Effect of four sedative and anesthetic protocols on quantitative thyroid scintigraphy in euthyroid cats.
To determine the effect of sedation and anesthesia on thyroid and salivary gland uptake of technetium Tc 99m pertechnetate ((99m)TcO(4)) in euthyroid cats. 6 euthyroid cats. Thyroid scintigraphy was performed by use of a high-resolution low-energy parallel-hole collimator after IV injection of 117 to 133 MBq (3.16 to 3.59 mCi) of (99m)TcO(4)(-). The procedure was performed 4 times on each cat during different sedative and anesthetic protocols in a rotating schedule as follows: propofol, ketamine-midazolam-atropine, ketaminemidazolam, and medetomidine. Regions of interest were drawn around thyroid and salivary glands and counts corrected for background and decay. Percentage of (99m)TcO(4)(-) uptake in salivary and thyroid glands and thyroid-to-salivary gland (99m)TcO(4)(-) uptake ratio were calculated at 20 and 40 minutes. Relative effects of anesthesia and sedation on salivary and thyroid gland (99m)TcO(4)(-) uptake were compared. Significant differences among sedativeanesthetic protocols were found for thyroid gland (99m)TcO(4)(-) uptake, salivary gland (99m)TcO(4)(-) uptake, and thyroid-to-salivary gland (99m)TcO(4)(-) uptake ratio. Thyroid gland (99m)TcO(4)(-) uptake for the ketamine-midazolam protocol at 20 and 40 minutes after (99m)TcO(4)(-) administration was significantly higher than for the propofol protocol. A significant difference in salivary gland(99m) TcO(4)(-) uptake was found between ketamine-midazolam and ketamine-midazolam-atropine protocols at 40 minutes. The thyroid-to-salivary gland (99m)TcO(4)(-) uptake ratio for the ketamine-midazolam protocol was significantly higher at 40 minutes than for propofol or ketamine-midazolam-atropine protocols. Sedation and anesthesia have a significant effect on thyroid and salivary gland (99m)TcO(4) uptake in euthyroid cats that may interfere with thyroid scintigraphic image interpretation.


Comparative Analysis of the Effect of Inorganic and Organic Chemicals with Silver Nanoparticles on Soybean under Flooding Stress.
Extensive utilization of silver nanoparticles (NPs) in agricultural products results in their interaction with other chemicals in the environment. To study the combined effects of silver NPs with nicotinic acid and potassium nitrate (KNO3), a gel-free/label-free proteomic technique was used. Root length/weight and hypocotyl length/weight of soybean were enhanced by silver NPs mixed with nicotinic acid and KNO3. Out of a total 6340 identified proteins, 351 proteins were significantly changed, out of which 247 and 104 proteins increased and decreased, respectively. Differentially changed proteins were predominantly associated with protein degradation and synthesis according to the functional categorization. Protein-degradation-related proteins mainly consisted of the proteasome degradation pathway. The cell death was significantly higher in the root tips of soybean under the combined treatment compared to flooding stress. Accumulation of calnexin/calreticulin and glycoproteins was significantly increased under flooding with silver NPs, nicotinic acid, and KNO3. Growth of soybean seedlings with silver NPs, nicotinic acid, and KNO3 was improved under flooding stress. These results suggest that the combined mixture of silver NPs, nicotinic acid, and KNO3 causes positive effects on soybean seedling by regulating the protein quality control for the mis-folded proteins in the endoplasmic reticulum. Therefore, it might improve the growth of soybean under flooding stress.


Islet-cell, thyroid, and gastric autoantibodies in diabetic identical twins.
Sera from 54 pairs of identical twins, 29 discordant and 25 concordant for insulin-dependent diabetes, and 11 pairs of concordant non-insulin dependent identical twins were examined for pancreatic islet-cell antibodies (ICAs). ICAs were found in 10 of the 29 diabetic discordant and eight of the 50 concordant twins (difference not significant P greater than 0-05). Six out of nine twins tested within one year of onset of diabetes were positive, whereas nine out of 29 tested after one to 10 years and three out of 41 tested after 10 years were positive. Only one of the 22 non-insulin-dependent twins had ICAs. Repeat ICA testing in five pair of insulin-dependent twins and in the siblings of one pair showed that ICAs may be present in people with normal glucose tolerance' may precede clinical diabetes by several years; and may decline in titre or disappear with increasing duration of disease. Thyroid or gastric autoantibodies, or both, were found in 36 out of 108 insulin-dependent twins and three out of 22 non-insulin dependent twins (difference not significant P less than 0-05). Only four twins had both ICAs and thyrogastric antibodies. There were no significant associations between autoantibodies and HLA histocompatibility types. As ICAs are more common in the diabetic than the non-diabetic twins of the discordant pairs they must be associated with juvenile onset diabetes. ICAs may appear some years before the onset of diabetes, but their prevalence declines with increasing duration of diabetes. The factors determining the production of ICA differ from those for thyroid and gastric autoantibodies.


De novo prediction of cancer-associated T cell receptors for noninvasive cancer detection.
The adaptive immune system recognizes tumor antigens at an early stage to eradicate cancer cells. This process is accompanied by systemic proliferation of the tumor antigen-specific T lymphocytes. While detection of asymptomatic early-stage cancers is challenging due to small tumor size and limited somatic alterations, tracking peripheral T cell repertoire changes may provide an attractive solution to cancer diagnosis. Here, we developed a deep learning method called DeepCAT to enable de novo prediction of cancer-associated T cell receptors (TCRs). We validated DeepCAT using cancer-specific or non-cancer TCRs obtained from multiple major histocompatibility complex I (MHC-I) multimer-sorting experiments and demonstrated its prediction power for TCRs specific to cancer antigens. We blindly applied DeepCAT to distinguish over 250 patients with cancer from over 600 healthy individuals using blood TCR sequences and observed high prediction accuracy, with area under the curve (AUC) ≥ 0.95 for multiple early-stage cancers. This work sets the stage for using the peripheral blood TCR repertoire for noninvasive cancer detection.


Long-term experience in sentinel node biopsy for early oral and oropharyngeal squamous cell carcinoma.
Long-term results of sentinel node biopsy (SNB) in early (T1/T2) oral and oropharyngeal squamous cell carcinoma (OSCC) in a single-institution experience. Prospective consecutive cohort analysis of 79 patients (67% male, median age 60 years, age range 34-87 years) included between 2000 and 2006. Lymphatic mapping consisted of preoperative lymphoscintigraphy, single photon emission computed tomography (SPECT/CT), and intraoperative use of a handheld gamma probe. Endpoints of the study were neck control rate, overall (OS), disease-specific (DSS), and disease-free survival (DFS). Twenty-nine of 79 patients (37%) had positive sentinel nodes (SN). Six of 29 (21%) patients showed isolated tumor cells, 14/29 (48%) micrometastases, and 9/29 (31%) macrometastases. OS, DFS, and DSS at 5 years for the entire cohort were 80, 85, and 87%, for SN-negative patients were 88, 96, and 96%, and for SN-positive patients were 74, 73, and 77%, respectively. Only the difference in DSS achieved statistical significance. The neck control rate after 5 years was 96% in SN-negative and 74% in SN-positive patients. This difference was statistically significant. SNB is a safe and accurate staging modality to select patients with clinically stage I/II OSCC with occult lymph node disease for elective neck dissection (END). The promising reported short-term results have been sustained by long-term follow-up. Patients with negative SN and no END achieve an excellent neck control rate which compares favorably with reports on primary END. The neck control rate in SN-negative patients is superior to that in SN-positive patients, which is reflected in superior DSS.


Permanent percutaneous devices.
A percutaneous device (PD) constitutes a foreign material penetrating through the skin. It provides a connection between an internal organ or cavity and an extracorporeal device. PDs serving a multitude of clinical and research purposes are described. Breakdown of the PD-skin interface relatively soon after implantation is the failure mode of all present devices. Using the pertinent literature the present understanding of the pathophysiology of PD-skin interface behavior is discussed: the peculiarity of epidermal healing, lack of biomaterials compatible to epidermis, and mechanical stresses at the interface, each independently and in combinations are considered causative to this failure. Clinical reports on various permanent PDs are presented and ongoing research efforts at various centers are discussed.


Regulation of gli activity by all-trans retinoic acid in mouse keratinocytes.
Sonic hedgehog (Shh) signaling is essential for many normal developmental processes. The Shh signal is interpreted by the Gli transcription factors. Elevated Gli-1 expression has been associated with several neoplasms, including basal cell carcinoma. All-trans retinoic acid (RA) has strong effects on epidermal growth and differentiation and has been used for the treatment of various epithelial disorders. In this report, we show that RA can inhibit Gli activity in immortalized murine keratinocytes in a RA receptor-specific manner. This inhibition may occur, at least in part, through sequestration of the transcriptional coactivator cyclic AMP-responsive element-binding protein-binding protein and suggests a novel effect of retinoid excess on Shh signaling.


Ivermectin inhibits replication of the malignant catarrhal fever virus alcelaphine herpesvirus 1.
Malignant catarrhal fever is a lymphoproliferative disease of cattle and other ungulates that is caused by genetically and antigenically related gamma herpesviruses of the genus Macavirus. Infection of the natural host species is efficient and asymptomatic but spread to susceptible hosts is often fatal with clinical signs including fever, depression, nasal and ocular discharge. There is no recognised treatment for MCF but a vaccine for one MCF virus, alcelaphine herpesvirus 1 (AlHV-1), has been described. In this paper we describe the inhibition of AlHV-1 replication and propagation by the anthelminthic drug ivermectin. Concentrations of 10 μM or greater led to significant reductions in both copy number and viable titre of virus tested in culture medium, with little replication detected at over 20 μM ivermectin. In the absence of alternative treatments, further testing of ivermectin as a candidate antiviral treatment for MCF may therefore be justified.


Corona Virus Disease 2019 patients with different disease severity or age range: A single-center study of clinical features and prognosis.
This study aimed to describe clinical characteristics and prognosis of Corona Virus Disease 2019 (COVID-19) patients, and to compare these features among COVID-19 patients with different disease severity or age range.Totally, 129 COVID-19 patients were retrospectively enrolled, and the information about demographics, comorbidities, medical histories, clinical symptoms, and laboratory findings at the time of hospital admission were collected. Meanwhile, their clinical outcomes were recorded. According to the fourth version of the guidelines on the Diagnosis and Treatment of COVID-19 by the National Health Commission of China, patients were divided into subgroups according to disease severity (moderate and severe/critical) or age (<40 years, 40-64 years and ≥65 years).In total patients, the most common clinical symptoms were fever and cough (all incidences over 50%). Other common clinical symptoms included tiredness/anorexia, shortness of breath, dyspnea, aching pain, expectoration, diarrhea, shivering, and nausea/vomiting. The mortality rate was 5.4%, and the median value of hospital stay was 16.0 (11.0-23.0) days. Subgroup analyses disclosed that severe/critical patients exhibited increased neutrophil count, neutrophils, C-reactive protein, calcitonin, alpha-hydroxybutyric dehydrogenase, lactate dehydrogenase, aspartate aminotransferase, gamma-glutamyl transferase, creatinine, and D-dimer levels, and more deaths compared with that in moderate patients. Regarding age, it correlated with more common fever, higher levels of red blood cell, neutrophil count, lymphocyte count, neutrophils, red cell volume distribution width standard deviation-coefficient of variation, calcitonin, alpha-hydroxybutyric dehydrogenase, Creatine Kinase, aspartate aminotransferase, gamma-glutamyl transferase, and D-dimer, raised death rate and prolonged hospital stay.Our findings provide valuable evidence regarding clinical characteristics and prognosis of COVID-19 patients to help with the understanding of the disease and prognosis improvement.


Chronic resistive airway loading reduces weight due to low serum IGF-1 in rats.
One of the consequences of chronic resistive airway loading in rats is malfunction in body weight gain post-surgery. The lower body weight of the obstructed animals was not related to lower caloric intake or to the oxygen consumption/food intake ratio. In the current study, we determined whether the retardation in body weight gain was related to impairment of serum insulin-like growth factor-1 (IGF-1) level or due to activation of inflammatory factors 21 weeks post-surgery. During the observation period, the airway-loaded animals (n=8) gained 44% less body weight (P<0.001) compared with controls (n=8) with no apparent effect on skeletal growth, i.e., body, tail and tibia length. Chronic airway-loaded animals had 32.5% lower serum IGF-1 levels (P<0.001) compared to the controls. Interleukin-6 and tumor necrosis factor-alpha levels were below 30 pg/ml in both groups. These data suggest that the weight loss in the chronic airway-loading rats is associated with a decreased IGF-1 level and not to activation of the inflammatory response.


Use of Ocular Hypotensive Medications in Portugal: PEM Study: A Cross-sectional Nationwide Analysis.
There is scarcity of European data about intraocular pressure (IOP)-lowering prescribing patterns. We aimed to describe and discuss the nationwide prescription of these medications in Portugal. This was a cross-sectional study including all patients who were prescribed at least 1 IOP-lowering medication in 2015 in Portugal. All ocular hypotensive drug prescriptions were gathered from the common electronic drug prescription system used by all hospitals and clinics in Portugal. Demographic data, medications prescribed (number and formulation), physician specialty, and costs of medications were provided in an encrypted and anonymous form. Statistical analyses were performed using STATA. A total of 231,634 participants (57% women) were prescribed IOP-lowering medications in 2015, representing 4.0% of the population older than 40 years of age and 2.2% of the Portuguese total population. Mean age was 72±13 years. Topical IOP-lowering therapy accounted for a total of 26 million euros (M&OV0556;) in costs, shared between patients and the national health system. General practitioners (GPs) accounted for 52% of all prescriptions. The most prescribed drugs were latanoprost (28%), timolol/dorzolamide (19%), and brimonidine (14%). Among all, 72% of patients were on monotherapy. Compared with ophthalmologists, GPs presented qualitative differences in their prescription pattern, such as a lower proportion of unit dose prescription. A significant percentage of the Portuguese population is currently treated with IOP-lowering medications, and the majority of them are on monotherapy. Although GPs are responsible for most prescriptions, their prescription pattern is different from that of ophthalmologists. This nationwide study revealed prescription patterns and disclosed the burden of the disease in terms of its medical management.


Modeling and experimental analyses reveals signaling plasticity in a bi-modular assembly of CD40 receptor activated kinases.
Depending on the strength of signal dose, CD40 receptor (CD40) controls ERK-1/2 and p38MAPK activation. At low signal dose, ERK-1/2 is maximally phosphorylated but p38MAPK is minimally phosphorylated; as the signal dose increases, ERK-1/2 phosphorylation is reduced whereas p38MAPK phosphorylation is reciprocally enhanced. The mechanism of reciprocal activation of these two MAPKs remains un-elucidated. Here, our computational model, coupled to experimental perturbations, shows that the observed reciprocity is a system-level behavior of an assembly of kinases arranged in two modules. Experimental perturbations with kinase inhibitors suggest that a minimum of two trans-modular negative feedback loops are required to reproduce the experimentally observed reciprocity. The bi-modular architecture of the signaling pathways endows the system with an inherent plasticity which is further expressed in the skewing of the CD40-induced productions of IL-10 and IL-12, the respective anti-inflammatory and pro-inflammatory cytokines. Targeting the plasticity of CD40 signaling significantly reduces Leishmania major infection in a susceptible mouse strain. Thus, for the first time, using CD40 signaling as a model, we show how a bi-modular assembly of kinases imposes reciprocity to a receptor signaling. The findings unravel that the signalling plasticity is inherent to a reciprocal system and that the principle can be used for designing a therapy.


Effects of 14 days of bed rest and following physical training on metabolic cost, mechanical work, and efficiency during walking in older and young healthy males.
In this study, we investigated: i) the effects of bed rest and a subsequent physical training program on metabolic cost (Cw), mechanical work and efficiency during walking in older and young men; ii) the mechanisms underlying the higher Cw observed in older than young men.Twenty-three healthy male subjects (N = 16 older adults, age 59.6±3.4 years; N = 7 young, age: 23.1±2.9 years) participated in this study. The subjects underwent 14 days of bed rest followed by two weeks of physical training (6 sessions). Cw, mechanical work, efficiency, and co-contraction time of proximal muscles (vastus lateralis and biceps femoris) and distal muscles (gastrocnemius medialis and tibialis anterior) were measured during walking at 0.83, 1.11, 1.39, 1.67 m·s-1 before bed rest (pre-BR), after bed rest (post-BR) and after physical training (post-PT).No effects of bed rest and physical training were observed on the analysed parameters in either group. Older men showed higher Cw and lower efficiency at each speed (average +25.1 and -20.5%, P<0.001, respectively) compared to young. Co-contraction time of proximal and distal muscles were higher in older than in young men across the different walking speeds (average +30.0 and +110.3%, P<0.05, respectively).The lack of bed rest and physical training effects on the parameters analyzed in this study may be explained by the healthy status of both young and older men, which could have mitigated the effects of these interventions on walking motor function. On the other hand, the fact that older adults showed greater Cw, overall higher co-contraction time of antagonist lower limb muscles, and lower efficiency compared to the young cohort throughout a wide range of walking speed may suggest that older adults sacrificed economy of walking to improve stability.


Using Point of Care Testing to estimate influenza vaccine effectiveness in the English primary care sentinel surveillance network.
Rapid Point of Care Testing (POCT) for influenza could be used to provide information on influenza vaccine effectiveness (IVE) as well as influencing clinical decision-making in primary care. We undertook a test negative case control study to estimate the overall and age-specific (6 months-17 years, 18-64 years, ≥65 years old) IVE against medically attended POCT-confirmed influenza. The study took place over the winter of 2019-2020 and was nested within twelve general practices that are part of the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC), the English sentinel surveillance network. 648 POCT were conducted. 193 (29.7%) of those who were swabbed had received the seasonal influenza vaccine. The crude unadjusted overall IVE was 46.1% (95% CI: 13.9-66.3). After adjusting for confounders the overall IVE was 26.0% (95% CI: 0-65.5). In total 211 patients were prescribed an antimicrobial after swab testing. Given a positive influenza POCT result, the odds ratio (OR) of receiving an antiviral was 21.1 (95%CI: 2.4-182.2, p = <0.01) and the OR of being prescribed an antibiotic was 0.6 (95%CI: 0.4-0.9, p = <0.01). Using influenza POCT in a primary care sentinel surveillance network to estimate IVE is feasible and provides comparable results to published IVE estimates. A further advantage is that near patient testing of influenza is associated with improvements in appropriate antiviral and antibiotic use. Larger, randomised studies are needed in primary care to see if these trends are still present and to explore their impact on outcomes.


[General mechanism of ozone decomposition in physiologic solutions and a method for evaluation of the ozone dose in solutions administered to patients].
Ozone solutions in water and in NaCl solutions found are widely used in technology and medicine. Some times ozone employment meets difficulties due to instability of ozone in solution. The paper describes the results of study of ozone decomposition prepared using solutions in distilled water, solutions of NaCl in water, including physiologic solutions from different manufacturers. Also it was proposed the reaction mechanisms explained influence of OH- and Cl- ions on the decomposition rate. Experimental follow the monomolecular law and are described by a straight line in Ig(Ct/C0) = f(t) coordinates. It can be used as a basis for a new method of evaluation of real ozone dose introduced to patients.


Multiple forms of DNA damage caused by UVA photoactivation of DNA 6-thioguanine.
Thiopurines are prescribed frequently as medication for cancer and for inflammatory disorders. One of them, azathioprine, has been the immunosuppressant of choice for organ transplant recipients for many years. Thiopurine use is associated with elevated sun sensitivity and skin cancer risk. Skin sensitization is selective for UVA. 6-TG integrates into DNA and unlike the canonical DNA bases, it is a strong UVA chromophore with an absorbance maximum at 342 nm. DNA 6-TG is a photosensitizer and a source of reactive oxygen species. Reactive oxygen that is generated from the photochemical activation of DNA 6-TG causes extensive damage to DNA and proteins. This damage is mutagenic and extremely toxic to cultured human cells. Here we describe some of the lesions that are known to be generated from UVA irradiation of DNA 6-TG. We discuss how this photochemical damage might contribute to the toxic effect of thiopurine/UVA treatment on cultured cells and to the high risk of skin cancer in thiopurine-treated patients.


Patient safety and quality improvement: Ethical principles for a regulatory approach to bias in healthcare machine learning.
Accumulating evidence demonstrates the impact of bias that reflects social inequality on the performance of machine learning (ML) models in health care. Given their intended placement within healthcare decision making more broadly, ML tools require attention to adequately quantify the impact of bias and reduce its potential to exacerbate inequalities. We suggest that taking a patient safety and quality improvement approach to bias can support the quantification of bias-related effects on ML. Drawing from the ethical principles underpinning these approaches, we argue that patient safety and quality improvement lenses support the quantification of relevant performance metrics, in order to minimize harm while promoting accountability, justice, and transparency. We identify specific methods for operationalizing these principles with the goal of attending to bias to support better decision making in light of controllable and uncontrollable factors.


Performance of a fungal based SBR under pH extreme and shock phenolic exposure.
An investigation was performed to explore the capabilities of a filamentous fungal biomass to grow non-aseptically in a glucose-fed Sequencing Batch Reactor system in very extreme environment (pH 3.5) conditions. Trichoderma viride Pers: Fr. Isolate 8/90 was used as inoculum. Microscopic investigations were carried out to confirm fungal dominance in the open culture. In batch tests, the fungal biomass showed a significant ability to grow and remove the applied organic load (2000 mg(Glucose) L(-1) d(-1)), with high biomass yields. Furthermore, the biomass showed an ability to resist gallic acid toxicity at high concentraions (1 g L(-1)) without any pre- exposure acclimation of the biomass. The biomass (about 2.5 g(VSS) L(-1)) demonstrated significant aerobic removal of gallic acid in a timeframe of 20 h from initial exposure. The robust characteristics of this SBR system demonstrate potential for future development of fungal based treatment for recalcitrant feedstocks or operation under extreme environmental conditions.


Social support and long-term lithium outcome.
The failure rate in long-term lithium treatment of bipolar affective disorder is in the range of 20 to 30%, even with rigorous diagnostic criteria an adequate serum lithium levels. This may be due to a variety of biologic and psychosocial factors. Psychosocial factors affecting treatment outcome were studied in 60 RDC diagnosed bipolar patients treated with lithium for one year. Outcome was measured using an affective episode score, a social adjustment scale and a global assessment scale. Social support was the factor most strongly correlated with a good outcome on all three measures.


Risk factors for Barrett's oesophagus: a population-based approach.
Given its often subclinical course, Barrett's oesophagus (BO) hardly lends itself to epidemiologically stringent evaluations. The objective of this study was to investigate risk factors for incident BO diagnosed in a defined population in southeast Sweden while paying particular attention to epidemiological aspects of the study design. Consecutive patients (aged 18-79 years) who were endoscoped with new indications at units exclusively responsible for all gastroscopies in defined catchment area populations were invited to take part in the study. Biopsies were taken above and immediately below the gastro-oesophageal junction, and exposure information was collected through self-administered questionnaires. Endoscopy-room-based cross-sectional data from 604 patients were supplemented with exposure data from 160 population controls. Associations, expressed as odds ratios (ORs), were modelled by means of multivariable logistic regression. In the comparison with population controls, reflux symptoms and smoking indicated a 10.7- and 3.3-fold risk, respectively, for BO (95% confidence interval (CI) 3.5-33.4 and 1.1-9.9, respectively). Body mass was unrelated to risk. In the cross-sectional analysis among endoscopy-room patients, reflux symptoms were associated with an OR of 2.0 (95% CI 0.8-5.0). This association was, however, modified by the subjunctional presence of Helicobacter pylori; although the infection was not in itself significantly connected with risk, a combination of reflux symptoms and H. pylori infection was linked to an almost 5-fold risk (95% CI 1.4-16.5) as compared with the absence of both factors. The BO prevalence increased by 5% per year of age (95% CI 1-9%). Reflux is the predominant risk factor for BO, and proximal gastric colonization of H. pylori seems to amplify this risk.


Magnetic resonance evaluation of the disk before and after arthroscopic surgery for temporomandibular joint disorders.
The purposes of this study were (1) to assess functional and pain outcomes after arthroscopic surgery on patients with temporomandibular joint disorders (TMD); (2) to evaluate postsurgical changes in disk position, mobility, and morphology on magnetic resonance imaging (MRI); and (3) to measure the association between changes in disk position, mobility, and morphology on MRI and clinical outcomes. A retrospective analysis was conducted of temporomandibular joints with internal derangement and osteoarthritis that were refractory to nonsurgical treatments and underwent arthroscopic surgery and on which MRI was performed within 1 month after the initial visit and 1 year after arthroscopic surgery. Clinical findings were assessed on the basis of mandibular range of motion and joint pain level on a visual analog scale at the initial visit and 1 year after arthroscopic surgery. The disk position, mobility, and morphology on MRI were compared with clinical findings and were statistically analyzed before and after arthroscopic surgery. The treatment outcome was judged according to our success criteria. The associations between changes in disk position, mobility, and morphology and clinical outcomes after arthroscopic surgery were statistically analyzed. Forty-three joints of 43 patients who underwent arthroscopic surgery were assessed in this study. After arthroscopic surgery, mandibular range of motion and visual analog scale results improved statistically. According to the criteria for clinical resolution, 32 surgeries were successful and 11 were unsuccessful. Preoperative and postoperative MRI showed that most joints had anterior disk displacement (ADD) without reduction. Postoperative MRI revealed that, statistically, the number of mobile disks had increased and deformity of the disks had progressed. In the successful group, postoperative MRI revealed that all joints had mobile disks. In both groups, most joints had ADD without reduction before and after arthroscopic surgery, and, statistically, deformity of the disks progressed after arthroscopic surgery. Arthroscopic surgery was an effective treatment for TMD refractory to nonsurgical treatments. This study provides important information of clinical significance. Disk position remained ADD without reduction, disk mobility increased, and deformity of the disks progressed after arthroscopic surgery.


[Analysis of the implementation of safety practices in the automated medication dispensing cabinets].
To determine the degree of implementation of recommended safety practices in the design and use of automated medication dispensing cabinets (ADCs) in Spanish hospitals. A descriptive study based on completion of the "Self- Evaluation Survey on the Safety of Automated Medication Dispensing Systems" from 10/10/2012 to 4/10/2013, at voluntarily participating hospitals. The survey contained 93 items grouped into 14 core processes. In the 36 participating hospitals the average score for the completed survey was 307.8 points (66.2% of the highest possible score [LC 95% CI: 63.2-69.2]). The lowest scores were obtained for core processes 9, 12, 13, 8, 3, 4 and 11 referring to the establishment of guidelines for medication removed using the override function (28.4%), training for healthcare professionals (52%), risk management (53%), defining removal procedures (55.3%), use of ADCs in connection with electronic prescribing (60.9%), information that appears on ADC screens (61.8%) and eliminating medications being returned to ADCs (63.9%), respectively. The hospitals that used ADCs in connection with electronic prescribing as their principal system for distribution presented a higher level of implantation of safety practices than those that used ADCs as a complementary distribution system. ADC installation has been accompanied by the implementation of various safety practices, but there are still numerous areas of risk for which technical, organizational, and system monitoring safety practices must be added in order to minimize errors with this technology.


Utilization of energy and amino acids of spray-dried egg, plasma protein, and soybean meal by ducks.
A study was conducted to determine AMEn, TMEn, apparent amino acid digestibility (AAAD), and true amino acid digestibility (TAAD) of spray-dried egg (SDE), plasma protein (PP), and soybean meal (SBM). AMEn and TMEn values for ducks fed SDE were higher (P < or = 0.001) than for ducks fed PP, which were higher than SBM. The AMEn values were 5.048, 3.230, and 2.605 kcal/g for SDE, PP, and SBM, respectively, with TMEn values of 5.373, 3.555, and 2.930 kcal/g, respectively. Spray-dried egg, PP, and SBM were similar in apparent digestibility of the indispensable amino acids except for methionine, histidine, and valine. Apparent methionine digestibility in SDE (95.5%) was higher (P < or = 0.01) than PP (88.3%) or SBM (91.3%). Apparent digestibilities of dispensable amino acids were similar for SDE, PP, and SBM except proline and alanine. Apparent alanine digestibility in SDE (89.9%) was higher (P < or = 0.05) than in SBM (85.7%). True digestibilities of indispensable amino acids were similar in SDE, PP, and SBM except for methionine, histidine, and valine. True methionine digestibility was higher (P < or = 0.05) for SDE (97.0%) than for PP (89.8%) or SBM (92.7%), with PP and SBM being similar. True histidine and valine digestibilities were significantly lower for SDE (P < or = 0.05) than for PP or SBM. True digestibilities of the dispensable amino acids were also similar in SDE, PP, and SBM except for proline and alanine. This study demonstrates that the energy value of SDE is greater than that of PP or SBM.


Endovascular aneurysm repair simulation can lead to decreased fluoroscopy time and accurately delineate the proximal seal zone.
The use of simulators for endovascular aneurysm repair (EVAR) is not widespread. We examined whether simulation could improve procedural variables, including operative time and optimizing proximal seal. For the latter, we compared suprarenal vs infrarenal fixation endografts, right femoral vs left femoral main body access, and increasing angulation of the proximal aortic neck. Computed tomography angiography was obtained from 18 patients who underwent EVAR at a single institution. Patient cases were uploaded to the ANGIO Mentor endovascular simulator (Simbionix, Cleveland, Ohio) allowing for three-dimensional reconstruction and adapted for simulation with suprarenal fixation (Endurant II; Medtronic Inc, Minneapolis, Minn) and infrarenal fixation (C3; W. L. Gore & Associates Inc, Newark, Del) deployment systems. Three EVAR novices and three experienced surgeons performed 18 cases from each side with each device in randomized order (n = 72 simulations/participant). The cases were stratified into three groups according to the degree of infrarenal angulation: 0° to 20°, 21° to 40°, and 41° to 66°. Statistical analysis used paired t-test and one-way analysis of variance. Mean fluoroscopy time for participants decreased by 48.6% (P < .0001), and total procedure time decreased by 33.8% (P < .0001) when initial cases were compared with final cases. When stent deployment accuracy was evaluated across all cases, seal zone coverage in highly angulated aortic necks was significantly decreased. The infrarenal device resulted in mean aortic neck zone coverage of 91.9%, 89.4%, and 75.4% (P < .0001 by one-way analysis of variance), whereas the suprarenal device yielded 92.9%, 88.7%, and 71.5% (P < .0001) for the 0° to 20°, 21° to 40°, and 41° to 66° cases, respectively. Suprarenal fixation did not increase seal zone coverage. The side of femoral access for the main body did not influence proximal seal zone coverage regardless of infrarenal angulation. Simulation of EVAR leads to decreased fluoroscopy times for novice and experienced operators. Side of femoral access did not affect precision of proximal endograft landing. The angulated aortic neck leads to decreased proximal seal zone coverage regardless of infrarenal or suprarenal fixation devices.


Combining accelerometry and HR for assessing preschoolers' physical activity.
With rising obesity and rapidly decreasing levels of physical activity (PA) in young children, accurate PA measurement is needed for early screening and intervention evaluation. Although the combination of accelerometry (ACC) with HR recordings is accurate in assessing PA intensity in older children, its utility in correctly classifying PA in preschoolers is unknown. Thirty-three children (64% were boys) were recruited from four German preschools. Data included direct observation and Actiheart (CamNtech, Cambridge, UK) monitoring during 2.5 T 0.7 h (derivation data) and 1.5 T 0.3 h (validation data). Observers assessed PA using the Children's Activity Rating Scale (CARS). Moderate-to-vigorous PA (MVPA) was defined by a CARS score of 4 or 5, and sedentary behavior (SB) was defined by a CARS score of 1 or 2. Actiheart recordings were linked to CARS level, with means and 95% confidence intervals calculated for ACC and HR at each observed CARS level and for MVPA/SB. Using receiver operating characteristic analysis, gender-specific ACC and HR cutoffs for correctly classifying MVPA and SB were first determined in a derivation data set and then tested in a separate validation data set of observations. By combining HR and ACC cutoffs, 91% and 87% of the 15-s intervals observed as MVPA were correctly classified in girls and boys, respectively. Although generally lower, correct classification rates for SB were highest when only ACC cutoffs were applied (69% for girls and 67% for boys) rather than when combined cutoffs were used. Devices that combine HR and ACC data yield an accurate classification of MVPA in preschoolers but perform less well for classifying SB. These differences underscore the need to match evaluation methods with the objectives of future PA interventions.


Safety, tolerability, and efficacy of idarucizumab for the reversal of the anticoagulant effect of dabigatran in healthy male volunteers: a randomised, placebo-controlled, double-blind phase 1 trial.
Idarucizumab is a monoclonal antibody fragment that binds dabigatran with high affinity in a 1:1 molar ratio. We investigated the safety, tolerability, and efficacy of increasing doses of idarucizumab for the reversal of anticoagulant effects of dabigatran in a two-part phase 1 study (rising-dose assessment and dose-finding, proof-of-concept investigation). Here we present the results of the proof-of-concept part of the study. In this randomised, placebo-controlled, double-blind, proof-of-concept phase 1 study, we enrolled healthy volunteers (aged 18-45 years) with a body-mass index of 18·5-29·9 kg/m(2) into one of four dose groups at SGS Life Sciences Clinical Research Services, Belgium. Participants were randomly assigned within groups in a 3:1 ratio to idarucizumab or placebo using a pseudorandom number generator and a supplied seed number. Participants and care providers were masked to treatment assignment. All participants received oral dabigatran etexilate 220 mg twice daily for 3 days and a final dose on day 4. Idarucizumab (1 g, 2 g, or 4 g 5-min infusion, or 5 g plus 2·5 g in two 5-min infusions given 1 h apart) was administered about 2 h after the final dabigatran etexilate dose. The primary endpoint was incidence of drug-related adverse events, analysed in all randomly assigned participants who received at least one dose of dabigatran etexilate. Reversal of diluted thrombin time (dTT), ecarin clotting time (ECT), activated partial thromboplastin time (aPTT), and thrombin time (TT) were secondary endpoints assessed by measuring the area under the effect curve from 2 h to 12 h (AUEC2-12) after dabigatran etexilate ingestion on days 3 and 4. This trial is registered with ClinicalTrials.gov, number NCT01688830. Between Feb 23, and Nov 29, 2013, 47 men completed this part of the study. 12 were enrolled into each of the 1 g, 2 g, or 5 g plus 2·5 g idarucizumab groups (nine to idarucizumab and three to placebo in each group), and 11 were enrolled into the 4 g idarucizumab group (eight to idarucizumab and three to placebo). Drug-related adverse events were all of mild intensity and reported in seven participants: one in the 1 g idarucizumab group (infusion site erythema and hot flushes), one in the 5 g plus 2·5 g idarucizumab group (epistaxis); one receiving placebo (infusion site haematoma), and four during dabigatran etexilate pretreatment (three haematuria and one epistaxis). Idarucizumab immediately and completely reversed dabigatran-induced anticoagulation in a dose-dependent manner; the mean ratio of day 4 AUEC2-12 to day 3 AUEC2-12 for dTT was 1·01 with placebo, 0·26 with 1 g idarucizumab (74% reduction), 0·06 with 2 g idarucizumab (94% reduction), 0·02 with 4 g idarucizumab (98% reduction), and 0·01 with 5 g plus 2·5 g idarucizumab (99% reduction). No serious or severe adverse events were reported, no adverse event led to discontinuation of treatment, and no clinically relevant difference in incidence of adverse events was noted between treatment groups. These phase 1 results show that idarucizumab was associated with immediate, complete, and sustained reversal of dabigatran-induced anticoagulation in healthy men, and was well tolerated with no unexpected or clinically relevant safety concerns, supporting further testing. Further clinical studies are in progress. Boehringer Ingelheim Pharma GmbH & Co KG.


Association between Risk Factors of Common Noncommunicable Diseases (Diabetes, Hypertension, and Cardiovascular Diseases) and SocioDemographic Factors in Young Adult Women.
During the past 50 years, there is a substantial rise in noncommunicable diseases (NCDs) mortality in developing countries. India is also undergoing demographic transitions. Lifestyle which increases the risk of NCDs in younger age group will lead to increase in NCDs burden further in future generation. The objective of this study is to determine the association between risk factors of common NCDs and sociodemographic factors in young adult women of Palam Village, New Delhi. A community-based cross-sectional study was conducted in Palam Village, New Delhi. A total of 585 study participants were interviewed using a predesigned, semi-structured questionnaire. Waist circumference, blood pressure (BP), and weight were measured using nonstretchable measuring tape, digital BP apparatus, and digital weighing scale, respectively. Qualitative data are expressed in proportions and Chi-square test is applied. Mean and standard deviation are used for quantitative data. As the socioeconomic status improved, the frequency of consuming adequate amount of fruits and vegetables in a day also increased. This association was statistically significant (P < 0.05). The present study reported varied prevalence of different risk factors with various sociodemographic characteristics and there is an urgent need to implement population, individual, and program wide prevention and control interventions.


Brazilian guidelines for the management of psychomotor agitation. Part 1. Non-pharmacological approach.
To present the essential guidelines for non-pharmacological management of patients with psychomotor agitation in Brazil. These guidelines were developed based on a systematic review of articles published from 1997 to 2017, retrieved from MEDLINE (PubMed), Cochrane Database of Systematic Review, and SciELO. Other relevant articles identified by searching the reference lists of included studies were also used to develop these guidelines. The search strategy used structured questions formulated using the PICO model, as recommended by the Guidelines Project of the Brazilian Medical Association. Recommendations were summarized according to their level of evidence, which was determined using the Oxford Centre for Evidence-based Medicine system and critical appraisal tools. We initially selected 1,731 abstracts among 5,362 articles. The final sample included 104 articles that fulfilled all the inclusion criteria. The management of agitated patients should always start with the least coercive approach. The initial non-pharmacological measures include a verbal strategy and referral of the patient to the appropriate setting, preferably a facility designed for the care of psychiatric patients with controlled noise, lighting, and safety aspects. Verbal de-escalation techniques have been shown to decrease agitation and reduce the potential for associated violence in the emergency setting. The possibility of underlying medical etiologies must be considered first and foremost. Particular attention should be paid to the patient's appearance and behavior, physical signs, and mental state. If agitation is severe, rapid tranquilization with medications is recommended. Finally, if verbal measures fail to contain the patient, physical restraint should be performed as the ultimate measure for patient protection, and always be accompanied by rapid tranquilization. Healthcare teams must be thoroughly trained to use these techniques and overcome difficulties if the verbal approach fails. It is important that healthcare professionals be trained in non-pharmacological management of patients with psychomotor agitation as part of the requirements for a degree and graduate degree. The non-pharmacological management of agitated patients should follow the hierarchy of less invasive to more invasive and coercive measures, starting with referral of the patient to an appropriate environment, management by a trained team, use of verbal techniques, performance of physical and mental assessment, use of medications, and, if unavoidable, use of the mechanical restraint. CRD42017054440.


Determining the stages of cellular differentiation using deep ultraviolet resonance Raman spectroscopy.
Cellular differentiation is a fundamental process in which one cell type changes into one or more specialized cell types. Cellular differentiation starts at the beginning of embryonic development when a simple zygote begins to transform into a complex multicellular organism composed of various cell and tissue types. This process continues into adulthood when adult stem cells differentiate into more specialized cells for normal growth, regeneration, repair, and cellular turnover. Any abnormalities associated with this fundamental process of cellular differentiation are linked to life-threatening conditions, including degenerative diseases and cancers. Detection of undifferentiated and different stages of differentiated cells can be used for disease diagnosis but is often challenging due to the laborious procedures, expensive tools, and specialized technical skills which are required. Here, a novel approach, called deep ultraviolet resonance Raman spectroscopy, is used to study various stages of cellular differentiation using a well-known myoblast cell line as a model system. These cells proliferate in the growth medium and spontaneously differentiate in differentiation medium into myocytes and later into myotubes. The cellular and molecular characteristics of these cells mimic very well actual muscle tissue in vivo. We have found that undifferentiated myoblast cells and myoblast cells differentiated at three different stages are able to be easily separated using deep ultraviolet resonance Raman spectroscopy in combination with chemometric techniques. Our study has a great potential to study cellular differentiation during normal development as well as to detect abnormal cellular differentiation in human pathological conditions in future studies.


The clinical spectrum of laryngeal dystonia includes dystonic cough: observations of a large series.
Laryngeal dystonia is a movement disorder of the muscles within the larynx, which most commonly manifests as spasmodic dysphonia (SD). Rarer reported manifestations include dystonic respiratory stridor and dyscoordinate breathing. Laryngeal dystonia has been treated successfully with botulinum neurotoxin (BTX) injections since 1984. We reviewed prospectively collected data in a consecutive series of 193 patients with laryngeal dystonia who were seen at St. Vincent's Hospital between 1991 and 2011. Patient data were analyzed in Excel, R, and Prism. Laryngeal dystonia manifested as SD (92.7%), stridor (11.9%), dystonic cough (6.2%), dyscoordinate breathing (4.1%), paroxysmal hiccups (1.6%), and paroxysmal sneezing (1.6%). There were more women (68.4%) than men (31.6%), and the average age at onset was 47 years. A positive family history of dystonia was present in 16.1% of patients. A higher incidence of extra-laryngeal dystonia (ie, torticollis and blepharospasm) and concurrent manifestations of laryngeal dystonia were present in patients with dystonic cough, dyscoordinate breathing, paroxysmal sneezing, and hiccups than in other patients (P = 0.003 and P < 0.0001, respectively). The average starting dose of BTX decreased from 2.3 to 0.5 units between 1991 and 2011. The median treatment rating was excellent across all subgroups. Patients with adductor SD, stridor, extra-laryngeal dystonia and male patients had relatively better treatment outcomes. Technical failures were rare (1.1%). Dysphonia secondary to vocal cord paresis followed 38.7% of treatments. Laryngeal dystonia manifests predominantly as SD, but other manifestations include stridor, dyscoordinate breathing, paroxysmal cough, hiccups, and sneezing. BTX injections are very effective across all subgroups. Severe adverse events are rare.


Efficacy and safety profile of a topical methyl salicylate and menthol patch in adult patients with mild to moderate muscle strain: a randomized, double-blind, parallel-group, placebo-controlled, multicenter study.
An occlusive patch formulation containing 10% methyl salicylate and 3% l-menthol was recently approved by the US Food and Drug Administration for the treatment of mild to moderate pain. Despite widespread use of counterirritants, including methyl salicylate and menthol, for topical pain relief, published efficacy and safety data regarding the use of the agents alone or in combination are limited. The goal of this study was to determine the efficacy and safety profile of a patch containing 10% methyl salicylate and 3% l-menthol compared with a placebo patch in adult patients with mild to moderate muscle strain. Eligible patients were men or women aged >or=18 years with a clinical diagnosis of mild to moderate muscle strain. Patients were randomly assigned to receive either 1 active patch or 1 placebo patch applied to the skin at the affected area (ie, shoulder, upper back, upper arm, neck, calf, thigh, forearm, abdomen). Pain intensity was assessed on a 100-mm visual analog scale while at rest and with movement for 12 hours after patch application. The primary efficacy end point was the summed pain intensity difference score through 8 hours (SPID8) with movement. Analyses included use of descriptive statistics and an ANOVA model. Safety data, including adverse events, and secondary efficacy end points were also evaluated. A total of 208 patients (104 men, 104 women; age range, 18-78 years) were randomized to 1 of 2 study groups (105 in the active-patch group [mean age, 37.3 years], 103 in the placebo-patch group [mean age, 38.1 years]). The primary efficacy analysis (SPID8 with movement) indicated that patients receiving the active patch experienced significantly greater pain relief (approximately 40%) than those patients receiving a placebo patch (mean [SD], 182.6 [131.2] vs 130.1 [144.1]; P = 0.005). Analysis of the per-protocol population also found significantly more relief (P = 0.024) in the active-patch group (176.2 [131.4]; n = 92) versus the placebo-patch group (130.2 [144.0]; n = 96). Statistical analysis of secondary efficacy measures supported the primary end-point results. The number of patients experiencing any type of adverse event was comparable between study groups (active patch, 6.7% [7 events]; placebo patch, 5.8% [6 events]). No serious adverse events were reported during the study. A single, 8-hour application of a patch containing methyl salicylate and l-menthol provided significant relief of pain associated with mild to moderate muscle strain in these adult patients compared with patients receiving a placebo patch.


Disturbance of lipid composition in spinal cord of rabbits with experimental allergic encephalomyelitis.
EAE in rabbits was induced by means of inoculation of purified myelin of homologous spinal cord with complete Freund's adjuvant. The content of all the major lipid classes was studied by biochemical and histochemical methods in the different parts of spinal cord and in the brain stem in combination with morphological control for the demyelinating process presence. The most expressed myelin damage was found in the lumbar and sacral parts of spinal cord. In the same parts the content of phospholipids, cerebrosides, and free cholesterol decreased and cholesterol esters were shown to accumulate. Histochemical analysis supported these findings and revealed that the loss of lipids occurred directly in the demyelination foci. Changes in total ganglioside content and in ganglioside fractions ratio were not observed. In the brain stem neither morphological, nor biochemical changes were found. On the basis of these data it was concluded that pathological processes of periaxonal demyelination, induced by the sensitization with purified myelin, have not damaged neuronal structures and not involved the brain.


The effect of tripelennamine alone and in combination with opiates to produce antinociception in mice.
Antinociception (ANTI) was assessed in male CD-1 mice by a modification of Haffner's tail clamp procedure. Studies revealed that tripelennamine (Tp) alone produced antinociception (ANTI) in mice and also caused potentiation when combined with morphine (M) or nalbuphene (NB). Naloxone (Nx) only partially blocked the effect of Tp, but fully blocked M. Although atropine (At) had no intrinsic ANTI activity, it enhanced that of Tp but not M. Histamine (Hm) had no intrinsic ANTI activity, nor did it interact with either Tp or M. The partial abolition of Tp ANTI, in contrast to complete blockade of M effects with Nx, appears to indicate that Tp can stimulate the opiate receptor as well as another receptor for ANTI at a different locus. The combination of Tp with various opiates may have considerable abuse potential.


Evaluation of perylenediimide derivatives for potential therapeutic benefits on cancer chemotherapy.
Perylene derivatives, known to have potential therapeutic benefits on particular cancer types as photosensitizers, may also function as small-molecule inhibitors with promising therapeutic value for diverse diseases. This recently recognized biological activity was attributed to their capacity to modulate the function of various enzymes as biological targets in vitro. Although the inhibitory activity on glutathione transferase and Src tyrosine kinase is important in determining the anticancer potential of compounds for target-specific drug design and development, to date, there are no successful inhibitors of this kind. Moreover, there are only a few studies about the effects of perylene derivatives on glutathione transferase and various kinases. In this study, four novel perylene compounds, N,N'-disubstituted perylenediimides and their 1,7-dibromo derivatives, were synthesized and evaluated for their biological activities. Here, among the compounds analyzed, one of them was identified with strong glutathione transferase inhibition and two with dual activity for both glutathione transferase and c-src inhibition. These results revealed that perylene derivatives may be employed as potential chemosensitizers to prevent chemotherapy-dependent drug resistance and identified as prospective anticancer agents with dual activity on both glutathione transferase and c-src enzymes.


Phylogenetic analyses and detection of viridans streptococci based on sequences and denaturing gradient gel electrophoresis of the rod shape-determining protein gene.
Population analysis of viridans streptococci is important because these species are associated with dental caries, bacteremia, and subacute endocarditis, in addition to being important members of the human oral commensal microbiota. In this study, we phylogenetically analyzed the rod shape-determining protein gene (rodA), which is associated with cellular morphology, cell division, and sensitivity for antibiotics, and demonstrated that the diversity of the rodA gene is sufficient to identify viridans streptococci at the species level. Moreover, we developed a more convenient denaturing gradient gel electrophoresis (DGGE) method based on the diversity of the rodA gene (rodA-DGGE) for detecting nine dominant streptococcal species in human saliva, namely, Streptococcus sanguinis, Streptococcus oralis, Streptococcus mitis, Streptococcus parasanguinis, Streptococcus gordonii, Streptococcus vestibularis, Streptococcus salivarius, Streptococcus mutans, and Streptococcus sobrinus. This rodA-DGGE method proved useful in detecting viridans streptococci without cultivation, isolation, and phenotypic characterization. Analysis of the oral microbiota by rodA-DGGE offers a higher resolution than the conventional DGGE using 16S rDNA and may be an alternative in the microbial diagnosis of streptococcal infection.


Pre-hospital care management of a potential spinal cord injured patient: a systematic review of the literature and evidence-based guidelines.
An interdisciplinary expert panel of medical and surgical specialists involved in the management of patients with potential spinal cord injuries (SCI) was assembled. Four key questions were created that were of significant interest. These were: (1) what is the optimal type and duration of pre-hospital spinal immobilization in patients with acute SCI?; (2) during airway manipulation in the pre-hospital setting, what is the ideal method of spinal immobilization?; (3) what is the impact of pre-hospital transport time to definitive care on the outcomes of patients with acute spinal cord injury?; and (4) what is the role of pre-hospital care providers in cervical spine clearance and immobilization? A systematic review utilizing multiple databases was performed to determine the current evidence about the specific questions, and each article was independently reviewed and assessed by two reviewers based on inclusion and exclusion criteria. Guidelines were then created related to the questions by a national Canadian expert panel using the Delphi method for reviewing the evidence-based guidelines about each question. Recommendations about the key questions included: the pre-hospital immobilization of patients using a cervical collar, head immobilization, and a spinal board; utilization of padded boards or inflatable bean bag boards to reduce pressure; transfer of patients off of spine boards as soon as feasible, including transfer of patients off spinal boards while awaiting transfer from one hospital institution to another hospital center for definitive care; inclusion of manual in-line cervical spine traction for airway management in patients requiring intubation in the pre-hospital setting; transport of patients with acute traumatic SCI to the definitive hospital center for care within 24 h of injury; and training of emergency medical personnel in the pre-hospital setting to apply criteria to clear patients of cervical spinal injuries, and immobilize patients suspected of having cervical spinal injury.


Alterations in cardiac sarcolemmal Ca2+ pump activity during diabetes mellitus.
Diabetes mellitus is frequently associated with a primary cardiomyopathy. The mechanisms responsible for this heart disease are not clear, but an alteration in myocardial Ca2+ transport is believed to be involved in its development. Even though sarcolemma plays a crucial role in cellular Ca2+ transport, little appears to be known about its Ca2+ transporting capability in the diabetic myocardium. In this regard, we have examined the status of the cardiac sarcolemmal Ca2+ pump during diabetes mellitus. Purified sarcolemmal membranes were isolated from male Wistar diabetic rat hearts 8 wk after streptozotocin injection (55 mg/kg iv). Ca2+ pump activity assessed by measuring its Ca2+-stimulated adenosine triphosphatase and Ca2+-uptake ability in the absence and presence of calmodulin was significantly depressed in the diabetic myocardium relative to controls. These results did not appear to have been influenced by the minimal sarcoplasmic reticular and mitochondrial contamination of this membrane preparation. Hence, it appears that the sarcolemmal Ca2+ pump is defective in the diabetic myocardium and may be involved in the altered Ca2+ transport of the heart during diabetes mellitus.


Phantom of the forest or successful citizen? Analysing how Northern Goshawks (Accipiter gentilis) cope with the urban environment.
By 2040, roughly two-thirds of humanity are expected to live in urban areas. As cities expand, humans irreversibly transform natural ecosystems, creating both opportunities and challenges for wildlife. Here, we investigate how the Northern Goshawk (Accipiter gentilis) is adjusting to urban environments. We measured a variety of behavioural and ecological parameters in three urban and four rural study sites. City life appeared related to all parameters we measured. Urban female goshawks were overall 21.7 (CI95% 5.13-130) times more likely to defend their nestlings from humans than rural females. Urban goshawks were 3.64 (CI95% 2.05-6.66) times more likely to feed on pigeons and had diets exhibiting lower overall species richness and diversity. Urban females laid eggs 12.5 (CI95% 7.12-17.4) days earlier than rural individuals and were 2.22 (CI95% 0.984-4.73) times more likely to produce a brood of more than three nestlings. Nonetheless, urban goshawks suffered more from infections with the parasite Trichomonas gallinae, which was the second most common cause of mortality (14.6%), after collisions with windows (33.1%). In conclusion, although city life is associated with significant risks, goshawks appear to thrive in some urban environments, most likely as a result of high local availability of profitable pigeon prey. We conclude that the Northern Goshawk can be classified as an urban exploiter in parts of its distribution.


Genetic rescue, the greater prairie chicken and the problem of conservation reliance in the Anthropocene.
A central question in conservation is how best to manage biodiversity, despite human domination of global processes (= Anthropocene). Common responses (i.e. translocations, genetic rescue) forestall potential extirpations, yet have an uncertain duration. A textbook example is the greater prairie chicken (GRPC: Tympanuchus cupido pinnatus), where translocations (1992-1998) seemingly rescued genetically depauperate Illinois populations. We re-evaluated this situation after two decades by genotyping 21 microsatellite loci from 1831 shed feathers across six leks in two counties over 4 years (2010-2013). Low migration rates (less than 1%) established each county as demographically independent, but with declining-population estimates (4 year average N = 79). Leks were genetically similar and significantly bottlenecked, with low effective population sizes (average Ne = 13.1; 4 year Ne/N = 0.166). Genetic structure was defined by 12 significantly different family groups, with relatedness r = 0.31 > half-sib r = 0.25. Average heterozygosity, indicating short-term survival, did not differ among contemporary, pre- and post-translocated populations, whereas allelic diversity did. Our results, the natural history of GRPC (i.e. few leks, male dominance hierarchies) and its controlled immigration suggest demographic expansion rather than genetic rescue. Legal protection under the endangered species act (ESA) may enhance recovery, but could exacerbate political-economic concerns on how best to manage 'conservation-reliant' species, for which GRPC is now an exemplar.


Conditions for production of 3-ketomaltose from Agrobacterium tumefaciens.
Up to 39% yields of 3-ketomaltose were achieved in 18 to 22 hr when Agrobacterium tumefaciens NRRL B-36 was cultured at 25 to 28 C in a simple medium containing 4.0 to 8.0% maltose, 0.09% urea, 0.5% CaCO(3), 0.6% KH(2)PO(4), and 0.025% MgSO(4).7H(2)O. For maximum production of 3-ketomaltose the culture had to be maintained approximately at pH 7.0.


A comparison of self recording audiometry in naval establishments and clinical audiometry in a hospital setting.
Following the introduction of self-recording audiometers into regular use in non-hospital Royal Naval medical facilities, there has been an increase in the rate of detection of hearing losses and consequent referral for formal audiometry and ENT evaluation at Naval Hospitals. Forty-two sets of audiograms have been examined and the hearing thresholds obtained by the two methods compared. The value of self-recording audiometry even in the often imperfect audiometric conditions available in a Naval sick bay has been confirmed and the midpoint of the tracing established as a reliable indicator of the hearing threshold.


Microneutalization of cytomegalovirus.
A simple microneutralization test for cytomegalovirus (CMV) is presented. Using a laboratory adapted stock virus, definite results were obtained after 10 days. All patients with primary CMV infection showed an antibody rise and/or seroconversion; however, neutralizing antibody appeared only seven weeks after the onset of clinical symptoms. In control patients without evidence of recent primary infection, there was a complete concordance of the presence of complement-fixing and neutralizing antibodies.


Testicular morphological damage in young rats after inguinotomy with vascular trauma.
Operations for the treatment of inguinal diseases are the most frequent in childhood. Bleeding owing to trauma to the spermatic vessels is frequent and can cause testicular atrophy. The goal of this work was to determine the effects of the trauma to the spermatic vessels in the prepubertal and postpubertal histopathologic alterations in an experimental model in Wistar rats. Eighty albino Wistar rats were divided in 4 groups for the histopathologic analysis. In group A, they were submitted to digital compression of the spermatic vessels for 45 seconds; in group B, the spermatic vessels were clamped with hemostats for 5 seconds; in group C, the spermatic vessels were cauterized for 2 seconds. Group D was the control group, in which the animals were submitted to inguinotomy solely. The prepubertal histopathologic alterations were significantly decreased in group A for testicular weight (0.97 +/- 0.10); in group B, for testicular weight (0.81 +/- 0.24), testicular volume (0.522 +/- 0.192), and mean testicular biopsy score (7.2 +/- 2.7); and in group C, for the 5 parameters studied, testicular weight (0.69 +/- 0.28), testicular weight per 100 g of body weight (0.498 +/- 0.188), testicular volume (0.765 +/- 0.308), mean seminiferous tubular diameter (236.6 +/- 62.5), and mean testicular biopsy score (6.9 +/- 3.1). The postpubertal histopathologic alterations were not significant for any of the 5 parameters studied, in the 3 groups. The prepubertal histopathologic alterations were more intense in the group submitted to cauterization of the spermatic vessels, intermediate in the group submitted to clamping of the spermatic vessels with hemostats, and less severe in the rats submitted to digital compression of the spermatic vessels. The postpubertal histopathologic alterations demonstrated the capability of the young testicle to recuperate from a vascular trauma.


Psychosocial functioning in chronic epilepsy: relation to hippocampal volume and histopathological findings.
MRI volumetric measurements of the ipsi- and contralateral hippocampal volume (HV) were performed in a group of 37 patients with lesional and non-lesional temporal (TLE), and extratemporal lobe (ETLE) lobe epilepsy. Twenty-six patients underwent surgery and the resected tissues subjected to histopathological examination. Psychosocial scores were calculated on the basis of employment, partnership/family status and presence of a positive psychiatric history. Poorest values were obtained for the group with right lesional and non-lesional TLE (RTLE, p < 0.001). In this group, significant positive correlations between psychosocial functioning and the left hippocampal volume or age of onset were observed. We found that the left hippocampal volume in RTLE was smaller with increasing epilepsy duration. We conclude that patients with RTLE represent a particular group with regard to the structural and psychosocial consequences of chronic epilepsy. With regard to histopathological analysis, no particular type of lesion was identified as the major determinant of the results described above.


Ages at Onset of 5 Cardiometabolic Diseases Adjusting for Nonsusceptibility: Implications for the Pathogenesis of Metabolic Syndrome.
To shed light on the etiology of metabolic syndrome development, it is important to understand whether its 5 component disorders follow certain onset sequences. To explore disease progression of the syndrome, we studied the ages at onset of 5 cardiometabolic diseases: abdominal obesity, diabetes, hypertension, hypertriglyceridemia, and hypo-α-lipoproteinemia. In analyzing longitudinal data from the Cardiovascular Disease Risk Factors Two-Township Study (1989-2002) in Taiwan, we adjusted for nonsusceptibility, utilizing the logistic-accelerated failure time location-scale mixture regression models for left-truncated and interval-censored data to simultaneously estimate the associations of township and sex with the susceptibility probability and the age-at-onset distribution of susceptible individuals for each disease. We then validated the onset sequences of 5 cardiometabolic diseases by comparing the overall probability density curves across township-sex strata. Visualization of these curves indicates that women tended to have onsets of abdominal obesity and hypo-α-lipoproteinemia in young adulthood, hypertension and hypertriglyceridemia in middle age, and diabetes later; men tended to have onsets of abdominal obesity, hypo-α-lipoproteinemia, and hypertriglyceridemia in young adulthood, hypertension in middle age, and diabetes later. Different onset patterns of abdominal obesity, hypo-α-lipoproteinemia, and male hypertension were identified between townships. Our proposed method provides a novel strategy for investigating both pathogenesis and preventive measures of complex syndromes.


A Doubly Kinetically-Gated Information Ratchet Autonomously Driven by Carbodiimide Hydration.
We report a rotaxane-based information ratchet in which the macrocycle distribution is pumped away from equilibrium using a carbodiimide fuel. A carboxylate group on the axle, nonequidistant between two macrocycle binding sites, efficiently catalyzes the hydration of a carbodiimide fuel to the corresponding urea waste, with >80% of the fuel molecules reacting through the machine-catalyzed pathway. The energy of the reaction is harnessed by kinetic differentiation of the mechanical states of the machine driving the macrocycle to the binding site distal to the catalyst. Steric hindrance between the macrocycle and the fuel slows the reaction of the carboxylate group (to form a barrier to macrocycle movement) in the proximal co-conformer, whereas hydrogen bonding between the macrocycle and the barrier accelerates hydrolysis of the activated ester proximal isomer. The two directionally biased processes reinforce each other's effect, resulting in a doubly kinetically gated ratchet that achieves 1:18 directionality, an exceptional degree of selectivity for a synthetic chemically fueled molecular motor.


Autoimmune oophoritis associated with polycystic ovaries.
Autoimmune oophoritis is a rare cause of premature ovarian failure. Previous histological descriptions are sparse, with even fewer reports of cystic ovaries associated with this condition. Two cases of autoimmune oophoritis presenting as cystic ovaries with menstrual abnormalities are described, with immunocytochemical analysis of the inflammatory cell infiltrate. Serum autoantibodies to ovary and adrenal were present in both cases. Although rare, recognition of the condition by histopathologists is important because of the strong association with other 'organ-specific' autoimmune diseases, especially idiopathic Addison's disease. A review of the 17 reported cases indicates five where cystic changes were present in the ovary.


[Anticholinergic treatment of Parkinson's disease (author's transl)].
Anticholinergic drugs retain their place even today in the treatment of Parkinson's disease in spite of the considerable success achieved by means of stereotactic surgery and substitution therapy with dopa or dopa derivatives. An investigation was made on 44 patients suffering from Parkinson's disease treated with the new anticholinergic drug, Sormodren (Knoll). Sormodren showed a selective action on the hyperkinetic and autonomic symptoms of this disease of the extrapyramidal system. Tolerance was good, no serious side effects being observed.


Comparison of the diagnostic performance of the 2017 ACR TI-RADS guideline to the Kwak guideline in children with thyroid nodules.
The Kwak Thyroid Imaging Reporting and Data System (Kwak-TI-RADS) guideline (2011) and American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) guideline (2017) were developed as ultrasound (US) risk stratification tools for detecting thyroid malignancy in adults. The purpose of this study was to investigate the inter-rater reliability and diagnostic performance of the ACR TI-RADS guideline in the pediatric population and compare it to the Kwak guideline. This retrospective study comprised 75 children who underwent thyroid US at a tertiary-level pediatric hospital. Three pediatric radiologists and one pediatric radiology fellow graded the US findings using the Kwak-TI-RADS and ACR TI-RADS guidelines. We assessed reliability of radiologists' ratings using percentage inter-rater agreement, and intra-class correlation coefficients (ICC2,1). We assessed area-under-the-receiver-operating-characteristic curve (AUROCC) to compare the discriminative diagnostic ability of the Kwak-TI-RADS and ACR TI-RADS scoring systems against histopathology/cytology, or stability on US over a 2-year follow-up period for cases without tissue diagnosis. The inter-rater agreement was significantly better for the ACR TI-RADS level compared to the Kwak-TI-RADS level (P<0.001) using the percentage pairwise agreement. The ROC curves for assessing the diagnostic performance of the two methods showed no significant difference between the methods. The AUROCCs for the Kwak-TI-RADS and ACR TI-RADS levels were 0.74 (95% confidence interval [CI] 0.67-0.82) and 0.72 (95% CI 0.61-0.82), respectively. Both the Kwak-TI-RADS and ACR TI-RADS guidelines provide moderate malignancy risk stratification for thyroid nodules in the pediatric population, with better inter-rater agreement for the ACR TI-RADS guideline. Further work to adjust the recommendations for pediatric patients is necessary.


Multiple drug resistance in cancer revisited: the cancer stem cell hypothesis.
The failure to eradicate cancer may be as fundamental as a misidentification of the target. Current therapies succeed at eliminating bulky disease but often miss a tumor reservoir that is the source of disease recurrence and metastasis. Recent advances in the understanding of tissue development and repair cause us to revisit the process of drug resistance as it applies to oncogenesis and tumor heterogeneity. The cancer stem cell hypothesis states that the cancer-initiating cell is a transformed tissue stem cell, which retains the essential property of self-protection through the activity of multiple drug resistance (MDR) transporters. This resting constitutively drug-resistant cell remains at low frequency among a heterogeneous tumor mass. In the context of this hypothesis, the authors review the discovery of MDR transporters in cancer and normal stem cells and the failure of MDR reversal agents to increase the therapeutic index of substrate antineoplastic agents.


Spectral resolution enhancement of acousto-optic tunable filter by double-filtering.
The development of the large angular aperture noncollinear acousto-optic tunable filter (AOTF) is based on the parallel tangents momentum-matching condition. In this letter, we have introduced a special double-filtering method that leads to an enhancement of the spectral resolution. And the birefringence together with the rotatory property of the interaction material has been considered to ensure the accuracy of designing an AOTF. The principle and availability of double-filtering are discussed in detail. It is confirmed that double-filtering method is effective to enhance the spectral resolution on the condition of keeping the quality of imaging, which is significant in practical applications of imaging AOTF.


Synthesis and bio-evaluation of human macrophage migration inhibitory factor inhibitor to develop anti-inflammatory agent.
Macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine, is involved in the development of an array of inflammatory disorders including rheumatoid arthritis, inflammatory bowel disease, psoriasis, multiple sclerosis and sepsis. The synthesis of MIF-inhibitor is a rationale approach to develop novel anti-inflammatory agent to treat multitude of inflammatory diseases. In this work, we have synthesized and evaluated MIF-inhibitory activity of a series of small molecules containing isoxazoline skeleton. Mode of binding of this inhibitor to human MIF (huMIF) was determined by docking studies. The synthesized molecules inhibit tautomerase activity of huMIF. The anti-inflammatory activity of the most active inhibitor, 4-((3-(4-hydroxy-3-methoxyphenyl)-4, 5-dihydroisoxazol-5-yl) methoxy) benzaldehyde (4b) was evaluated against huMIF-induced inflammation in a cellular model (RAW 264.7 cell). Compound 4b significantly inhibits huMIF-mediated NF-κB translocation to the nucleus, up-regulation of inducible nitric oxide synthase and nitric oxide production in RAW 264.7 cell which are the markers for inflammation. The compound 4b is not cytotoxic as evident from cell viability assay. Hence, the compound 4b has potential to be a novel anti-inflammatory agent.


Specific binding of soluble peptidoglycan and muramyldipeptide to CD14 on human monocytes.
Previously, we were able to show that soluble peptidoglycan (sPG)-induced monokine production in human peripheral monocytes is inhibited by anti-CD14 monoclonal antibodies and by lipid A partial structures. This suggested but did not prove that monocytic surface protein CD14 is involved in the activation of human monocytes not only by cell wall components of gram-negative bacteria such as lipopolysaccharide (LPS) but also by cell wall components of gram-positive bacteria such as sPG. In the present study, we provide experimental evidence that CD14 indeed constitutes a binding site for sPG recognition and activation of human monocytes. The results show that fluorescein isothiocyanate-sPG (FITC-sPG) binds to human monocytes in a saturable, dose-dependent, and specific manner. For maximal binding, 2 to 3 microg of FITC-sPG per ml was sufficient, and this binding is completed within 90 min; about 40% of the binding is completed within the first 3 min. The FITC-sPG binding is considered specific because unlabeled sPG and also muramyldipeptide (MDP), the minimal bioactive structure of sPG, inhibit the binding of sPG to monocytes in a dose-dependent manner. This specific binding was also inhibited by an anti-CD14 monoclonal antibody, LPS, and lipid A partial structure compound 406. Direct evidence for an interaction of sPG with CD14 is provided by experiments involving native polyacrylamide gel electrophoresis that showed a shift of the electrophoretic mobility of CD14 by LPS as well as by sPG. These results allow the conclusion that sPG binds directly to CD14, that MDP represents the active substructure of sPG, and that CD14 may be a lectin-like receptor which plays a key role in cellular stimulation by bioactive components of not only gram-negative but also gram-positive bacteria.


Inhibition of serine proteases by a new class of cyclosulfamide-based carbamylating agents.
A new class of carbamylating agents based on the cyclosulfamide scaffold is reported. These compounds were found to be efficient time-dependent inhibitors of human neutrophil elastase (HNE). Exploitation of the three sites of diversity present in the cyclosulfamide scaffold yielded compounds which inhibited HNE but not proteinase 3 (PR 3) or bovine trypsin. The findings reported herein suggest that the introduction of appropriate recognition elements into the cyclosulfamide scaffold may lead to highly selective agents of potential value in the design of activity-based probes suitable for investigating proteases associated with the pathogenesis of chronic obstructive pulmonary disease.


Regimen for the control of blood pressure and symptoms during clonidine withdrawal.
Abrupt withdrawal of the centrally-acting antihypertensive agent, clonidine, is associated with a high incidence of rebound hypertension and tachycardia, with symptoms of sympathetic overactivity and increased catecholamine excretion. Gradual clonidine withdrawal has been recommended, but does not always avoid the reaction. A regimen is described comprising high doses of the alpha 1-adrenoceptor antagonist, prazosin, the cardioselective beta-blocker, atenolol, and chlordiazepoxide, specifically designed to counter both central and peripheral effects of sudden withdrawal of a central alpha 2-adrenoceptor agonist. This combination was completely successful in preventing the haemodynamic and symptomatic features of clonidine withdrawal in eight hypertensive patients.


HLA-B*58: 01 carrier status of Hmong in Minnesota: first in Hmong genotyping for prevalence of this biomarker of risk for severe cutaneous adverse reactions caused by allopurinol.
Allopurinol, a common medication to treat gout, is associated with severe cutaneous adverse reactions, and the occurrence is highly predicted by an individual's HLA-B*58:01 carrier status. Guidelines endorse preemptive testing in select Asian populations before initiating allopurinol. The Hmong, an Asian subpopulation originally from China who now live dispersed around the world, have a 2.5-fold higher risk of gout when compared to non-Hmong in Minnesota. Given the concern for severe cutaneous adverse reactions when prescribing allopurinol, we quantified the carrier status of HLA-B*58:01 in Hmong from two independent cohorts in Minnesota. Using a community-based participatory research approach, HLA-B*58:01 carrier status was determined in 49 US-born Hmong without a history of gout or allopurinol use. Further, 47 Hmong patients undergoing clinical evaluation to receive gout pharmacotherapy were also tested. The frequency of HLA-B*58:01 positive carrier status in these two cohorts were compared to published data from a Han Chinese (n = 2910) and a Korean cohort (n = 485) using a Fisher's exact test with a Bonferroni-corrected P-value <0.025 for significance. With one uninterpretable result, we identified two out of 95 people (2.1%) who carried HLA-B*58:01. This 2.1% incidence in these Hmong adults is notably lower than Han Chinese (19.6%, P < 0.0001) and Korean (12.2%, P = 0.0016) populations. Though commonly understood to be of Chinese descent, the lower prevalence within the Hmong underscores the risk of generalizing genotypic findings from Chinese to Asian subpopulations. We suggest no change to the current guidelines recommending which populations should be tested for HLA-B*58:01 before allopurinol use until further validation.


Enrichment of LOVD-USHbases with 152 USH2A genotypes defines an extensive mutational spectrum and highlights missense hotspots.
Alterations of USH2A, encoding usherin, are responsible for more than 70% of cases of Usher syndrome type II (USH2), a recessive disorder that combines moderate to severe hearing loss and retinal degeneration. The longest USH2A transcript encodes usherin isoform b, a 5,202-amino-acid transmembrane protein with an exceptionally large extracellular domain consisting notably of a Laminin N-terminal domain and numerous Laminin EGF-like (LE) and Fibronectin type III (FN3) repeats. Mutations of USH2A are scattered throughout the gene and mostly private. Annotating these variants is therefore of major importance to correctly assign pathogenicity. We have extensively genotyped a novel cohort of 152 Usher patients and identified 158 different mutations, of which 93 are newly described. Pooling this new data with the existing pathogenic variants already incorporated in USHbases reveals several previously unappreciated features of the mutational spectrum. We show that parts of the protein are more likely to tolerate single amino acid variations, whereas others constitute pathogenic missense hotspots. We have found, in repeated LE and FN3 domains, a nonequal distribution of the missense mutations that highlights some crucial positions in usherin with possible consequences for the assessment of the pathogenicity of the numerous missense variants identified in USH2A.


Gravity-dependent changes in bioconvection of Tetrahymena and Chlamydomonas during parabolic flight: increases in wave number induced by pre- and post-parabola hypergravity.
Bioconvection emerges in a dense suspension of swimming protists as a consequence of their negative-gravitactic upward migration and later settling as a blob of density greater than that of water. Thus, gravity is an important parameter governing bioconvective pattern formation. However, inconsistencies are found in previous studies dealing with the response of bioconvection patterns to increased gravity acceleration (hypergravity); the wave number of the patterns has been reported to decrease during the hypergravity phases of parabolic aircraft flight, while it increases in centrifugal hypergravity. In this paper, we reassess the responses of bioconvection to altered gravity during parabolic flight on the basis of vertical and horizontal observations of the patterns formed by Tetrahymena thermophila and Chlamydomonas reinhardtii. Spatiotemporal analyses of the horizontal patterns revealed an increase in the pattern wave number in both pre- and post-parabola hypergravity. Vertical pattern analysis was generally in line with the horizontal pattern analysis, and further revealed that hypergravity-induced changes preceded at the top layer of the suspensions while microgravity-induced changes appeared to occur from the bottom part of the settling blobs. The responses to altered gravity were rather different between the two sample species: T. thermophila tended to drastically modify its bioconvection patterns in response to changes in gravity level, while the patterns of C. reinhardtii responded to a much lesser extent. This difference can be attributed to the distinct physical and physiological properties of the individual organisms, suggesting a significant contribution of the gyrotactic property to the swimming behavior of some protists.


A quality improvement initiative to achieve high nursing presence during patient- and family-centered rounds.
The objectives of this study were to: (1) identify local barriers to nursing presence on patient- and family-centered rounds (PFCR); and (2) increase nursing attendance during PFCR. An electronic survey needs assessment was administered to nursing staff on a single acute medical care unit to identify local barriers to nursing presence on PFCR. Daily tracking of nursing presence on rounds was then performed over a 7-month period. During this time period, 2 Plan-Do-Study Act cycles were conducted. The first intervention was a workshop for nurses about PFCR. The second intervention was the development of a strategy to contact nurses by using a hands-free communication device so that nurses were notified when rounds were starting on their patients. To evaluate the impact of our interventions, a p-chart was generated for the outcome of average daily nursing attendance (%) on PFCR per week over the 7-month period. Two barriers identified on the survey were: (1) nurses were uncertain if physicians valued their input during PFCR; and (2) nurses were unsure when the physician team would be conducting rounds on their patients. On the p-chart, the average percentage of nursing attendance before interventions was 47%. After the nursing workshop, no change in the mean nursing attendance on PFCR was noted. After initiation of the hands-free contact strategy, nursing attendance on PFCR rose to 80%. A nursing contact strategy using a hands-free device led to a sustained increase in nursing attendance during PFCR.


Observer-Based Consensus Protocol for Directed Switching Networks With a Leader of Nonzero Inputs.
We aim to address the consensus tracking problem for multiple-input-multiple-output (MIMO) linear networked systems under directed switching topologies, where the leader is subject to some nonzero but norm bounded inputs. First, based on the relative outputs, a full-order unknown input observer (UIO) is designed for each agent to track the full states' error among neighboring agents. With the aid of such an observer, a discontinuous feedback protocol is subtly designed. And it is proven that consensus tracking can be achieved in the closed-loop networked system if the average dwell time (ADT) for switching among different interaction graph candidates is larger than a given positive threshold. By using the boundary layer technique, a continuous feedback protocol is skillfully designed and employed. It is shown that the consensus error converges into a bounded set under the designed continuous protocol. Second, as part of the full states' error can be constructed via the agents' outputs, a reduced-order UIO is thus designed based on which discontinuous and continuous feedback protocols are, respectively, proposed. By using the stability theory of the switched systems, it is proven that the consensus error converges asymptotically to 0 under the designed discontinuous protocol, and converges into a bounded set under the designed continuous protocol. Finally, the obtained theoretical results are validated through simulations.


Molecular epidemiology of prostate cancer: androgens and polymorphisms in androgen-related genes.
In most western countries prostate cancer is the most commonly diagnosed non-skin cancer in men. Despite its high morbidity and mortality the etiology of prostate cancer remains obscure. The involvement of androgens has been examined extensively in prostate carcinogenesis but the results of most epidemiological studies remain inconclusive. This review focuses on current perspectives of androgen levels and polymorphisms in androgen-related genes. Racial differences in genetic polymorphisms that have a role in the biosynthesis and metabolism of androgens may partly account for racial differences in prostate cancer risk. Reasons are also given for inconsistent results in molecular epidemiological studies and insights and directions for future research are discussed. The development of a polygenic model for prostate cancer, incorporating multiple loci from the individual genes, may maximize the chance of identifying individuals with high-risk genotypes, resulting in better preventive, diagnostic, and therapeutic strategies.


Bandgap mapping for III-V quantum well by electron spectroscopy imaging.
The concept of 'bandgap mapping' was proposed originally to map the inhomogeneity of band energy in III-V semiconductors with a spatial resolution of a few nanometres in a scanning transmission electron microscope with the focus beam mode. In this paper, several techniques were developed to demonstrate the possibility to map the distribution of bandgap energies for GaN/AlN quantum-well structures using electron spectroscopy imaging (ESI). The phase correlation function was used to register different energy-loss images among ESI series with an accuracy of 1 pixel. The energy dispersion of ESI series was improved by a fast Fourier transform interpolation method. An iterative multivariable least square algorithm was derived to refine the fitting of the single scattering distribution to an analytic form of the density of states function a(E - E(g))(0.5). The inhomogeneity of the band energy of the quantum well can be revealed from the band-energy map. A threshold filter method is applied to estimate the average value and SD of the bandgap energy from barrier and well regions in the energy map. The average bandgap energy of AlN and GaN is determined to be 5.62 +/- 0.35 and 3.87 +/- 0.36 eV, respectively. The effect of delocalization on the accuracy of band-energy determination is discussed. The 2sigma(E(g)) accuracy of this analysis is comparable to half of the energy resolution of the ESI experiment.


Use1p is a yeast SNARE protein required for retrograde traffic to the ER.
SNAREs on transport vesicles and target membranes are required for vesicle targeting and fusion. Here we describe a novel yeast protein with a typical SNARE motif but with low overall amino acid homologies to other SNAREs. The protein localized to the endoplasmic reticulum (ER) and was therefore named Use1p (unconventional SNARE in the ER). A temperature-sensitive use1 mutant was generated. use1 mutant cells accumulated the ER forms of carboxypeptidase Y and invertase. More specific assays revealed that use1 mutant cells were defective in retrograde traffic to the ER. This was supported by strong genetic interactions between USE1 and the genes encoding SNAREs in retrograde traffic to the ER. Antibodies directed against Use1p co-immunoprecipitated the SNAREs Ufe1p, myc-Sec20p and Sec22p, which form a SNARE complex required for retrograde traffic from the Golgi to the ER, but neither Bos1p nor Bet1p (members of the SNARE complex in anterograde traffic to the Golgi). Therefore, we conclude that Use1p is a novel SNARE protein that functions in retrograde traffic from the Golgi to the ER.


Reconstructive techniques in transoral robotic surgery for head and neck cancer: a North American survey.
Although the use of transoral robotic surgery for tumor extirpation is expanding, little is known about national trends in the reconstruction of resultant defects. An 18-question electronic survey was created by an expert panel of surgeons from the Department of Otolaryngology-Head and Neck Surgery and the Department of Plastic and Reconstructive Surgery at the University of Tennessee. Eligible participants were identified by the American Head and Neck Society Web site and from the Intuitive Surgical, Inc., Web site after review of surgeons trained in transoral robotic surgery techniques. Twenty-three of 27 preselected head and neck surgeons (85.18 percent) completed the survey. All respondents use transoral robotic surgery for head and neck tumor extirpation. The majority of the respondents [n = 17 (77.3 percent)] did not use any means of reconstruction. With respect to methods of reconstruction following transoral robotic surgery defects, the majority [n = 4 (80.0 percent)] used a free flap, a pedicled local flap [n = 3 (60.0 percent)], or a distant flap [n = 3 (60.0 percent)]. The radial forearm flap was the most commonly used free flap by all respondents. In general, the majority of survey respondents allow defects to heal secondarily or close primarily. Based on this survey, consensus indications for pedicled or free tissue transfer following transoral robotic surgery defects were primary head and neck tumors (stage T3 and T4a), pharyngeal defects with exposure of vital structures, and prior irradiation or chemoradiation to the operative site and neck.


Seaweeds as a reservoir for diverse Vibrio parahaemolyticus populations in Japan.
Gastroenteritis caused by Vibrio parahaemolyticus has recently been associated with foods prepared with seaweeds, but little is known about the bacterium's abundance and diversity among seaweeds in coastal environment. Therefore, we determined its phenotypic and genotypic diversity in relation to its seasonal abundance in seawater and seaweed samples from three areas of Kii Channel, Japan during June 2003 to May 2004. Isolates were obtained by selective enrichment of samples and detection of V. parahaemolyticus by colony hybridization with a species-specific probe. A total of 128 isolates comprising 16 from each source in each season were characterized by serotyping and ribotyping. V. parahaemolyticus was more abundant in seaweeds (3,762 isolates) than in water samples (2,238 isolates). Twenty and 17 serotypes were found among the selected seaweed and seawater isolates, respectively. Cluster analysis revealed 19, 11, 7 and 9 ribotypes during summer, autumn, winter and spring, respectively. Seaweeds supported a diverse V. parahaemolyticus population throughout the year and thus seaweeds are a reservoir for the organism. However, V. parahaemolyticus occurrence had positive correlation with water temperature and its abundance in seaweeds was at least 50 times higher during summer than in winter.


INF2-mediated actin filament reorganization confers intrinsic resilience to neuronal ischemic injury.
During early ischemic brain injury, glutamate receptor hyperactivation mediates neuronal death via osmotic cell swelling. Here we show that ischemia and excess NMDA receptor activation cause actin to rapidly and extensively reorganize within the somatodendritic compartment. Normally, F-actin is concentrated within dendritic spines. However, <5 min after bath-applied NMDA, F-actin depolymerizes within spines and polymerizes into stable filaments within the dendrite shaft and soma. A similar actinification occurs after experimental ischemia in culture, and photothrombotic stroke in mouse. Following transient NMDA incubation, actinification spontaneously reverses. Na+, Cl-, water, and Ca2+ influx, and spine F-actin depolymerization are all necessary, but not individually sufficient, for actinification, but combined they induce activation of the F-actin polymerization factor inverted formin-2 (INF2). Silencing of INF2 renders neurons vulnerable to cell death and INF2 overexpression is protective. Ischemia-induced dendritic actin reorganization is therefore an intrinsic pro-survival response that protects neurons from death induced by cell edema.