Protein Complexation and pH Dependent Release Using Boronic Acid Containing PEG-Polypeptide Copolymers.
New poly(L-lysine)-b-poly(ethylene glycol) copolypeptides have been prepared, where the side-chain amine groups of lysine residues are modified to contain ortho-amine substituted phenylboronic acid, i.e., Wulff-type phenylboronic acid (WBA), groups to improve their pH responsive, carbohydrate binding properties. These block copolymers form nanoscale complexes with glycosylated proteins that are stable at physiological pH, yet dissociate and release the glycoproteins under acidic conditions, similar to those found in endosomal and lysosomal compartments within cells. These results suggest that WBA modified polypeptide copolymers are promising for further development as degradable carriers for intracellular protein delivery.


Hormonal regulation of bone growth and remodelling.
Many systemic and local hormones influence bone growth and remodelling. These include calcium regulating hormones, systemic growth regulators and local growth factors. Parathyroid hormone (PHT) is a potent stimulator of osteoclastic bone resorption and a direct inhibitor of osteoblastic collagen synthesis. However, intermittent low-dose PTH administration can increase bone formation in vivo. PTH may act indirectly via local factors. It has been shown to increase prostaglandin E2 (PGE2) and transforming growth factor beta (TGF-beta) release from bone. Both PGE2 and TGF-beta have complex effects on bone metabolism and are likely to be physiological regulators of bone remodelling. Oestradiol has been shown to inhibit bone resorption in vivo but not in vitro. While there is evidence for oestrogen receptors in cultured bone cells, the effect could still be indirect. Oestradiol can inhibit bone PGE2 release in an in vivo-in vitro model in the rat. Glucocorticoids are potent inhibitors of bone formation and inhibit PGE2 and interleukin 1 production both in vivo and in vitro. While many regulatory factors affect prostaglandin production in bone, the complex effects of PGE2 on bone metabolism make it difficult to predict the ultimate response. The major effects of PGE2 are stimulation of bone formation and resorption and an increase in bone turnover. However, opposite effects can occur at certain times and concentrations. Interactions among these factors could explain some physiological, pathological, and therapeutic responses in skeletal tissue.


Biological evaluation of subgingivally placed direct resin composite materials.
Placement of composite resin restorations in deep subgingival cavities can damage surrounding soft tissues. In addition, commonly used resin-based composites (RBCs) might interfere with wound healing and periodontal health. To clarify cellular interactions with RBCs, we used an MTT assay to investigate adhesion of primary human gingival fibroblasts and human osteoblasts (hFOB 1.19) on five RBC materials with and without surface modifications (alumina blasting with 50- or 110-μm Al2O3). In addition, high-performance liquid chromatography (HPLC) was used to determine release of resin monomers from RBCs after 1 h, 1 day, and 7 days. As compared with tissue culture plastics (the control), cellular adhesion was significantly lower (P < 0.001) for human gingival fibroblasts and osteoblasts. Only minor, nonsignificant differences between individual RBCs were identified. HPLC analyses identified the release of three bifunctional methacrylates bisphenol A glycerolate dimethacrylate, triethylene glycol dimethacrylate, and diurethane dimethacrylate from RBCs and showed that monomer release increased between 1 h and 1 day but remained low. The present findings suggest that surface adhesion in the subgingival area is limited for the tested RBCs. Although residual monomer release was low for all tested RBCs, it might be sufficient to adversely affect cell adhesion.


Sample size determination for phase II clinical trials based on Bayesian decision theory.
This paper describes an application of Bayesian decision theory to the determination of sample size for phase II clinical studies. The approach uses the method of backward induction to obtain group sequential designs that are optimal with respect to some specified gain function. A gain function is proposed focussing on the financial costs of, and potential profits from, the drug development programme. On the basis of this gain function, the optimal procedure is also compared with an alternative Bayesian procedure proposed by Thall and Simon. The latter method, which tightly controls type I error rate, is shown to lead to an expected gain considerably smaller than that from the optimal test. Gain functions with respect to which Thall and Simon's boundary is optimal are sought and it is shown that these can only be of the form considered, that is, with constant cost for phase III study and cost of the phase II study proportional to the sample size, if potential profit increases over time.


Optimal ratio of 18α- and 18β-glycyrrhizic acid for preventing alcoholic hepatitis in rats.
The glycyrrhizic acid (GA) epimers 18α- and 18β-GA exert anti-inflammatory and hepatoprotective activities, which may help to protect against alcoholic liver disease, particularly alcoholic hepatitis (AH). The aim of the present study was to investigate the optimal ratio of 18α- and 18β-GA for preventing AH in rats. Different groups of rats were administered seven different ratios of 18α- and 18β-GA (10:0, 8:2, 6:4, 5:5, 4:6, 2:8 and 0:10; 10.83 mg/kg), vehicle control, or silymarin (22.75 mg/kg) as a positive control, followed by administration of 40% alcohol (10 ml/kg) once a day for four weeks. Subsequently, livers were isolated and routinely processed for histological examination. The serum levels of 23 cytokines and chemokines associated with AH were examined with a Bio-Plex 200 Luminex assay. It was revealed that all ratios of 18α- and 18β-GA prevented alcohol-induced liver injury, as evidenced by a lesser degree of histopathological changes in the liver as compared with those in the model group. Furthermore, the levels of 15 cytokines/chemokines were significantly altered after alcohol administration, which was significantly inhibited by, pre-treatment with different proportions of 18α- and 18β-GA, particularly at a ratio of 4:6, for most cytokines/chemokines associated with AH, including tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-7, IL-6, monocyte chemotactic protein 1 (MCP-1), macrophage inflammatory protein (MIP)-1α, MIP-3α, macrophage- and granulocyte macrophage colony-stimulating factor, chemokine (C-X-C motif) ligand 1(GRO/KC), vascular endothelial growth factor and C-C motif chemokine ligand 5 (RANTES). Taken together, based on these results the optimal ratio of 18α- and 18β-GA to prevent AH in model rats was considered to be 4:6.


Transcriptional regulation of soluble methane monooxygenase via enhancer-binding protein derived from Methylosinus sporium 5.
Methane is a major greenhouse gas, and methanotrophs regulate the methane level in the carbon cycle. Soluble methane monooxygenase (sMMO) is expressed in various methanotroph genera, including Alphaproteobacteria and Gammaproteobacteria, and catalyzes the hydroxylation of methane to methanol. It has been proposed that MmoR regulates the expression of sMMO as an enhancer-binding protein under copper-limited conditions; however, details on this transcriptional regulation remain limited. Herein, we elucidate the transcriptional pathway of sMMO depending on copper ion concentration, which affects the interaction of MmoR and sigma factor. MmoR and sigma-54 (σ54) from Methylosinus sporium 5 were successfully overexpressed in Escherichia coli and purified to investigate sMMO transcription in methanotrophs. The results indicated that σ54 binds to a promoter positioned -24 (GG) and -12 (TGC) upstream between mmoG and mmoX1. The binding affinity and selectivity are lower (Kd = 184.6 ± 6.2 nM) than those of MmoR. MmoR interacts with the upstream activator sequence (UAS) with a strong binding affinity (Kd = 12.5 ± 0.5 nM). Mutational studies demonstrated that MmoR has high selectivity to its binding partner (ACA-xx-TGT). Titration assays have demonstrated that MmoR does not coordinate with copper ions directly; however, its binding affinity to UAS decreases in a low-copper-containing medium. MmoR strongly interacts with adenosine triphosphate (Kd = 62.8 ± 0.5 nM) to generate RNA polymerase complex. This study demonstrated that the binding events of both MmoR and σ54 that regulate transcription in M. sporium 5 depend on the copper ion concentration. IMPORTANCE This study provides biochemical evidence of transcriptional regulation of soluble methane monooxygenase (sMMO) in methanotrophs that control methane levels in ecological systems. Previous studies have proposed transcriptional regulation of MMOs, including sMMO and pMMO, while we provide further evidence to elucidate its mechanism using a purified enhancer-binding protein (MmoR) and transcription factor (σ54). The characterization studies of σ54 and MmoR identified the promoter binding sites and enhancer-binding sequences essential for sMMO expression. Our findings also demonstrate that MmoR functions as a trigger for sMMO expression due to the high specificity and selectivity for enhancer-binding sequences. The UV-visible spectrum of purified MmoR suggested an iron coordination like other GAF domain, and that ATP is essential for the initiation of enhancer elements. Binding assays indicated that these interactions are blocked by the copper ion. These results provide novel insights into gene regulation of methanotrophs.


Malignant Infantile Osteopetrosis.
Two main forms of osteopetrosis are recognized, a severe autosomal recessive form (MIM 259700) with an incidence of approximately 1 in 250,000 births and a mild autosomal dominant form (MIM166600) with an incidence of 1 in 20,000 births. Intrinsic disturbances of osteoclastic function due to mutations in genes encoding osteoclast-specific subunits of the vacuolar proton pump (TCIRG1, CLCN7) are found in most patients with recessive form. Mutations of CLCN7 are observed in dominant form of osteopetrosis .The recessive form of ostreopetrosis, i.e., malignant infantile osteopetrosis (MIOP) presents early in life with extreme sclerosis of the skeleton and reduction of marrow space. Signs/symptoms of MIOP appear as early as neonatal age. As there is defect in bone marrow children present with deficiency of red blood cells, white blood cells and platelets. There is extramedullary haemopoiesis, cranial nerve compressions and severe growth failure. The condition also presents with early and late onset neonatal sepsis and is often lethal in the first decade of life due to secondary infections. Treatment is mainly supportive. The only curative treatment is stem cell transplantation. This is a case report of a new-born who was admitted in nursery of Ayub Teaching Hospital initially with complains of neonatal jaundice and sepsis , and a second time with lower respiratory tract infection. Death was eventually due to sepsis. Workup led to diagnosis of Malignant infantile osteopetrosis.


Machine learning model to predict the width of maxillary central incisor from anthropological measurements.
To improve smile esthetics, clinicians should comprehensively analyze the face and ensure that the sizes selected for the maxillary anterior teeth are compatible with the available anthropological measurements. The inter commissural (ICW), interalar (IAW), intermedial-canthus (MCW), interlateral-canthus (LCW), and interpupillary (IPW) widths are used to determine the width of maxillary central incisors (CW). The aim of this study was to develop an automated approach using machine learning (ML) algorithms to predict central incisor width in a young Turkish population using anthropological measurements. This automation can contribute to digital dentistry and clinical decision-making. In the initial phase of this cross-sectional study, several ML regression models-including multiple linear regression (MLR), multi-layer-perceptron (MLP), decision-tree (DT), and random forest (RF) models-were validated to confirm the central width prediction accuracy. Datasets containing only male and female measurements, as well as combined were considered for ML model implementation, and the performance of each model was evaluated for an unbiased population dataset. Compared with the other algorithms, the RF algorithm showed improved performance for all cases, with an accuracy of 96%, which represents the percentage of correct predictions. The plot reveals the applicability of the RF model in predicting the CW from anthropological measurements irrespective of the candidate's sex. These results demonstrated the possibility of predicting central incisor widths based on anthropometric measurements using ML models. The accurate central incisor width prediction from these trials also indicates the applicability of the proposed model to be deployed for enhanced clinical decision-making.


Pre-clerkship medical students' perceptions of medical professionalism.
Professionalism instruction and assessment is a core component of medical education, and essential for professional identity formation (PIF). Thus, understanding the socialization of medical students to the values of the profession (i.e., medical professionalism), and how these may evolve, warrants continued understanding. The purpose of this study was to examine and compare pre-clerkship (first and second year) medical students' perceptions of professionalism. First and second year medical students participate in this study. This was a two-phase mixed-methods cohort study conducted across two academic years (2014-2015 and 2015-2016). In Phase I, first and second year medical students participated in a nominal group technique (NGT) session. NGT data was analyzed qualitatively to generate a card-sorting exercise of professionalism attributes for Phase II. In Phase II, data from the sorting task was analyzed using Principle Component Analysis (PCA). The PCA for first year students derived a 7-factor solution. Factors (i.e., professionalism domains) identified were: Self-management and patient-centeredness, ethics and professional reputation, dependability, self-awareness and self-improvement, image, proficiency and lifelong learning and integrity. The PCA for second year students derived a 5-factor solution; factors identified were: "Good Doctor" attributes, responsibility, ethics, innovation and self-improvement and unbiased. Identification and organization of attributes into an overarching professionalism mental model provide a window into the active reconstruction of students' professional identity during the nascent stages of medical education. M1 professionalism domains were more consistent with the conventional professional image of the physician (e.g. Ethics and Professional reputation, Dependability, Integrity), whereas, M2 domains reflected a more global view (e.g., "Good Doctor" attributes, Responsibility, Ethics). This study provides a lens into the dynamic nature of students' PIF and encourages educators to evaluate PIF pedagogy at their own institutions.


Severe hepatotoxicity during valproate therapy: an update and report of eight new fatalities.
Since our last report on valproate (VPA)-related hepatotoxicity in 1988, 8 other children have died of VPA-associated liver failure in Germany and Switzerland. We compared the clinical course of these children with that of 6 children with a reversible outcome of severe hepatotoxicity related to VPA. Thirty-five percent of patients with fatal liver failure were normally developed, 23.5% were receiving VPA monotherapy, and 35.3% were aged < or = 2 years. The initial clinical symptoms of VPA-related hepatotoxicity were nausea, vomiting, apathy or coma, and increasing seizures in more than 50% of patients, in combination with febrile infections at onset of symptoms. As compared with the series of German patients reported in 1988, one third of the fatalities occurred after the first 6 months of therapy as compared with 6% in the 1988 series. Clinical symptoms and laboratory findings were the same in patients with reversible and with fatal outcome. Early or immediate withdrawal of VPA after the first signs of VPA-associated hepatotoxicity may be responsible for the increased number of children who recovered after VPA-related severe liver failure. The pathogenesis of liver failure during VPA treatment remains unknown; metabolic defects and cofactors such as polypharmacy or infections have become increasingly likely to contribute by depleting intracellular CoA. Worldwide, 132 patients have died of VPA-associated liver failure and/or pancreatitis. Because a group at risk for fatalities with VPA cannot be defined precisely, patients treated with VPA and their families must be made well aware of the clinical symptoms of hepatotoxicity such as apathy, vomiting, or increased seizure frequency, especially in the presence of febrile infections. Laboratory tests and clinical controls during the first 6 months of therapy should not be neglected.


Parvovirus infections in childhood.
Human parvovirus (HPV) infections have been associated with several clinical syndromes. The virus is the etiologic agent of erythema infectiosum (fifth disease) and the primary cause of aplastic crises in children with sickle cell disease and other hemolytic anemias. Some individuals with an acute symmetric polyarthritis were found to have a recent HPV infection. Although two stillborn infants with proved HPV infections have been identified, the exact relationship among HPV, intrauterine infection, and subsequent fetal damage requires further research.


Seizures in Iatrogenic Cerebral Arterial Gas Embolism.
Iatrogenic cerebral arterial gas embolism occurs when gas enters the cerebral arterial circulation during a medical procedure and is considered a severe complication. Seizures have been described in these patients, but information on clinical characteristics, treatment, and outcome is lacking in current literature. The aim of the study was to explore seizures in patients with iatrogenic cerebral arterial gas embolism and to evaluate management strategies. Retrospective single-center observational study. The only university hospital in the Netherlands with a hyperbaric oxygen therapy facility. All patients presenting at or referred to our center with iatrogenic cerebral arterial gas embolism between May 2016 and December 2020. Not applicable. Fifteen patients with iatrogenic cerebral arterial gas embolism were identified, of whom 11 (73%) developed seizures. Five patients developed their first seizure prior to hyperbaric oxygen therapy, three during hyperbaric oxygen therapy, and three after hyperbaric oxygen therapy. Of the 11 patients with seizures, all but one were treated with anti-epileptic drugs. With a median follow-up time of 5 months (range, 1-54 mo), five patients showed complete neurologic recovery, five had minor neurologic deficit, two had moderate to severe neurologic deficit, and three had died. Four patients still used anti-epileptic drugs at follow-up. No patients had recurrent seizures after hospital discharge. `Seizures are a common symptom in iatrogenic cerebral arterial gas embolism. They are often treated with anti-epileptic drugs and do not seem to lead to chronic epilepsy.


Synthesis of Allene Substituted Nipecotic Acids by Allenylation of Terminal Alkynes.
The relative reactivities of several secondary amines serving as hydride donors in propargylic amines undergoing a [1,5]-hydride transfer reaction to yield the respective terminal and 1,3-disubstituted allenes were studied. For this study, a two-step procedure was employed. At first, the synthesis of propargylic amines via the CuI-catalyzed aldehyde-alkyne-amine reactions (A3 coupling) was accomplished. The obtained propargylic amines were subsequently transformed to the desired allenes under CdI2 or ZnI2 catalysis. As a result, among the various secondary amines employed, differing in steric bulk, electronic nature, and conformational properties, allyl(tert-butyl)amine was found to be the best hydride donor for the synthesis of terminal allenes. For the synthesis of 1,3-disubstituted allenes, the propyne derivatives containing either a allyl(tert-butyl)amine or a 1,2,3,6-tetrahydropyridine unit in propargylic position performed best. Finally, with the developed procedure, nipecotic acid derivatives containing an N-allenyl substituent were synthesized with good yields using either ZnI2 as catalyst for the preparation of 1-substituted or CdI2 for the synthesis of 1,3-disubstitued allenes.


Constructing Human Skin Equivalents on Porcine Acellular Peritoneum Extracellular Matrix for In Vitro Irritation Testing.
The irritancy of topical products has to be investigated to ensure the safety and compliance. Although several reconstructed human epidermal models have been adopted by the Organization for Economic Cooperation and Development (OECD) to replace in vivo animal irritation testing, these models are based on a single cell type and lack dermal components, which may be insufficient to reflect all of the components of irritation. In our study, we investigated the use of acellular porcine peritoneum extracellular matrix as a substrate to construct full-thickness human skin equivalents (HSEs) for use as irritation screening tool. The acellular peritoneum matrix (APM) exhibited excellent skin cell attachment (>80%) and proliferation for human dermal fibroblasts (HDF) and immortalized human keratinocytes (HaCaT). APM-HSEs based on coculture of HDF and HaCaT were prepared. Increased HDF seeding density up to 5 × 10(4)/cm(2) resulted in APM-HSEs with a thicker and more organized epidermis. The epidermis of APM-HSEs expressed keratin 15, a keratinocyte proliferation marker, and involucrin, a differentiation marker, respectively. To assess the use of APM-HSEs for irritation testing, six proficiency chemicals, including three nonirritants (phosphate-buffered saline, polyethylene glycol 400, and isopropanol) and three irritants (1-bromohexane, heptanol, and sodium dodecyl sulfate) were applied. The APM-HSEs were able to discriminate nonirritants from irritants based on the viability. Levels of cytokines (interleukin [IL]-1α, IL-1ra, IL-6, IL-8, and granulocyte macrophage colony-stimulating factor [GM-CSF]) in these treatment groups further assisted the irritancy ranking. In conclusion, we have developed partially differentiated full-thickness APM-HSEs based on acellular porcine peritoneum matrix, and these APM-HSEs demonstrated utility as an in vitro irritation screening tool.


[Chemical composition of the meat from does].
The meat was studied of 9 does killed at the age of 2.5 years and live weight of up to 35 kg. Ascertained were the contents of water; the total, extractive, and protein nitrogen; fats; ash; essential amino acids ( triptophane ) and nonessential ( hydroxiproline ) proteins. Determined was also the nutritive value of meat. It was found that the proteins of musculus gracilis have higher nutritive value as compared with those of the neck muscles between the fifth and the seventh vertebra.


Hydroxylysine glycosides: preparation and analysis by reverse phase high performance liquid chromatography.
Hydroxylysine diglycoside was prepared from hydrolyzed sponge by a combination of ion-exchange chromatography and gel filtration. The product obtained was chemically pure on amino acid analyzer and was active as substrate of the enzyme alpha-(1----2)glucosidase. Hyl monoglycoside was prepared by mild acid hydrolysis from diglycoside. A reverse phase HPLC system was devised for Hyl glycosides, hydroxylysine and other basic amino acids. The separation was achieved using an octadecyl bonded silica column on the compounds derivatized with dabsyl chloride to produce di-dabsyl derivatives. Elution was followed in the visible region at 436 nm. In the conditions used no or very low amount of mono-dabsyl derivatives was observed. Hyl di- and monoglycoside resulted a mixture of two diastereoisomers, which form during the alkaline hydrolysis. The separation of the diastereoisomers of each compound depended on pH and ionic strength of the eluent in the HPLC column, whereas they were not separated by our short column on amino acid analyzer. The HPLC system was also used for the analysis of Hyl glycosides on two collagen preparations.


Protein-Remodeling Factors As Potential Therapeutics for Neurodegenerative Disease.
Protein misfolding is implicated in numerous neurodegenerative disorders including amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease, and Huntington's disease. A unifying feature of patients with these disorders is the accumulation of deposits comprised of misfolded protein. Aberrant protein folding can cause toxicity through a loss or gain of protein function, or both. An intriguing therapeutic approach to counter these disorders is the application of protein-remodeling factors to resolve these misfolded conformers and return the proteins to their native fold and function. Here, we describe the application of protein-remodeling factors to alleviate protein misfolding in neurodegenerative disease. We focus on Hsp104, Hsp110/Hsp70/Hsp40, NMNAT, and HtrA1, which can prevent and reverse protein aggregation. While many of these protein-remodeling systems are highly promising, their activity can be limited. Thus, engineering protein-remodeling factors to enhance their activity could be therapeutically valuable. Indeed, engineered Hsp104 variants suppress neurodegeneration in animal models, which opens the way to novel therapeutics and mechanistic probes to help understand neurodegenerative disease.


A review and evaluation of orthodontic brackets, molar bands and orthodontic auxiliaries during orthognathic surgery: A prospective cohort study.
The primary aim of this study was to provide a review of the types and frequency of orthodontic brackets, molar bands and orthodontic auxiliaries used for patients undergoing orthognathic surgery. The secondary aim was to evaluate the risk of failure of these items during orthognathic surgery. From three Dutch hospitals, 124 adult patients were included in this prospective cohort study. Five independent researchers collected the data during surgery using a specifically created data extraction form. The type of surgery, surgeon, orthodontist and type of orthodontic bracket, molar band or auxiliary were noted for each tooth. To evaluate their failure risk, the following variables were noted: failure and site; and type and cause of failure. Stainless-steel brackets were the most frequently used bracket type seen in patients undergoing orthognathic surgery. Ceramic brackets were seen in 24.2% of the cases and were only applied in the anterior region. Molar bands were present in 58.9% of the patients and mostly with bands on the first molars in combination with bonded tubes on the second molars. In 32.2% of all cases, one or more failures were noted. One-third of all failures were described as detachment of the molar tube on the most posterior molar. Kobayashi ligatures and powerpins showed the highest risk of failure (95% confidence interval [CI] = 1.91-7.15). No significant difference in failure rate was found between stainless-steel brackets, molar bands (95% CI = 0.08-1.43) and ceramic brackets (95% CI = 0.14-1.45). Stainless-steel brackets, ceramic brackets, molar bands and surgical hooks are suitable for orthognathic cases. Kobayashi ligatures and powerpins had a significantly higher risk of failure so are not recommended for temporary intraoperative maxillomandibular fixation (TIO-MMF).


Altered intracardiac conduction after acute administration of ethanol in the dog.
Varying concentrations of ethyl alcohol were injected either into the left main coronary artery or intravenously in anesthetized intact dogs. Effects of alcohol on intracardiac conduction (by His bundle electrogram) were examined at spontaneous and paced (atrial) heart rates. Alcohol by the intracoronary route prolonged atrioventricular node and intraventricular conduction times by approximately 5 to 15%. These changes preceded a depression of left ventricular systolic pressure and of the rate of rise of left ventricular pressure and an elevation of left ventricular end-diastolic pressure. Intracoronary injections of contrast medium (sodium diatriozoate) or iso-osmolar solutions of sucrose and injections of similar amounts of alcohol in the ascending or descending aorta did not affect intracardiac conduction. Increasing atrial pacing rates resulted in prolongation of atrioventricular nodal conduction intervals, but did not influence intraventricular conduction time. At each pacing rate, alcohol depressed both atrioventricular nodal and intraventricular conduction. The data suggest that alcohol has a direct depressant effect on intracardiac conduction.


[Pharmacotherapy effectiveness for some symptoms of borderline personality disorder].
A high percentage of patients with borderline personality disorder (BPD) are prescribed psychotropic medications. Recent meta-analyses of randomized controlled trials suggested evidence of effects of antiepileptics on impulsivity and anger and of atypical antipsychotics on cognitive-perceptual symptoms and anger. Antidepressants had no or negligible effect. Total BPD severity was not significantly reduced by pharmacotherapy. Longitudinal studies suggest that BPD tends to improve, but it is not clarified whether long-term pharmacotherapy make the naturalistic recovery occur more rapidly.


Association Between Midlife Cardiorespiratory Fitness and Risk of Stroke: The Cooper Center Longitudinal Study.
Low cardiorespiratory fitness (CRF) is associated with an increased risk of stroke. However, the extent to which this association is explained by the development of stroke risk factors such as diabetes mellitus, hypertension, and atrial fibrillation is unknown. We evaluated the relationship between midlife CRF and risk of stroke after the age of 65 years, independent of the antecedent risk factor burden. Linking participant data from the Cooper Center Longitudinal Study with Medicare claims files, we studied 19 815 individuals who survived to receive Medicare coverage from 1999 to 2009. CRF estimated at baseline by Balke treadmill time was analyzed as a continuous variable (in metabolic equivalents) and according to age- and sex-specific quintiles (Q1=low CRF). Associations between midlife CRF and stroke hospitalization after the age of 65 years were assessed by applying a proportional hazards recurrent events model to the failure time data with hypertension, diabetes mellitus, and atrial fibrillation as time-dependent covariates. After 129 436 person-years of Medicare follow-up, we observed 808 stroke hospitalizations. After adjustment for baseline risk factors, higher midlife CRF was associated with a lower risk of stroke hospitalization (hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.49-0.76; quintiles 4-5 versus 1]. This association remained unchanged after additional adjustment for burden of Medicare-identified stroke risk factors (hypertension, diabetes mellitus, and atrial fibrillation; HR, 0.63; 95% CI, 0.51-0.79; quintiles 4-5 versus 1). There is a strong, inverse association between midlife CRF and stroke risk in later life independent of baseline and antecedent burden of risk factors, such as hypertension, diabetes mellitus, and atrial fibrillation.


Advances in Idiosyncratic Drug-Induced Liver Injury Issues: New Clinical and Mechanistic Analysis Due to Roussel Uclaf Causality Assessment Method Use.
Clinical and mechanistic considerations in idiosyncratic drug-induced liver injury (iDILI) remain challenging topics when they are derived from mere case narratives or iDILI cases without valid diagnosis. To overcome these issues, attempts should be made on pathogenetic aspects based on published clinical iDILI cases firmly diagnosed by the original RUCAM (Roussel Uclaf Causality Assessment Method) or the RUCAM version updated in 2016. Analysis of RUCAM-based iDILI cases allowed for evaluating immune and genetic data obtained from the serum and the liver of affected patients. For instance, strong evidence for immune reactions in the liver of patients with RUCAM-based iDILI was provided by the detection of serum anti-CYP 2E1 due to drugs like volatile anesthetics sevoflurane and desflurane, partially associated with the formation of trifluoroacetyl (TFA) halide as toxic intermediates that form protein adducts and may generate reactive oxygen species (ROS). This is accompanied by production of anti-TFA antibodies detected in the serum of these patients. Other RUCAM-based studies on serum ANA (anti-nuclear antibodies) and SMA (anti-smooth muscle antibodies) associated with AIDILI (autoimmune DILI) syn DIAIH (drug-induced autoimmune hepatitis) provide additional evidence of immunological reactions with monocytes as one of several promoting immune cells. In addition, in the blood plasma of patients, mediators like the cytokines IL-22, IL-22 binding protein (IL-22BP), IL-6, IL-10, IL 12p70, IL-17A, IL-23, IP-10, or chemokines such as CD206 and sCD163 were found in DILI due to anti-tuberculosis drugs as ascertained by the prospective updated RUCAM, which scored a high causality. RUCAM-based analysis also provided compelling evidence of genetic factors such as HLA (human leucocyte antigen) alleles contributing to initiate iDILI by a few drugs. In conclusion, analysis of published RUCAM-based iDILI cases provided firm evidence of immune and genetic processes involved in iDILI caused by specific drugs.


Vasopressin V1a receptor is required for nucleocytoplasmic transport of mineralocorticoid receptor.
We previously reported that a deficiency in the vasopressin V1a receptor (V1aR) results in type 4 renal tubular acidosis, which suggests that vasopressin exerts direct effects on the physiological actions of aldosterone. We investigated the role of vasopressin for nucleocytoplasmic transport of mineralocorticoid receptor (MR) in the intercalated cells. Vasopressin V1aR-deficient (V1aR(-/-)) mice showed largely decreased expression of MR and 11β-hydroxysteroid dehydrogenase type 2 (11βHSD2) in the medulla of the kidney, which was partially ameliorated by fludrocortisone treatment. The incubation of IN-IC cells, an intercalated cell line established from temperature-sensitive SV40 large T antigen-expressing rats, with aldosterone or vasopressin increased the nuclear-to-cytoplasmic ratio of the MR from 11.2 to 47.2% and from 18.7 to 61.2%, respectively, in 30 min without any changes in MR expression from the whole cell extract. The immunohistochemistry analysis of the IN-IC cells revealed the nuclear accumulation of MRs after a 30-min incubation with aldosterone or vasopressin. These effects were accompanied by an increase in regulator of chromosome condensation-1 (RCC-1) due to aldosterone and a decrease in Ran GTPase-activating protein 1 (Ran Gap1) due to vasopressin. RNA interference against V1aR abolished the nuclear accumulation of MR induced by aldosterone or vasopressin. Vasopressin increased PKCα and -β(1) expression, and aldosterone increased PKCδ and -ζ expression, but these effects were abolished with a V1aR knockdown. These results suggest that vasopressin directly regulates the nucleocytoplasmic transport of MRs via the V1aR in the intercalated cells of the collecting ducts.


Interrater Agreement for Consensus Definitions of Delayed Ischemic Events After Aneurysmal Subarachnoid Hemorrhage.
Thirty percent of patients with subarachnoid hemorrhage experience delayed cerebral ischemia or delayed ischemic neurologic decline (DIND). Variability in the definitions of delayed ischemia makes outcome studies difficult to compare. A recent consensus statement advocates standardized definitions for delayed ischemia in clinical trials of subarachnoid hemorrhage. We sought to evaluate the interrater agreement of these definitions. Based on consensus definitions, we assessed for: (1) delayed cerebral infarction, defined as radiographic cerebral infarction; (2) DIND type 1 (DIND1), defined as focal neurologic decline; and (3) DIND2, defined as a global decline in arousal. Five neurologists retrospectively reviewed electronic records of 58 patients with subarachnoid hemorrhage. Three reviewers had access to and reviewed neuroradiology imaging. We assessed interrater agreement using the Gwet kappa statistic. Interrater agreement statistics were excellent (95.83%) for overall agreement on the presence or absence of any delayed ischemic event (DIND1, DIND2, or delayed cerebral infarction). Agreement was "moderate" for specifically identifying DIND1 (56.58%) and DIND2 (48.66%) events. We observed greater agreement for DIND1 when there was a significant focal motor decline of at least 1 point in the motor score. There was fair agreement (39.20%) for identifying delayed cerebral infarction; CT imaging was the predominant modality. Consensus definitions for delayed cerebral ischemia yielded near-perfect overall agreement and can thus be applied in future large-scale studies. However, a strict process of adjudication, explicit thresholds for determining focal neurologic decline, and MRI techniques that better discriminate edema from infarction seem critical for reproducibility of determination of specific outcome phenotypes, and will be important for successful clinical trials.


Isoprenylcysteine carboxy methyltransferase (ICMT) is associated with tumor aggressiveness and its expression is controlled by the p53 tumor suppressor.
Isoprenyl cysteine carboxyl methyltransferase (ICMT) plays a key role in post-translational regulation of prenylated proteins. On the basis of previous results, we hypothesized that the p53 pathway and ICMT expression may be linked in cancer cells. Here, we studied whether WT p53 and cancer-associated p53 point mutants regulate ICMT levels and whether ICMT overexpression affects tumor progression. Studying the effect of p53 variants on ICMT mRNA and protein levels in cancer cells, we found that WT p53 and p53 mutants differentially affect ICMT expression, indicating that p53 status influences ICMT levels in tumors. To investigate the underlying mechanisms, we constructed ICMT-luciferase reporters and found that WT p53 represses ICMT transcription. In contrast, p53 mutants showed a positive effect on ICMT expression. Promoter truncation analyses pinpointed the repressive effect of WT p53 to the -209 and -14 region on the ICMT promoter, and ChIP assays indicated that WT p53 is recruited to this region. Instead, a different promoter region was identified as responsible for the mutant p53 effect. Studying the effect of ICMT overexpression on tumor-associated phenotypes in vitro and in vivo, and analyzing breast and lung cancer databases, we identified a correlation between p53 status and ICMT expression in breast and lung cancers. Moreover, we observed that ICMT overexpression is correlated with negative clinical outcomes. Our work unveils a link between postprenylation protein processing and the p53 pathway, indicating that the functional interplay between WT and mutant p53 alters ICMT levels, thereby affecting tumor aggressiveness.


Clinical characteristics of patients with heart failure and intracardiac thrombus.
Heart failure (HF) patients are in a hypercoagulable state that predisposes them to an intracardiac thrombus. We aim to assess the clinical features of patients with HF and intracardiac thrombus. Patients diagnosed with HF with intracardiac thrombus were enrolled in this study. Patients' demographics, clinical comorbidities, laboratory tests, and cardiac imaging parameters are recorded. Baseline characteristics are described; the relationship between intracardiac thrombus location and cardiac underlying diseases, New York Heart Association (NYHA) class, and left ventricular ejection fraction (LVEF) are analyzed; and the anticoagulation rate is summarized. A total of 1,248 patients were included in the study. Most patients were men (72.2%) with a mean age of 54 years. The left ventricle is the most frequently involved (66.8%), and the prevalence of left ventricular thrombus is more in patients complicated with coronary artery diseases, ventricular noncompaction cardiomyopathy, and dilated cardiomyopathy (86.3%, 86.4%, and 78.2%, respectively). When combined with atrial fibrillation, atrial flutter, hypertrophic cardiomyopathy, restrictive cardiomyopathy, or valvular cardiomyopathy, the intracardiac thrombus is mostly likely to occur in the left atrium. The incidence rate of left cardiac thrombosis increased with the decline of LVEF, an increase of NYHA class, and enlargement of a cardiac chamber. Overall, the anticoagulation rate was 56.8%, with warfarin still the mainstay drug (45.1%), while the prescription of non-vitamin K antagonist oral anticoagulants rose year by year. As for imaging modalities for thrombus detection and diagnosis, transthoracic echocardiography was the most widely performed (75.1%). This study summarizes the underlying disease constitution, thrombus location and related factors, imaging modalities, and antithrombotic profile in HF patients with intracardiac thrombus comprehensively.


Influence of a Dietary Vegetable Oil Blend on Serum Lipid Profiles in Large Yellow Croaker ( Larimichthys crocea).
Serum lipid metabolic responses are associated with certain metabolic disorders induced by dietary habits in mammals. However, such associations have not been reported in fish. Lipidomic analyses were performed to investigate fish lipid metabolic responses to a dietary vegetable oil (VO) blend and to elucidate the mechanism of how the dietary VO blend affects serum lipid profiles. Results showed that the dietary VO blend strongly affects serum lipid profiles, especially the ratio of triglyceride/phosphatidylcholine (TAG/PC), via inhibiting hepatic PC biosynthesis and facilitating hepatic and intestinal lipoprotein assembly. Studies in vitro suggested that changes of serum TAG/PC ratio may be partially attributed to altered fatty acid composition in diets. Additionally, the reduction of 16:0/18:1-PC induced by the dietary VO blend may play a role in abnormal lipid deposition through inhibiting PPARA-mediated activation of β-oxidation. These findings suggested that the serum TAG/PC ratio might be a predictive parameter for abnormal lipid metabolism induced by dietary nutrition in fish.


Angiosarcoma of the breast: a report of two cases and a review of the literature.
Angiosarcoma of the breast, a rare tumor with very poor prognosis and insidious early manifestations, frequently is far advanced when first detected clinically. The clinical and pathologic changes in two women with primary, unilateral angiosarcoma of the breast are reviewed and the results are compared with 46 cases already published in the literature. Both patients were middle aged with symptoms for approximately 6 months prior to operation. Both frozen section reports were benign and only called malignant on permanent section. Microscopically the tumors were composed of varying sized, tortuous, elongated vascular channels. The operation varied--a modified radical and a simple mastectomy--and both patients are free from disease 4 and 2 years following operation. It is considered that, in view of the proclivity of this tumor for hematogenous metastases, an axillary dissection may not be justified.


In vitro and in vivo anti-inflammatory active copper(II)-lawsone complexes.
We report in vitro and in vivo anti-inflammatory activities of a series of copper(II)-lawsone complexes of the general composition [Cu(Law)2(LN)x(H2O)(2-x)]·yH2O; where HLaw = 2-hydroxy-1,4-naphthoquinone, x = 1 when LN = pyridine (1) and 2-aminopyridine (3) and x = 2 when LN = imidazole (2), 3-aminopyridine (4), 4-aminopyridine (5), 3-hydroxypyridine (6), and 3,5-dimethylpyrazole (7). The compounds were thoroughly characterized by physical techniques, including single crystal X-ray analysis of complex 2. Some of the complexes showed the ability to suppress significantly the activation of nuclear factor κB (NF-κB) both by lipopolysaccharide (LPS) and TNF-alpha (complexes 3-7 at 100 nM level) in the similar manner as the reference drug prednisone (at 1 μM level). On the other hand, all the complexes 1-7 decreased significantly the levels of the secreted TNF-alpha after the LPS activation of THP-1 cells, thus showing the anti-inflammatory potential via both NF-κB moderation and by other mechanisms, such as influence on TNF-alpha transcription and/or translation and/or secretion. In addition, a strong intracellular pro-oxidative effect of all the complexes has been found at 100 nM dose in vitro. The ability to suppress the inflammatory response, caused by the subcutaneous application of λ-carrageenan, has been determined by in vivo testing in hind-paw edema model on rats. The most active complexes 1-3 (applied in a dose corresponding to 40 μmol Cu/kg), diminished the formation of edema simalarly as the reference drug indomethacine (applied in 10 mg/kg dose). The overall effect of the complexes, dominantly 1-3, shows similarity to anti-inflammatory drug benoxaprofen, known to induce intracellular pro-oxidative effects.


[Effect of biofeedback and electrostimulation on sphincter function in fecal incontinence].
The following study reports on the effect of biofeedback and transanal electric stimulation as a conservative method in the therapy of idiopathic fecal incontinence. 22 consecutive patients in whom the diagnosis "idiopathic incontinence" was established after endoscopy, endoanal ultrasound and measurement of pudendal nerve terminal motor latency underwent combined sphincter training for 3 months. The results were evaluated prospectively by clinical classification using a modified Kelly-Holschneider-score and anal manometry before and after treatment. Combined biofeedback led to a significant increase of the continence score in 18 of 22 patients (7.7 +/- 3.8 vs. 9.3 +/- 3.0, p = 0.004). Both squeeze (77 +/- 28 mmHg vs. 92 +/- 32 mmHg, p = 0.047) and resting pressures (40 +/- 19 vs. 52 +/- 23 mmHg, p = 0.015) increased significantly during the training period. There were no significant differences in squeeze and resting asymmetry indexes, sensory and urge thresholds and maximal tolerable volumes. The prolongation of biofeedback training from 3 to 6 months in 9 patients did not change clinical or manometric results significantly. The combination of biofeedback training with anal electrostimulation increases anal squeeze and resting pressures, thus leading to an improvement of clinical incontinence symptoms. Therefore it should be the first choice in the therapy of idiopathic fecal incontinence. A training period of 3 months seems to be sufficient.


A Robust Statistical Model to Predict the Future Value of the Milk Production of Dairy Cows Using Herd Recording Data.
The future value of an individual dairy cow depends greatly on its projected milk yield. In developed countries with developed dairy industry infrastructures, facilities exist to record individual cow production and reproduction outcomes consistently and accurately. Accurate prediction of the future value of a dairy cow requires further detailed knowledge of the costs associated with feed, management practices, production systems, and disease. Here, we present a method to predict the future value of the milk production of a dairy cow based on herd recording data only. The method consists of several steps to evaluate lifetime milk production and individual cow somatic cell counts and to finally predict the average production for each day that the cow is alive. Herd recording data from 610 Danish Holstein herds were used to train and test a model predicting milk production (including factors associated with milk yield, somatic cell count, and the survival of individual cows). All estimated parameters were either herd- or cow-specific. The model prediction deviated, on average, less than 0.5 kg from the future average milk production of dairy cows in multiple herds after adjusting for the effect of somatic cell count. We conclude that estimates of future average production can be used on a day-to-day basis to rank cows for culling, or can be implemented in simulation models of within-herd disease spread to make operational decisions, such as culling versus treatment. An advantage of the approach presented in this paper is that it requires no specific knowledge of disease status or any other information beyond herd recorded milk yields, somatic cell counts, and reproductive status.


Desmoid Tumor of Rectus Abdominis Presenting with Grey-Turner's and Cullen's Sign: A Report of a Rare Case.
Desmoid tumor of rectus abdominis presenting with Grey-Turner's and Cullen's sign is rare. Herein, we report desmoid tumor of rectus abdominis in a 64-year-old multiparous female who presented with ecchymosis involving left flank and around the umbilicus. Histopathological examination of biopsy from the tumor confirmed the diagnosis of the desmoid tumor. She was referred to a surgeon for radical resection.


Modified ultrafast Papanicolaou staining technique: A comparative study.
Ultrafast Papanicolaou stain (UFP) was introduced as a hybrid of Romanowsky and Papanicolaou (PAP) stain. It enhances the quality and reduces the time. In the present study, a modified staining technique was adapted where Gill's Hematoxylin was replaced by Harris Hematoxylin. The aim of the study was to assess the use of the modified ultrafast Papanicolaou (MUFP) stain for fine needle aspiration cytology (FNAC) of head and neck swellings in comparison with the routine PAP stain, hematoxylin and eosin (H and E), and Giemsa. Forty FNACs of head and neck swellings were collected. FNAC procedure was performed by standard method; two smears were fixed in 95% propanol and stained with PAP and H and E. Two smears were air dried, 1 was stained with Giemsa, and 1 was rehydrated with normal saline, fixed in alcoholic formalin, and stained with MUFP. Four parameters were considered and scored background, cell morphology, nuclear staining, and overall staining pattern). The quality of MUFP smears were better when compared to routine PAP, H and E, and Giemsa, and was statistically significant by Wilcoxon matched pair test. MUFP stain in comparison to routine PAP, H and E, and Giemsa provides an excellent and suitable alterative in cytological staining for the study of various organs.


[Effects of chondroitinase ABC combined with bone marrow mesenchymal stem cells transplantation on repair of spinal cord injury in rats].
To investigate the effects of chondroitinase ABC (ChABC) combined with bone marrow mesenchymal stem cells (BMSCs) in repair spinal cord injury of rats. Primary BMSCs were isolated and cultured from the femur and tibia of neonatal Sprague Dawley (SD) rats. The spinal cord injury model was established in 24 adult SD male rats (weighing, 200-230 g), which were randomly divided into control group (group A), BMSCs transplantation group (group B), ChABC injection group (group C), and ChABC and BMSCs transplantation group (group D), 6 rats in each group. At 7 and 14 days after injury, Basso-Beattie-Bresnahan (BBB) score criteria was used to evaluate the hindlimb motor function; at 14 days after injury, the injured spinal cord tissue was perfused and stained by HE for further calculation of the injury area. Immunofluorescence staining were used for observing the expressions of glial fibrillary acidic protein (GFAP)/chondroitin sulfate proteoglycan (CSPG) and GFAP/growth associated protein 43 (GAP43). At 7 days after injury, three joints movement of the hindlimbs were recovered in all groups, and no significant difference in the BBB score was found among 4 groups (P > 0.05). At 14 days after injury, no load drag was observed in 3 joints of the hindlimbs in groups A, B, and C, but weight-bearing plantar or occasional dorsalis pedis weight-bearing walking was observed in group D with no plantar walking. The BBB score of group D was significantly higher than that of the other 3 groups (P < 0.05). HE staining showed that the cavity formed in the damage zone, and there were a large number of macrophages in the cavity and its surrounding, which was wrapped by scar tissue. The damage area of group D was significantly smaller than that of the other 3 groups (P < 0.05). At 14 days after injury, the GFAP/CSPG double immunofluorescence staining showed that the astroglial scar damage zone in group D was significantly reduced, and no cavity formation was found. And the fluorescence intensity in groups C and D was significantly lower than that in group B (P < 0.05). The GFAP/GAP43 double immunofluorescence staining showed that GAP43-positive fibers passed through the damage zone in group D and the fluorescence intensity in group D was significantly higher than those in groups B and C (P < 0.05). Inhibition of astrocytes secreting CSPG by ChABC combined with BMSCs transplantation in early injury may promote the regeneration of nerve fibers, and repair spinal cord injury in rats.


Human cytotoxic T lymphocyte responses to Epstein-Barr virus infection.
Epstein-Barr virus (EBV) provides one of the most informative systems with which to study cytotoxic T lymphocyte (CTL) responses in humans. The virus establishes a highly immunogenic growth-transforming infection of B lymphocytes, associated with the coordinate expression of six virus-coded nuclear antigens (EBNAs 1, 2, 3A, 3B, 3C, -LP) and two latent membrane proteins (LMPs 1 and 2). This elicits both primary and memory CT8+ CTL responses that are markedly skewed toward HLA allele-specific epitopes drawn from the EBNA3A, 3B, 3C subset of latent proteins, with reactivities to other antigens being generally much less frequent. This hierarchy of immunodominance among the different latent proteins may at least partly reflect their differential accessibility to the HLA class I-processing pathway. Furthermore, CTLs to some of the immunodominant epitopes involve highly conserved T cell receptor (TCR) usage, a level of focusing which evidence suggests could have immunopathological consequences from cross-reactive recognition of other target structures. EBV is associated with a range of human tumors, and there is increasing interest in the possibility of targeting such malignancies using virus-specific CTLs. The dramatic reversal of EBV-driven lymphoproliferations in bone marrow transplant patients following CTL infusion demonstrates the potential of this approach, and here we discuss prospects for its extension to other EBV-positive tumors in which the immunodominant EBNA3A, 3B, 3C proteins are not expressed.


Energy metabolism and valve closure behaviour in the Asian clam Corbicula fluminea.
Since its invasion of Europe in the early 1980s, the Asian clam Corbicula fluminea has become very abundant in nearly all western river systems. Today this species is one of the most important biomass producers in the River Rhine. Monitoring the valve movements of C. fluminea over a period of 2 years revealed a circadian rhythm in summer, with extended periods (10-12 h) of valve closure, predominantly in the morning hours. Altogether valve movements were very scarce, frequently fewer than four movements per individual per day. Simultaneous measurements of heat dissipation and oxygen consumption (calorespirometry) revealed an intermittent metabolism in the clam. With the onset of valve closure, C. fluminea reduced its metabolic rate to 10% of the standard metabolic rate (SMR) measured when the valves were open. Nevertheless, this depressed metabolism remained aerobic for several hours, enabling the clam to save energy and substrates compared to the requirements of the tenfold higher SMR. Only during long-lasting periods of valve closure (more than 5-10 h) did the clams become anaerobic and accumulate succinate within their tissues (2 micromol g(-1) fresh mass). Succinate is transported into the mantle cavity fluid, where it reaches concentrations of 4-6 mmol l(-1). Because this succinate-enriched fluid must pass the gills when the valves open again, we suggest that this anaerobic end product is at least partly reabsorbed, thus reducing the loss of valuable substrates during anaerobiosis. Propionate was also produced, but only during experimental N2-incubation, under near-anoxic conditions. The intermittent metabolism of C. fluminea is discussed as an adaption to efficiently exploit the rare food supply, saving substrates by the pronounced metabolic depression during valve closure.


Effect of packaging during storage time on retail display shelf life of longissimus muscle from two different beef production systems.
Two studies were conducted to evaluate the influence of packaging and production system (PS) on retail display life color (L*, a*, and b*), fatty acid profile (% of total fatty acids), lipid oxidation (thiobarbituric acid reactive substances; mg malondialdehyde/kg of muscle), vitamin E content (µg/g of muscle), and odor (trained panelists) during storage of LM. Four (or 3) different packaging treatments were applied to LM from steers fattened on grazing systems (Uruguayan) or on high-concentrate diets (U.S.). From fabrication to application of treatments, Uruguayan LM were vacuum packaged for air shipment and U.S. LM were also vacuum packaged and kept in a cooler until Uruguayan samples arrived. Treatments were applied 7 d after slaughter. In Exp. 1, treatments were vacuum packaging (VP), low-oxygen (O) modified atmosphere packaging (MAP) with nitrogen (N2) and carbon dioxide (MAP/CO), low-O MAP with N2 plus CO and carbon monoxide (MAP/CO), and VP plus an application of peroxyacetic acid (VP/PAA). In Exp. 2 block 1, treatments were VP, MAP/CO, and VP with ethyl-arginate HCl incorporated into the film as an antimicrobial agent (VP/AM). In Exp. 2 block 2, treatments were VP, MAP/CO, MAP/CO, and VP/AM. After 35 d storage, steaks were evaluated during simulated retail display for up to 6 d. In Exp. 1, Uruguayan steaks under MAP/CO had greater ( < 0.05) a* values than VP/PAA and MAP/CO on d 6 of display. For U.S. beef, the MAP/CO had the reddest lean color ( < 0.05) compared with the other 3 packaging treatments on d 6 of display in Exp. 1. Packaging × PS × time interaction was significant ( < 0.05) in Exp. 1. In Exp. 2, MAP/CO in Uruguayan steaks also had the greatest a* values on d 6 of display, but no differences ( > 0.05) were detected among both VP and MAP/CO in U.S. steaks at this time. No significant ( > 0.05) packaging × PS × time interaction was observed in Exp. 2. Only PS (both experiments) and time (Exp. 1) affected ( < 0.05) L* values. In both experiments, U.S. steaks had greater ( < 0.05) L* values than Uruguayan steaks. Vitamin E content in Uruguayan steaks was greater ( < 0.05) than in U.S. steaks. Packaging × PS, PS × time, and packaging × PS × time interactions were not significant ( > 0.05) for any of the fatty acids. Beef from Uruguayan had lower ( < 0.05) SFA and MUFA and greater ( < 0.05) PUFA and n-6 and n-3 fatty acid percentages than U.S. beef. Complexity of fresh meat postmortem chemistry warrants a more comprehensive approach to maximize shelf life.


Sharps safety. Five steps for maintaining an effective program.
Although most hospitals have had sharps safety programs in place for years, these programs may be out of date or may fail to address new procedures. Facilities should therefore regularly take stock of their current practices and evaluate new devices on the market. In this article, we describe a five-step process for developing, assessing, or revising a sharps safety program. Such programs are typically broad based, addressing several types of risks and the activities of multiple departments. Facilities may have well-established procedures for dealing with one of these aspects, while having few if any measures in place to address another. Consequently, the steps in the program described in this article may need to be applied in different ways to different areas within a single hospital. Yet even well-established programs require ongoing review, so these five steps are recommended regardless of how complete or effective a facility's current efforts may seem.


Cardiorenal Syndrome: An Overview.
It is well established that a large number of patients with acute decompensated heart failure present with various degrees of heart and kidney dysfunction usually primary disease of heart or kidney often involve dysfunction or injury to the other. The term cardiorenal syndrome increasingly had been used without a consistent or well-accepted definition. To include the vast array of interrelated derangements and to stress the bidirectional nature of heart-kidney interactions, a new classification of the cardiorenal syndrome with 5 subtypes that reflect the pathophysiology, the time frame, and the nature of concomitant cardiac and renal dysfunction was proposed. Cardiorenal syndrome can generally be defined as a pathophysiological disorder of the heart and kidneys, in which acute or chronic dysfunction of one organ may induce acute or chronic dysfunction to the other. Although cardiorenal syndrome was usually referred to as acute kidney dysfunction following acute cardiac disease, it is now clearly established that impaired kidney function can have an adverse impact on cardiac function.


Combined ab-interno trabeculectomy and cataract surgery induces comparable intraocular pressure reduction in supine and sitting positions.
To analyze the therapeutic effect of combined ab-interno trabeculectomy and cataract surgery on intraocular pressure (IOP) levels in supine and sitting postures during a 24-hour IOP profile. Twenty-six eyes of twenty-six patients receiving ab-interno trabeculectomy using electroablation of the trabecular meshwork combined with cataract surgery or stand-alone were included in this retrospective analysis. IOP change during 24-hour IOP profiles within two years postoperatively were analyzed for eyes receiving surgery ("study eyes") and compared to fellow eyes, which had not received surgery. Clinical data including mean sitting IOP (siIOP), mean supine IOP (suIOP) and the number of topical antiglaucomatous medications (TAM) were extracted from patients' files. Preoperatively, siIOP was 17.6±5.3 mm Hg in study and 17.1±4.7 mm Hg in fellow eyes (P=0.347). Patients were treated with an average of 2.8±1.0 TAM. Best corrected visual acuity (BCVA) was significantly worse in study eyes (P<0.001), visual field function was marginally not significantly different (P=0.057). After surgery 9.6±6.8mo, study eyes had a mean siIOP of 14.5±3.6 mm Hg (IOP reduction: -3.2 mm Hg, P=0.009), a mean suIOP of 18.0±3.5 mm Hg, and an average of 1.3±1.34 TAM (P<0.001), while in fellow eyes, mean siIOP was 16.2±3.4 mm Hg and mean suIOP was 20.5±5.1 mm Hg. Postoperatively, the relative IOP increase between sitting and supine postures was approximately 30% in both study and fellow eyes (P=0.99). IOP after ab-interno trabeculectomy shows a comparable relative reduction in both supine and sitting position. Classical trabeculectomy is known to lower suIOP overproportionally.


Reassortment and interspecies transmission of North American H6N2 influenza viruses.
H6N2 influenza viruses were isolated from California chickens in 2000 and 2001. Here we report the characterization of these H6N2 viruses, one of the few descriptions of non-H5, non-H7 subtype influenza viruses in this host. The H6N2 viruses were nonpathogenic in experimentally infected chickens and could be divided into three genotypes. All three genotypes of virus had similar surface glycoproteins and all contained an 18 amino acid deletion in the neuraminidase, a characteristic of other chicken influenza viruses. Differences were apparent, however, in the complement of replicative protein genes between the genotypes. The presence of multiple H6N2 genotypes suggests that independent transmission and/or reassortment events may have taken place between aquatic bird and chicken influenza viruses.


[Retrospective evaluation of eyes with high progressive myopia in children and youth ten years after Snyder and Thompson's scleroplasty].
Of the study was, to assess the safety and efficiency of scleral reinforcement after Snyder and Thompson surgery. The scleroplasty was performed on 129 eyes of 75 children with progressive myopia from 6 to 10 years of age. The control study group included 40 eyes of 25 children with similar age, mean eyeball axial length and refraction. In the control study group scleroplasty was not performed. The main indication criteria for surgery included: severe myopia more than -6.0 D, and the increase in refraction error more than -1.0 D per year. We evaluated the eyeball axial length in all subjects, before time of surgery and ten years after surgery, using Ultrasound Alcon Imaging System. The visual acuity, tonometry, visual field were evaluated as well. In the study group the mean eyeball axial length measured before surgery was 25.95 mm +/- 0.62 mm. Ten years after surgery the length of the eyeball was 26.97 mm +/- 0.64 mm. The average increase was 1.03 mm +/- 0.29 mm. In the control group, at the time when study group children were operated, the mean eyeball axial length was 25.91 mm +/- 0.48 mm, and ten years later it was 28.06 mm +/- 0.59 mm. The average increase in the eyeball length was 2.13 mm +/- 0.3 mm. There was statistically significant difference between the eyeball axial length progression in the study group and the control group, where surgery was not performed. In the study group no serious complications after surgery were reported. Scleral reinforcement is an effective and safe surgery, that can stabilize the progression of severe myopia in children.


Cryptococcus neoformans ADS lyase is an enzyme essential for virulence whose crystal structure reveals features exploitable in antifungal drug design.
There is significant clinical need for new antifungal agents to manage infections with pathogenic species such as Cryptococcus neoformans Because the purine biosynthesis pathway is essential for many metabolic processes, such as synthesis of DNA and RNA and energy generation, it may represent a potential target for developing new antifungals. Within this pathway, the bifunctional enzyme adenylosuccinate (ADS) lyase plays a role in the formation of the key intermediates inosine monophosphate and AMP involved in the synthesis of ATP and GTP, prompting us to investigate ADS lyase in C. neoformans. Here, we report that ADE13 encodes ADS lyase in C. neoformans. We found that an ade13Δ mutant is an adenine auxotroph and is unable to successfully cause infections in a murine model of virulence. Plate assays revealed that production of a number of virulence factors essential for dissemination and survival of C. neoformans in a host environment was compromised even with the addition of exogenous adenine. Purified recombinant C. neoformans ADS lyase shows catalytic activity similar to its human counterpart, and its crystal structure, the first fungal ADS lyase structure determined, shows a high degree of structural similarity to that of human ADS lyase. Two potentially important amino acid differences are identified in the C. neoformans crystal structure, in particular a threonine residue that may serve as an additional point of binding for a fungal enzyme-specific inhibitor. Besides serving as an antimicrobial target, C. neoformans ADS lyase inhibitors may also serve as potential therapeutics for metabolic disease; rather than disrupt ADS lyase, compounds that improve the stability the enzyme may be used to treat ADS lyase deficiency disease.


Towards more accurate pharmacogenomic variant effect predictions.
Tweetable abstract Accurate variant interpretation has become a key bottleneck for the translation of an individual's pharmacogenome into actionable recommendations. We recommend an integrated use of multiplexed assays, structure-based predictions and biobank data to develop more accurate effect predictors.


Angiopoietins and non-vascular endothelial growth factor antiangiogenic targets in advanced renal cell carcinoma.
The treatment of metastatic renal cell carcinoma has evolved from an era dominated by immune modulation to an era of antiangiogenesis agents. Blockade of vascular endothelial growth factor-mediated pathways and mammalian target of rapamycin pathways has accounted for most of these gains. Although these agents have offered dramatic improvements in survival for kidney cancer patients, resistance inevitably occurs, and new classes of agents are needed to continue to improve outcomes in this setting. We discuss several alternative pathways of angiogenesis, which are being investigated as targets to overcome treatment resistance, including angiopoietin family proteins, fibroblast growth factor, platelet-derived growth factor, and vascular disrupting agents.


Effect of polymeric adsorbents on the production of sanguinarine by Papaver somniferum cell cultures.
The suitability of adsorbent polymeric resins, Amberlite XAD-4 and XAD-7 (Rohm and Hass, Inc.), was investigated for the accumulation of sanguinarine from Papaver somniferum cell cultures. The adsorption and desorption of sanguinarine from aqueous solution was most effective with XAD-7. In addition to sanguinarine, the resins were found to absorb growth regulators and vitamins from the culture medium. Growth inhibition was overcome by delaying for approximately 4 days resin addition after cell inoculation in fresh medium. Resin addition (5% wt/vol) to actively growing uneclicited cultures led to increases in sanguinarine production and release of 30% to 40% and 60%, respectively. The addition of resins to elicited cultures led to increases in alkaloid production of up to 50% to 85% with similar increases in alkaloid release as observed for nonelicited cells. Overall yield of sanguinarine increased from 21 mg . g biomass dry weight(-1) (dw) for elicited cultures to more than 39 mg . gdw(-1) when elicitation was combined with resin addition. Higher quantities of resin (10% to 20% wt/vol) increased marginally the release of sanguinarine into the medium, and on the resin, up to 85% of total production. The use of resin appears promising for the development of a bioprocess for sanguinarine production by cultured plant cells.


Coordination abilities of polycyano anions in the solid state: coordination geometries and d-d transition energies of mixed-ligand solvatochromic copper(ii) complexes with B(CN)4, C(CN)3, and N(CN)2 anions.
B(CN)4-, C(CN)3-, and N(CN)2- are highly versatile polycyano anions that produce various functional compounds. To investigate the coordination abilities of these anions in the solid state quantitatively, we synthesized mixed-ligand Cu(ii) complexes: [Cu(R-acac)(tmen)X] (X = polycyano anion, R-acac = acetylacetonate or butyl-acetylacetonate, tmen = tetramethylethylenediamine). The coordination abilities of the anions, increasing in the order B(CN)4- < C(CN)3- < N(CN)2-, result in a decrease in the d-d transition energies of the complexes and the shortening of the axial coordination distance. The influence of crystal packing on the coordination geometries and d-d transition energies of the complexes was also demonstrated. The donor numbers of the anions were determined from the d-d transition energies in solution.


Effects of smartphone texting on the visual perception and dynamic walking stability.
Mobile phone use while walking can cause dual-task interference and increases safety risks by increasing attentional and cognitive demands. While the interference effect on cognitive function has been examined extensively, how perception of the environment and walking dynamics are affected by mobile phone use while walking is not well understood. The amount of visual information loss and its consequent impact on dynamic walking stability was examined in this study. Young adults (mean, 20.3 years) volunteered and walked on a treadmill while texting and attending to visual tasks simultaneously. Performance of visual task, field of regard loss, and margin of stability under dual-task conditions were compared with those of single-task conditions (i.e., visual task only). The results revealed that the size of visual field and visual acuity demand were varied across the visual task conditions. Approximately half of the visual cues provided during texting while walking were not perceived as compared to the visual task only condition. The field of regard loss also increased with increased dual-task cost of mobile phone use. Dynamic walking stability, however, showed no significant differences between the conditions. Taken together, the results demonstrate that the loss of situational awareness is unavoidable and occurs simultaneously with decrements in concurrent task performance. The study indicates the importance of considering the nature of attentional resources for the studies in dual-task paradigm and may provide practical information to improve the safe use of mobile phones while walking.


Graduating medical students' exercise prescription competence as perceived by deans and directors of medical education in the United States: implications for Healthy People 2010.
This study examined perceptions of deans and directors of medical education at 128 allopathic schools of medicine in the US about the importance of physical activity and exercise topics, and their perceptions about the competence of graduating medical students to perform six fundamental skills related to exercise prescription. Healthy People 2010 recommends that clinicians counsel all patients about regular physical activity. However, in previous studies physicians identified lack of training as a barrier to physical activity counseling, and they questioned their own ability to advise patients properly. Using the 17-item Exercise and Physical Activity Competence Questionnaire, data were collected from 72 of 128 medical schools, for a response rate of 56%. While 58% of respondents indicated their typical graduate was competent in conducting a patient evaluation for the purpose of approving that patient to begin an exercise program, only 10% said their students could design an exercise prescription. Only 6% of respondents reported that their school provided a core course addressing the American College of Sports Medicine Guidelines for Exercise Testing and Prescription. Findings suggest a need for more undergraduate medical training in physical activity and exercise prescription.


From the operating room of the present to the operating room of the future. Human-factors lessons learned from the minimally invasive surgery revolution.
The minimally invasive surgical revolution has changed the way surgery is practiced. It has also helped surgical innovators to break the tethers that anchored the practice of surgery in an early 20th century operating room environment. To some in surgery, the Operating Room of the Future will be seen as a revolution but to others, an inevitable evolution of the changes ushered in by the adoption of minimally invasive surgery. Although minimally invasive surgery has conferred considerable advantages on the patient, it has imposed significant difficulties on the surgeon, which in turn, have impacted outcomes. These difficulties were primarily human factor in nature and were poorly understood by critical groups such as device manufacturers, surgeons, and surgery educators and trainers. This article details what these human factors were, how they related to the practice of minimally invasive surgery, and how they will impact on the practice of surgery in the Operating Room of the Future. Much of the technology for the Operating Room of the Future currently exists (eg, surgical robotics, virtual reality, and telemedicine). However, for it to function optimally it must be integrated in a fashion that takes on board the human factor strengths and limitations of the surgeon. These advanced technologies should then be harnessed to optimize surgical practice. In some cases, this will involve rethinking existing technologies (ie, three-dimensional camera systems), applying technologies that currently exist in a manner that is more systematic and better managed (ie, surgical robots and virtual reality), and a reconsideration of who should be applying these technologies for the practice of surgery in the 21st century. In all cases, there will be education and training implications for the practitioner. Lastly, there must be unequivocal demonstration that these changes bring about positive benefits for patients in terms of better outcomes and for surgeons in terms of ability and ease of doing their job. After the experiences of the last decade with minimally invasive surgery, the Operating Room of the Future should be seen as a well-grounded evolution, not a revolution.


Report from the Radiation Oncology Committee of the Southwest Oncology Group (SWOG): Research Objectives Workshop 2003.
To achieve the ultimate goal of cancer treatment, which is 100% cancer control with negligible toxicity, the therapeutic window must be enlarged, allowing for higher doses of beneficial treatments with reduced toxicity. The advent of image- and metabolism-guided therapy offers the best opportunity to date for combining modern radiation targeting and imaging techniques. Indeed, for the first time, it is reasonable to locally target metastatic disease with the goal of sterilization. Combining these focal radiation techniques with novel targeted antiproliferative agents and full-dose classic cytotoxic chemotherapy will become more effective as we learn to use these compounds in a less systemically toxic manner and as radiation fields become more defined. In addition, increasing numbers of biologic modifiers of normal tissue response are becoming available, and they suggest great promise for decreasing the normal tissue toxicity resulting from both radiation and chemotherapy treatments. Thus, radiation metastectomy for gross metastases, used together with systemic control of micrometastatic disease, may yield improved survival rates. This hypothesis is ready for testing in cancers of the breast, prostate, colon, and in sarcomas. Enlarging the therapeutic window is a major goal that would allow for an increasingly favorable therapeutic gain.


How Hot Electron Generation at the Solid-Liquid Interface Is Different from the Solid-Gas Interface.
Excitation of hot electrons by energy dissipation under exothermic chemical reactions on metal catalyst surfaces occurs at both solid-gas and solid-liquid interfaces. Despite extensive studies, a comparative operando study directly comparing electronic excitation by electronically nonadiabatic interactions at solid-gas and solid-liquid interfaces has not been reported. Herein, on the basis of our in situ techniques for monitoring energy dissipation as a chemicurrent using a Pt/n-Si nanodiode sensor, we observed the generation of hot electrons in both gas and liquid phases during H2O2 decomposition. As a result of comparing the current signal and oxygen evolution rate in the two phases, surprisingly, the efficiency of reaction-induced excitation of hot electrons increased by ∼100 times at the solid-liquid interface compared to the solid-gas interface. The boost of hot electron excitation in the liquid phase is due to the presence of an ionic layer lowering the potential barrier at the junction for transferring hot electrons.


Aggregate formation is more strongly inhibited at high shear rates by dRGDW, a synthetic RGD-containing peptide.
The effect of D-Arg-Gly-Asp-Trp (dRGDW), a synthetic RGD-containing peptide, on platelet adhesion and aggregate formation on various purified adhesive proteins and the extracellular matrix of endothelial cells was investigated with anticoagulated blood recirculating through a parallel-plate perfusion chamber. Aggregate formation on the extracellular matrix of phorbol myristate acetate (PMA)-stimulated endothelial cells and on collagen type I was more strongly inhibited by dRGDW at higher shear rates than at a low shear rate. Platelet adhesion to the extracellular matrix of nonactivated and PMA-stimulated endothelial cells was inhibited by dRGDW, especially at high shear rates, probably as a consequence of the inhibition of platelet spreading. Inhibition by dRGDW of platelet adhesion to von Willebrand factor, fibronectin, and fibrinogen was almost complete, indicating that platelet adhesion to these substrates is mediated through RGD-directed receptors. Platelet adhesion to laminin was not inhibited by the peptide, whereas platelet adhesion to collagen was increased as a consequence of the inhibition of aggregate formation. Our results show that dRGDW is a strong inhibitor of platelet adhesion and aggregate formation, especially at high shear rates.


Biomimetic niche for neural stem cell differentiation using poly-L-lysine/hyaluronic acid multilayer films.
Polyelectrolyte multilayer films have been suggested as tunable substrates with flexible surface properties that can modulate cell behavior. However, these films' biological effects on neural stem/progenitor cells have rarely been studied. Herein, biomimetic multilayer films composed of hyaluronic acid and poly-L-lysine were chosen to mimic the native extracellular matrix niche of brain tissue and were evaluated for their inductive effects, without the addition of chemical factors. Because neural stem/progenitor cells are sensitive to substrate properties, it is important that this system provides control over the surface charge, and slight stiffness variations are also possible. Both of these factors affect neural stem/progenitor cell differentiation. The results showed that neural stem/progenitor cells were induced to differentiate on the poly-L-lysine/hyaluronic acid multilayer films with 0.5-4 alternating layers. In addition, the neurite outgrowth length was regulated by the surface charge of the terminal layer but did not increase with the layer number. In contrast, the quantity of differentiated neurons was enhanced slightly as the number of layers increased but was not affected by the surface charge of the terminal layer. In sum, material pairs in the form of native poly-L-lysine/hyaluronic acid films achieved important targets for neural regenerative medicine, including enhancement of the neurite outgrowth length, regulation of neuron differentiation, and the formation of a network. These extracellular matrix-mimetic poly-L-lysine/hyaluronic acid multilayer films may provide a versatile platform that could be useful for surface modification for applications in neural engineering.


What is ageing?
The absolute numbers and proportion of elderly people within society is increasing and will continue to increase into the next century. An understanding of normal biology, physiology and anatomy of ageing are an essential prerequisite for the treatment of pathology in the elderly. Gerontology is a young scientific discipline where important developments are being made. Progress in increasing longevity has so far been limited, but continuing improvements in the quality of life for the elderly remain an attainable goal.


An investigation on the antibacterial and antibiofilm efficacy of cationic nanoparticulates for root canal disinfection.
This study aimed to investigate the antibacterial and antibiofilm efficacy of cationic nanoparticulates for root canal disinfection. Experiments were performed in two stages. In stage 1, experiments were conducted to examine the physical properties of three types of nanoparticulates. The antibacterial properties of nanoparticulates alone and nanoparticulates mixed with zinc oxide-eugenol-based sealer were studied. In stage 2, the ability of nanoparticulates-treated dentin to prevent bacterial adherence was examined. Zinc oxide nanoparticulates, chitosan nanoparticulates, a mixture of zinc oxide and chitosan nanoparticulates, and zinc oxide nanoparticulates with multilayered coating of chitosan were tested. This study showed that the incorporation of nanoparticulates did not alter the flow characteristics of sealer but improved the direct antibacterial property and the ability to leach out antibacterial components. There was a significant reduction in the adherence of Enterococcus faecalis to nanoparticulates-treated dentin (p < 0.05). These experiments highlighted the potential advantage of nanoparticulates in root canal disinfection.


Classification of lymphoid neoplasms: the microscope as a tool for disease discovery.
In the past 50 years, we have witnessed explosive growth in the understanding of normal and neoplastic lymphoid cells. B-cell, T-cell, and natural killer (NK)-cell neoplasms in many respects recapitulate normal stages of lymphoid cell differentiation and function, so that they can be to some extent classified according to the corresponding normal stage. Likewise, the molecular mechanisms involved the pathogenesis of lymphomas and lymphoid leukemias are often based on the physiology of the lymphoid cells, capitalizing on deregulated normal physiology by harnessing the promoters of genes essential for lymphocyte function. The clinical manifestations of lymphomas likewise reflect the normal function of lymphoid cells in vivo. The multiparameter approach to classification adopted by the World Health Organization (WHO) classification has been validated in international studies as being highly reproducible, and enhancing the interpretation of clinical and translational studies. In addition, accurate and precise classification of disease entities facilitates the discovery of the molecular basis of lymphoid neoplasms in the basic science laboratory.


[Effects of HCY-2 gene transfer on the development of chick neural tube].
In order to explore the relationship between novel gene HCY-2 and neural tube defects (NTDs) and to investigate whether HCY-2 gene was genotoxic, a mammalian expression vector containing HCY-2 cDNA (2014 bp) was transferred into chick fertilized ovum by using lipofectin reagent, then the biological effects of HCY-2 gene on embryos in culture for 3.5 days were observed. Western blotting and immunohistochemistry were used to analyse the expression and distribution of HCY-2 after gene being transferred. HCY-2 gene (5-20 micrograms/chick ovum) could induce NTDs in organogenesis period. Western blotting and immunohistochemical staining showed that HCY-2 protein could be greatly expressed by day 3.5, the time which NTDs developed, with stronger staining at the site of embryonic brain as compared with controls. Under electron microscope, it was observed that HCY-2 gene could damage embryonic cellular ultrastructures and cause excessive apoptosis of neurocytes. These findings suggested that HCY-2 gene with its product was dysmorphogenic to the neural tube, might be a genotoxic factor or teratogenic agent and should be responsible for chick NTDs and probably human NTDs as well.


Prevalence and clinical classification of tremor in elderly--a community-based survey in Brazil.
Prevalence data on different types of tremor among the elderly population are very scarce. The objective of this study was to study the prevalence of tremor in a community-dwelling elderly population in the town of Bambuí, Brazil. The authors studied 1186 inhabitants aged≥64 years. This was a 2-phase study in which all participants who screened positive in a questionnaire for tremor and parkinsonism or who used drugs capable of causing/suppressing tremor were examined. In this population, the prevalence rate was 17.4% for tremor, 7.4% for essential tremor, 5.6% for parkinsonian tremor, 2.8% for enhanced physiological tremor, and 1.6% for other causes. There were no gender differences in prevalence rates for all types. Patients who had Parkinson's disease with tremor were older than those who had essential tremor, whereas patients who had enhanced physiological tremor were significantly younger. The age-specific prevalence of tremor increased with advancing age for both men and women. The prevalence of tremor in the studied population was high and increased with advancing age. Essential tremor, parkinsonian tremor, and enhanced physiological tremor were the most commonly identified causes. © 2013 Movement Disorder Society.


Pay rise should be at least 10.
I think a minimum 10% pay rise would retain homegrown nurses. Morale and nursing levels need to be improved to help reduce stress. When you go to the wire with nothing to spare in the establishment, and it all goes pear-shaped, everyone becomes stretched and stressed. Managers should listen to staff at the coal face about this.


Diffuse Idiopathic Skeletal Hyperostosis (DISH) and Impaired Physical Function: The Rancho Bernardo Study.
Investigate associations of diffuse idiopathic skeletal hyperostosis (DISH) with self-reported and measured physical function in older adults. Cross-sectional analyses of data collected in 1992-96 from a longitudinal cohort. Research clinic within a community. Community-dwelling men (n = 630) and women (n = 961), mean age 71.5 years (SD = 10.8), from the Rancho Bernardo Study. DISH assessed from lateral thoracic and lumbar spine radiographs; self-reported difficulty bending over to the floor, walking 2-3 level blocks, or climbing 1 flight of stairs; performance-based measures of grip strength and chair-stand testing (ability to stand up and sit down in a chair 5 times without using chair arms). DISH was present in 25.6% of men and 5.5% of women. In age and sex-adjusted models, those with DISH had 1.72-fold increased odds (95% CI: 1.13, 2.62) of self-reported difficulty bending; this remained significant after further adjustment for Cobb angle, weight, stroke, arthritis, and exercise, OR = 1.69, (95% CI: 1.07, 2.66). In fully adjusted multivariate models, those with DISH had worse grip strength, -1.08 kg, P = .01, but did not differ from those without DISH on walking or climbing stairs. In sex-stratified, fully adjusted models, among men only, those with DISH were 2.17-times (95% CI: 1.04, 4.52) more likely to be unable to complete 5 chair stands without using their arms. DISH was less prevalent in women but affected almost one-quarter of older white men. People with DISH are more likely to experience physical functional impairment, suggesting that DISH has clinical correlations and is not an incidental radiographic finding.


Total flavonoids from Rhizoma Drynariae (Gusuibu) for treating osteoporotic fractures: implication in clinical practice.
This systematic review was performed to determine the clinical efficacy and safety of total flavonoids from Rhizoma Drynariae (TFRD) for osteoporotic fractures and to provide clear evidence for clinical practice. Eight databases were searched to identify relevant randomized controlled trials (RCTs) until December 2016. Six RCTs involving 846 patients were included. The primary outcomes included fracture recurrence and death. Meta-analysis showed that both the combination therapy and TFRD alone were better than conventional treatments in improving bone mineral density (BMD) value (weighted mean difference [WMD] =3.68, 95% confidence interval [CI]: 0.01 to 0.04, P=0.0002), (WMD =0.14; 95% CI: 0.11 to 0.16; P<0.00001), respectively, and enhancing therapeutic effect (OR =0.25; 95% CI: 0.12 to 0.51; P=0.0002). Thirty-three patients experienced adverse drug reactions (ADRs), none of the ADRs were severe and all were resolved after symptomatic treatments. Gastrointestinal symptoms were the most common ADRs in the usage of TFRD. Overall, the effect of TFRD on osteoporotic fractures was supported by improving BMD and therapeutic effect. Due to the methodological drawbacks of the included studies, the conclusions should be treated with caution for future research. Registration number: CRD42017052797.


Serological and genotypic diversity among serogroup 5- reacting environmental Legionella isolates.
Five strains of bacteria (strains 684, 687, U7W, U8W, and MICU-B) that were biochemically and morphologically indistinguishable from Legionella pneumophila were recovered from the environment. Strains U7W, U8W, and MICU-B were antigenically identical to L. pneumophila strain Dallas 1E (serogroup 5), as determined by direct fluorescent antibody staining and immunodiffusion. Although strains 694 and 687 shared antigenic determinants with L. pneumophila Dallas 1E, they could be distinguished by immunodiffusion and differential absorption studies. However, as determined by DNA hybridization, the antigenically distinct strains 684 belong to the same DNA homology cluster as previously described authentic strains of L. pneumophila, whereas strain U7W, U8W, and MICU-B belong to a separate homology group. Therefore, two groups could be identified among these environmental isolates; one represents an antigenic subclass of serogroup 5 L. pneumophila (strains 684, and 687), and the other, although antigenically indistinguishable from serogroup 5 L. pneumophila, probably represents a new Legionella species (strains U7W, U8W, and MICU-B).


A Tracer Study of Psychosocial Counselling Graduates Working in Different Healthcare Facilities Across Malawi.
Graduate Tracer Studies plays a key role in informing higher education institutions worldwide about the effectiveness of their programs and preparing graduates for the job market. The study aimed to trace its psychosocial counselling graduates working in different healthcare facilities across Malawi. The tracer study employed a descriptive cross-sectional research design where the quantitative research method, specifically a survey was used. Data was gathered from Psychosocial counselling graduates of Saint John of God College of Health Sciences using a questionnaire. The data were analyzed using Statistical Package for Social Sciences (SPSS). Out of 123 participants, 72 responded, yielding a response rate of 59%. Of these, there were 40 (55.6%) females and 32 (44.4%) males. Results indicated strong belief among participants that the program provided them with valuable skills. The majority of graduates reported successful employment outcomes, with an impressive 62 (86.1%) securing jobs, often within a short period. Many participants effectively utilized the knowledge and skills acquired during the program within their workplace settings. However, a subset of graduates faced challenges in applying their training. Recommendations for program improvement included the addition of courses such as Project Management and Monitoring and Evaluation. The identified key challenges encompassed low staffing levels and limited resources. The study confirms program effectiveness based on positive outcomes reported by graduates in job relevance, skill development, and knowledge use. Addressing identified gaps and implementing recommended improvements can enhance graduates' employability, meet market demands, and improve the psychosocial counselling health sector in Malawi. The study recommends that the College should consider collaborating with industry partners, monitoring employment outcomes, and proactively adapting the curriculum is vital for program success and professional development.


Astronaut-induced disturbances to the microgravity environment of the Mir Space Station.
In preparation for the International Space Station, the Enhanced Dynamic Load Sensors Space Flight Experiment measured the forces and moments astronauts exerted on the Mir Space Station during their daily on-orbit activities to quantify the astronaut-induced disturbances to the microgravity environment during a long-duration space mission. An examination of video recordings of the astronauts moving in the modules and using the instrumented crew restraint and mobility load sensors led to the identification of several typical astronaut motions and the quantification of the associated forces and moments exerted on the spacecraft. For 2806 disturbances recorded by the foot restraints and hand-hold sensor, the highest force magnitude was 137 N. For about 96% of the time, the maximum force magnitude was below 60 N, and for about 99% of the time the maximum force magnitude was below 90 N. For 95% of the astronaut motions, the rms force level was below 9.0 N. It can be concluded that expected astronaut-induced loads from usual intravehicular activity are considerably less than previously thought and will not significantly disturb the microgravity environment.


Anterior vs lateral symmetric interstitial syndrome in the diagnosis of acute heart failure.
Acute dyspnea due to acute heart failure (AHF) is one of the most common reasons for admission to the Emergency Department (ED). The importance of lung ultrasound (LUS) examination in the diagnostic workup of AHF has been widely established. Limited anterior LUS examination for the diagnosis of AHF is controversial. This study compares the accuracy of LUS examination limited to the anterior or lateral lung zones for the diagnosis of AHF and their accuracy among patients with different levels of hypoxemia according to PO2/FiO2 ratio evaluation. We analyzed 170 patients admitted to the ED for acute dyspnea, who underwent multi-organ ultrasound examination of lung, heart and inferior vena cava for differential diagnosis. The thorax was examined following a simplified protocol that provides two scans at each side (anterior and lateral) to sample upper and lower lobes and the presence or the absence of interstitial syndrome (IS) was evaluated. The presence of anterior symmetric IS exhibited lower accuracy than lateral symmetric IS in the diagnosis of AHF in the whole population, but its diagnostic accuracy improves in sub-groups of patients with severe and critical hypoxemia.