease-causing mutation. The Cx50 gene was cloned from a human lens cDNA library. Connexin protein distributions were assessed by fluorescence microscopy. Hemichannel functions were analyzed by dye uptake assay. Formation of functional channels was assessed by dye transfer experiments. Direct sequencing of the candidate GJA8 gene revealed a novel c.131T>C transition in exon 2, which cosegregated with the disease in the family and resulted in the substitution of a valine residue with alanine at codon 44 (p. V44A) in the extracellular loop 1 of the Cx50 protein. Both Cx50 and Cx50V44A formed functional gap junctions, as shown by the neurobiotin transfer assay. However, unlike wild-type Cx50, Cx50V44A was unable to form open hemichannels in dye uptake experiments. This work identified a unique congenital cataract in the Chinese population, caused by the novel mutation Cx50V44A, and it showed that the V44A mutation specifically impairs the gating of the hemichannels but not the gap junction channels. The dysfunctional hemichannels resulted in the development of human congenital cataracts.


A late-diagnosed phenylketonuria case presenting with autism spectrum disorder in early childhood.
Phenylketonuria is one of the most prevalent autosomal recessive hereditary disorders in Turkey. If untreated, it results in severe brain damage and can also be associated with autism in certain patients. We present a three-year old boy who exhibited the symptoms of autism and was subsequently diagnosed with phenylketonuria. This case illustrates that because the majority of autism cases are idiopathic, an occasional patient with a metabolic disorder might be overlooked especially in the era of newborn screening. We also discuss the possible pathogenetic processes leading to autistic symptoms in phenylketonuria, and wish to draw attention to the possibility of cases missed in the screening program because of less than 100% coverage or insufficient food intake before blood sampling. Clinicians should keep in mind the possibility of treatable disorders in children with autism even when such disorders appear unlikely.


Discordance in the diagnostic assessment of vulnerable plaques between radiofrequency intravascular ultrasound versus optical coherence tomography among patients with acute myocardial infarction: insights from the IBIS-4 study.
We aimed to evaluate the diagnostic agreement between radiofrequency (RF) intravascular ultrasound (IVUS) and optical coherence tomography (OCT) for thin-cap fibroatheroma (TCFA) in non-infarct-related coronary arteries (non-IRA) in patients with ST-segment elevation myocardial infarction (STEMI). In the Integrated Biomarker Imaging Study (IBIS-4), 103 STEMI patients underwent OCT and RF-IVUS imaging of non-IRA after successful primary percutaneous coronary intervention and at 13-month follow-up. A coronary lesion was defined as a segment with ≥ 3 consecutive frames (≈1.2 mm) with plaque burden ≥ 40% as assessed by grayscale IVUS. RF-IVUS-derived TCFA was defined as a lesion with > 10% confluent necrotic core abutting to the lumen in > 10% of the circumference. OCT-TCFA was defined by a minimum cap thickness < 65 μm. The two modalities were matched based on anatomical landmarks using a dedicated matching software. Using grayscale IVUS, we identified 276 lesions at baseline (N = 146) and follow-up (N = 130). Using RF-IVUS, 208 lesions (75.4%) were classified as TCFA. Among them, OCT identified 14 (6.7%) TCFA, 60 (28.8%) thick-cap fibroatheroma (ThCFA), and 134 (64.4%) non-fibroatheroma. All OCT-TCFA (n = 14) were confirmed as RF-TCFA. The concordance rate between RF-IVUS and OCT for TCFA diagnosis was 29.7%. The reasons for discordance were: OCT-ThCFA (25.8%); OCT-fibrous plaque (34.0%); attenuation due to calcium (23.2%); attenuation due to macrophage (10.3%); no significant attenuation (6.7%). There was a notable discordance in the diagnostic assessment of TCFA between RF-IVUS and OCT. The majority of RF-derived TCFA were not categorized as fibroatheroma using OCT, while all OCT-TCFA were classified as TCFA by RF-IVUS.ClinicalTrials.gov Identifier NCT00962416.


Transplanted Human Amniotic Epithelial Cells Secrete Paracrine Proangiogenic Cytokines in Rat Model of Myocardial Infarction.
Human amniotic epithelial cells (h-AECs) have been shown to differentiate into cardiomyocyte-like cells in vivo that can regenerate myocardial tissue and improve cardiac function in a rat model of myocardial infarction (MI). In this study, we investigated the paracrine factors released from h-AECs under hypoxic conditions to elucidate the possible mechanisms underlying this previously reported phenomenon of h-AEC-mediated cardiac repair. We used hypoxic cell culture conditions to simulate myocardial infarction in vitro. In comparison to normal conditions, we found that h-AECs secreted higher levels of several cytokines, including angiogenin (ANG), epidermal growth factor (EGF), interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1. To determine whether transplanted h-AECs express these proangiogenic cytokines in vivo, we ligated the coronary artery of rats to cause MI and injected either h-AECs or saline into the infarcted area. We found that the infarct and border zones of rat myocardium treated with h-AECs had higher expression levels of the human-origin cytokines ANG, EGF, IL-6, and MCP-1 compared to the tissues of saline-treated rats. In conclusion, h-AECs secreted proangiogenic cytokines in a rat model of MI, which may suggest that the paracrine effect by h-AECs could regenerate myocardial tissue and improve cardiac function.


Spatial and temporal trends of persistent organic pollutants and mercury in beluga whales (Delphinapterus leucas) from Alaska.
Remote locations, such as the Arctic, are often sinks for persistent contaminants which can ultimately bioaccumulate in local wildlife. Assessing temporal contaminant trends in the Arctic is important in understanding whether restrictions on legacy persistent organic pollutants (POPs) have led to concentration declines. Beluga whale (Delphinapterus leucas) tissue samples were collected from two subpopulations (Cook Inlet, Alaska and the eastern Chukchi Sea) between 1989 and 2006. Several POPs (polychlorinated biphenyls (PCBs), dichlorodiphenyldichloroethane and related compounds (DDTs), chlordanes, hexachlorocyclohexanes (HCHs), chlorobenzenes, mirex, polybrominated diphenyl ethers (PBDEs) and semi-quantitatively hexabromocyclododecanes (HBCDs)) were measured in 70 blubber samples, and total mercury (Hg) was measured in 67 liver samples from a similar set of individuals. Legacy POPs (PCBs, chlordanes, DDTs, and HCHs) were the predominant organic compound classes in both subpopulations, with median concentrations of 2360ng/g lipid for Σ80PCBs and 1890 ng/g lipid for Σ6DDTs. Backward stepwise multiple regressions showed that at least one of the four independent variables (subpopulation, sampling year, sex, and animal length) influenced the POP and Hg concentrations. ΣPCBs, ΣDDTs, Σchlordanes, Σchlorobenzenes, mirex, and Hg were significantly higher in belugas from the eastern Chukchi Sea than from the Cook Inlet (p≤0.0001). In contrast, Σ8PBDE and α-HBCD concentrations were significantly lower in belugas from the eastern Chukchi Sea than from the Cook Inlet (p<0.0001). Significant temporal increases in concentrations of Σ8PBDE and α-HBCD were observed for both subpopulations (p≤0.0003), and temporal declines were seen for ΣHCHs and Σchlorobenzenes in eastern Chukchi Sea belugas only (p≤0.0107). All other POP and Hg concentrations were stable, indicating either a lagging response of the Arctic to source reductions or the maintenance of concentrations by unregulated sources. Sex and length also significantly influenced some concentrations, and these findings are discussed.


Targeting the melanoma-associated antigen CSPG4 with HLA-C*07:01-restricted T-cell receptors.
Chondroitin sulfate proteoglycan 4 (CSPG4), also known as high molecular weight-melanoma associated antigen, is expressed in melanoma but also other tumor entities and constitutes an attractive target for immunotherapeutic approaches. While recent preclinical reports focused on anti-CSPG4 chimeric antigen receptors (CAR), we here explore T-cell receptor (TCR)-based approaches targeting CSPG4. The TCRs of two CSPG4-reactive T-cell clones (11C/73 and 2C/165) restricted by the highly prevalent HLA-C*07:01 allele were isolated and the respective αβTCR pairs were retrovirally expressed in CRISPR/Cas9-edited TCR-knockout T cells for functional testing. We also combined alpha and beta TCR chains derived from 11C/73 and 2C/165 in a cross-over fashion to assess for hemichain dominance. CSPG4+ melanoma, glioblastoma and lung cancer cell lines were identified and, if negative, retrovirally transduced with HLA-C*07:01. Functional tests confirmed specific recognition of CSPG4+HLA-C*07:01+ target cells by the αβTCR retrieved from the parental T-cell clones and in part also by the cross-over TCR construct 2Cα-11Cβ. Despite high surface expression, the 11Cα-2Cβ combination, however, was not functional. Collectively, 11C/73- and 2C/165-expressing T cells specifically and efficiently recognized CSPG4+HLA-C*07:01+ cancer cells which warrants further preclinical and clinical evaluation of these TCRs.


Inducible protein-10 as a predictive marker of antiviral hepatitis C treatment: A systematic review.
To investigate interferon-γ-inducible protein-10's (IP-10) potential to anticipate rapid (RVR)- and sustained virological responses (SVR) to chronic hepatitis C (CHC) treatment. We included case series examining RVR or SVR in relation to 24 or 48 wk treatment for CHC, in patients treatment free for at least six months, with genotype 1 or 4, and in relation to 24 wk treatment for genotype 2 and 3, with pegylated interferon in combination with ribavirin. Patients had to have both a baseline IP-10 level as well as a hepatitis C virus (HCV)-RNA determination 4 wk after treatment initiation or 24 wk after end of treatment. Studies including patients with liver diseases other than CHC, human immunodeficiency virus-infection, treatment with immunosuppresents or cytostatica, alcohol dependency or active intravenous drug-use were excluded. We found 81 articles by searching the MEDLINE and EMBASE databases. Eight studies were eligible for inclusion. Their quality were assesed using an 18 point checklist for case series, developed using a modified Delphi technique. Information was extracted from the articles, and no raw data was requisitioned. The review protocol was registered at the International Prospective Register of Systematic Reviews (reg. number: CRD42014008736). Three studies reported on baseline IP-10 level in association with RVR. A signigficant association was found for HCV genotype 1 infection by two studies. Only two studies reported on HCV genotype 4 infected and genotype 2 and 3 infected patients, respectively. A trend was seen for an association between RVR and baseline IP-10 for genotype 4, while no association was found for genotype 2 and 3. Seven studies provided information regarding baseline IP-10 and SVR. Following the pattern regarding rapid virological response all five studies examining SVR in relation to baseline IP-10 levels for HCV, genotype 1 infected patients showed a significant association. Likewise a significant association was seen for HCV, genotype 4 infected, while no association was found for HCV, genotype 2 and 3 infected. Though only two studies examined the assosiation for HCV genotype 4 infected and HCV genotype 2 and 3 infected respectively. We found indications of a possible association between baseline IP-10 level and virological responses in patients with CHC genotype 1 and 4.


The state-of-the-art pharmacotherapeutic options for the treatment of chronic non-cancer pain.
Pharmacotherapeutic options continue to expand for the treatment of chronic non-cancer pain. There has been an increasing emphasis on multimodal analgesia. This strategy employs use of multiple analgesic medications each with a distinct mechanism of action, which when administered concomitantly may provide profound analgesia. The authors describe evidence from randomized controlled trials and systematic reviews on a variety of established medications including anti-inflammatory agents, opioids, anti-convulsants, anti-depressants, N-methyl-D-aspartate receptor antagonists, sodium channel blockers, cannabinoids, and alpha-2-receptor blockers. Furthermore, they provide developing evidence on more novel pharmacotherapeutics including alpha lipoic acid, acetyl-L-carnitine, low-dose naltrexone, calcitonin gene-related peptide antagonists, targeted toxin therapy, Nav1.7 inhibitors, neurotensin agonists, purinoceptor antagonists, and sigma-1 receptor antagonists. Furthermore, the authors review the safety and adverse effect profile for these agents. In this era of the opioid epidemic, clinicians should first offer non-opioid analgesics and employ a multimodal analgesic strategy. Current guidelines recommend a personalized approach to the chronic pain treatment, in each case accounting for type, location, severity, and chronicity of pain. Clinicians should also carefully consider the risk-to-benefit ratio to the patient based on the drug side effect profile, patient age, and comorbidities.


Temporary right ventricular mechanical circulatory support for the management of right ventricular failure in critically ill patients.
Management of right ventricular (RV) failure after left ventricular assist device (LVAD) implantation is not evidence based. Temporary circulatory assistance has recently been reported to be of value for managing postoperative RV failure after LVAD implantation, but only in small series of patients or isolated case reports. We report here our experience with the use of temporary right ventricular assist devices (RVADs) in LVAD recipients. Forty-five of the 488 (9%) patients undergoing LVAD implantation between 2001 and 2011 at the Clinic for Thoracic and Cardiovascular Surgery in Bad Oeynhausen had RV failure requiring temporary RVAD. We analyzed preoperative data, complications, mortality at 6 months, and risk factors of death. The LVAD patients receiving temporary RVAD were younger than the 443 recipients of LVAD alone. They were more likely to have mechanical ventilation and haemofiltration and their Michigan right ventricular risk score was higher. The LVAD patients with temporary RVAD had a higher mortality at 6 months: 53%, versus 25% for patients receiving LVAD only (P < .001). The univariate risk factors for death were high blood urea nitrogen and C-reactive protein concentrations, preoperative mechanical ventilation, preoperative hemofiltration, destination therapy, the use of temporary RVAD, and the development of RV failure. Multivariate analyses did not identify predictors of death. The development of RV failure in LVAD recipients is a serious problem associated with high mortality. Temporary RV mechanical support is an acceptable way to manage postoperative RV failure in these severely ill LVAD recipients.


Changing patterns of lung cancer among socio-cultural groups in New York City.
Mortality statistics for New York City were used to examine lung cancer trends and differentials among Whites in three major religious groups. The percentage of deaths attributed to lung cancer increased among all groups of females and among all categories of males except those under age 45. The relatively low lung cancer levels among Jewish men observed in earlier studies have continued and are consistent with patterns of smoking reported for socio-cultural groups. Mortality from lung cancer among Jewish women was still relatively higher than for other women at some age groups.


Synthesis of Reabsorption-Suppressed Type-II/Type-I ZnSe/CdS/ZnS Core/Shell Quantum Dots and Their Application for Immunosorbent Assay.
We report a phosphine-free one-pot method to synthesize ZnSe/CdS/ZnS core-shell quantum dots (QDs) with composite type-II/type-I structures and consequent reabsorption suppression properties. The as-synthesized QDs possess high efficient red emission (with quantum yield of 82%) and high optical stability. Compared to type-I QDs, the ZnSe/CdS/ZnS QDs show larger Stokes shift and lower reabsorption which can reduce the emission loss and improve the level of fluorescence output. The ZnSe/CdS/ZnS QDs are used as fluorescent labels to exploit their application in fluorescence-linked immunosorbent assay (FLISA) for the first time in the detection of C-reactive protein (CRP) with a limit of detection (LOD) of 0.85 ng/mL, which is more sensitive than that of CdSe/ZnS type-I QDs based FLISA (1.00 ng/mL). The results indicate that the ZnSe/CdS/ZnS type-II/type-I QDs may be good candidates for applications in biomedical information detection.


Phylogenetic conservation and homology modeling help reveal a novel domain within the budding yeast heterochromatin protein Sir1.
The yeast Sir1 protein's ability to bind and silence the cryptic mating-type locus HMRa requires a protein-protein interaction between Sir1 and the origin recognition complex (ORC). A domain within the C-terminal half of Sir1, the Sir1 ORC interaction region (Sir1OIR), and the conserved bromo-adjacent homology (BAH) domain within Orc1, the largest subunit of ORC, mediate this interaction. The structure of the Sir1OIR-Orc1BAH complex is known. Sir1OIR and Orc1BAH interacted with a high affinity in vitro, but the Sir1OIR did not inhibit Sir1-dependent silencing when overproduced in vivo, suggesting that other regions of Sir1 helped it bind HMRa. Comparisons of diverged Sir1 proteins revealed two highly conserved regions, N1 and N2, within Sir1's poorly characterized N-terminal half. An N-terminal portion of Sir1 (residues 27 to 149 [Sir1(27-149)]) is similar in sequence to the Sir1OIR; homology modeling predicted a structure for Sir1(27-149) in which N1 formed a submodule similar to the known Orc1BAH-interacting surface on Sir1. Consistent with these findings, two-hybrid assays indicated that the Sir1 N terminus could interact with BAH domains. Amino acid substitutions within or near N1 or N2 reduced full-length Sir1's ability to bind and silence HMRa and to interact with Orc1BAH in a two-hybrid assay. Purified recombinant Sir1 formed a large protease-resistant structure within which the Sir1OIR domain was protected, and Orc1BAH bound Sir1OIR more efficiently than full-length Sir1 in vitro. Thus, the Sir1 N terminus exhibited both positive and negative roles in the formation of a Sir1-ORC silencing complex. This functional duality might contribute to Sir1's selectivity for silencer-bound ORCs in vivo.


Bayesian inference of phylogeny, morphology and range evolution reveals a complex evolutionary history in St. John's wort (Hypericum).
The genus Hypericum L. ("St. John's wort", Hypericaceae) comprises nearly 500 species of shrubs, trees and herbs distributed mainly in temperate regions of the Northern Hemisphere, but also in high-altitude tropical and subtropical areas. Until now, molecular phylogenetic hypotheses on infra-generic relationships have been based solely on the nuclear marker ITS. Here, we used a full Bayesian approach to simultaneously reconstruct phylogenetic relationships, divergence times, and patterns of morphological and range evolution in Hypericum, using nuclear (ITS) and plastid DNA sequences (psbA-trnH, trnS-trnG, trnL-trnF) of 186 species representing 33 of the 36 described morphological sections. Consistent with other studies, we found that corrections of the branch length prior helped recover more realistic branch lengths in by-gene partitioned Bayesian analyses, but the effect was also seen within single genes if the overall mutation rate differed considerably among sites or regions. Our study confirms that Hypericum is not monophyletic with the genus Triadenum embedded within, and rejects the traditional infrageneric classification, with many sections being para- or polyphyletic. The small Western Palearctic sections Elodes and Adenotrias are the sister-group of a geographic dichotomy between a mainly New World clade and a large Old World clade. Bayesian reconstruction of morphological character states and range evolution show a complex pattern of morphological plasticity and inter-continental movement within the genus. The ancestors of Hypericum were probably tropical shrubs that migrated from Africa to the Palearctic in the Early Tertiary, concurrent with the expansion of tropical climates in northern latitudes. Global climate cooling from the Mid Tertiary onwards might have promoted adaptation to temperate conditions in some lineages, such as the development of the herbaceous habit or unspecialized corollas.


Ultrastructure and Morphology of Compound Eyes of the Scorpionfly Panorpa dubia (Insecta: Mecoptera: Panorpidae).
Mecoptera are unique in holometabolous insects in that their larvae have compound eyes. In the present study the cellular organisation and morphology of the compound eyes of adult individuals of the scorpionfly Panorpa dubia in Mecoptera were investigated by light, scanning electron, and transmission electron microscopy. The results showed that the compound eyes of adult P. dubia are of the apposition type, each eye comprising more than 1200 ommatidia. The ommatidium consists of a cornea, a crystalline cone made up of four cone cells, eight photoreceptors, two primary pigment cells, and 18 secondary pigment cells. The adult ommatidium has a fused rhabdom with eight photoreceptors. Seven photoreceptors extend from the proximal end of the crystalline cone to the basal matrix, whereas the eighth photoreceptor is shorter, extending from the middle level of the photoreceptor cluster to the basal matrix. The fused rhabdom is composed of the rhabdomeres of different photoreceptors at different levels. The adult ommatidia have the same cellular components as the larval ommatidia, but the tiering scheme is different.


Validity of the BodyGem calorimeter and prediction equations for the assessment of resting energy expenditure in overweight and obese Saudi males.
To assess the accuracy of resting energy expenditure (REE) measurement in a sample of overweight and obese Saudi males, using the BodyGem device (BG) with whole room calorimetry (WRC) as a reference, and to evaluate the accuracy of predictive equations. Thirty-eight subjects (mean +/- SD, age 26.8+/- 3.7 years, body mass index 31.0+/- 4.8) were recruited during the period from 5 February 2007 to 28 March 2008. Resting energy expenditure was measured using a WRC and BG device, and also calculated using 7 prediction equations. Mean differences, bias, percent of bias (%bias), accurate estimation, underestimation and overestimation were calculated. Repeated measures with the BG were not significantly different (accurate prediction: 81.6%; %bias 1.1+/- 6.3, p>0.24) with limits of agreement ranging from +242 to -200 kcal. Resting energy expenditure measured by BG was significantly less than WRC values (accurate prediction: 47.4%; %bias: 11.0+/- 14.6, p = 0.0001) with unacceptably wide limits of agreement. Harris-Benedict, Schofield and World Health Organization equations were the most accurate, estimating REE within 10% of measured REE, but none seem appropriate to predict the REE of individuals. There was a poor agreement between the REE measured by WRC compared to BG or predictive equations. The BG assessed REE accurately in 47.4% of the subjects on an individual level.


Effect of the parent ligand on the photophysical properties of closely-coupled, binuclear ruthenium(II) tris(2,2'-bipyridine) complexes.
The photophysical properties of closely-coupled, binuclear complexes formed by connecting two ruthenium(II) tris(2,2'-bipyridine) complexes via an alkynylene group differ significantly from those of the relevant mononuclear complex. In particular, the energy of the first triplet excited state is lowered relative to the parent complex, because of the presence of the alkynylene substituent, while the triplet lifetime is prolonged, in part, because of extended electron delocalization. We now report that the triplet lifetime is also affected by the nature of the spectator 2,2'-bipyridyl ligands. Thus, replacing the parent 2,2'-bipyridine ligands with the corresponding 4,4'-dinitro-substituted ligands serves to decrease the luminescence yield and lifetime. With the corresponding carboxylate ester, the luminescence yield and lifetime are increased. Perdeuteration of the parent 2,2'-bipyridine ligands also leads to a modest increase in the luminescence yield. Such observations are indicative of electronic coupling between the various metal-to-ligand, charge-transfer excited triplet states. Temperature dependence studies confirm that these excited states are closely spaced and thermally accessible at ambient temperature. For some of the binuclear complexes, the quantum yield for formation of the lowest-energy triplet state is significantly less than unity.


Introducing a probabilistic definition of the target in a robust treatment planning framework.
The 'clinical target distribution' (CTD) has recently been introduced as a promising alternative to the binary clinical target volume (CTV). However, a comprehensive study that considers the CTD, together with geometric treatment uncertainties, was lacking. Because the CTD is inherently a probabilistic concept, this study proposes a fully probabilistic approach that integrates the CTD directly in a robust treatment planning framework. First, the CTD is derived from a reported microscopic tumor infiltration model such that it explicitly features the probability of tumor cell presence in its target definition. Second, two probabilistic robust optimization methods are proposed that evaluate CTD coverage under uncertainty. The first method minimizes the expected-value (EV) over the uncertainty scenarios and the second method minimizes the sum of the expected value and standard deviation (EV-SD), thereby penalizing the spread of the objectives from the mean. Both EV and EV-SD methods introduce the CTD in the objective function by using weighting factors that represent the probability of tumor presence. The probabilistic methods are compared to a conventional worst-case approach that uses the CTV in a worst-case optimization algorithm. To evaluate the treatment plans, a scenario-based evaluation strategy is implemented that combines the effects of microscopic tumor infiltrations with the other geometric uncertainties. The methods are tested for five lung tumor patients, treated with intensity-modulated proton therapy. The results indicate that for the studied patient cases, the probabilistic methods favor the reduction of the esophagus dose but compensate by increasing the high-dose region in a low conflicting organ such as the lung. These results show that a fully probabilistic approach has the potential to obtain clinical benefits when tumor infiltration uncertainties are taken into account directly in the treatment planning process.


The nutrition and health transition in Malaysia.
The accelerated phase of industrialisation and urbanisation in recent decades has inevitably brought about changes in the lifestyle of Malaysians. Changes in dietary habits and sedentary lifestyles are known to be associated with changes in health and increased prevalence of chronic diseases in the population. The objective of this paper is to provide a better understanding of the link between demographic variables and food consumption patterns related to the nutrition transition in Malaysia. This review uses various reports and publications from several ministries and selected local studies. The statistics compiled over the last two decades have shown that as the population achieves affluence, intakes of calories, fats and sugars increase, which may account for the substantial increase in food importation bills over the same period. Similarly, the rapid growth of the fast food industry during the last decade has added another dimension to the change in food consumption patterns of Malaysians. With the exception of a study on adolescents, the prevalences of overweight and obesity in children and adults are not strictly comparable due to the difference in body mass index (BMI) cut-off points in children and the study protocol in adults, and hence should not be misinterpreted as trends. The recent recommendation to lower the BMI cut-off points for Asians would only increase the magnitude of the existing prevalence among adults. The need to promote healthy nutrition for the population must be pursued vigorously, as the escalation of nutrition-related chronic degenerative diseases - once an urban phenomenon--has now spread to the rural population at an alarming rate. This paper indicates that the problem is real and needs urgent attention because it may be just the tip of the iceberg.


Ganciclovir therapy for congenital cytomegalovirus infection in six infants.
Congenital cytomegalovirus (CMV) infection is common, and its morbidity rate is high. Ganciclovir (GCV) treatment has been used for congenital CMV infection, but there are few reports on viral loads associated with GCV therapy. A real-time PCR assay was used to monitor viral load in 6 cases of symptomatic CMV infection that received GCV therapy. Initially GCV was given at a dose of 5-12 mg/kg/d for 2-7 weeks. In 2 cases, additional doses were given as symptoms returned. After GCV administration, active signs of chorioretinitis, thrombocytopenia and anemia disappeared or improved in all cases. During GCV therapy, viral loads decreased while patients improved clinically and increased again when GCV therapy was stopped. Although CMV DNA continued to be detectable for a long period, clinical findings did not always worsen. In 2 cases, an improvement of hearing loss was observed. GCV therapy transiently suppresses the CMV concentrations. Subsequent increases of viral titers do not appear to be correlated with the clinical course or neurologic outcome.


[Pathophysiology of idiopathic pulmonary fibrosis].
Despite renewed interest in IPF the precise biological mechanisms underlying the development of pulmonary fibrosis and irreversible lung destruction remain elusive. Inflammation seems to play a minor role at initial onset. Excessive apoptosis of alveolar epithelial cells in this setting suggests that IPF may result from repeated alveolar epithelial cell injury and activation. This would induce the recruitment, proliferation and activation of mesenchymal cells, leading to the formation of fibroblastic foci and abnormal accumulation of extracellular matrix. The fibroblastic foci are inter-connected in a three-dimensional reticulum. Circulating mesenchymal precursors called fibrocytes, and transdifferentiation of epithelial cells, endothelial cells and/or mesothelial cells, may all contribute to fibroblast accumulation in the lung.


Positive emotions and favorable cardiovascular health: A 20-year longitudinal study.
No studies have examined whether positive emotions lead to favorable cardiovascular health (CVH) early in the lifespan, before cardiovascular disease is diagnosed. Moreover, the direction of the association has not been thoroughly investigated. Among younger adults, we investigated whether baseline positive emotions were associated with better CVH over 20 years. We also considered whether baseline CVH was associated with subsequent positive emotions during the same period. Participants included 4196 Black and White men and women from the Coronary Artery Risk Development in Young Adults Study. Positive emotions and cardiovascular-related parameters were each assessed in 1990 (this study's baseline), with repeated assessment through 2010. CVH was defined by blood pressure, lipids, body mass index, diabetes, and smoking status. Primary analyses used linear mixed effects models adjusting for potential confounders; secondary analyses stratified by race and sex. Controlling for sociodemographic factors, greater baseline positive emotions were associated with better CVH across time (β = 0.03, 95% confidence interval = 0.007-0.06). However, positive emotions were unrelated to rate of change in CVH across time. Baseline CVH was also associated with greater average positive emotions across time (β = 0.09, 95% confidence interval = 0.02-0.15), but not rate of change. Positive emotions' association with CVH was stronger for women than men, but race did not modify associations. Positive emotions in early to middle adulthood were associated with better CVH across several decades. Baseline CVH was also associated with greater positive emotions during follow-up. Future research may be able to disentangle these relationships by assessing positive emotions and CVH earlier in life.


The Evaluation of Geroprotective Effects of Selected Flavonoids in Drosophila melanogaster and Caenorhabditis elegans.
Flavonoids is an intensively studied group of natural compounds with antioxidant, antineoplastic, antihyperglycemic, cardioprotective, and neuroprotective properties. The present study intends to investigate the geroprotective action of three selected flavonoids (naringin, luteolin, chrysin) in two model organisms, Caenorhabditis elegans and Drosophila melanogaster. Luteolin and chrysin were shown to improve lifespan parameters when administered to both model organisms. The observed positive effects of these flavonoids in D. melanogaster were limited to females and were not associated with reduced fecundity or locomotor impairment. The life-extending effects of flavonoids were observed in N2 wild-type worms but absent in aak-2(gt33) mutants implying that these effects can be associated with AMP-activated protein kinase activity. Naringin improved lifespan parameters of C. elegans, but had no effect on D. melanogaster females; in some cases, naringin was found to decrease the lifespan of males. Compared to chrysin and luteolin, however, naringin more effectively activates Nrf2 target genes (particularly, GstD1) under oxidative stress. Then we compared molecular mechanisms of studied compounds and a well-known geroprotector rapamycin, using software tool GeroScope. There are no transcriptomic data on luteolin or chrysin provided by LINCS Project database. The bioinformatics comparison of transcriptomics data for A549 and MCF7 human cell lines treated with rapamycin or naringin revealed that these compounds share just a few common signaling pathways and quite distinct in their geroprotective action. Thus, based on C. elegans effects of naringin, luteolin, chrysin on lifespan we have revealed new potential geroprotectors.


Genome-wide survey for chromosomal imbalances in ganglioglioma using comparative genomic hybridization.
Ganglioglioma is a mixed neuronal and glial tumor first described by Perkin in 1926. Because of its rare occurrence in the central nervous system, the pathogenesis of this neoplasm is still largely unknown. Previous studies of ganglioglioma mainly focused on histologic features, immunohistochemical analysis, clinical treatment, and patient outcome. Very few cytogenetic and molecular genetic studies have been reported on this neoplasm. To better understand the mechanism underlying the development of ganglioglioma, we performed comparative genomic hybridization analysis to investigate chromosomal imbalances across the entire genome in five cases of gangliogliomas. Loss of genetic material on the short arm of chromosome 9 was a common genetic alteration found in three of five cases. Overrepresentation of partial or the whole chromosome 7 was another recurrent chromosomal imbalance, confirmed by fluorescence in situ hybridization. Immunohistochemical analysis was performed; all five cases revealed no reaction or low expression for epidermal growth factor receptor antibody. Our study highlights chromosomal regions for further fine mapping and investigation of candidate tumor suppressor genes involved in the pathogenesis of ganglioglioma.


Ocular allergy. Scratching the surface of the red eye.
The primary care physician may be the first physician to evaluate conjunctivitis caused by allergy or infection. A proper diagnosis can usually be made by asking the patient a few simple questions. Treatment with eyedrops is not always necessary. When the diagnosis is uncertain, treatment is best withheld, because "shotgun" therapy is seldom beneficial. Corticosteroid eyedrops are rarely necessary. When they are used, the physician must monitor intraocular pressure and examine the eye with a slit-lamp microscope for signs of cataract and opportunistic infection. Because there is a tendency to overtreat eye disorders, improvement of ocular inflammation is more often accomplished by stopping drug administration than by starting it.


First report of Stenotrophomonas maltophilia causing root soft rot of Sanqi (Panax notoginseng) in China.
Sanqi (Panax notoginseng (Burk.) F. H. Chen) is a traditional Chinese medicinal plant with a long planting cycle of 2-3 years that makes it vulnerable to root diseases caused by several pathogens, including Fusarium solani, Alternaria panax, Phytophthoracactorum, and Pseudomonas sp. In April 2019, root soft rot samples of Sanqi were collected from a plantation site in Songming, southwest of China. Typical symptoms included root softening and necrosis, yellow leaf, and stem wilting. Ten diseased roots samples were collected and sterilized with 0.1% HgCl2 for 1 min, 75% ethanol for 2min, and then rinsed thrice with sterile water. Sterilized roots were cut into small pieces of 5 × 5 mm and cultured on the nutrient agar (NA) medium for 48 h at 28°C. From the root cultures, a total of thirteen bacterial strains were obtained. Three strains, SM 2-5, SM 2-13, and SM 2-14 were selected for further study. These three strains were gram-negative, short rod-shaped (1~2×0.5~1μm), non-spore-forming and had polar tufted flagella as observed under a transmission electron microscope (TEM). Also, the strains were positive for oxidase, beta-galactosidase, arginine dihydrolase, and lysine decarboxylase while negative for amylase and urease tested by biochemical methods (Wang 2017). To further determine the pathogenic species, genomic DNA of these three strains was extracted using a Genomic DNA Kit (Tsing Ke, Beijing, China), to PCR amplify 16S rDNA using universal primers 27F/1492R (Wang et al. 2017). Also, S. maltophilia 23S rDNA specific primers SM1/SM4 (Whitby et al. 2000) were used for PCR amplification to confirm the species. 16S rDNA sequence analysis showed that SM 2-5 (GenBank Accession No. MW555227), SM 2-13 (GenBank Accession No. MW555228), and SM 2-14 (GenBank Accession No. MW555229) shared the highest identity (>99.9%) with the S. maltophilia strains (GenBank Accession No. MT323142, MH669295, MN826555). Furthermore, 23S rDNA sequence analysis of SM 2-5 (GenBank Accession No. MZ707732), SM 2-13 (GenBank Accession No. MZ645941) and SM 2-14 (GenBank Accession No. MZ707733) revealed their high identity (>99.8%) with the S. maltophilia species. 16S and 23S rDNA phylogenetic analysis (Mega6.06) using the neighbor-joining (NJ) method with 1,000 bootstrap replicates revealed the three strains clustering with the other S. maltophilia strains. Therefore, based on morphology, metabolic profile, and sequence analysis, the three strains were identified as Stenotrophomonas maltophilia. To test pathogenicity, the strains were grown in the nutrient broth (NB) medium for 48h at 28°C until bacterial suspension reached to OD600≈1.0 (2.0×109CFU/mL). Then, healthy roots of one-year-old Sanqi plants, pre-washed with sterilized water and -poked with a sterilized needle, were soaked in bacterial suspension (2.0×109CFU/mL) of the three strains separately for inoculation 10min. Sterilized water treatment was used as a control. Subsequently, bacteria-inoculated plants were planted in sterile soil pots and cultured in a greenhouse at 28°C with shading rate of 70%. Each treatment group included 3 plants with 3 replicates. Ten days post inoculation, symptoms similar to the ones in natural conditions were observed in the bacteria-inoculated plants. Based on the disease index (Li et al. 2020), we found that among the three strains, SM 2-13 displayed the highest virulence, while no symptoms were observed in the control plants. The same bacterial strains were re-isolated from these inoculated roots and identified by the methods described above. Previous studies showed that some Stenotrophomonas species cause plant diseases such as rice white stripe (Singh et al. 2001), strawberry leaf black spot (Wang et al. 2017), Cyclobalanopsis patelliformis leaf spot (Bian et al. 2020), and Jatropha curcas L. seed borne and stem necrosis (Wang et al. 2018). To our knowledge, this is the first report confirming Stenotrophomonas maltophilia causing root soft rot of Panax notoginseng in China.


Organochlorine Pesticides (OCPs) in raft mussels coming from Galician rías.
This survey gives an overview of the range of organochlorine pesticides (OCPs) α and γ-HCH (lindane), HCB, pp´-DDE, pp´-DDD, op´-DDT, pp´-DDT, aldrin, dieldrin, endrin, isodrin and trans-nonachlor in raft mussels cultivated in several polygons of the Galician Rías (Ares-Betanzos, Muros-Noia, Arousa, Pontevedra and Vigo) during the period 1998-2014. A significant number of OCPs were detected, but the levels found were generally low, mainly in the recent samplings (2010-2014). The levels of ∑DDs (sum of DDTs and its metabolites, pp´-DDE and pp´-DDD) ranged between 0.22 ng/g dry weight (dw) in samples from the Ría of Pontevedra and 46.4 ng/g dw in mussels from the Ría of Arousa. Both aldrin and endrin were not detected or were below the analytical limits of detection. With regard to other pesticides, dieldrin is the major compound, followed by γ-HCH, isodrin, α-HCH and transnonachlor. Significant ANOVA regressions indicated variations in levels of some OCPs with the biological parameters (lipid, condition index and shell length). Univariate and multivariate analysis of OCP levels revealed no significant differences between Rías. Temporal trends showed an important decline of OCPs in the studied samples during the period 1998-2014.


The development of magnesium-based biomaterials in bone tissue engineering: A review.
Bone regeneration is a vital clinical challenge in massive or complicated bone defects. Recently, bone tissue engineering has come to the fore to meet the demand for bone repair with various innovative materials. However, the reported materials usually cannot satisfy the requirements, such as ideal mechanical and osteogenic properties, as well as biocompatibility at the same time. Mg-based biomaterials have considerable potential in bone tissue engineering owing to their excellent mechanical strength and biosafety. Moreover, the biocompatibility and osteogenic activity of Mg-based biomaterials have been the research focuses in recent years. The main limitation faced in the applications of Mg-based biomaterials is rapid degradation, which can produce excessive Mg2+ and hydrogen, affecting the healing of the bone defect. In order to overcome the limitations, researchers have explored several ways to improve the properties of Mg-based biomaterials, including alloying, surface modification with coatings, and synthesizing other composite materials to control the degradation rate upon implantation. This article reviewed the osteogenic mechanism and requirement for appropriate degradation rate and focused on current progress in the biomedical use of Mg-based biomaterials to inspire more clinical applications of Mg in bone regeneration in the future.


Quadriceps atrophy in the anterior cruciate insufficient knee.
Atrophy of the quadriceps musculature is frequently associated with chronic knee instability. This atrophy may persist despite the patient's ability to return to athletic competition. When open biopsies of the quadriceps muscle from unstable knees were compared with those from normal acutely injured knees, it was found that clinical evidence of atrophy correlated with a relative decrease in the size of Type II or fast twitch muscle fibers. This supports the subjective, clinical impression that the unstable knee is less effective in explosive push-off. The findings also indicate the necessity of including exercise specific for the training of Type II fast twitch fibers in any program designed to rehabilitate the injured knee.


A neural basis for inference in perceptual ambiguity.
When looking at ambiguous visual stimuli, the observer experiences frequent spontaneous transitions between two competing percepts while physical stimulation remains unchanged. Despite recent advances in understanding the neural processes underlying such perceptual rivalry, a key question has remained unresolved: Does perceptual rivalry result merely from local bistability of neural activity patterns in sensory stimulus representations, or do higher-order areas play a causal role by shifting inference and, thus, initiating perceptual changes? We used functional MRI to measure brain activity while human observers reported successive spontaneous changes in perceived direction for an ambiguous apparent motion stimulus. In a control condition, the individual sequences of spontaneous perceptual switches during bistability were replayed by using a disambiguated version of the stimulus. Greater activations during spontaneous compared with stimulus-driven switches were observed in inferior frontal cortex bilaterally. Subsequent chronometric analyses of event-related signal time courses showed that, relative to activations in motion-sensitive extrastriate visual cortex, right inferior frontal cortex activation occurred earlier during spontaneous than during stimulus-driven perceptual changes. The temporal precedence of right inferior frontal activations suggests that this region participates in initiating spontaneous switches in perception during constant physical stimulation. Our findings can thus be seen as a signature of when and where the brain "makes up its mind" about competing perceptual interpretations of a given sensory input pattern.


Analysis of Voiding Impairment after Prostate Biopsy and the Effect of Doxazosin Treatment: Outcomes from a Regional Cancer Center.
The aim of this study was to investigate the association of transrectal ultrasound (TRUS)-guided prostate biopsy with voiding impairment and the efficacy of doxazosin treatment. A prospective observational study including 200 male patients undergoing TRUS-guided prostate biopsy was performed between May 2020 and December 2020. One hundred patients underwent biopsy with doxazosin (doxazosin group). The remaining 100 patients underwent biopsy without doxazosin (control group). All patients were questioned regarding post-biopsy voiding difficulty and acute urinary retention. The International Prostate Symptom Score (IPSS), maximal urinary flow rate (Qmax), and residual urine volume were recorded before biopsy and at 7 and 30 days after biopsy. There were no significant differences in baseline parameters between the two groups. The rate of post-biopsy voiding difficulty in the doxazosin group was significantly lower than that in the control group. Compared with baseline values, doxazosin treatment significantly improved IPSS, quality of life scores, and Qmax after biopsy (p < 0.05). The baseline values of IPSS and prostate size may be risk factors for post-biopsy voiding difficulty. TRUS-guided prostate biopsy causes transient voiding impairments, which may be improved by doxazosin treatment.


The phosphate transporters LjPT4 and MtPT4 mediate early root responses to phosphate status in non mycorrhizal roots.
Arbuscular mycorrhizal (AM) symbiosis improves host plant phosphorous (P) status and elicits the expression of AM-inducible phosphate transporters (PTs) in arbuscule-containing cells, where they control arbuscule morphogenesis and P release. We confirmed such functions for LjPT4 in mycorrhizal Lotus japonicus. Promoter-GUS experiments showed LjPT4 transcription not only in arbusculated cells but also in root tips, in the absence of the fungus: here LjPT4 transcription profile depended on the phosphate level. In addition, quantitative RT-PCR confirmed the expression of Lotus and Medicago truncatula PT4 in the tips of non-mycorrhizal roots. Starting from these observations, we hypothesized that AM-inducible PTs may have a regulatory role in plant development, irrespective of the fungal presence. Firstly, we focused on root development responses to different phosphate treatments in both plants demonstrating that phosphate starvation induced a higher number of lateral roots. By contrast, Lotus PT4i plants and Medicago mtpt4 mutants did not show any differential response to phosphate levels, suggesting that PT4 genes affect early root branching. Phosphate starvation-induced genes and a key auxin receptor, MtTIR1, showed an impaired expression in mtpt4 plants. We suggest PT4 genes as novel components of the P-sensing machinery at the root tip level, independently of AM fungi.


The impact of birth weight on infectious disease hospitalization in childhood.
Low birth weight, a result of preterm birth or intrauterine growth restriction, is a well-established indicator of survival in childhood. However, corresponding epidemiologic studies of the association between low birth weight and morbidity from infections throughout childhood are sparse. The authors evaluated the relation between birth weight and infectious diseases throughout childhood in a population-based cohort study comprising all children born in Denmark from 1977 through 2004 (n = 1.7 million). Information on birth weight, gestational age, and potential confounding variables was linked to the children in the cohort, together with information on hospitalization with infectious disease. Poisson regression yielded rate ratios of hospitalization according to birth weight. The authors found that birth weight was inversely associated with risk of infectious disease hospitalization; among children aged 0-14 years, the risk of hospitalization increased 9% for each 500-g reduction in birth weight (increase in rate ratio = 1.09, 95% confidence interval: 1.09, 1.11). The effect was found to peak in infancy and to persist until 10 years of age. It was present also in children born at term (37-41 weeks of gestation). The present study is the first to demonstrate the measurable impact of birth weight on infectious diseases throughout childhood.


Catalytic CO2 Reduction with Heptacoordinated Polypyridine Complexes: Switching the Selectivity via Metal Replacement.
The discovery of molecular catalysts for the CO2 reduction reaction (CO2 RR) in the presence of water, which are both effective and selective towards the generation of carbon-based products, is a critical task. Herein we report the catalytic activity towards the CO2 RR in acetonitrile/water mixtures by a cobalt complex and its iron analog both featuring the same redox-active ligand and an unusual seven-coordination environment. Bulk electrolysis experiments show that the cobalt complex mainly yields formate (52 % selectivity at an applied potential of -2.0 V vs Fc+ /Fc and 1 % H2 O) or H2 (up to 86 % selectivity at higher applied bias and water content), while the iron complex always delivers CO as the major product (selectivity >74 %). The different catalytic behavior is further confirmed under photochemical conditions with the [Ru(bpy)3 ]2+ sensitizer (bpy=2,2'-bipyridine) and N,N-diisopropylethylamine as electron donor, where the cobalt complex leads to preferential H2 formation (up to 89 % selectivity), while the iron analog quantitatively generates CO (up to 88 % selectivity). This is ascribed to a preference towards a metal-hydride vs. a metal-carboxyl pathway for the cobalt and the iron complex, respectively, and highlights how metal replacement may effectively impact on the reactivity of transition metal complexes towards solar fuel formation.


Epidemiology of genital prolapse: observations from the Oxford Family Planning Association Study.
To explore the epidemiology of uterovaginal and post-hysterectomy prolapse. Cohort study. Seventeen large family planning clinics in England and Scotland. 17,032 women who attended family planning clinics between 1968 and 1974, aged between 25 and 39 years at study entry. Annual follow up by interview, postal or telephone questionnaire until July 1994. Further details on all hospital admissions were obtained from the hospital discharge summaries. All women were flagged at time of recruitment in the NHS central registers. In-patient admission with diagnosis of prolapse (ICD codes 8th Revision 623.0-623-9). The incidence of hospital admission with prolapse is 2.04 per 1000 person-years of risk. Age, parity, calendar period and weight were significantly associated with risk of an inpatient admission with prolapse after adjustment for principal confounding factors. Significant trends were observed with regard to smoking status and obesity (Quetelet Index) at entry to the study and risk of prolapse. Social class, oral contraceptive use and height were not significantly associated with risk of prolapse. The incidence of prolapse which required surgical correction following hysterectomy was 3.6 per 1000 person-years of risk. The cumulative risk rises from 1% three years after a hysterectomy to 5% 15 years after hysterectomy. The risk of prolapse following hysterectomy is 5.5 times higher (95% CI 3.1-9.7) in women whose initial hysterectomy was for genital prolapse as opposed to other reasons. Among the potential risk factors that were investigated, parity shows much the strongest relation to prolapse.


Association between platelet endothelial cellular adhesion molecule-1 polymorphisms and atherosclerosis: results of a study on patients from northern Italy.
Adhesion of circulating cells to the arterial surface is among the first detectable events in atherogenesis. Cellular adhesion molecules, expressed by the vascular endothelium and by circulating leukocytes, mediate cell recruitment and their transendothelial migration. Platelet endothelial cellular adhesion molecule-1 (PECAM-1), involved in this migration, has been associated with the development of atherosclerosis. Studies have investigated an association between coronary artery disease (CAD) and single-nucleotide polymorphisms (SNPs) located in functionally important domains of the PECAM-1 gene with inconsistent results. Thus, we have analyzed the distribution of V125L, N563S, and G670R SNPs in patients and controls from northern Italy, and also analyzed another functional variant identified in the 5'-untranslated region (UTR) of the PECAM-1 gene (53 G-->A). The polymorphisms of PECAM-1 were genotyped by PCR amplification with sequence-specific primers (PCR-SSP) in 119 controls and 431 CAD patients. Our results demonstrate that genotype and allele frequencies for the 53 G/A polymorphism are significantly different in patients affected by CAD compared to healthy controls, whereas, as regards the V125L and N563S polymorphisms, only the allelic frequency is significantly different. We have shown that there were a significant differences for the 53 G/A and V125L and N563S polymorphisms of PECAM-1 in patients affected by CAD compared to controls. This demonstrates a possible involvement of this gene in contributing to the development of CAD. Therefore, an understanding of the role of the PECAM-1 molecule in this complex mechanism is of pivotal significance in further development of innovative and suitable medical therapies in the future.


Rational strain engineering of single-atom ruthenium on nanoporous MoS2 for highly efficient hydrogen evolution.
Maximizing the catalytic activity of single-atom catalysts is vital for the application of single-atom catalysts in industrial water-alkali electrolyzers, yet the modulation of the catalytic properties of single-atom catalysts remains challenging. Here, we construct strain-tunable sulphur vacancies around single-atom Ru sites for accelerating the alkaline hydrogen evolution reaction of single-atom Ru sites based on a nanoporous MoS2-based Ru single-atom catalyst. By altering the strain of this system, the synergistic effect between sulphur vacancies and Ru sites is amplified, thus changing the catalytic behavior of active sites, namely, the increased reactant density in strained sulphur vacancies and the accelerated hydrogen evolution reaction process on Ru sites. The resulting catalyst delivers an overpotential of 30 mV at a current density of 10 mA cm-2, a Tafel slope of 31 mV dec-1, and a long catalytic lifetime. This work provides an effective strategy to improve the activities of single-atom modified transition metal dichalcogenides catalysts by precise strain engineering.


Refolding of laccase from Trametes versicolor using aqueous two phase systems: Effect of different additives.
Protein refolding is a strategy used to obtain active forms of proteins from inclusion bodies. On its part, laccase is an enzyme with potential for different biotechnological applications but there are few reports regarding its refolding which in many cases is considered inefficient due to the poor obtained refolding yields. Aqueous Two-Phase Systems (ATPS) have been used for the refolding of proteins getting acceptable recovery percentages since PEG presents capacity to avoid protein aggregation. In this work, 48 PEG-phosphate ATPS were analyzed to study the impact of different parameters (i.e. tie line length (TLL), volume ratio (VR) and PEG molecular weight) upon the recovery and refolding of laccase. Additionally, since laccase is a metalloprotein, the use of additives (individually and in mixture) was studied with the aim of favoring refolding. Results showed that laccase presents a high affinity for the PEG-rich phase obtaining recovery values of up to 90%. Such affinity increases with increasing TLL and decreases when PEG molecular weight and VR increase. In denatured state, this PEG-rich phase affinity decreases drastically. However, the use of additives such as l-cysteine, glutathione oxidized, cysteamine and Cu+2 was critical in improving refolding yield values up to 100%. The best conditions for the refolding of laccase were obtained using the PEG 400gmol-1, TLL 45% w/w, VR 3 ATPS and a mixture of 2.5mM cysteamine with 1mM Cu+2. To our knowledge, this is the first time that the use of additives and the behavior of the mixture of such additives to enhance refolding performance in ATPS is reported.


Prevalence and clinical correlation of dysphagia in Parkinson disease: a study on Chinese patients.
Dysphagia is relatively common in patients with Parkinson disease (PD) and can have a negative impact on their quality of life; therefore, it is imperative that its prevalence in PD patients is studied. The aim of this study was to explore the prevalence and clinical correlation of dysphagia in Chinese PD patients. We recruited 116 Chinese PD patients. A videofluoroscopic study of swallowing (VFSS) was used to identify dysphagia. Assessments, including water drinking test, relative motor symptoms, non-motor symptoms (NMS) and quality of life, were performed to analyze the risks of dysphagia. The prevalence of dysphagia was 87.1%. The comparison of demographic and clinical features between patients with and without dysphagia included sex, education level, disease course, Mini-mental State Examination (MMSE), Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), Question 6, 7 of the Unified Parkinson Disease Rating Scale (UPDRS Part II), Hoehn-Yahr stage (H&Y), water drinking test, 39-item Parkinson Disease Questionnaire (PDQ-39) and Non-Motor Symptoms Quest (NMSQ). We found significant correlations between dysphagia and age. Using age, disease course, and H&Y stage as the independent variable in our regression analysis for assessing the risk factors of dysphagia in PD patients, age and H&Y stage displayed a strong correlation as the risk factors. The risk of dysphagia in elderly PD patients is 1.078 times greater than that of younger PD patients. Also, the risk of dysphagia in PD patients of a greater H&Y staging is 3.260 times greater than that of lower staging PD patients. Our results suggest that dysphagia is common in Chinese PD patients. Older patients or those in higher H&Y stages are more likely to experience dysphagia. There is no correlation between dysphagia and PD duration.


The AutGO Initiative: A Conceptual Framework for Developing Genetics-Outcomes Research Hypotheses.
The increasing emphasis on translational approaches to complex neuropsychiatric and neurodevelopmental conditions research requires scientists from a broad range of disciplines to build dynamic collaborations when formulating hypotheses and framing study designs. The need to integrate the knowledge and perspectives not only from multiple scientific silos but also from the populations impacted by these conditions presents a significant challenge to researchers, particularly for a heterogeneous condition like autism. As one path toward addressing these challenges, we have previously introduced Autism Genetics Outcomes (AutGO), an initiative to support broad stakeholder partnerships and promote a new integrated concept called GO (i.e., research approaches that draw on both genetics and clinical outcomes perspectives). Herein, we developed a workflow for collecting stakeholders' feedback toward the development of a GO hypothesis. AutGO is an evolving initiative, and here we describe how its three essential components (conceptual framework, applicability, and implementation) have been developed. As a proof-of-concept, the AutGO team sought to demonstrate how a GO hypothesis could be developed using a semi-structured literature review workflow. We also developed a prototype from published reports and formulated a GO hypothesis for autism. Rather than seeking community stakeholder input after a research project is conceptualized and designed, the developed conceptual framework demonstrates the feasibility of formulating scientific hypotheses by engaging stakeholders in retrospective semi-structured literature reviews. The presented workflow, prototype, and discussed recommendations will bring awareness in the autism research community about the benefits of applying the GO approach in order to promote translational aspects in genetics research. LAY SUMMARY: We used a community-based engagement approach to develop AutGO (Autism Genetics Outcomes), an initiative to establish stakeholder partnerships and to promote research approaches (we refer to as GO) that draw on both genetics and clinical outcomes perspectives. Specifically, we developed a conceptual framework that includes a literature review process for developing GO hypotheses and stakeholder feedback collection protocol. Our work will bring awareness in the autism research community about the benefits of integrating patient perspectives in genetics research. Autism Res 2020, 13: 1286-1299. © 2020 The Authors. Autism Research published by International Society for Autism Research published by Wiley Periodicals LLC.


The effects of sodium bicarbonate ingestion on cycling performance and acid base balance recovery in acute normobaric hypoxia.
This study investigated the effects of two separate doses of sodium bicarbonate (NaHCO3) on 4 km time trial (TT) cycling performance and post-exercise acid base balance recovery in hypoxia. Fourteen club-level cyclists completed four cycling TT's, followed by a 40 min passive recovery in normobaric hypoxic conditions (FiO2 = 14.5%) following one of either: two doses of NaHCO3 (0.2 g.kg-1 BM; SBC2, or 0.3 g.kg-1 BM; SBC3), a taste-matched placebo (0.07 g.kg-1 BM sodium chloride; PLA), or a control trial in a double-blind, randomized, repeated-measures and crossover design study. Compared to PLA, TT performance was improved following SBC2 (p = 0.04, g = 0.16, very likely beneficial), but was improved to a greater extent following SBC3 (p = 0.01, g = 0.24, very likely beneficial). Furthermore, a likely benefit of ingesting SBC3 over SBC2 was observed (p = 0.13, g = 0.10), although there was a large inter-individual variation. Both SBC treatments achieved full recovery within 40 min, which was not observed in either PLA or CON following the TT. In conclusion, NaHCO3 improves 4 km TT performance and acid base balance recovery in acute moderate hypoxic conditions, however the optimal dose warrants an individual approach.


Pseudoangiomatous stromal hyperplasia causing massive breast enlargement.
Pseudoangiomatous stromal hyperplasia (PASH) of the breast is a benign mesenchymal proliferative process, initially described by Vuitch et al. We report an unusual case of a 46-year-old woman who presented with a 6-week history of bilateral massive, asymmetrical, painful enlargement of her breasts, without a history of trauma. On clinical examination, both breasts were markedly enlarged and oedematous, but there were no discrete palpable masses. Preoperative image-guided core biopsies and surgery showed PASH. PASH is increasingly recognised as an incidental finding on image-guided core biopsy performed for screen detected lesions. There are a few reported cases of PASH presenting as rapid breast enlargement. In our case, the patient presented with painful, asymmetrical, massive breast enlargement. Awareness needs to be raised of this entity as a differential diagnosis in massive, painful breast enlargement.


Tuberculosis notifications in Australia, 2010.
The National Notifiable Diseases Surveillance System received 1,353 tuberculosis (TB) notifications in 2010, representing a rate of 6.1 cases per 100,000 population. While rates of 5 to 6 cases per 100,000 population for TB have been maintained in Australia, since first achieved in the mid-1980s, there has been a steady increase in incidence over the past decade. The incidence in the Australian-born Indigenous population was 7.5 per 100,000 population, which is 11 times the incidence reported in the Australian-born non-Indigenous population of 0.7 per 100,000 population. Overseas-born people accounted for 90% of all cases notified in 2010 and represented a rate of 24 per 100,000 population. International students have been recognised as an increasingly important group, representing 25% of all overseas-born cases notified in 2010, and are a focus of this report. Household or other close contact with TB or past residence in a high risk country were the most commonly reported risk factors for TB infection. Outcome data for the 2009 TB cohort indicate that treatment success was attained in more than 95% of cases. As Australia continues to contribute to global TB control it is important to maintain good centralised national reporting of TB to identify populations at risk and monitor trends in TB.


Bright light exposure at night and light attenuation in the morning improve adaptation of night shift workers.
With practical applicability in mind, we wanted to observe whether nocturnal alertness, performance, and daytime sleep could be improved by light exposure of tolerable intensity and duration in a real work place. We also evaluated whether attenuating morning light was important in adaptation of real night shift workers. Twelve night shift nurses participated in this study. The study consisted of three different treatment procedures: Room Light (RL), Bright Light (BL), and Bright Light with Sunglasses (BL/S). In RL, room light exposure was given during the night shift and followed by 1 hr exposure to sunlight or 10,000 lux light the next morning (from 08:30 to 09:30). In BL, a 4-hour nocturnal light exposure of 4,000-6,000 lux (from 01:00 to 05:00) was applied and followed by the same morning light exposure as in RL. In BL/S, the same nocturnal light exposure as in BL was done with light attenuation in the morning. Each treatment procedure was continued for 4 days in a repeated measures, cross-over design. Nocturnal alertness was measured by a visual analog scale. Computerized performance tests were done. Daytime sleep was recorded with actigraphy. The most significant overall improvement of sleep was noted in BL/S. BL showed less improvement than BL/S but more than RL. Comparison of nocturnal alertness among the 3 treatments produced similar results: during BL/S, the subjects were most alert, followed by BL and then by RL. Real night shift workers can improve nocturnal alertness and daytime sleep by bright light exposure in their work place. These improvements can be maximized by attenuating morning light on the way home.


Impact of the National Institute for Health and Care Excellence (NICE) guidance on medical technology uptake: analysis of the uptake of spinal cord stimulation in England 2008-2012.
The National Institute for Health and Care Excellence (NICE) Technology Appraisal Guidance on spinal cord stimulation (SCS) was published in 2008 and updated in 2012 with no change. This guidance recommends SCS as a cost-effective treatment for patients with neuropathic pain. To assess the impact of NICE guidance by comparing SCS uptake in England pre-NICE (2008-2009) and post-NICE (2009-2012) guidance. We also compared the English SCS uptake rate with that of Belgium, the Netherlands, France and Germany. SCS implant data for England was obtained from the Hospital Episode Statistics (HES) database and compared with other European countries where comparable data were available. The HES data showed small increases in SCS implantation and replacement/revision procedures, and a large increase in SCS trials between 2008 and 2012. The increase in the total number of SCS procedures per million of population in England is driven primarily by revision/replacements and increased trial activity. Marked variability in SCS uptake at both health regions and primary care trust level was observed. Despite the positive NICE recommendation for the routine use of SCS, we found no evidence of a significant impact on SCS uptake in England. Rates of SCS implantation in England are lower than many other European countries.