Proxalutamide Reduces the Rate of Hospitalization for COVID-19 Male Outpatients: A Randomized Double-Blinded Placebo-Controlled Trial.
Antiandrogens have demonstrated a protective effect for COVOD-19 patients in observational and interventional studies. The goal of this study was to determine if proxalutamide, an androgen receptor antagonist, could be an effective treatment for men with COVID-19 in an outpatient setting. A randomized, double-blinded, placebo-controlled clinical trial was conducted at two outpatient centers (Brasilia, Brazil). Patients were recruited from October 21 to December 24, 2020 (clinicaltrials.gov number, NCT04446429). Male patients with confirmed COVID-19 but not requiring hospitalization (COVID-19 8-point ordinal scale <3) were administered proxalutamide 200 mg/day or placebo for up to 7 days. The primary endpoint was hospitalization rate at 30 days post-randomization. A total of 268 men were randomized in a 1:1 ratio. 134 patients receiving proxalutamide and 134 receiving placebo were included in the intention-to-treat analysis. The 30-day hospitalization rate was 2.2% in men taking proxalutamide compared to 26% in placebo, P < 0.001. The 30-day hospitalization risk ratio was 0.09; 95% confidence interval (CI) 0.03-0.27. Patients in the proxalutamide arm more frequently reported gastrointestinal adverse events, however, no patient discontinued treatment. In placebo group, 6 patients were lost during follow-up, and 2 patients died from acute respiratory distress syndrome. Here we demonstrate the hospitalization rate in proxalutamide treated men was reduced by 91% compared to usual care.


Origin of the glomerular basement membrane visualized after in vivo labeling of laminin in newborn rat kidneys.
To examine the origin and assembly of glomerular basement membranes (GBMs), affinity purified anti-laminin IgG was directly coupled to horseradish peroxidase (HRP) and intravenously injected into newborn rats. Kidneys were then processed for peroxidase histochemistry and microscopy. Within 1 h after injection, anti-laminin bound to basement membranes of nephrons in all developmental stages (vesicle, comma, S-shaped, developing capillary loop, and maturing glomeruli). In S-shaped and capillary loop glomeruli, anti-laminin-HRP labeled a double basal lamina between the endothelium and epithelium. Sections incubated with anti-laminin in vitro showed labeling within the rough endoplasmic reticulum of endothelium and epithelium, indicating that both cell types synthesized laminin for the double basement membrane. In maturing glomeruli, injected anti-laminin-HRP bound throughout the GBMs, and double basement membranes were rarely observed. At this stage, however, numerous knobs or outpockets of basement membrane material extending far into the epithelial side of the capillary wall were identified and these were also labeled throughout their full thickness. No such outpockets were found in the endothelial cell layer of newborn rats (and they normally are completely absent in fully mature, adult glomeruli). In contrast with these results, in kidneys fixed 4-6 d after anti-laminin IgG-HRP injection, basement membranes of vesicle, comma, and S-shaped nephrons were unlabeled, indicating that they were assembled after injection. GBM labeling was seen in maturing glomeruli, however. In addition, the outpockets of basement membrane extending into the epithelium were often completely unlabeled whereas GBMs lying immediately beneath them were labeled intensely, which indicates that the outpockets were probably assembled by the epithelium. Injections of sheep anti-laminin IgG followed 8 d later with injections of biotin-rabbit anti-laminin IgG and double-label immunofluorescence microscopy confirmed that GBM formation continued during individual capillary loop expansion. GBM assembly therefore occurs by at least two different processes at separate times in development: (a) fusion of endothelial and epithelial basement membranes followed by (b) addition of new basement membrane from the epithelium into existing GBMs.


Radiograph Interpretation Discrepancies in a Community Hospital Emergency Department.
In many hospitals, off-hours emergency department (ED) radiographs are not read by a radiologist until the following morning and are instead interpreted by the emergency physician (EP) at the time of service. Studies have found conflicting results regarding the radiographic interpretation discrepancies between EPs and trained radiologists. The aim of this study was to identify the number of radiologic interpretation discrepancies between EPs and radiologists in a community ED setting. Using a pre-existing logbook of radiologic discrepancies as well as our institution's picture archiving and communication system, all off-hours interpretation discrepancies between January 2012 and January 2015 were reviewed and recorded in a de-identified fashion. We recorded the type of radiograph obtained for each patient. Discrepancy grades were recorded based on a pre-existing 1-4 scale defined in the institution's protocol logbook as Grade 1 (no further action needed); Grade 2 (call to the patient or pharmacy); Grade 3 (return to ED for further treatment, e.g., fracture not splinted); Grade 4 (return to ED for serious risk, e.g., pneumothorax, bowel obstruction). We also recorded the total number of radiographs formally interpreted by EPs during the prescribed time-frame to determine overall agreement between EPs and radiologists. There were 1044 discrepancies out of 16,111 EP reads, indicating 93.5% agreement. Patients averaged 48.4 ± 25.0 years of age and 53.3% were female; 25.1% were over-calls by EPs. The majority of discrepancies were minor with 75.8% Grade 1 and 22.3% Grade 2. Only 1.7% were Grade 3, which required return to the ED for further treatment. A small number of discrepancies, 0.2%, were Grade 4. Grade 4 discrepancies accounted for two of the 16,111 total reads, equivalent to 0.01%. A slight disagreement in finding between EP and radiologist accounted for 8.3% of discrepancies. Results suggest that plain radiographic studies can be interpreted by EPs with a very low incidence of clinically significant discrepancies when compared to the radiologist interpretation. Due to rare though significant discrepancies, radiologist interpretation should be performed when available. Further studies are needed to determine the generalizability of this study to EDs with differing volume, patient population, acuity, and physician training.


In silico study of PEI-PEG-squalene-dsDNA polyplex formation: the delicate role of the PEG length in the binding of PEI to DNA.
Biocompatible hydrophilic polyethylene glycol (PEG) is widely used in biomedical applications, such as drug or gene delivery, tissue engineering or as an antifouling component in biomedical devices. Experimental studies have shown that the size of PEG can weaken polycation-polyanion interactions, like those between branched polyethyleneimine (b-PEI) and DNA in gene carriers, but details of its cause and underlying interactions on the atomic scale are still not clear. To better understand the interaction mechanisms in the formation of polyplexes between b-PEI-PEG based carriers and DNA, we have used a combination of in silico tools and experiments on three multicomponent systems differing in PEG MW. Using the PEI-PEG-squalene-dsDNA systems of the same size, both in the all-atom MD simulations and in experimental in-gel electrophoresis measurements, we found that the binding between DNA and the vectors is highly influenced by the size of PEG, with the binding efficiency increasing with a shorter PEG length. The mechanism of how PEG interferes with the binding between PEI and DNA is explained using a two-step MD simulation protocol that showed that the DNA-vector interactions are influenced by the PEG length due to the hydrogen bond formation between PEI and PEG. Although computationally demanding we find it important to study molecular systems of the same size both in silico and in a laboratory and to simulate the behaviour of the carrier prior to the addition of bioactive molecules to understand the molecular mechanisms involved in the formation of the polyplex.


Modeling of off-gas emissions from wood pellets during marine transportation.
After a fatal accident during the discharge of wood pellets at Helsingborg, emissions from pellets during marine transportation became a concern for the safe handling and storage of wood pellets. In this paper, a two-compartment model has been developed for the first time to predict the concentrations of CO, CO₂, CH₄, and O₂ inside the cargo ship and the time and rate of forced ventilation required before the safe entry into the stairway adjacent to the storage hatch. The hatch and stairway are treated as two perfectly mixed tanks. The gas exchange rate between these two rooms and the gas exchange rate with the atmosphere are fitted to satisfy a measured tracer final concentration of 33 p.p.m.v. in the stairway and an average final hatch to stairway CO, CO₂, and CH₄ concentration ratio of 1.62 based on measurement from five other hatch and stairway systems. The reaction kinetics obtained from a laboratory unit using a different batch of pellets, however, need to be scaled in order to bring the prediction to close agreement with onboard measured emission data at the end of voyage. Using the adjusted kinetic data, the model was able to predict the general trend of data recorded in the first 12.5 days of the voyage. Further validation, however, requires the data recorded over the whole journey. The model was applied to predict the effect of ocean temperature on the off-gas emissions and the buildup of concentrations in the hatch and stairway. For safe entry to the cargo ship, the current model predicted that a minimal ventilation rate of 4.4 hr⁻¹ is required for the stairway's CO concentration to lower to a safe concentration of 25 p.p.m.v. At 4.4 hr⁻¹, 10 min of ventilation time is required for the safe entry into the stairway studied.


Metabolic response to dietary fibre composition in horses.
The hypothesis for this study was that a higher dietary proportion of soluble fibre would result in stable and constant plasma metabolite and regulatory hormone concentrations. The study was a 4×4 Latin Square design with a sequence of 17 days adaptation to the ration followed by 8 sampling days. The feed rations consisted of only timothy hay (H), hay plus molassed sugar beet pulp combined with either whole oats (OB) or barley (BB) and hay plus a loose chaff-based concentrate (M). Four horses were fitted with permanent caecal cannulas and liquid caecal content was withdrawn manually and blood was drawn from the jugular vein at 0, 3 and 9 h postprandial. The horses were exercised daily at medium level for about 1 h. Samples were analysed for short-chain fatty acids (SCFA) and metabolic traits. Caecal SCFA and propionic acid concentrations increased with increased dietary starch and soluble fibre. The diet highest in soluble fibre (M) resulted in the highest plasma glucose and insulin concentrations in the morning, which then remained stable and constant throughout the day. A strong interaction (P<0.01) between time and diet was measured for plasma urea, glucose, insulin and leptin. The greatest variations in plasma glycaemic and insulinaemic responses were associated with the cereal grain diets (OB and BB). There were indications of a negative energy balance, which was reflected in a significantly higher plasma β-hydroxybutyrate concentration and a numerically higher non-esterified fatty acid concentration. In conclusion, this study found that inclusion of soluble fibre resulted in increased total caecal SCFA and propionic acid concentrations. This consequently resulted in stable and constant plasma glycaemic and insulinaemic responses. Diets with a high content of soluble fibre provided enough energy for horses at medium work level.


Effectiveness of Motivational Interviewing on adult behaviour change in health and social care settings: A systematic review of reviews.
The challenge of addressing unhealthy lifestyle choice is of global concern. Motivational Interviewing has been widely implemented to help people change their behaviour, but it is unclear for whom it is most beneficial. This overview aims to appraise and synthesise the review evidence for the effectiveness of Motivational Interviewing on health behaviour of adults in health and social care settings. A systematic review of reviews. Methods were pre-specified and documented in a protocol (PROSPERO-CRD42016049278). We systematically searched 7 electronic databases: CDSR; DARE; PROSPERO; MEDLINE; CINAHL; AMED and PsycINFO from 2000 to May 2018. Two reviewers applied pre-defined selection criteria, extracted data using TIDIER guidelines and assessed methodological quality using the ROBIS tool. We used GRADE criteria to rate the strength of the evidence for reviews including meta-analyses. Searches identified 5222 records. One hundred and four reviews, including 39 meta-analyses met the inclusion criteria. Most meta-analysis evidence was graded as low or very low (128/155). Moderate quality evidence for mainly short term (<6 months) statistically significant small beneficial effects of Motivational Interviewing were found in 11 of 155 (7%) of meta-analysis comparisons. These outcomes include reducing binge drinking, frequency and quantity of alcohol consumption, substance abuse in people with dependency or addiction, and increasing physical activity participation. We have created a comprehensive map of reviews relating to Motivational Interviewing to signpost stakeholders to the best available evidence. More high quality research is needed to be confident about the effectiveness of Motivational Interviewing. We identified a large volume of low quality evidence and many areas of overlapping research. To avoid research waste, it is vital for researchers to be aware of existing research, and the implications arising from that research. In the case of Motivational Interviewing issues relating to monitoring and reporting fidelity of interventions need to be addressed.


Dopamine Triggers CTCF-Dependent Morphological and Genomic Remodeling of Astrocytes.
Dopamine is critical for processing of reward and etiology of drug addiction. Astrocytes throughout the brain express dopamine receptors, but consequences of astrocytic dopamine receptor signaling are not well established. We found that extracellular dopamine triggered rapid concentration-dependent stellation of astrocytic processes that was not a result of dopamine oxidation but instead relied on both cAMP-dependent and cAMP-independent dopamine receptor signaling. This was accompanied by reduced duration and increased frequency of astrocytic Ca2+ transients, but little effect on astrocytic voltage-gated potassium channel currents. To isolate possible mechanisms underlying these structural and functional changes, we used whole-genome RNA sequencing and found prominent dopamine-induced enrichment of genes containing the CCCTC-binding factor (CTCF) motif, suggesting involvement of chromatin restructuring in the nucleus. CTCF binding to promoter sites bidirectionally regulates gene transcription and depends on activation of poly-ADP-ribose polymerase 1 (PARP1). Accordingly, antagonism of PARP1 occluded dopamine-induced changes, whereas a PARP1 agonist facilitated dopamine-induced changes on its own. These results indicate that astrocyte response to elevated dopamine involves PARP1-mediated CTCF genomic restructuring and concerted expression of gene networks. Our findings propose epigenetic regulation of chromatin landscape as a critical factor in the rapid astrocyte response to dopamine.SIGNIFICANCE STATEMENT Although dopamine is widely recognized for its role in modulating neuronal responses both in healthy and disease states, little is known about dopamine effects at non-neuronal cells in the brain. To address this gap, we performed whole-genome sequencing of astrocytes exposed to elevated extracellular dopamine and combined it with evaluation of effects on astrocyte morphology and function. We demonstrate a temporally dynamic pattern of genomic plasticity that triggers pronounced changes in astrocyte morphology and function. We further show that this plasticity depends on activation of genes sensitive to DNA-binding protein CTCF. Our results propose that a broad pattern of astrocyte responses to dopamine specifically relies on CTCF-dependent gene networks.


Current research and recent breakthroughs on the mental health effects of disasters.
A large existing academic disaster mental health literature provides a foundation to help guide disaster mental health response. Recent studies, however, have indicated that reconceptualization of certain mental health aspects of disasters may be indicated to guide further research to inform the planning and implementation of disaster mental health interventions. In particular, there is need to more carefully measure specific postdisaster disorders and syndromes using full diagnostic assessments, differentiate pre-existing from incident (new) postdisaster psychopathology, appropriately consider disaster trauma exposure groups in assessing psychopathology, and conduct prospective follow-up assessments over time from the acute postdisaster period to the long term. Further descriptive and longitudinal research is needed to better characterize the occurrence and course of fully-assessed psychiatric disorders after different disasters, clarify the role of disaster trauma exposures in the development of postdisaster psychopathology, and deconstruct confounding effects in determination of causalities in mental health consequences of disasters.


Relaxin promotes in vitro tumour growth, invasion and angiogenesis of human Saos-2 osteosarcoma cells by AKT/VEGF pathway.
In the present study, we determine the role of relaxin on cellular growth, invasion and angiogenesis of osteosarcoma Saos-2 cells in vitro, and discuss the molecular mechanisms of this action. Saos-2 cells were transfected with Akt1/2 siRNA or VEGF siRNA for 24 hours then treated with 10-100 ng/mL recombinant human relaxin-2 (rh-RLN) for 48 h. MTT, matrigel and bone marrow-derived endothelial cells (BMDECs) was used for cell proliferation, invasion and angiogenesis assay. Western blot was used for relaxin-2, pAKT and VEGF protein assay. The results showed treatment with 10-100 ng/mL rh-RLN resulted in 18%, 48%, 107%, 212% increase in cell proliferation, respectively (vs control, *p < 0.05;**p < 0.01), the relative invasive cells was 1.4;1.9;2.6;4.8 (control was defined to 1) (vs control, #p < 0.01; ##p < 0.001) and the relative anglogenic branch points in Saos-2 cells was 1.04;1.36;1.69;2.10 (control was defined to 1.00) (vs control, *p < 0.05; **p < 0.01). Furthermore, treatment with rh-RLN exhibited a significant increase in the expression level of pAKT and VEGF proterin in dose-dependent manner. Saos-2 cells were transfected with AKT1/2 siRNA for 24 h. No significant increase of VEGF protein expression was shown after rh-RLN treatment. These results suggested that rh-RLN could promoted proliferation, invasion and angiogenesis by upregulation pAKT-dependent VEGF expression.


MTF and DQE enhancement using an apodized-aperture x-ray detector design.
Acquisition of high-quality x-ray images using low patient exposures requires detectors with high detective quantum efficiency (DQE). We describe a novel apodized-aperture pixel (AAP) design that increases high-frequency modulation transfer function (MTF) and DQE values. The AAP design makes a separation of physical sensor elements from image pixels by using very small sensor elements (e.g., 0.010-0.025 mm) to synthesize desired larger image pixels (e.g., 0.1-0.2 mm). A cascaded systems model of signal and noise propagation is developed to describe the benefits of the AAP approach in terms of the MTF, Wiener noise power spectrum (NPS), and DQE. The theoretical model was validated experimentally using a CMOS/CsI detector with 0.05 mm sensor elements to synthesize 0.20 mm image pixels and a clinical Se detector with 0.07 mm sensor elements to synthesize 0.28 mm pixels. A Monte Carlo study and x-ray images of a star-pattern and rat leg are used to visually compare AAP images. When used with a high-resolution converter layer and sensor elements one quarter the size of image pixels, the MTF is increased by 53% and the DQE by a factor of 2.3× at the image sampling cut-off frequency. Both simulated and demonstration images show improved detectability of high-frequency content and removal of aliasing artifacts. Evidence of Gibbs ringing is sometimes seen near high-contrast edges. It is shown that the AAP approach preserves the MTF of the small sensor elements and attenuates frequencies above the image sampling cut-off frequency. This has the double benefit of improving the MTF while reducing both signal and noise aliasing, resulting in an increase of the DQE at high spatial frequencies. For optimal implementation, the converter layer must have very high spatial resolution and the detector must have low readout noise.


[Radionuclide and thermographic diagnosis of head and neck neoplasms].
Radionuclide and thermographic studies using 67Ga-citrate and 111In-bleomycin were performed in 129 patients with laryngeal cancer, chemodectoma of the neck, retinoblastoma, rhabdomyosarcoma of the orbital and facial soft tissues and cancer of the tongue. Elevated amounts of the radiopharmaceutical drug were found in patients with tumors. In thermographic studies higher thermogenic activity corresponding to the tumor was noted. Radionuclide thermographic studies extend diagnostic opportunities for head and neck tumors.


Requirement of tyrosine phosphorylation for rapid activation of a DNA binding factor by IL-4.
Interleukin-4 (IL-4) is an immunoregulatory cytokine produced by activated T lymphocytes to promote the growth and differentiation of cells that participate in immune defense. This study demonstrates the rapid activation of a specific DNA binding factor by IL-4. The IL-4 nuclear-activated factor (IL-4 NAF) appeared within minutes of IL-4 stimulation and recognized a specific DNA sequence found in the promoters of IL-4-responsive genes. Activation of this putative transcription factor required tyrosine phosphorylation, and antibodies specific for phosphotyrosine recognize the IL-4 NAF-DNA complex. Thus, IL-4 appears to transduce a signal to the nucleus through tyrosine phosphorylation of a latent DNA binding factor.


Recent advances in the synthesis of nitrogen heterocycles via radical cascade reactions using isonitriles as radical acceptors.
Nitrogen heterocycles belong to a highly important class of compounds which are found in various natural products, biologically active structures, and medicinally relevant compounds. Therefore, there is continuing interest in the development of novel synthetic methods for the construction of nitrogen containing heterocycles. Recently, radical insertion reactions into isonitriles have emerged as an efficient and powerful strategy for the construction of nitrogen heterocycles, such as phenanthridines, indoles, quinolines, quinoxalines, and isoquinolines. This review highlights recent advances in this fast growing research area and also includes important pioneering studies in this area.


The type 2 diabetes associated rs7903146 T allele within TCF7L2 is significantly under-represented in Hereditary Multiple Exostoses: insights into pathogenesis.
Hereditary Multiple Exostoses (HME) is an autosomal-dominant disorder characterized by benign cartilage tumors (exostoses) forming near the growth plates, leading to severe health problems. EXT1 and EXT2 are the two genes known to harbor heterozygous loss-of-function mutations that account for the vast majority of the primary genetic component of HME. However, patients present with wide clinical heterogeneity, suggesting that modifier genes play a role in determining severity. Our previous work has pointed to an imbalance of β-catenin signaling being involved in the pathogenesis of osteochondroma formation. TCF7L2 is one of the key 'gate-keeper' TCF family members for Wnt/β-catenin signaling pathway, and TCF7L2 and EXT2 are among the earliest associated loci reported in genome wide appraisals of type 2 diabetes (T2D). Thus we investigated if the key T allele of single nucleotide polymorphism (SNP) rs7903146 within the TCF7L2 locus, which is strongly over-represented among T2D cases, was also associated with HME. We leveraged genotype data available from ongoing GWAS efforts from genomics and orthopedic centers in the US, Canada and Italy. Collectively 213 cases and 1890 controls were analyzed and, surprisingly, the T allele was in fact significantly under-represented in the HME patient group [P = 0.009; odds ratio = 0.737 (95% C.I. 0.587-0.926)]; in addition, the direction of effect was consistent within each individual cohort. Immunohistochemical analyses revealed that TCF7L2 is differentially expressed and distributed in normal human growth plate zones, and exhibits substantial variability in human exostoses in terms of staining intensity and distribution. In summary, the data indicate that there is a putative genetic connection between TCF7L2 and EXT in the context of HME. Given this observation, we suggest that these loci could possibly modulate shared pathways, in particular with respect to β-catenin, and their respective variants interplay to influence HME pathogenesis as well as T2D.


Damped oscillatory hysteretic behaviour of butyrylcholinesterase with benzoylcholine as substrate.
Steady-state kinetics for the hydrolysis of benzoylcholine (BzCh) and benzoylthiocholine (BzSCh) by wild-type human butyrylcholinesterase (BuChE) and by the peripheral anionic site mutant D70G were compared. kcat/Km for the hydrolysis of BzSCh was 17-fold and 32-fold lower than that for hydrolysis of BzCh by wild-type and D70G, respectively. The rate-limiting step for hydrolysis of BzCh was deacylation, whereas acylation was rate-limiting for hydrolysis of BzSCh. Wild-type enzyme and the D70G mutant were found to reach steady-state velocity slowly with BzCh as the substrate. At pH 6, the approach to steady-state for both enzymes consisted of a mono-exponential acceleration upon which a set of damped oscillations was superimposed. From pH 7 to 8.5, the approach to steady-state consisted of a simple exponential acceleration. The damped oscillations were analyzed by both a numerical approximation and simulation based on a theoretical model. BuChE-catalyzed hydrolysis of the thiocholine analogue of BzCh showed neither lags nor oscillations, under the same conditions. The frequency and amplitude of the damped oscillations decreased as the BzCh concentration increased. The apparent induction time for the exponential portion of the lag was calculated from the envelope of the damped oscillations or from the smooth lag. Wild-type BuChE showed a hyperbolic increase in induction time as the BzCh concentration increased (tau max = 210 s at pH 6.0). However, the induction time for D70G was constant over the whole range of BzCh concentrations (tau max = 60 s at pH 6.0). Thus, the induction time does not conform to a simple hysteretic model in which there is a slow conformational transition of the enzyme from an inactive form E to an active form E'. No pH-dependence of the induction time was found between pH 6.0 and 8.5 in sodium phosphate buffers of various concentrations (from 1 mm to 1 m). However, increasing the pH tended to abolish the oscillations (increase the damping factor). This effect was more pronounced for D70G than for wild-type. Although the lyotropic properties of phosphate change from chaotropic at pH 6.0 to kosmotropic at pH > 8.0, no effect of phosphate concentration on the oscillations was noticed at the different pH values, suggesting that the oscillations are not related to a pH-dependent Hofmeister effect of phosphate ions. Simulation and theoretical analysis of the oscillatory behaviour of the approach to the steady-state for BuChE led us to propose a model for the hysteresis of BuChE with BzCh. In this model, the substrate-free enzyme is present as an equilibrium mixture of two forms, E and E'. Substrate binds to E and E', but only Epsilon'S makes products. It is proposed that oscillations originate from a time-dependent change in the local concentration, solvation and/or conformation of substrate in the bulk solution. 1H-NMR measurements provided evidence for a slow equilibrium between two BzCh conformers. Binding of the conformationally preferred substrate conformer leads to products.


[Robotic and systems technology for advanced endoscopic procedures].
The advent of endoscopic techniques changed surgery in many regards. This paper intends to describe an overview about technologies to facilitate endoscopic surgery. The systems described have been developed for the use in general surgery, but an easy application also in other fields of endoscopic surgery seems realistic. The introduction of system technology and robotic technology enables today to design a highly ergonomic solo-surgery platform. This consists of a system of devices for endoscopic surgery (HF, light source, etc...) with which the surgeon interacts directly, positioning systems for optic and instruments that the surgeon drives as the likes without assistance, and a chair to increase the comfort of the surgeon during surgery. The system of endoscopic devices named OREST (Dornier, München) designed already in 1992 opened the way to a number of systems available today that allow to the surgeon a direct control of the instrumentation. A considerable step ahead in endoscopic technology is the introduction of robotic technology to design assisting systems for solo-surgery and microsurgical instrument manipulators. Results of a number of experimental trials on combinations of different positioning devices are presented and commented. A further step in the employment of robotic technology is the design of "master-slave manipulators" to provide the surgeon with additional degrees of freedom of instrumentation. In 1996 a first prototype of an endoscopic manipulator system, named ARTEMIS, designed in cooperation with the Research Center in Karlsruhe, could be used in experimental applications. Clinical use of the system, however, will require further development of the arm mechanics and the control system. The combination with the implementation of telecommunication technology will open new frontiers, such as teleconsulting, teleassistance and telemanipulation.


The N-terminal Pro-BNP investigation of dyspnea in the emergency department (PRIDE) study.
The utility of aminoterminal pro-brain natriuretic peptide (NT-proBNP) testing in the emergency department to rule out acute congestive heart failure (CHF) and the optimal cutpoints for this use are not established. We conducted a prospective study of 600 patients who presented in the emergency department with dyspnea. The clinical diagnosis of acute CHF was determined by study physicians who were blinded to NT-proBNP results. The primary end point was a comparison of NT-proBNP results with the clinical assessment of the managing physician for identifying acute CHF. The median NT-proBNP level among 209 patients (35%) who had acute CHF was 4,054 versus 131 pg/ml among 390 patients (65%) who did not (p <0.001). NT-proBNP at cutpoints of >450 pg/ml for patients <50 years of age and >900 pg/ml for patients >or=50 years of age were highly sensitive and specific for the diagnosis of acute CHF (p <0.001). An NT-proBNP level <300 pg/ml was optimal for ruling out acute CHF, with a negative predictive value of 99%. Increased NT-proBNP was the strongest independent predictor of a final diagnosis of acute CHF (odds ratio 44, 95% confidence interval 21.0 to 91.0, p <0.0001). NT-proBNP testing alone was superior to clinical judgment alone for diagnosing acute CHF (p = 0.006); NT-proBNP plus clinical judgment was superior to NT-proBNP or clinical judgment alone. NT-proBNP measurement is a valuable addition to standard clinical assessment for the identification and exclusion of acute CHF in the emergency department setting.


Quality Characteristics for Clinical Ethics Support in the Netherlands.
Background: This article presents a set of quality characteristics of clinical ethics support (CES) in the Netherlands.Methods: The quality characteristics were developed with a large group of stakeholders working with CES, participating in the Dutch Network for Clinical Ethics Support (NEON).Results: The quality characteristics concern the following domains: (1) goals of CES, (2) methods of CES, (3) competences of CES practitioners, and (4) implementation of CES. Conclusions: We discuss suggestions for how to use the quality characteristics, discuss some aspects that stand out about these quality characteristics, and reflect on the method and the status of the quality characteristics. The quality characteristics are meant as a heuristic instrument, helping CES practitioners to explore and improve the quality of CES in a health care organization, but at the same time they can be improved based on experiences during their application to CES practices.


Very low-carbohydrate, high-fat, weight reduction diet decreases hepatic gene response to glucose in obese rats.
Very low carbohydrate (VLC) diets are used to promote weight loss and improve insulin resistance (IR) in obesity. Since the high fat content of VLC diets may predispose to hepatic steatosis and hepatic insulin resistance, we investigated the effect of a VLC weight-reduction diet on measures of hepatic and whole body insulin resistance in obese rats. In Phase 1, adult male Sprague-Dawley rats were made obese by ad libitum consumption of a high-fat (HF1, 60% of energy) diet; control rats ate a lower-fat (LF, 15%) diet for 10 weeks. In Phase 2, obese rats were fed energy-restricted amounts of a VLC (5%C, 65%F), LC (19%C, 55%F) or HC (55%C, 15%F) diet for 8 weeks while HF2 rats continued the HF diet ad libitum. In Phase 3, VLC rats were switched to the HC diet for 1 week. At the end of each phase, measurements of body composition and metabolic parameters were obtained. Hepatic insulin resistance was assessed by comparing expression of insulin-regulated genes following an oral glucose load,that increased plasma insulin levels, with the expression observed in the feed-deprived state. At the end of Phase 1, body weight, percent body fat, and hepatic lipid levels were greater in HF1 than LF rats (p < 0.05). At the end of Phase 2, percent body fat and intramuscular triglyceride decreased in LC and HC (p < 0.05), but not VLC rats, despite similar weight loss. VLC and HF2 rats had higher HOMA-IR and higher insulin at similar glucose levels following an ip glucose load than HC rats (p < 0.05). HC, but not VLC or HF2 rats, showed changes in Srebf1, Scd1, and Cpt1a expression (p < 0.05) in response to an oral glucose load. At the end of Phase 3, switching from the VLC to the HC diet mitigated differences in hepatic gene expression. When compared with a high-carbohydrate, low-fat diet that produced similar weight loss, a commonly used VLC diet failed to improve whole body insulin resistance; it also reduced insulin's effect on hepatic gene expression, which may reflect the development of hepatic insulin resistance.


TLR expression in peripheral monocyte subsets of patients with idiopathic inflammatory myopathies: association with clinical and immunological features.
Monocytes and toll-like receptors (TLR) have been found in the inflammatory infiltrate of muscle biopsies in patients with idiopathic inflammatory myopathies (IIM), suggesting an important role of these cells in the pathogenesis of myositis. The monocyte subsets, their TLR expression in peripheral blood and their relationship with the clinical characteristics of patients with IIM has not been addressed. We recruited 45 patients with IIM diagnosis and 15 age and sex-adjusted healthy controls. We assessed the disease activity and damage, performed a nailfold capillaroscopy and registered the cardio-pulmonary parameters from the medical charts. Monocyte subsets, their expression of TLR2 and TLR4 and the serum Th1/Th2/Th17 cytokines levels were evaluated by flow cytometry. We expressed quantitative variables as medians and interquartile ranges (IQR) or minimum and maximum (min-max). Differences between groups were assessed with Mann-Whitney U and the Kruskal-Wallis tests. Correlation between quantitative variables was assessed with Spearman Rho. Twenty-nine patients were women (64.4%) and 32 (71.1%) had dermatomyositis. In comparison to healthy controls, patients with active IIM had a higher percentage of intermediate monocytes and lower amounts of classical monocytes. Patients with IIM had a higher expression of TLR4 in all their monocyte subsets, regardless of disease activity and prednisone treatment. Serum IL-6 correlated with the TLR2 expression in every monocyte subset and the expression of TLR2 in intermediate monocytes was higher among patients with dysphagia. Subjects with nailfold capillaroscopy abnormalities had a higher amount of TLR2+ classical and non-classical monocytes and those with interstitial lung disease (ILD) had a higher percentage of TLR4+ non-classical monocytes. The classical and intermediate monocytes from patients with anti Mi2 antibodies had a higher expression of TLR4. The percentage of intermediate monocytes and the expression of TLR4 in all monocyte subsets showed a good diagnostic capacity in patients with IIM. Patients with IIM have a differential pool of monocyte subsets with an enhanced expression of TLR2 and TLR4, which correlates with disease activity and distinctive clinical features including dysphagia, ILD, vasculopathy, and pro-inflammatory cytokines. These immunological features might be useful as a potential diagnostic tool as well as novel disease activity biomarkers in IIM.


Functional MRI of basal ganglia responsiveness to levodopa in parkinsonian rhesus monkeys.
Functional MRI (fMRI) was used to study striatal sensitivity to levodopa in hemiparkinsonian rhesus monkeys. Responses consistent with increased neuronal activity were seen in areas whose normal dopaminergic input from the substantia nigra pars compacta had been ablated by MPTP. Sites of increased activity following levodopa included the lateral putamen, the ventral region of the caudate head, septal areas, and midlateral amygdala in the MPTP-lesioned hemisphere. Increased activity was also observed in the same areas in the nonlesioned hemisphere, but was less pronounced in spatial extent and magnitude, suggesting either subclinical contralateral damage and/or functional adaptations in the contralateral dopamine systems. The increases in neuronal activity following levodopa treatment were temporally correlated with increases in striatal dopamine levels. Chronic levodopa treatment reduced behavioral responsiveness to levodopa and abolished the fMRI response. These results suggest that fMRI can detect changes in dopamine receptor-mediated neuronal sensitivity to dopaminergic agents.


Effect of physical restraint on the limits of thermoregulation in telemetered rats.
Physical restraint of rodents is needed for nose-only exposure to airborne toxicants and is also used as a means of psychological stress. Hyperthermia is often observed in restrained rats, presumably as a result of impairments in heat dissipation. However, such a hyperthermic response should be dependent on the prevailing ambient conditions. To understand how ambient temperature (T(a)) affects the thermoregulatory response to restraint, core temperature (T(c)) and heart rate (HR) were monitored by telemetry in rats subjected to 1 h of physical restraint while T(a) was maintained at 14-30 °C in 2 °C increments. The T(c) of unrestrained rats was unaffected by T(a). During restraint, T(c) was elevated at ambient temperatures with the exception of 14 °C, at which the rats became mildly hypothermic. There was an inverse relationship between T(a) and HR in both unrestrained and restrained rats; however, HR was significantly elevated in restrained rats at all ambient temperatures except 22 and 24 °C. Heat loss from the tail, estimated from T(c) and tail skin temperature, was markedly reduced at all but the highest ambient temperatures in restrained rats. The data suggest that the T(a) limits of normothermia are narrowed in the restrained rat. That is, between 16 and 20 °C, the rat maintains a relatively stable T(c) that is slightly elevated above that of the unrestrained rat. At ambient temperatures above or below this range, the rat shows signs of hyperthermia and hypothermia, respectively. In contrast, the limits of normothermia for unrestrained rats range from 14 (or lower) to 30 °C. Overall, the ideal T(a) for restrained rats appears to be 20 °C and no higher than 22 °C for the thermoregulatory system to maintain a regulated T(c) in rats well adapted to physical restraint.


Optical matter: crystallization and binding in intense optical fields.
Properly fashioned electromagnetic fields coupled to microscopic dielectric objects can be used to create arrays of extended crystalline and noncrystalline structures. Organization can be achieved in two ways: In the first, dielectric matter is transported in direct response to the externally applied standing wave optical fields. In the second, the external optical fields induce interactions between dielectric objects that can also result in the creation of complex structures. In either case, these new ordered structures, whose existence depends on the presence of both light and polarizable matter, are referred to as optical matter.


Associations between childhood biomedical factors, maternal smoking, personality traits, Body and Mass Index and the prevalence of asthma in adulthood.
The study set out to investigate socio-economic, biomedical, health and behavioural and psychological factors in childhood and adulthood associated with the prevalence of asthma in adulthood, drawing data from The National Child Development Studies (NCDS), a birth cohort in the UK. The National Child Development Study, a nationally representative sample of 17,415 babies born in Great Britain in 1958 and followed up at 7, 11, 33 and 50 years was used. The prevalence of asthma at age 50 was the outcome measure. The analytic sample consists of 5118 participants with complete data on a set of measures at birth, at ages 7, 11, 33 and 50 years. Using logistic regression analyses, results showed that childhood asthma (OR = 6.77: 4.38-10.48, p < .001) and respiratory symptoms (OR = 1.83: 1.18-2.86, p < .01), maternal smoking during pregnancy (OR = 1.26: 1.00-1.59, p < .05), Body and Mass Index (BMI) (OR = 1.03: 1.02-1.05, p < .001), traits Neuroticism (OR = 1.13: 1.01-1.21, p < .05) and Conscientiousness (OR = 0.76: 0.76-0.96, p < .01), as well as sex (OR = 1.49: 1.15-1.94, p < .001) were all significantly associated with the prevalence of asthma in adulthood. The study shows that both childhood and adulthood psychological and sociological factors are significantly associated with the prevalence of asthma in adulthood, though more work need to be done in this area.


Acupuncture for cardiovascular disorders.
Experimental studies in animals and clinical studies in humans have demonstrated that acupuncture can exert significant effects on the cardiovascular system and provide effective therapy for a variety of cardiovascular ailments. In veterinary practice, acupuncture should be considered as adjunctive therapy in cases of shock and cardiac arrest. Acupuncture may also be beneficial as adjunctive or sole therapy in the management of congestive heart failure, arrhythmias, and systemic hypertension.


Conceiving Time? Women who do or do not conceive.
This article explores the importance of time for an understanding of women's experiences of reproductive identity. In order to do this we draw on data from two separate qualitative research projects. The first project is concerned with the experiences of conception, pregnancy, childbirth and early motherhood in primagravidae, whilst the second focuses on the experiences of individuals (especially women) who defined themselves (at the time of the fieldwork, or some time previously) as 'involuntarily childless' and/or 'infertile'. These two areas are usually treated as separate; this article, however, explores similarities between them in terms of time and medicalisation. Our central concern, then, is with exploring the similarities of experience for women who do or do not conceive.


Mandibular fractures treated with maxillomandibular fixation screws (MMFS method).
The purpose of the treatment of mandibular fractures is to restore proper dental occlusion and stable temporomandibular joint movement, as well as the reduction of the displaced fracture. Consideration must be given to the selection of the most appropriate surgical and rehabilitation methods in such patients. Typical surgical methods for the treatment of mandibular fractures include the arch bar method or plating at the location of the fracture combined with fixing the mandible to the maxilla using the arch bar method. However arch bars and circumdental wires, which require teeth for fixation, damage teeth and periodontal tissue, and tend to be uncomfortable for patients during the fixation period. Moreover, daily maintenance of oral hygiene is difficult for patients with an arch bar. Surgeons are also exposed to the risk of blood-transmitted diseases through skin punctures by wires when affixing these devices. For these reasons, we chose to study the potential of the MMFS method, which is thought to lessen all of the following problems: tissue damage, operating time, patient discomfort, and possible exposure to percutaneous infectious disease due to puncture of gloves and skin by the wires. We demonstrated the utility of the MMFS method in the present study.


Ziprasidone in the treatment of mania in bipolar disorder.
Ziprasidone is an atypical antipsychotic with a unique receptor-binding profile. Currently, ziprasidone is approved by the US Food and Drug Administration for the acute treatment of psychosis in schizophrenia and mania in bipolar disorder. When compared to certain other atypical antipsychotics, ziprasidone appears to have a relatively benign side effect profile, especially as regards metabolic effects eg, weight gain, serum lipid elevations and glucose dysregulation. Taken together, these data suggest that ziprasidone may be a first line treatment for patients with bipolar mania. However, ziprasidone is a relatively new medication for which adverse events after long-term use and/or in vulnerable patient populations must be studied. Unstudied areas of particular importance include the efficacy and safety of ziprasidone in the treatment of bipolar depression and relapse prevention of mania as, well as in the subpopulations of pregnant women, the elderly and pediatric patients. The emergence of mania in patients taking ziprasidone is another topic for further study.


Decision-Support Needs of Caregivers Considering Hospice Enrollment for a Family Member With Dementia.
Background: There are few evidence-based interventions to support the growing number of family caregivers of persons living with advanced dementias (PWADs) in surrogate decision-making roles. This study identifies needs for decision support among family caregivers considering hospice enrollment for PWADs, in order to better inform efforts for decision support. Method: Individual and focus group interviews were conducted with caregivers (n = 13) and healthcare professionals (n = 14). Directed content analysis was used to identify and organize themes that emerged from interview transcripts. Results: Analysis revealed 2 themes concerning PWAD caregivers' hospice-related decision-support needs: (1) detailed and practical information about hospice and (2) discussions clarifying meaning around quality of life (QOL) for PWADs. Caregivers needed to know when they should consider hospice, what treatments would be stopped, what services would help caregivers, and what costs would be involved. Caregivers varied in their perceptions of what it might mean for a PWAD to have QOL at the end of life and whether or not hospice would enhance it. Discussion: This study's findings underscore the importance of decision-support tools and patient- and family-centered education for PWADs and caregivers about the trajectory of dementia and end-stage symptoms, along with practical information for hospice care planning and discussions addressing end of life values.


Small cell lung cancer tumors and preclinical models display heterogeneity of neuroendocrine phenotypes.
Small cell lung cancer (SCLC) is a deadly, high grade neuroendocrine (NE) tumor without recognized morphologic heterogeneity. However, over 30 years ago we described a SCLC subtype with "variant" morphology which did not express some NE markers and exhibited more aggressive growth. To quantitate NE properties of SCLCs, we developed a 50-gene expression-based NE score that could be applied to human SCLC tumors and cell lines, and genetically engineered mouse (GEM) models. We identified high and low NE subtypes of SCLC in all of our sample types, and characterized their properties. We found that 16% of human SCLC tumors and 10% of SCLC cell lines were of the low NE subtype, as well as cell lines from the GEM model. High NE SCLC lines grew as non-adherent floating aggregates or spheroids while Low NE lines had morphologic features of the variant subtype and grew as loosely attached cells. While the high NE subtype expressed one of the NE lineage master transcription factors ASCL1 or NEUROD1, together with NKX2-1, the entire range of NE markers, and lacked expression of the neuronal and NE repressor REST, the low NE subtype had lost expression of most NE markers, ASCL1, NEUROD1 and NKX2-1 and expressed REST. The low NE subtype had undergone epithelial mesenchymal transition (EMT) and had activated the Notch, Hippo and TGFβ pathways and MYC oncogene . Importantly, the high and low NE group of SCLC lines had similar gene expression profiles as their SCLC tumor counterparts. SCLC tumors and cell lines can exhibit distinct inter-tumor heterogeneity with respect to expression of NE features. Loss of NE expression results in major alterations in morphology, growth characteristics, and molecular properties. These findings have major clinical implications as the two subtypes are predicted to have very different responses to targeted therapies.


Self-reported pH1N1 influenza vaccination coverage for Ontario.
In the fall of 2009, Canada undertook a mass vaccination campaign against pH1N1. This report provides an overview of self-reported pH1N1 vaccination coverage of the Ontario population, building on an existing random digit-dialling telephone survey, in which 9,010 Ontario adults participated. Based on the results, 34.5% of Ontario residents were vaccinated: 33.3% of adults aged 18 or older and 38.6% of children and adolescents younger than age 18. Respondents reporting high-risk chronic conditions were significantly more likely to report being vaccinated than were people who did not report such conditions. Determining vaccination uptake for the Ontario population is important in the evaluation of the province's pH1N1 prevention program.


Structural and functional characterization of three DsbA paralogues from Salmonella enterica serovar typhimurium.
In prototypic Escherichia coli K-12 the introduction of disulfide bonds into folding proteins is mediated by the Dsb family of enzymes, primarily through the actions of the highly oxidizing protein EcDsbA. Homologues of the Dsb catalysts are found in most bacteria. Interestingly, pathogens have developed distinct Dsb machineries that play a pivotal role in the biogenesis of virulence factors, hence contributing to their pathogenicity. Salmonella enterica serovar (sv.) Typhimurium encodes an extended number of sulfhydryl oxidases, namely SeDsbA, SeDsbL, and SeSrgA. Here we report a comprehensive analysis of the sv. Typhimurium thiol oxidative system through the structural and functional characterization of the three Salmonella DsbA paralogues. The three proteins share low sequence identity, which results in several unique three-dimensional characteristics, principally in areas involved in substrate binding and disulfide catalysis. Furthermore, the Salmonella DsbA-like proteins also have different redox properties. Whereas functional characterization revealed some degree of redundancy, the properties of SeDsbA, SeDsbL, and SeSrgA and their expression pattern in sv. Typhimurium indicate a diverse role for these enzymes in virulence.


Universal Two-Component Dynamics in Supercritical Fluids.
Despite the technological importance of supercritical fluids, controversy remains about the details of their microscopic dynamics. In this work, we study four supercritical fluid systems─water, Si, Te, and Lennard-Jones fluid─via classical molecular dynamics simulations. A universal two-component behavior is observed in the intermolecular dynamics of these systems, and the changing ratio between the two components leads to a crossover from liquidlike to gaslike dynamics, most rapidly around the Widom line. We find evidence to connect the liquidlike component dominating at lower temperatures with intermolecular bonding and the component prominent at higher temperatures with free-particle, gaslike dynamics. The ratio between the components can be used to describe important properties of the fluid, such as its self-diffusion coefficient, in the transition region. Our results provide an insight into the fundamental mechanism controlling the dynamics of supercritical fluids and highlight the role of spatiotemporally inhomogeneous dynamics even in thermodynamic states where no large-scale fluctuations exist in the fluid.


Failure of endotoxic shock to elicit superoxide anion production in pig brain.
Endotoxin shock in pigs alters cerebral blood flow regulation. This study sought 1) to evaluate global cerebral electrical function using somatosensory evoked potential and 2) to determine if superoxide anion free radical (O2-) is generated in brain following endotoxin infusion. Five female pigs received E. coli endotoxin (0.1 mg/kg i.v.) and supplemental fluid to maintain cardiac output at control levels. Somatosensory evoked potential was generated before and after endotoxin infusion, and nitroblue tetrazolium (NBT) precipitation in cranial windows was used to determine O2- production by brain. Following endotoxin infusion, mean arterial blood pressure, cerebral perfusion pressure, and systemic vascular resistance fell by 50% and cerebral oxygen extraction increased. The amplitude and the latency of somatosensory evoked potential performed 60 min after endotoxin were unchanged from that generated at control. No precipitation of NBT in cranial windows was observed, indicating that O2- was not generated. Since endotoxin shock did not alter cerebral electrical function and O2- was not generated by brain, we conclude that alterations in cerebral blood flow regulation observed in fluid-resuscitated endotoxic shock do not result from inadequate cerebral oxygen consumption, nor is the extracellular production of O2- involved in the pathogenesis of this disorder.


A pilot study examining undesirable events among emergency department-boarded patients awaiting inpatient beds.
We describe the frequency of undesirable events among patients boarding at a single, urban, tertiary, teaching emergency department (ED) through retrospective chart abstraction. This was a chart review of all patients admitted during 3 randomly selected days in 2003 (n=162) to track the frequency of undesirable events such as missed relevant home medications, missed laboratory test results, arrhythmias, or other adverse events. One hundred fifty-one charts were abstracted (93.2%); 27.8% had an undesirable event, 17.9% missed a relevant home medication, and 3.3% had a preventable adverse event. There was a higher frequency of undesirable events among older patients (35.9%, aged >50 years; 7.3%, aged 20 to 49 years; 28.6%, aged 0 to 19 years) and those with more comorbidities (44.4% among Charlson score >or=3; 30.8% score 2; 36.1% score 1; 14.5% score 0). A substantial frequency of undesirable events occurs while patients board in the ED. These events are more frequent in older patients or those with more comorbidities. Future studies need to compare the rates of undesirable events among patients boarding in the ED versus inpatient units.


Lactobacillus rhamnosus as additive for maize and sorghum ensiling.
The effects of Lactobacillus rhamnosus AT195, a potential probiotic microorganism cultured in buffalo "scotta" whey, on chemical and microbiological composition in maize and sorghum ensiling were evaluated. Both crops were harvested, chopped, and treated or not with the selected strain prior to ensiling in fiberglass vertical silos; 90 days after ensiling, silages were sensorially evaluated and sampled. Different chemical components were evaluated both on fresh crops and silages: in particular, the water-soluble carbohydrates content was investigated by high-field NMR spectroscopy and the carbohydrate fermentation profile was performed by GC. Besides phenotypic identification and typing, microbiological studies included Lb. rhamnosus genotype typing by RAPD-PCR. All silages, inoculated or not, were well preserved, as their chemical and microbiological data along with the fermentation profiles showed. The selected strain used as inoculum influenced the lactic acid population of silages and evidenced a good survival performance during the ensiling process of both maize and sorghum. Moreover, the use of Lb. rhamnosus strain efficiently improved the quality of the multifactorial ensiling process by significantly reducing the ammonia nitrogen content of both maize and sorghum silages.


Antigen concentration, viral load, and test performance for SARS-CoV-2 in multiple specimen types.
The relationship between N-antigen concentration and viral load within and across different specimens guides the clinical performance of rapid diagnostic tests (RDT) in different uses. A prospective study was conducted in Porto Velho, Brazil, to investigate RDT performance in different specimen types as a function of the correlation between antigen concentration and viral load. The study included 214 close contacts with recent exposures to confirmed cases, aged 12 years and older and with various levels of vaccination. Antigen concentration was measured in nasopharyngeal swab (NPS), anterior nares swab (ANS), and saliva specimens. Reverse transcriptase (RT)-PCR was conducted on the NPS and saliva specimens, and two RDTs were conducted on ANS and one RDT on saliva. Antigen concentration correlated well with viral load when measured in the same specimen type but not across specimen types. Antigen levels were higher in symptomatic cases compared to asymptomatic/oligosymptomatic cases and lower in saliva compared to NPS and ANS samples. Discordant results between the RDTs conducted on ANS and the RT-PCR on NPS were resolved by antigen concentration values. The analytical limit-of-detection of RDTs can be used to predict the performance of the tests in populations for which the antigen concentration is known. The antigen dynamics across different sample types observed in SARS-CoV-2 disease progression support use of RDTs with nasal samples. Given lower antigen concentrations in saliva, rapid testing using saliva is expected to require improved RDT analytical sensitivity to achieve clinical sensitivity similar to rapid testing of nasal samples.


Field-induced Fermi surface reconstruction and adiabatic continuity between antiferromagnetism and the hidden-order state in URu2Si2.
Shubnikov-de Haas oscillations reveal at high fields an abrupt reconstruction of the Fermi surface within the hidden-order (HO) phase of URu2Si2. Taken together with reported Hall effect results, this implies an increase in the effective carrier density and suggests that the field suppression of the HO state is ultimately related to destabilizing a gap in the spectrum of itinerant quasiparticles. While hydrostatic pressure favors antiferromagnetism in detriment to the HO state, it has a modest effect on the complex H-T phase diagram. Instead of phase separation between HO and antiferromagnetism our observations indicate adiabatic continuity between both orderings with field and pressure changing their relative weight.


Assessment of mortality risks due to a strong cold spell in 2022 in China.
With the intensification of global climate warming, extreme low temperature events such as cold spells have become an increasingly significant threat to public health. Few studies have examined the relationship between cold spells and mortality in multiple Chinese provinces. We employed health impact functions for temperature and mortality to quantify the health risks of the first winter cold spell in China on November 26th, 2022, and analyzed the reasons for the stronger development of the cold spell in terms of the circulation field. This cold spell was a result of the continuous reinforcement of the blocking high-pressure system in the Ural Mountains, leading to the deepening of the cold vortex in front of it. Temperature changes associated with the movement of cold fronts produced additional mortality risks and mortality burdens. In general, the average excess risk (ER) of death during the cold spell in China was 2.75%, with a total cumulative excess of 369,056 deaths. The health risks associated with temperatures were unevenly distributed spatially in China, with the ER values ranging from a minimum of 0.14% to a maximum of 5.72%, and temperature drops disproportionately affect southern regions of China more than northern regions. The cumulative excess deaths exibited the highest in eastern and central China, with 87,655 and 80,230 respectively, and the lowest in northwest China with 27,474 deaths. Among the provinces, excess deaths pronounced the highest in Shandong with 29,492 and the lowest in Tibet with only 196. The study can provide some insight into the mortality burden of cold spells in China, while emphasising the importance of understanding the complex relationship between extreme low temperature events and human health. The outcomes could provide valuable revelations for informing pertinent public health policies.


Analysis of 3-D myocardial motion in tagged MR images using nonrigid image registration.
Tagged magnetic resonance imaging (MRI) is unique in its ability to noninvasively image the motion and deformation of the heart in vivo, but one of the fundamental reasons limiting its use in the clinical environment is the absence of automated tools to derive clinically useful information from tagged MR images. In this paper, we present a novel and fully automated technique based on nonrigid image registration using multilevel free-form deformations (MFFDs) for the analysis of myocardial motion using tagged MRI. The novel aspect of our technique is its integrated nature for tag localization and deformation field reconstruction using image registration and voxel based similarity measures. To extract the motion field within the myocardium during systole we register a sequence of images taken during systole to a set of reference images taken at end-diastole, maximizing the normalized mutual information between the images. We use both short-axis and long-axis images of the heart to estimate the full four-dimensional motion field within the myocardium. We also present validation results from data acquired from twelve volunteers.


Synthesis and Comprehensive in Vivo Activity Profiling of Olean-12-en-28-ol, 3β-Pentacosanoate in Experimental Autoimmune Encephalomyelitis: A Natural Remyelinating and Anti-Inflammatory Agent.
Multiple sclerosis (MS) treatment has received much attention, yet there is still no certain cure. We herein investigate the therapeutic effect of olean-12-en-28-ol, 3β-pentacosanoate (OPCA) on a preclinical model of MS. First, OPCA was synthesized semisynthetically and characterized. Then, the mice with MOG35-55-induced experimental autoimmune/allergic encephalomyelitis (EAE) were given OPCA along with a reference drug (FTY720). Biochemical, cellular, and molecular analyses were performed in serum and brain tissues to measure anti-inflammatory and neuroprotective responses. OPCA treatment protected EAE-induced changes in mouse brains maintaining blood-brain barrier integrity and preventing inflammation. Moreover, the protein and mRNA levels of MS-related genes such as HLD-DR1, CCL5, TNF-α, IL6, and TGFB1 were significantly reduced in OPCA-treated mouse brains. Notably, the expression of genes, including PLP, MBP, and MAG, involved in the development and structure of myelin was significantly elevated in OPCA-treated EAE. Furthermore, therapeutic OPCA effects included a substantial reduction in pro-inflammatory cytokines in the serum of treated EAE animals. Lastly, following OPCA treatment, the promoter regions for most inflammatory regulators were hypermethylated. These data support that OPCA is a valuable and appealing candidate for human MS treatment since OPCA not only normalizes the pro- and anti-inflammatory immunological bias but also stimulates remyelination in EAE.


Reduction of extended-spectrum-β-lactamase- and AmpC-β-lactamase-producing Escherichia coli through processing in two broiler chicken slaughterhouses.
Whilst broilers are recognised as a reservoir of extended-spectrum-β-lactamase (ESBL)- and AmpC-β-lactamase (AmpC)-producing Escherichia coli, there is currently limited knowledge on the effect of slaughtering on its concentrations on poultry meat. The aim of this study was to establish the concentration of ESBL/AmpC producing E. coli on broiler chicken carcasses through processing. In addition the changes in ESBL/AmpC producing E. coli concentrations were compared with generic E. coli and Campylobacter. In two slaughterhouses, the surface of the whole carcasses was sampled after 5 processing steps: bleeding, scalding, defeathering, evisceration and chilling. In total, 17 batches were sampled in two different slaughterhouses during the summers of 2012 and 2013. ESBL/AmpC producing E. coli was enumerated on MacConkey agar with 1mg/l cefotaxime, and the ESBL/AmpC phenotypes and genotypes were characterised. The ESBL/AmpC producing E. coli concentrations varied significantly between the incoming batches in both slaughterhouses. The concentrations on broiler chicken carcasses were significantly reduced during processing. In Slaughterhouse 1, all subsequent processing steps reduced the concentrations except evisceration which led to a slight increase that was statistically not significant. The changes in concentration between processing steps were relatively similar for all sampled batches in this slaughterhouse. In contrast, changes varied between batches in Slaughterhouse 2, and the overall reduction through processing was higher in Slaughterhouse 2. Changes in ESBL/AmpC producing E. coli along the processing line were similar to changes in generic E. coli in both slaughterhouses. The effect of defeathering differed between ESBL/AmpC producing E. coli and Campylobacter. ESBL/AmpC producing E. coli decreased after defeathering, whereas Campylobacter concentrations increased. The genotypes of ESBL/AmpC producing E. coli (blaCTX-M-1, blaSHV-12, blaCMY-2, blaTEM-52c, blaTEM-52cvar) from both slaughterhouses match typical poultry genotypes. Their distribution differed between batches and changed throughout processing for some batches. The concentration levels found after chilling were between 10(2) and 10(5)CFU/carcass. To conclude, changes in ESBL/AmpC producing E. coli concentrations on broiler chicken carcasses during processing are influenced by batch and slaughterhouse, pointing to the role of both primary production and process control for reducing ESBL/AmpC producing E. coli levels in final products. Due to similar changes upon processing, E. coli can be used as a process indicator of ESBL/AmpC producing E. coli, because the processing steps had similar impact on both organisms. Cross contamination may potentially explain shifts in genotypes within some batches through the processing.


Heterogeneity of synthetic factor Xa inhibitors.
Heparins and vitamin K antagonists are the landmarks of antithrombotic treatment. Both of them were discovered by serendipity; they are multi-targeted drugs and share several limitations. New molecules have been designed in order to be both more selective concerning their biological target and more homogeneous in their biochemical structure aiming at an improved benefit/risk ratio in the treatment of thrombotic disease. In this article, we will review the pharmacological characteristics of the new synthetic direct or antithrombin dependent inhibitors of FXa in the light of the modern concept of blood coagulation process. We will also present the most recent data from the clinical trials with synthetic inhibitors of FXa. Among them, the synthetic pentasaccharide fondaparinux is the first synthetic and specific FXa inhibitor, which has been approved by health authorities in Europe and in the USA for the prophylaxis of venous thromboembolism in major orthopaedic surgery and is being approved for the treatment of pulmonary embolism and DVT as a single daily subcutaneous injection. The phase II dose-finding trial of the "meta-pentasaccharide" idraparinux administered subcutaneously once weekly in the secondary prevention of VTE has been completed. DX-9065a is the first direct synthetic inhibitor which has been studied in patients with coronary disease. Razaxaban, BAY59-7939, ZK-807834 and JTV-803 are orally active direct FXa inhibitors, which have been studied in phase II trials. Several other synthetic direct inhibitors of FXa (such as FXV673, YM60828, KFA-1411) are in a pre-clinical stage of research. From a clinical point of view, the results of recent trials with the synthetic specific FXa inhibitors clearly show that the inhibition of FXa is a critical point in the antithrombotic strategy.


Oat ingestion reduces systolic and diastolic blood pressure in patients with mild or borderline hypertension: a pilot trial.
We assessed the short-term antihypertensive effects of soluble fiber-rich whole oat cereals when added to a standard American diet. In addition, multiple assessments of insulin sensitivity were conducted. This was a randomized, controlled, parallel-group pilot study designed to compare an oat cereal group (standardized to 5.52 g/day beta-glucan) to a low-fiber cereal control group (less than 1.0 g/day total fiber) over 6 weeks. A total of 18 hypertensive and hyperinsulinemic (= 10 U/mL or more) men and women completed the trial. Primary study outcomes were changes in systolic blood pressure (SBP) and diastolic blood pressure (DBP). Secondary outcomes included blood lipid, fasting glucose, and insulin levels and side effects related to elevated blood pressure and increased dietary fiber intake. The oat cereal group experienced a 7.5 mm Hg reduction in SBP (P &lt.01) and a 5.5 mm Hg reduction in DBP (P &lt.02), while there was virtually no change in either SBP or DBP in the control group. In the oat cereal group, a trend was observed for a lower total insulin response to a glucose load, suggesting improved insulin sensitivity. However, this could not be confirmed using estimates from the Bergman Minimal Model, perhaps because of our small sample size. The oats group experienced a significant reduction in both total cholesterol (9%) and low-density lipoprotein cholesterol (14%). The addition of oat cereals to the normal diet of patients with hypertension significantly reduces both SBP and DBP. Soluble fiber-rich whole oats may be an effective dietary therapy in the prevention and adjunct treatment of hypertension.


Does weight loss prognosis depend on genetic make-up?
The prevalence of obesity is rising throughout the world. Indeed, obesity has reached epidemic proportions in many developed and transition countries. Obesity is a complex disease with multifactorial origin, which in many cases appears as a polygenic condition affected by environmental factors. Treatment or prevention of obesity is necessary to reverse or avoid the onset of type 2 diabetes and other obesity-related diseases. Weight loss is a complex trait that depends on many environmental, behavioural and genetic influences. An effective programme for the management of overweight and obesity must take into account all of these factors. Individual responses to weight loss interventions vary widely and reliable predictors of successful slimming are poorly understood. The individual genetic make-up participating in energy expenditure regulation, appetite control, lipid metabolism and adipogenesis, have been reported to affect the risk of treatment failure in some subjects. In addition, the genotype could also help to predict the changes in lipid profile, cardiovascular risk factors and insulin sensitivity in response to weight loss. Herein, the current evidence from human studies that support the existence of a genetic component and the participation of different polymorphisms in the prognosis of weight loss induced by interventions leading to a negative energy balance are reviewed.


Profile of dengue patients admitted to a tertiary care hospital in Mumbai.
Dengue is a mosquito-borne arboviral infection that has become a public health concern in India and particularly Mumbai, where endemicity is on the rise. Fifty-seven children having dengue infection admitted over 12 months (2008) in a child health unit of a teaching hospital in Mumbai and who were positive for IgM antibodies by ELISA test were retrospectively studied for clinical profile and outcome. Common clinical findings were fever (100%), hepatomegaly (66.6%), vomiting (40.3%), and significant bleeding manifestations (38.5%). Common laboratory findings were thrombocytopenia (platelet < 100,000/mm3 in 96.5% patients), increased liver enzymes (59.6%), hypoalbuminemia (50.8%), hyponatremia (40.3%), and deranged prothrombin time/partial thromboplastin time (PT/PTT) (33.3%). Third spacing in the form of ascites and pleural effusion was present in 15.7% and 31.5% of patients, respectively. There was no correlation between platelet count and bleeding manifestation. Patients with dengue shock syndrome required more supportive therapy with blood products and inotropes and had a longer recovery time. Mortality in the study was 3.5%. PT/PTT, serum sodium, albumin, and white blood cell (WBC) counts were predictors of severity of dengue. To summarize, fever, hemorrhagic manifestations, hepatomegaly, thrombocytopenia, and evidence of plasma leakage (hemoconcentration, pleural effusion, ascites or hypoproteinemia) should lead a clinician to suspect dengue infection.


The influence of soil age on ecosystem structure and function across biomes.
The importance of soil age as an ecosystem driver across biomes remains largely unresolved. By combining a cross-biome global field survey, including data for 32 soil, plant, and microbial properties in 16 soil chronosequences, with a global meta-analysis, we show that soil age is a significant ecosystem driver, but only accounts for a relatively small proportion of the cross-biome variation in multiple ecosystem properties. Parent material, climate, vegetation and topography predict, collectively, 24 times more variation in ecosystem properties than soil age alone. Soil age is an important local-scale ecosystem driver; however, environmental context, rather than soil age, determines the rates and trajectories of ecosystem development in structure and function across biomes. Our work provides insights into the natural history of terrestrial ecosystems. We propose that, regardless of soil age, changes in the environmental context, such as those associated with global climatic and land-use changes, will have important long-term impacts on the structure and function of terrestrial ecosystems across biomes.


[Acute renal failure, neuropathy and deafness due to sodium bromate intoxication: report of one case].
The clinical manifestations of sodium bromate intoxication include among others acute renal failure and deafness. Most of the toxic manifestations are reversible with the exception of renal failure and deafness. This patient ingested about 7.5 g of sodium bromate powder, which produced gastrointestinal irritation, hypotension, fatigue, deafness, acute renal failure, anemia and peripheral neuropathy. Hemodialysis was performed three times due to acute renal failure, although the renal function improved, it did not recover completely. The patient was discharged with BUN: 42 mg/dL and creatinine: 3.4 mg/dL; she was still deaf.


[Thoracic and lumbar fractures in adolescents. An eight-year study].
In order to know the characteristics of these lesions in our environment and compare with those the adults, a transversal and descriptive study of adolescents between 12 and 18 years who were hospitalized for thoracic and lumbar fracture in two centers of high level trauma in our country for 8 years was performed. The variables studied were applied statistical analysis descriptive and correlation. They were found significant date by associating the causes of damage with associated lesions (p = 0.006) and the initial neurological damage associated with the final neurological damage (p = 0.000). They were registered seven teenagers with 10 fractures firearm, as rare cause of injury. An increase in the frequency of thoracic and lumbar fractures in adolescents with increasing age was found. The thoracic and lumbar fractures in adolescents caused by road accidents are associated with lesions in the chest and abdomen. And when are caused by falls are associated with lower extremity fractures. In addition, 13.5% of cases showed significant changes toward improvement in the initial neurological damage.


In vitro fracture resistance of premolar teeth restored with fibre-reinforced composite posts using a single or a multi-post technique.
The purpose of this study was to evaluate the reinforcing effect of fibre-reinforced composites (FRC) applied in premolar teeth with different techniques and minimally invasive post space preparation. Fifty extracted and endodontically treated premolar teeth were used. The teeth were divided into five groups (n = 10) depending on the restorative technique (Groups 1-5). Group 1: one single conventional post, Group 2: one main conventional and one collateral post, Group 3: one elastic post, Group 4: one main elastic and one collateral post, and Group 5: individual post formed of elastic posts. After cementation and core build-up, the specimens were submitted to static fracture resistance test. Fracture thresholds and fracture patterns were measured and evaluated. Group 4 showed the highest average fracture resistance among the tested groups. The multi-post techniques (group 2 and 4) exhibited statistically higher fracture resistance compared to group 1. Regarding fracture patterns, there was no statistically significant difference between the tested groups. Within the limitations of this study, the application of multiple elastic or conventional FRC posts or a single elastic post in the same root canal is beneficial in terms of fracture resistance compared to a single conventional FRC post. The elasticity or the number of posts did not influence the fracture patterns.


Incidence and Risk Factors for Hepatitis C Virus Infection among Illicit Drug Users in Italy.
So far, only three small outdated studies have investigated hepatitis C virus (HCV) incidence and risk factors among illicit drug users (DUs) in Italy. Thus, during 2007-2010, we conducted a prospective cohort study among DUs attending 17 Italian rehabilitation centers serving urban areas. Two hundred eighty-four HCV-uninfected DUs were prospectively followed by interview and anti-HCV antibody and RNA testing every 6 months. Incidence was calculated using the person-years method. Infection predictors were assessed by time-dependent Cox analysis. Participants were mostly male (83.4%), under opioid substitution therapy (OST) (78.9%), non-injecting DUs (67.9%), and with a mean age of 30.8. Ninety-one of 224 DUs initially under OST interrupted treatment during the follow-up. Overall HCV incidence was 5.83/100 person-years at risk (PYAR) [95% confidence intervals (CI), 3.63-9.38]. The incidence did not significantly differ according the participants' sociodemographic characteristics or the degree of urbanization of the towns involved in the study. The incidence was higher for DUs under than for those not under OST (6.23 vs 4.50/100 PYAR; p = 0.681). Incidence was also higher for those with than for those without OST interruption (7.17 vs 5.04/100 PYAR; p = 0.55). However, all these differences were non-significant. At last follow-up visit, a significant decrease in frequency of sharing equipment for preparation/using drugs (by injection or not) was observed by analyzing either the whole cohort or DUs under OST only. Anti-HCV seroconversion resulted independently associated with sharing drug preparation/use equipment, backloading, having a HCV-positive sexual partner, or household and (marginally) intravenous injection. In this study, HCV incidence was non-negligible and OST seemed to lack effectiveness in reducing it. In Italy, implementation of combined harm reduction interventions and antiviral treatment of chronically infected DUs would be needed.


Position Paper for the State-of-the-Art Application of Respiratory Support in Patients with COVID-19.
Against the background of the pandemic caused by infection with the SARS-CoV-2 virus, the German Respiratory Society has appointed experts to develop therapy strategies for COVID-19 patients with acute respiratory failure (ARF). Here we present key position statements including observations about the pathophysiology of (ARF). In terms of the pathophysiology of pulmonary infection with SARS-CoV-2, COVID-19 can be divided into 3 phases. Pulmonary damage in advanced COVID-19 often differs from the known changes in acute respiratory distress syndrome (ARDS). Two types (type L and type H) are differentiated, corresponding to early- and late-stage lung damage. This differentiation should be taken into consideration in the respiratory support of ARF. The assessment of the extent of ARF should be based on arterial or capillary blood gas analysis under room air conditions, and it needs to include the calculation of oxygen supply (measured from the variables of oxygen saturation, hemoglobin level, the corrected values of Hüfner's factor, and cardiac output). Aerosols can cause transmission of infectious, virus-laden particles. Open systems or vented systems can increase the release of respirable particles. Procedures in which the invasive ventilation system must be opened and endotracheal intubation carried out are associated with an increased risk of infection. Personal protective equipment (PPE) should have top priority because fear of contagion should not be a primary reason for intubation. Based on the current knowledge, inhalation therapy, nasal high-flow therapy (NHF), continuous positive airway pressure (CPAP), or noninvasive ventilation (NIV) can be performed without an increased risk of infection to staff if PPE is provided. A significant proportion of patients with ARF present with relevant hypoxemia, which often cannot be fully corrected, even with a high inspired oxygen fraction (FiO2) under NHF. In this situation, the oxygen therapy can be escalated to CPAP or NIV when the criteria for endotracheal intubation are not met. In ARF, NIV should be carried out in an intensive care unit or a comparable setting by experienced staff. Under CPAP/NIV, a patient can deteriorate rapidly. For this reason, continuous monitoring and readiness for intubation are to be ensured at all times. If the ARF progresses under CPAP/NIV, intubation should be implemented without delay in patients who do not have a "do not intubate" order.


Practices associated with Highly Pathogenic Avian Influenza spread in traditional poultry marketing chains: Social and economic perspectives.
In developing countries, smallholder poultry production contributes to food security and poverty alleviation in rural areas. However, traditional poultry marketing chains have been threatened by the epidemics caused by the Highly Pathogenic Avian Influenza (H5N1) virus. The article presents a value chain analysis conducted on the traditional poultry marketing chain in the rural province of Phitsanulok, Thailand. The analysis is based on quantitative data collected on 470 backyard chicken farms, and on qualitative data collected on 28 poultry collectors, slaughterhouses and market retailers, using semi-structured interviews. The article examines the organization of poultry marketing chains in time and space, and shows how this may contribute to the spread of Highly Pathogenic Avian Influenza H5N1 in the small-scale poultry sector. The article also discusses the practices and strategies developed by value chain actors facing poultry mortality, with their economic and social determinants. More broadly, this study also illustrates how value chain analysis can contribute to a better understanding of the complex mechanisms associated with the spread of epidemics in rural communities.


Long-term effects of latitude, ambient temperature, and ultraviolet radiation on the incidence of multiple sclerosis in two cohorts of US women.
Differences in multiple sclerosis (MS) risk by latitude have been observed worldwide; however, the exposures driving these associations are unknown. Ultraviolet radiation (UV) has been explored as a risk factor, and ambient temperature has been correlated with disease progression. However, no study has examined the impact of all three exposures. We examined the association between these exposures and incidence of MS within two nationwide prospective cohorts of women, the Nurses' Health Study (NHS) and Nurses' Health Study II (NHSII). Both cohorts were followed with biennial questionnaires to ascertain new diagnoses and risk factors. Time-varying exposures to latitude, cumulative average July temperature (°C), and cumulative average July erythemal UV (mW/m2) were predicted at each participant's biennially updated residential addresses. Using Cox proportional hazards models adjusted for MS risk factors, we calculated hazard ratios (HR) and 95% confidence intervals (CIs) within each cohort and pooled via meta-analyses. In multivariable models, there were suggestions that decreasing latitude (meta-analysis multivariable-adjusted HR = 0.72; 95% CI 0.55, 0.94 for women living <35.73° compared with those ≥42.15°, P-for-trend = 0.007) and increasing cumulative average July temperature (meta-analysis multivariable-adjusted HR = 0.81; 95% CI 0.72, 0.91 for each interquartile range increase [3.91°]) were associated with decreasing risk of MS. There was no evidence of heterogeneity between cohorts. We did not observe consistent associations with cumulative average UV. Our results suggest that adult exposures to decreasing latitude and increasing temperature, but not UV, were associated with reduced MS risk in these two cohorts of women. Studies of MS incidence may want to consider temperature as a risk factor.


Extending Förster resonance energy transfer measurements beyond 100 Å using common organic fluorophores: enhanced transfer in the presence of multiple acceptors.
Using commercially available organic fluorophores, the current applications of Förster (fluorescence) resonance energy transfer (FRET) are limited to about 80 Å. However, many essential activities in cells are spatially and/or temporally dependent on the assembly/disassembly of transient complexes consisting of large-size macromolecules that are frequently separated by distances greater than 100 Å. Expanding the accessible range for FRET to 150 Å would open up many cellular interactions to fluorescence and fluorescence-lifetime imaging. Here, we demonstrate that the use of multiple randomly distributed acceptors on proteins/antibodies, rather than the use of a single localized acceptor, makes it possible to significantly enhance FRET and detect interactions between the donor fluorophore and the acceptor-labeled protein at distances greater than 100 Å. A simple theoretical model for spherical bodies that have been randomly labeled with acceptors has been developed. To test the theoretical predictions of this system, we carried out FRET studies using a 30-mer oligonucleotide-avidin system that was labeled with the acceptors DyLight649 or Dylight750. The opposite 5'-end of the oligonucleotide was labeled with the Alexa568 donor. We observed significantly enhanced energy transfer due to presence of multiple acceptors on the avidin protein. The results and simulation indicate that use of a nanosized body that has been randomly labeled with multiple acceptors allows FRET measurements to be extended to over 150 Å when using commercially available probes and established protein-labeling protocols.


[On the legal aspects of the term "diabetic angiopathy of the lower extremities". Part I. Clinico-morphological parallels of the lower diabetic angiopathy].
The clinico-morphological data analysis was done in 100 examined patients with diabetic angiopathy of the lower extremities. The morphological changes revealed have corresponded to severity of the disease clinical symptoms in 70% only. Purulent affection of extremities have characterized not the end stage of angiopathy only but it was observed in another stages of the disease.


Depression in mothers and fathers of children with intellectual disability.
Parental depression was assessed using the Beck Depression Inventory (BDI) in 216 families with children with autism and/or intellectual disability (ID), and in 214 control families. Mothers with children with autism had higher depression scores (mean = 11.8) than mothers of children with ID without autism (mean = 9.2), who in turn, had higher depression scores than fathers of children with autism (mean = 6.2), fathers of children with ID without autism (mean = 5.0), and control mothers (mean = 5.0) and fathers (mean = 4.1). Forty-five per cent of mothers with children with ID without autism and 50% of mothers with children with autism had elevated depression scores (BDI > 9), compared to 15-21% in the other groups. Single mothers of children with disabilities were found to be more vulnerable to severe depression than mothers living with a partner.


The nature of the transactions that enhance the progressive phases of a psychoanalysis.
The nature of the analysand's progressive responses to interpretative statements is discussed. Emphasis is placed upon two types of verbal transactions. In the first, the analyst encourages or challenges the analysand to take the risk of intentionally elaborating language to answer the question of what it is he is experiencing, the "what" representing the language which denotes the "it" of archaic, unarticulated experiences of desire and anger. In the second, the analyst suggests a new, more flexible, broader causal sequence or context for events, one that links the events of desire and anger with prior and subsequent events, using conjunctives such as "because" to make these links. There is an interdependence between the two types of transactions but the first is considered to be the more significant in effecting meaningful changes in neurotic individuals.


Genetic regulatory networks that count to 3.
Sensing a graded input and differentiating between its different levels is at the core of many developmental decisions. Here, we want to examine how this can be realized for a simple system. We model gene regulatory circuits that reach distinct states when setting the underlying gene copy number to 1, 2 and 3. This distinction can be considered as counting the copy number. We explore different circuits that allow for counting and keeping memory of the count after resetting the copy number to 1. For this purpose, we sample different architectures and parameters, only considering circuits that contain repressive links, which we model by Michaelis-Menten terms. Interestingly, we find that counting to 3 does not require a hierarchy in Hill coefficients, in contrast to counting to 2, which is known from lambda phage. Furthermore, we find two main circuit architectures: one design also found in the vertebrate neural tube in a development governed by the sonic hedgehog morphogen and the more robust design of a repressilator supplemented with a weak repressilator acting in the opposite direction.


A descriptive analysis of the impact of moral distress on the evaluation of unsatisfactory nursing students.
Nurse educators assume a difficult role when evaluating unsatisfactory students, including those at risk for failure in clinical and classroom settings. While the decisional dilemma inherent in evaluating unsatisfactory students has been well documented in literature, little is known about how moral distress impacts the nurse educators' decisions regarding whether to pass or to fail unsatisfactory students. This article aims to provide a descriptive analysis of the moral dilemmas and the potential impact of moral distress experienced by nurse educators when evaluating the performance of unsatisfactory students in clinical and classroom courses. Nathaniel's theory of moral reckoning guided the descriptive analysis of six studies to understand how nurse educators work through moral dilemmas, make decisions, and provide justification for their decisions when evaluating the performance of unsatisfactory students. Nathaniel's theory has been shown to be helpful in discussing the dilemma of evaluating unsatisfactory students, and it is a suitable framework for nurse educators in working through their dilemmas as a form of structured reflection. The outcomes of this descriptive analysis highlight the need for educational administrators to provide support to undergraduate nurse educators experiencing moral distress in this type of situation.


Acute disseminated encephalomyelitis.
Acute disseminated encephalomyelitis (ADEM) is a monophasic, demyelinating disease of the central nervous systemthat predominately affects prepubertal children. It is typically characterized by an abrupt onset of neurologic symptoms preceded by an infection or recent immunization. ADEM is a diagnosis of exclusion in many cases, though the differential diagnosis is extensive. An adult female diagnosed with ADEMrepresents an atypical presentation; she was subsequently treated successfully with high-dose steroids. Nursing considerations for patients with ADEM include teaching patients and families about the disease, its clinical course, treatment, and prognosis.


Secure fixation of femoral bone plug with a suspensory button in anatomical anterior cruciate ligament reconstruction with bone-patellar tendon-bone graft.
the efficacy and safety of using a suspensory button for femoral fixation in anatomical anterior cruciate ligament (ACL) reconstruction with bone-patellar tendon-bone (BPTB) graft have not been established. The purpose of the current study was to evaluate bone plug integration onto the femoral socket and migration of the bone plug and the EndoButton (EB) (Smith & Nephew, Andover, MA, USA) after rectangular tunnel ACL reconstruction with BPTB autograft. thirty-four patients who underwent anatomical rectangular ACL reconstruction with BPTB graft using EB for femoral fixation and in whom three-dimensional (3D) computed tomography (CT) was performed one week and one year after surgery were included in this study. Bone plug integration onto the femoral socket, bone plug migration, soft tissue interposition, EB migration and EB rotation were evaluated on 3D CT. The clinical outcome was also assessed and correlated with the imaging outcomes. the bone plug was integrated onto the femoral socket in all cases. The incidence of bone plug migration, soft tissue interposition, EB migration and EB rotation was 15, 15, 9 and 56%, respectively. No significant association was observed between the imaging outcomes. The postoperative mean Lysholm score was 97.1 ± 5.0 points. The postoperative side-to-side difference, evaluated using a KT-2000 arthrometer, averaged 0.5 ± 1.3 mm. There were no complications associated with EB use. Imaging outcomes did not affect the postoperative KT side-to-side difference. the EB is considered a reliable device for femoral fixation in anatomical rectangular tunnel ACL reconstruction with BPTB autograft. Level IV, therapeutic case series.


Developmental word acquisition and grammar learning by humanoid robots through a self-organizing incremental neural network.
We present a new approach for online incremental word acquisition and grammar learning by humanoid robots. Using no data set provided in advance, the proposed system grounds language in a physical context, as mediated by its perceptual capacities. It is carried out using show-and-tell procedures, interacting with its human partner. Moreover, this procedure is open-ended for new words and multiword utterances. These facilities are supported by a self-organizing incremental neural network, which can execute online unsupervised classification and topology learning. Embodied with a mental imagery, the system also learns by both top-down and bottom-up processes, which are the syntactic structures that are contained in utterances. Thereby, it performs simple grammar learning. Under such a multimodal scheme, the robot is able to describe online a given physical context (both static and dynamic) through natural language expressions. It can also perform actions through verbal interactions with its human partner.