Physical properties of root cementum: part 24. Root resorption of the first premolars after 4 weeks of occlusal trauma.
In orthodontics, adding restorative materials on occlusal or lingual surfaces is a common method to create a mini-biteplane to increase patients' vertical dimension temporarily to facilitate several treatment procedures. However, this method transmits excessive occlusal forces through the periodontal ligament and causes trauma. In this prospective randomized clinical trial, we measured and compared quantitatively the volumes of root resorption after 4 weeks of occlusal trauma. Forty-eight maxillary and mandibular first premolars of 12 patients (6 girls, 6 boys) comprised the sample for this study. One side of each patient was randomly selected as the control. On the contralateral side, a light-cured glass ionomer cement (Transbond Plus Light Cure Band Adhesive; 3M Unitek, Monrovia, Calif) was bonded onto the occlusal surface of the mandibular first premolar so that the cement was in contact with the maxillary first premolar. After 4 weeks, both first premolars were extracted. Each sample was imaged using a microcomputed tomography system (1172; SkyScan, Aartselaar, Belgium) and analyzed with specially designed software for volumetric measurements of resorption craters. Furthermore, pain was evaluated with a visual analog scale for 7 days. There were significant differences in the amounts of root resorption between the control and the experimentally traumatized teeth. No significant difference among the buccal, lingual, mesial, and distal surfaces was found in either jaw. Furthermore, no significant difference existed in the amount of root resorption among the cervical, middle, and apical thirds of both jaws. There was no correlation between age, sex, volume of the root resorption craters, and pain. Restorative buildups, used to increase the vertical dimension by 2 mm for 4 weeks, caused root resorption along the sides of the teeth during the active bite-increase period.


Triage of Persons With Tuberculosis Symptoms Using Artificial Intelligence-Based Chest Radiograph Interpretation: A Cost-Effectiveness Analysis.
In settings without access to rapid expert radiographic interpretation, artificial intelligence (AI)-based chest radiograph (CXR) analysis can triage persons presenting with possible tuberculosis (TB) symptoms, to identify those who require additional microbiological testing. However, there is limited evidence of the cost-effectiveness of this technology as a triage tool. A decision analysis model was developed to evaluate the cost-effectiveness of triage strategies with AI-based CXR analysis for patients presenting with symptoms suggestive of pulmonary TB in Karachi, Pakistan. These strategies were compared to the current standard of care using microbiological testing with smear microscopy or GeneXpert, without prior triage. Positive triage CXRs were considered to improve referral success for microbiologic testing, from 91% to 100% for eligible persons. Software diagnostic accuracy was based on a prospective field study in Karachi. Other inputs were obtained from the Pakistan TB Program. The analysis was conducted from the healthcare provider perspective, and costs were expressed in 2020 US dollars. Compared to upfront smear microscopy for all persons with presumptive TB, triage strategies with AI-based CXR analysis were projected to lower costs by 19%, from $23233 per 1000 persons, and avert 3%-4% disability-adjusted life-years (DALYs), from 372 DALYs. Compared to upfront GeneXpert, AI-based triage strategies lowered projected costs by 37%, from $34346 and averted 4% additional DALYs, from 369 DALYs. Reinforced follow-up for persons with positive triage CXRs but negative microbiologic tests was particularly cost-effective. In lower-resource settings, the addition of AI-based CXR triage before microbiologic testing for persons with possible TB symptoms can reduce costs, avert additional DALYs, and improve TB detection.


Case report: effect of umbilical cord mesenchymal stem cells on immunoglobulin A nephropathy after acute renal failure.
Immunoglobulin A nephropathy is an inflammatory, autoimmune condition that may lead to renal impairment in its most aggressive forms. In this case report, a 50-year-old male with acute renal failure was diagnosed with IgA nephropathy, having elevated creatinine levels (3.0 mg/dL) and hypertension. He received intravenous infusions of a total of 120 million umbilical cord-derived mesenchymal stem cells (UC-MSCs) and was followed-up for 6 months. No adverse events were reported during or after administration or any of the follow-up visits. Creatinine levels decreased to and remained normal (1.0 mg/dL) in the 6 months following treatment. Anti-hypertensive medications were no longer needed. UC-MSC administration was safe, well-tolerated, and beneficial for this patient with IgA nephropathy.


The impact of COVID-19 on neurosurgeons and the strategy for triaging non-emergent operations: a global neurosurgery study.
The COVID-19 pandemic has disrupted all aspects of society globally. As healthcare resources had to be preserved for infected patients, and the risk of in-hospital procedures escalated for uninfected patients and staff, neurosurgeons around the world have had to postpone non-emergent procedures. Under these unprecedented conditions, the decision to defer cases became increasingly difficult as COVID-19 cases skyrocketed. Data was collected by self-reporting surveys during two discrete periods: the principal survey accrued responses during 2 weeks at the peak of the global pandemic, and the supplemental survey accrued responses after that to detect changes in opinions and circumstances. Nine hypothetical surgical scenarios were used to query neurosurgeons' opinion on the risk of postponement and the urgency to re-schedule the procedures. An acuity index was generated for each scenario, and this was used to rank the nine cases. There were 494 respondents to the principal survey from 60 countries. 258 (52.5%) reported that all elective cases and clinics have been shut down by their main hospital. A total of 226 respondents (46.1%) reported that their operative volume had dropped more than 50%. For the countries most affected by COVID-19, this proportion was 54.7%. There was a high degree of agreement among our respondents that fast-evolving neuro-oncological cases are non-emergent cases that nonetheless have the highest risk in postponement, and selected vascular cases may have high acuity as well. We report on the impact of COVID-19 on neurosurgeons around the world. From their ranking of the nine case scenarios, we deduced a strategic scheme that can serve as a guideline to triage non-emergent neurosurgical procedures during the pandemic. With it, hopefully, neurosurgeons can continue to serve their patients without endangering them either neurologically or risking their exposure to the deadly virus.


Platelet-activating factor acetylhydrolase activity indicates angiographic coronary artery disease independently of systemic inflammation and other risk factors: the Ludwigshafen Risk and Cardiovascular Health Study.
Platelet-activating factor acetylhydrolase (PAF-AH), also denoted as lipoprotein-associated phospholipase A2, is a lipoprotein-bound enzyme that is possibly involved in inflammation and atherosclerosis. This study investigates the relationship of PAF-AH activity to angiographic coronary artery disease (CAD), the use of cardiovascular drugs, and other established risk factors. PAF-AH activity, lipoproteins, sensitive C-reactive protein (sCRP), fibrinogen, serum amyloid A, and white blood cell count were determined in 2454 subjects with angiographically confirmed CAD and in 694 control subjects. PAF-AH activity was highly correlated with LDL cholesterol (r=0.517), apolipoprotein B (r=0.644), and non-HDL cholesterol (r=0.648) but not with sCRP or fibrinogen. PAF-AH activity was lower in women than in men and was affected by the intake of lipid-lowering drugs (-12%; P<0.001), aspirin (-6%; P<0.001), beta-blockers (-6%; P<0.001), and digitalis (+7%; P<0.001). Unlike sCRP, fibrinogen, and serum amyloid A, PAF-AH activity was not elevated in unstable angina, non-ST-elevation myocardial infarction, or ST-elevation myocardial infarction. When nonusers of lipid-lowering drugs were examined, PAF-AH activity was associated with the severity of CAD and the number of coronary vessels with significant stenoses. In individuals not taking lipid-lowering drugs and after adjustment for use of aspirin, beta-blocker, and digitalis, the odds ratio for CAD associated with increasing PAF-AH activity was 1.39 (95% CI 1.26 to 1.54, P<0.001), a finding that was robust against further adjustments. PAF-AH activity is not an indicator of the systemic inflammation that accompanies acute coronary syndromes. PAF-AH activity is affected by a number of cardiovascular drugs; however, after such medication use was accounted for, PAF-AH activity was associated with angiographic CAD, complementary to sCRP and independently of established risk factors such as LDL cholesterol.


Optimization of the isolation, culture, and characterization of equine umbilical cord blood mesenchymal stromal cells.
Mesenchymal stromal cells (MSC) represent a promising population for supporting new clinical concepts in cellular therapy. A wide diversity of isolation procedures for MSC from umbilical cord blood (UCB) has been described for humans. In contrast, a few data are available in horses. In the current study, a sedimentation method using hydroxyethyl starch and a method based on the lysis of red blood cells using ammonium chloride (NH(4)Cl) were compared with two density gradient separation methods (Ficoll-Paque and Percoll). Adherent cell colonies could be established using all four isolation methods. The mononuclear cell recovery after Percoll separation, however, resulted in significantly more putative MSC colonies; and, therefore, this isolation method was used for all further experiments. Culture conditions such as cell density and medium or serum coating of the wells did not significantly affect putative MSC recovery. Isolated MSC using Percoll were subsequently differentiated toward the osteogenic, chondrogenic, and adipogenic lineage. In addition, MSC were phenotyped by multicolor flow cytometry based on their expression of different cell protein markers. Cultured MSC were CD29, CD44, and CD90-positive and CD79α, Macrophage/Monocyte and MHC II-negative. In conclusion, this study reports optimized protocols to isolate, culture, and characterize solid equine MSC from UCB.


Exploring young adult perspectives on the use of gamification and social media in a smartphone platform for improving vegetable intake.
Young adults are the poorest consumers of vegetables. Social media and smartphones are frequently used by this demographic and could serve as an engaging medium for nutrition promotion. Five focus groups were conducted to capture participants' perceptions of a theory-based gamified self-monitoring app for improving vegetable intake of young adults. Ranking activities were used to gather feedback on preferences for social media posts. Data arising from group discussion were analysed using NVivo software using a deductive approach to group common ideas into themes. Thirty two participants (14 males) attended (mean age 23.1 (SD 2.7) years). Qualitative analyses of open discussion revealed two major themes regarding preferred features for a smartphone app; (1) the use of visual guides for estimating quantities of vegetables and tracking progress, and (2) a simple interface. Gamification strategies such as earning badges were viewed more positively than the use of a self-reward framework. Social media posts which presented food pictures and recipes were ranked most motivating, while awareness-raising posts received lower scores. Participants indicated a preference for viewing but reluctance to post information onto social media. "Just in time" situational cues were ranked highly and the use of an "authoritative" tone was preferred and associated with credibility. Young adults also ranked messages containing "Gen Y" language highly, with a preference for those which were personally relevant. The proposed use of social media and mobile-gaming was seen as an acceptable approach for improving vegetable intake. Materials should be visually appealing, simply designed, credible, and personally relevant to appeal to this population. This feedback may inform future mobile-phone based interventions targeting improved nutrition in young adults.


Helicobacter pylori, transmission routes and recurrence of infection: state of the art.
Helicobacter pylori (H. pylori) infection is one of the most common infection in humans, affecting more than half of the population. The prevalence of the infection varies widely in rural developing areas (more than 80%) compared to urban developed ones (less than 40%), as a consequence of different socioeconomic and hygienic conditions. H. pylori infection is usually acquired during childhood; infected people usually remain asymptomatic, but about 30% of individuals may develop mild to severe upper gastrointestinal diseases such as gastritis, peptic ulcer, gastric cancer or MALT lymphoma. The transmission route is not clear yet; the person-to-person transmission, especially within the same family appears to be prevalent, but also environmental contamination is possible. The eradication without a specific therapeutic regimen is very unlikely and the reinfection rate after an effective eradication therapy is quite rare. The reinfection rate will increase if there are family members affected.


Gene therapy for malignant neoplasms of the CNS.
Five different gene transfer protocols have progressed into human clinical trials for the treatment of brain tumors. Two utilize the in vivo transfer of the Herpes Simplex-thymidine kinase (HS-tk) gene by either retroviral or adenoviral gene transfer. HS-tk confers a sensitivity to the anti-herpes drug ganciclovir (GCV). Insertion of HS-tk into tumors and subsequent treatment with GCV has successfully eliminated tumors in experimental animal models despite less than a 100% gene transfer efficiency. This phenomenon, the 'bystander effect', allows the destruction of neighboring tumor cells not transduced with HS-tk. Two other approaches use ex vivo gene transfer of either the IL-2 or antisense insulin-like growth factor type 1 (IGF-1) genes into autologous tumor cells. In animal models, tumor cells genetically altered with antisense IGF-1 or IL-2 genes induce a potent cell-mediated antitumor response. The fifth approach uses the genetic modification of hematopoietic stem cells instead of tumor cells. In this approach, the multiple drug resistance (MDR-1) gene is transferred into stem cells to protect them from the toxic effects of certain chemotherapy drugs. This may allow the administration of higher doses without increasing bone marrow toxicity. Together, these clinical trials will provide critical information needed to develop improved gene transfer technologies for humans and to attain clinical benefit for cancer patients.


Reliability and Validity of the Avoidance of Daily Activities Photo Scale for Patients with Shoulder Pain (ADAP Shoulder Scale).
The Avoidance of Daily Activities Photo Scale for Patients With Shoulder Pain (ADAP Shoulder Scale) was developed to assess pain-related avoidance behavior during daily activities in people with shoulder pain. However, its measurement properties must be verified according to international guidelines. As such, this study investigated the following 4 measurement properties of the ADAP Shoulder Scale: reliability, measurement errors, convergent validity, and floor and ceiling effects. The sample comprised 100 individuals with chronic shoulder pain (43 men and 57 women; mean duration of symptoms of 29.7 [SD = 89.0] months; mean age of 44.9 [SD = 15.9] years). The mean test-retest reliability range was 5 days via the ICC. Measurement errors included the standard error of measurement and the minimal detectable change. Convergent validity was analyzed by applying the Pearson correlation with the Tampa Scale for Kinesiophobia, Pain Catastrophizing Scale, and Shoulder Pain and Disability Index. The ADAP Shoulder Scale showed excellent test-retest reliability, both in all domains and in the total score [ICC(2,1) = 0.94; 95% CI = 0.92-0.96]. The standard errors of measurement for the free-movement, high-effort, and self-care domains were 8.1%, 6.0%, and 7.6%, respectively. The minimal detectable change for the total score of the ADAP Shoulder Scale was 16.0%. The total score of the ADAP Shoulder Scale was low to moderately correlated with the total scores of the Tampa Scale for Kinesiophobia (r = 0.52), Pain Catastrophizing Scale (r = 0.30), and Shoulder Pain and Disability Index (r = 0.72). No floor or ceiling effects were detected in the total score. The ADAP Shoulder Scale is a reliable, valid instrument for assessing avoidance behavior in adults who have chronic shoulder pain and are not athletes. This study provides evidence that the ADAP Shoulder Scale is appropriate for clinical and practical use in people with chronic shoulder pain.


Mobility of concanavalin A receptors and distribution of cytoplasmic actin in odontogenic epithelial and mesenchymal cells.
The distribution of concanavalin A (Con A) surface receptors and cytoplasmic actin in the same cell was studied in monolayer cultures of 2 odontogenic epithelial cells of different developmental age and in ecto-mesenchymal cells derived from the same tooth germ. Con A receptors were demonstrated by fluorescein-isothiocyanate-labelled Con A (FITC-Con A) and cytoplasmic actin by a specific anti-actin autoantibody (AAA) traced with a rhodamine-labelled goat anti-human globulin (R-AHG). All 3 cell types, incubated with FITC-Con A at 37 degrees C for increasing time periods, showed progressive changes in staining patterns from clusters, caps to perinuclear globules. Capping was seen in the majority of immature epithelial cells at 120--180 min, in cells of more mature epithelium at 180--240 min and in ecto-mesenchymal cells at 240--360 min. Binding of FITC-Con A to cell surfaces resulted in sequential changes in AAA staining from filamentous to an aggregated or diffuse pattern, co-capping of aggregated or diffusely stained areas with those capped by FITC-Con A, presence of aggregated or diffusely stained areas in sites similar to the perinuclear globules stained by FITC-Con A, to final re-emergence of filamentous staining. Prior treatment of cells with cytochalasin B or colchicine promoted capping in epithelial but not in ecto-mesenchymal cells while presence of either drug throughout the staining procedure inhibited capping. The results show that Con A receptors are more mobile in epithelial compared to ecto-mesenchymal cells and in immature epithelial cells compared to their more mature counterparts, and that binding and mobility of Con A receptors on the cell surface is associated with redistribution of cytoplasmic actin. The cytochalasin B and colchicine experiments suggest that both microfilaments and microtubules may have synergistic roles in the opposing functions of receptor anchorage and mobility, and that the relative receptor immobility of ectomesenchymal compared to epithelial cells may be attributed to firmer receptor anchorage to the cytoskeleton.


Accumulation of 4-Hydroxynonenal Characterizes Diabetic Fat and Modulates Adipogenic Differentiation of Adipose Precursor Cells.
Redox imbalance in fat tissue appears to be causative of impaired glucose homeostasis. This "proof-of-concept" study investigated whether the peroxidation by-product of polyunsaturated n-6 fatty acids, namely 4-hydroxynonenal (4-HNE), is formed by, and accumulates in, the adipose tissue (AT) of obese patients with type 2 diabetes (OBT2D) as compared with lean, nondiabetic control subjects (CTRL). Moreover, we studied the effects of 4-HNE on the cell viability and adipogenic differentiation of adipose-derived stem cells (ASCs). Protein-HNE adducts in subcutaneous abdominal AT (SCAAT) biopsies from seven OBT2D and seven CTRL subjects were assessed using Western blot. The effects of 4-HNE were then studied in primary cultures of ASCs, focusing on cell viability, adipogenic differentiation, and the "canonical" Wnt and MAPK signaling pathways. When compared with the controls, the OBT2D patients displayed increased HNE-protein adducts in the SCAAT. The exposure of ASCs to 4-HNE fostered ROS production and led to a time- and concentration-dependent decrease in cell viability. Notably, at concentrations that did not affect cell viability (1 μM), 4-HNE hampered adipogenic ASCs' differentiation through a timely-regulated activation of the Wnt/β-catenin, p38MAPK, ERK1/2- and JNK-mediated pathways. These "hypothesis-generating" data suggest that the increased accumulation of 4-HNE in the SCAAT of obese patients with type 2 diabetes may detrimentally affect adipose precursor cell differentiation, possibly contributing to the obesity-associated derangement of glucose homeostasis.


Unsuspected human immunodeficiency virus infection presenting as immunoglobulin G4-related lymphadenopathy: a case report.
Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is an immune-mediated condition characterized by infiltration of the involved organs by IgG4-bearing plasma cells. The prevalence of autoimmune diseases, associated with or occurring in patients with human immunodeficiency virus (HIV) infection, has been increasing. We describe a 58-year-old man with an undiagnosed HIV infection, which presented as chronic cervical lymphadenopathy with an elevated serum IgG4 and a very high IgE. Histologically, lymph nodes showed expanded sinusoids and burnt-out germinal centers with increased plasmacytic infiltration and collagen fiber deposition. The absolute number of IgG4+ plasma cells and the IgG4+/IgG+ plasma cell ratio was increased. The lymph nodes were enlarged and clinically the patient improved after steroid treatment. Nine months later, he was diagnosed with acquired immune deficiency syndrome, following presentation with a cavitary left lung lesion. Immunohistochemical studies on the previously resected lymph node revealed complete absence of CD4+ T-lymphocytes and increased CD8+ T-lymphocytes. The pathologic findings met the criteria of both HIV infection and IgG4-related lymphadenopathy. Our case demonstrates that further investigations for underlying HIV infection in a case of IgG4-RD are critical, especially when extremely elevated IgE is concomitantly present.


An application of the health belief model to patient education and compliance: acute otitis media.
This study made use of concepts from the health belief model to test the influence of educational intervention on patient attitude and subsequent sick-role behavior. The hypothesis tested was as follows: Mothers of pediatric patients in an experimental group (N-29) receiving specially designed education about otitis media, would consequently acquire greater awareness of their children's susceptibility to the disease, the possibility of its serious effects, and the benefits of treatment than a comparable control group (N-30) not receiving the educational intervention. It was further hypothesized that patient compliance would be higher in the experimental group. Experimental group health beliefs changed in a significant, positive direction with respect to illness susceptibility and severity, the benefits of treatment, and patient modifying factors. Control group attitudes did not significantly change. Compliance rates for both groups were very high; 91.8% compliance was noted for experimental subjects and 85.6% for controls. This may reflect the additional time and attention given all those participating in the study.


The structure of integral dimensions: contrasting topological and Cartesian representations.
Diverse evidence shows that perceptually integral dimensions, such as those composing color, are represented holistically. However, the nature of these holistic representations is poorly understood. Extant theories, such as those founded on multidimensional scaling or general recognition theory, model integral stimulus spaces using a Cartesian coordinate system, just as with spaces defined by separable dimensions. This approach entails a rich geometrical structure that has never been questioned but may not be psychologically meaningful for integral dimensions. In particular, Cartesian models carry a notion of orthogonality of component dimensions, such that if 1 dimension is diagnostic for a classification or discrimination task, another can be selected as uniquely irrelevant. This article advances an alternative model in which integral dimensions are characterized as topological spaces. The Cartesian and topological models are tested in a series of experiments using the perceptual-learning phenomenon of dimension differentiation, whereby discrimination training with integral-dimension stimuli can induce an analytic representation of those stimuli. Under the present task design, the 2 models make contrasting predictions regarding the analytic representation that will be learned. Results consistently support the Cartesian model. These findings indicate that perceptual representations of integral dimensions are surprisingly structured, despite their holistic, unanalyzed nature.


[Pancreatoduodenal resection with application of suturing device].
Operation of Whipple (pancreatoduodenal resection) is one of the most complicated in abdominal surgery; it is accompanied by great number of postoperative complications and lethal outcomes. The authors were the first in Russia to use suturing apparates by the firm USSC in pancreatoduodenal resection. The apparates were used in 8 patients, control group consisted of 10 patients previously operated conventionally with the use of uses UO series instruments. The application of the suturing devices made it possible to cut by half the duration of the operation, to secure painless postoperative course, to unify the operative procedure and makes it available for additional medical institutions.


Unacceptable failure of hemiarthroplasty combined with biological glenoid resurfacing in the treatment of glenohumeral arthritis in the young.
Treatment of glenohumeral osteoarthritis in young patients is challenging. Total shoulder arthroplasty reliably addresses pain and dysfunction but compromises glenoid bone stock. Various efforts have been made to avoid a prosthetic glenoid component or to prevent glenoid erosion after hemiarthroplasty. Capsular interposition, meniscal allograft, and more recently, GraftJacket (Wright Medical Technology Inc, Arlington, TN, USA), a human dermal collagen allograft, have been proposed for interposition arthroplasty in young patients with glenohumeral osteoarthritis. From 2009 to 2010, GraftJacket was used for glenoid resurfacing combined with humeral resurfacing or a stemmed hemiarthroplasty in 6 patients with a mean age of 47 years (34-57 years). Before GraftJacket was available, 5 patients were treated with a meniscal allograft and 6 with capsular interposition arthroplasty. At a mean of 16 months (9-22 months) after the GraftJacket was implanted, 5 of the 6 patients were revised to a total shoulder arthroplasty or a reverse total shoulder arthroplasty. The sixth patient was dissatisfied but declined further surgery. The mean relative, preoperative Constant score decreased from 35% (range, 13%-61%) to 31% (range, 15%-43%) at revision or latest follow-up. Of the 5 patients with meniscal allograft, 3 underwent revision at a mean of 22 months (range, 12-40 months), and 4 of the 6 patients with capsular interposition were revised at a mean of 34 months (range, 23-45 months). The mean relative Constant scores preoperatively and at revision or latest follow-up were 44% (range, 19%-68%) and 58% (range, 9%-96%) for the meniscal allograft patients and 47% (range, 38%-62%) and 63% (range, 32%-92%) for the capsular interposition cases. In our hands, 3 different types of biological resurfacings combined with humeral hemiarthroplasty have an unacceptable early failure rate.


Multicellular photo-magnetotactic bacteria.
Multicellular magnetotactic bacteria (MMB) are unique microorganisms typically comprised of 10-40 bacterial cells arranged around a central acellular compartment. Their life cycle has no known unicellular stage and division occurs by separation of a single MMB aggregate into two identical offspring. In this study, South-seeking multicellular magnetotactic bacteria (ssMMB) were enriched from a New England salt marsh. When exposed to light, ssMMB reversed their magnetotactic behaviour to become North-seeking. The exposure time needed to generate the reversal response varied with light wavelength and intensity. Extensive exposure to light appeared to be lethal. This is the first report of a Northern hemisphere MMB displaying South-seeking behaviour and the first time a MMB is found to exhibit photo-magnetotaxis. We suggest that this mechanism enables ssMMB to optimize their location with regard to chemical gradients and light intensities, and propose a model to explain the peculiar balance between photo- and magnetotaxis.


A case of delayed cardiac perforation of active ventricular lead.
A 65-year-old man was admitted as for one month of repetitive dizziness and one episode of syncope. Electrocardiogram showed sinus bradycardia and his Holter monitoring also showed sinus bradycardia with sinus arrest, sino-atrial block and a longest pause of 4.3 s. Then sick sinus syndrome and Adam-Stokes syndrome were diagnosed. Then a dual chamber pacemaker (Medtronic SDR303) was implanted and the parameters were normal by detection. The patient was discharged 1 week later with suture removed. Then 1.5 month late the patient was presented to hospital once again for sudden onset of chest pain with exacerbation after taking deep breath. Pacemaker programming showed both pacing and sensing abnormality with threshold of > 5.0V and resistance of 1200Ω. Lead perforation was revealed by chest X-ray and confirmed by echocardiogram. Considering the fact that there was high risk to remove ventricular lead, spiral tip of previous ventricular lead was withdrew followed by implantation of a new ventricular active lead to the septum. Previous ventricular lead was maintained. As we know that the complications of lead perforation in the clinic was rare. Here we discuss the clinical management and the possible reasons for cardiac perforation of active ventricular lead.


Archaeogenomic evidence from the southwestern US points to a pre-Hispanic scarlet macaw breeding colony.
Hundreds of scarlet macaw (Ara macao cyanoptera) skeletons have been recovered from archaeological contexts in the southwestern United States and northwestern Mexico (SW/NW). The location of these skeletons, >1,000 km outside their Neotropical endemic range, has suggested a far-reaching pre-Hispanic acquisition network. Clear evidence for scarlet macaw breeding within this network is only known from the settlement of Paquimé in NW dating between 1250 and 1450 CE. Although some scholars have speculated on the probable existence of earlier breeding centers in the SW/NW region, there has been no supporting evidence. In this study, we performed an ancient DNA analysis of scarlet macaws recovered from archaeological sites in Chaco Canyon and the contemporaneous Mimbres area of New Mexico. All samples were directly radiocarbon dated between 900 and 1200 CE. We reconstructed complete or near-complete mitochondrial genome sequences of 14 scarlet macaws from five different sites. We observed remarkably low genetic diversity in this sample, consistent with breeding of a small founder population translocated outside their natural range. Phylogeographic comparisons of our ancient DNA mitogenomes with mitochondrial sequences from macaws collected during the last 200 years from their endemic Neotropical range identified genetic affinity between the ancient macaws and a single rare haplogroup (Haplo6) observed only among wild macaws in Mexico and northern Guatemala. Our results suggest that people at an undiscovered pre-Hispanic settlement dating between 900 and 1200 CE managed a macaw breeding colony outside their endemic range and distributed these symbolically important birds through the SW.


Association of systemic lupus erythematosus disease activity index score with clinical and laboratory parameters in pediatric onset systemic lupus erythematosus.
To determine the association of systemic lupus erythematosus disease activity index (SLEDAI) score in pediatric onset SLE (p-SLE) with clinical and laboratory parameters. This cross sectional observational study was conducted at Division of Rheumatology, Fatima Memorial Hospital, Lahore from November 2018 to January 2019. Total 23 patients diagnosed with p-SLE having onset of symptoms at ≤ 18 years of age, irrespective of their current age at presentation, of either gender, fulfilling criteria of 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria were enrolled. Patients' clinical symptoms and laboratory parameters were reviewed, SLEDAI scores were calculated. Collected Data were entered in proforma and analyzed on SPSS version 23. There were 91.3% females. Mean age at diagnosis was 11years ± 4years. At presentation patients had hematological involvement 69.6% followed by mucocutaneous symptoms 65.2% and renal involvement 21.6%. ANA by IFA was positive in all, while anti-ds-DNA was positive in 78.3% patients. SLEDAI score was ≥6 in 87% patients, average SLEDAI score was higher in patients with renal involvement (p=0.06). Elevated ESR (r=0.48, p=0.02), Anti-dsDNA (r=0.44, p=0.05) and low complement levels (p=0.03) were significantly positively correlated, while hemoglobin (r= -0.43, p=0.04) was negatively correlated with the SLEDAI score. In this study, patients with Lupus Nephritis had high SLEDAI scores. Elevated Anti-dsDNA titer, ESR, low complement levels and hemoglobin were significantly associated with high SLEDAI scores. We recommend that SLEDAI score should be calculated in p-SLE patients for stringent disease monitoring and treatment.


Modulated anticonvulsant block of sodium channels in nerve and muscle.
We have looked at several anticonvulsant drugs regarding their potency for basal block of sodium channels in both skeletal muscle and myelinated nerve preparations under voltage clamp conditions. There is an inverse relationship observed between the half-blocking concentration of each drug and its lipid distribution coefficient. Furthermore the anticonvulsants which are cyclic amides show a systematically weaker potency for blocking channels than do local anesthetics (linear amides) of comparable solubility. Additional kinetic characterizations of drug block are described that may contribute to accumulation of frequency-dependent block and to the appearance of 'inactivation shift' phenomena. Finally, evidence is provided showing that phenytoin and carbamazepine (as well as phenobarbital) selectively block the inactive form of closed sodium channels, thus giving these anticonvulsants a capability for selective action in depolarized tissue.


A new spectrally sharpened sensor basis to predict color naming, unique hues, and hue cancellation.
When light is reflected off a surface, there is a linear relation between the three human photoreceptor responses to the incoming light and the three photoreceptor responses to the reflected light. Different colored surfaces have different linear relations. Recently, Philipona and O'Regan (2006) showed that when this relation is singular in a mathematical sense, then the surface is perceived as having a highly nameable color. Furthermore, white light reflected by that surface is perceived as corresponding precisely to one of the four psychophysically measured unique hues. However, Philipona and O'Regan's approach seems unrelated to classical psychophysical models of color constancy. In this paper we make this link. We begin by transforming cone sensors to spectrally sharpened counterparts. In sharp color space, illumination change can be modeled by simple von Kries type scalings of response values within each of the spectrally sharpened response channels. In this space, Philipona and O'Regan's linear relation is captured by a simple Land-type color designator defined by dividing reflected light by incident light. This link between Philipona and O'Regan's theory and Land's notion of color designator gives the model biological plausibility. We then show that Philipona and O'Regan's singular surfaces are surfaces which are very close to activating only one or only two of such newly defined spectrally sharpened sensors, instead of the usual three. Closeness to zero is quantified in a new simplified measure of singularity which is also shown to relate to the chromaticness of colors. As in Philipona and O'Regan's original work, our new theory accounts for a large variety of psychophysical color data.


Limit setting on drug abuse in methadone maintenance patients.
In this prospective study the authors examined the effects of setting limits on continued drug abuse in patients receiving methadone maintenance. Subjects were randomly assigned either to structured treatment (drug use exceeding set limits resulted in methadone withdrawal) or to unstructured treatment (no consequences attended continued drug use). The structured treatment resulted in significantly less drug use and greater retention in the program. The authors conclude that these results confirm the importance of external structure in the treatment of addiction-related psychopathology.


Pre-therapy Neural State of Bilateral Motor and Premotor Cortices Predicts Therapy Gain After Subcortical Stroke: A Pilot Study.
The aim of the study was to examine whether neural state of spared motor and premotor cortices captured before a therapy predicts therapy-related motor gains in chronic subcortical stroke. Ten survivors, presenting chronic moderate upper limb impairment, underwent proton magnetic resonance spectroscopy, magnetic resonance imaging, clinical, and kinematics assessments before a 4-wk impairment-oriented training. Clinical/kinematics assessments were repeated after therapy, and motor gain was defined as positive values of clinical upper limb/elbow motion changes and negative values of trunk motion changes. Candidate predictors were N-acetylaspartate-neuronal marker, glutamate-glutamine-indicator of glutamatergic neurotransmission, and myo-inositol-glial marker, measured bilaterally within the upper limb territory in motor and premotor (premotor cortex, supplementary motor area) cortices. Traditional predictors (age, stroke length, pre-therapy upper limb clinical impairment, infarct volume) were also investigated. Poor motor gain was associated with lower glutamate-glutamine levels in ipsilesional primary motor cortex and premotor cortex (r = 0.77, P = 0.01 and r = 0.78, P = 0.008, respectively), lower N-acetylaspartate in ipsilesional premotor cortex (r = 0.69, P = 0.02), higher glutamate-glutamine in contralesional primary motor cortex (r = -0.68, P = 0.03), and lower glutamate-glutamine in contralesional supplementary motor area (r = 0.64, P = 0.04). These predictors outperformed myo-inositol metrics and traditional predictors (P ≈ 0.05-1.0). Glutamatergic state of bilateral motor and premotor cortices and neuronal state of ipsilesional premotor cortex may be important for predicting motor outcome in the context of a restorative therapy.


A Case of Non-Tachycardic Atrial Fibrillation Whose Left Ventricular Systolic Dysfunction Improved After Catheter Ablation.
It is difficult to identify the causes and optimal treatment of heart failure (HF) in patients with atrial fibrillation (AF) and HF with reduced ejection fraction (EF) (HFrEF). Tachyarrhythmia can cause left ventricular (LV) systolic dysfunction called tachycardia-induced cardiomyopathy (TIC). In patients with TIC, conversion to sinus rhythm may lead to improvement in LV systolic dysfunction. However, it is unclear whether we should try to convert patients with AF without tachycardia to sinus rhythm. A 46-year-old man with chronic AF and HFrEF came to our hospital. His New York Heart Association (NYHA) classification was class II. The blood test showed a brain natriuretic peptide of 105 pg/mL. Electrocardiogram (ECG) and 24-h ECG showed AF without tachycardia. Transthoracic echocardiography (TTE) showed left atrial (LA) dilatation, LV dilatation, and diffuse LV hypokinesis (EF was 40%). Although he was optimized medically, NYHA classification II persisted. Therefore, he underwent direct current cardioversion and catheter ablation. After his AF converted to a sinus rhythm of heart rate (HR) 60 - 70 beats per minute (bpm), TTE showed improvement in LV systolic dysfunction. We gradually reduced oral medications for arrhythmia and HF. We subsequently succeeded in discontinuing all medications 1 year after catheter ablation. TTE performed between 1 and 2 years after catheter ablation showed normal LV function and normal cardiac size. During the 3 years of follow-up, there was no recurrence of AF, and he was not readmitted to the hospital. This patient showed the effectiveness of converting AF to sinus rhythm in patients without tachycardia.


No increase in the incidence of acute kidney injury in a population-based annual temporal trends epidemiology study.
Recent literature suggests an increase in the incidence of acute kidney injury (AKI). We evaluated population-based trends of AKI over the course of nine years, using a validated electronic health record tool to detect AKI. All adult residents (18 years of age and older) of Olmsted County, Minnesota (MN), admitted to the Mayo Clinic Hospital between 2006 and 2014 were included. The incidence rate of AKI was calculated and temporal trends in the annual AKI incident rates assessed. During the nine-year study period, 10,283, and 41,847 patients were admitted to the intensive care unit or general ward, with 1,740 and 2,811 developing AKI, respectively. The unadjusted incidence rates were 186 and 287 per 100,000 person years in 2006 and reached 179 and 317 per 100,000 person years in 2014. Following adjustment for age and sex, there was no significant change in the annual AKI incidence rate during the study period with a Relative Risk of 0.99 per year (95% confidence interval 0.97-1.01) for intensive care unit patients and 0.993 per year (0.98-1.01) for the general ward patients. Similar results were obtained when the ICD-9 codes or administrative data for dialysis-requiring AKI was utilized to determine incident cases. Thus, despite the current literature that suggests an epidemic of AKI, we found that after adjusting for age and sex the incidence of AKI in the general population remained relatively stable over the last decade.


Online Influence and Sentiment of Fitness Tweets: Analysis of Two Million Fitness Tweets.
Publicly available fitness tweets may provide useful and in-depth insights into the real-time sentiment of a person's physical activity and provide motivation to others through online influence. The goal of this experimental approach using the fitness Twitter dataset is two-fold: (1) to determine if there is a correlation between the type of activity tweet (either workout or workout+, which contains the same information as a workout tweet but has additional user-generated information), gender, and one's online influence as measured by Klout Score and (2) to examine the sentiment of the activity-coded fitness tweets by looking at real-time shared thoughts via Twitter regarding their experiences with physical activity and the associated mobile fitness app. The fitness tweet dataset includes demographic and activity data points, including minutes of activity, Klout Score, classification of each fitness tweet, the first name of each fitness tweet user, and the tweet itself. Gender for each fitness tweet user was determined by a first name comparison with the US Social Security Administration database of first names and gender. Over 184 days, 2,856,534 tweets were collected in 23 different languages. However, for the purposes of this study, only the English-language tweets were analyzed from the activity tweets, resulting in a total of 583,252 tweets. After assigning gender to Twitter usernames based on the Social Security Administration database of first names, analysis of minutes of activity by both gender and Klout influence was determined. The mean Klout Score for those who shared their workout data from within four mobile apps was 20.50 (13.78 SD), less than the general Klout Score mean of 40, as was the Klout Score at the 95th percentile (40 vs 63). As Klout Score increased, there was a decrease in the number of overall workout+ tweets. With regards to sentiment, fitness-related tweets identified as workout+ reflected a positive sentiment toward physical activity by a ratio of 4 to 1. The results of this research suggest that the users of mobile fitness apps who share their workouts via Twitter have a lower Klout Score than the general Twitter user and that users who chose to share additional insights into their workouts are more positive in sentiment than negative. We present a novel perspective into the physical activity messaging from within mobile fitness apps that are then shared over Twitter. By moving beyond the numbers and evaluating both the Twitter user and the emotions tied to physical activity, future research could analyze additional relationships between the user's online influence, the enjoyment of the physical activity, and with additional analysis a long-term retention strategy for the use of a fitness app.


Interplay between the specific chaperone-like proteins HybG and HypC in maturation of hydrogenases 1, 2, and 3 from Escherichia coli.
The hybG gene product from Escherichia coli has been identified as a chaperone-like protein acting in the maturation of hydrogenases 1 and 2. It was shown that HybG forms a complex with the precursor of the large subunit of hydrogenase 2. As with HypC, which is the chaperone-like protein involved in hydrogenase 3 maturation, the N-terminal cysteine residue is crucial for complex formation. Introduction of a deletion into hybG abolished the generation of active hydrogenase 2 but only quantitatively reduced hydrogenase 1 activity since HypC could replace HybG in this function. In contrast, HybG could not take over the role of HypC in a DeltahypC genetic background. Overproduction of HybG, especially of the variants with the replaced N-terminal cysteine residue, strongly interfered with hydrogenase 3 maturation, apparently by titrating some other component(s) of the maturation machinery. The results indicate that the three hydrogenase isoenzymes not only are interacting at the functional level but are also interconnected during the maturation process.


17 Is the New 15: Changing Alcohol Consumption among Swedish Youth.
To examine and compare trends in drinking prevalence in nationally representative samples of Swedish 9th and 11th grade students between 2000 and 2018. A further aim is to compare drinking behaviours in the two age groups during years with similar drinking prevalence. Data were drawn from annual surveys of a nationally representative sample of students in year 9 (15-16 years old) and year 11 (17-18 years old). The data covered 19 years for year 9 and 16 years for year 11. Two reference years where the prevalence of drinking was similar were extracted for further comparison, 2018 for year 11 (n = 4878) and 2005 for year 9 (n = 5423). The reference years were compared with regard to the volume of drinking, heavy episodic drinking, having had an accident and quarrelling while drunk. The prevalence of drinking declined in both age groups during the study period. The rate of decline was somewhat higher among year 9 students. In 2018, the prevalence of drinking was the same for year 11 students as it was for year 9 students in 2005. The volume of drinking was lower among year 11 students in 2018 than year 9 students in 2005. No differences were observed for heavy episodic drinking. The decline in drinking has caused a displacement of consumption so that today's 17-18-year-olds have a similar drinking behaviour to what 15-16-year-olds had in 2005.


The effect of femtosecond laser capsulotomy on the development of posterior capsule opacification.
To evaluate and compare the effects of femtosecond laser-assisted anterior capsulotomy and manual anterior capsulorhexis on posterior capsule opacification (PCO) development. Femtosecond laser-assisted anterior capsulotomy was performed in 40 eyes of 40 patients (FS group) and manual anterior capsulorhexis was performed in 39 eyes of 39 patients (CCC group). An AcrySof one-piece hydrophobic acrylic intraocular lens (Alcon Laboratories, Inc., Fort Worth, TX) was implanted in all eyes. The PCO level was measured using Open-Access Systematic Capsule Assessment (OSCA) software 18 to 26 months after surgery. Postoperative intraocular lens position (ie, tilt and decentration) was measured using Scheimpflug images (Pentacam; Oculus Optikgeräte GmbH, Wetzlar, Germany). There was no statistically significant difference in age, axial length, and follow-up time between the two groups (P > .05). Vertical tilt, horizontal and total decentration of intraocular lenses, and PCO proved to be significantly higher in the CCC group (P = .03, .04, .03, and .01, respectively). After adjusting for axial length and follow-up time, manual anterior capsulorhexis was found to be a significant predictor of higher PCO scores in the multivariable regression model (β: 0.33; 95% CI: 0.01 to 0.65; P = .04). Vertical tilt affected PCO scores after adjusting for axial length and follow-up time (β: 0.07; 95% CI: 0.01 to 0.12; P = .02). No capsulotomies were performed during follow-up in either group. Femtosecond laser-assisted anterior capsulotomy proved to be a safe procedure for postoperative PCO rates. Due to better intraocular lens position, femtosecond laser-assisted anterior capsulotomy resulted in slightly decreased PCO scores; however, evaluating its clinical significance requires further studies.


A pea nuclear protein that is induced by dehydration belongs to the vicilin superfamily.
The purification to homogeneity of p16, a protein with an electrophoretic mobility compatible with an apparent molecular mass of 16 kDa, from nuclei of ungerminated pea embryonic axes is described. A cDNA clone of its gene, which was designated psp54, was also isolated. The psp54 cDNA contains an open reading frame coding for a 54.4-kDa polypeptide (p54). p16 corresponds to the C-terminal third of p54, although the mechanisms by which the primary polypeptide could be processed are not yet known. The sequence of p54 is 60% identical with that of the precursor of a sucrose-binding soybean protein, and, to a lesser extent (31-34%), it shares homology with some storage proteins. p16 is also 30% homologous with Nhp2p, a yeast nuclear protein. The psp54 gene, present in a single copy in pea genome, starts being expressed during seed desiccation. Soon after rehydration in seed germination, p54 mRNA disappears and is no longer detectable in vegetative tissues, except in response to hydric stress (exposure to abscisic acid, osmolites or desiccation). p16 can be recovered from nuclei cross-linked to histone H3, when the disulfide bridges that occur in vivo are preserved. On the other hand, p16 shares some properties with dehydrins, which are thought to protect cellular structures against desiccation. We propose that the possible precursor polypeptide p54 belongs to the vicilin superfamily, members of which play a variety of roles. The function of p16 may be related to the protection of chromatin structure against desiccation during seed development.


Infiltrating cell phenotypes and patterns associated with hepatic allograft rejection or acceptance.
The association of inflammatory cell infiltration with orthotopic rat liver transplant rejection was studied by immunopathologic evaluation of allografts at different time points using high- and low-responder strain combinations. PVG(RT-1c) recipients of ACI (RT-1a) liver transplants had prolonged survival (greater than 100 days) without immunosuppression. In contrast, Lewis (RT-1l) recipients of ACI liver transplants had severe acute rejection with mean survival of 10.7 +/- 0.5 days (n = 9). Graft recipients of both strain combinations, as well as control syngeneic PVG-to-PVG and Lewis-to-Lewis graft recipients were sacrificed at various time points posttransplant. Sections of livers were evaluated in a masked fashion for histologic changes as well as the extent and phenotype of cellular infiltrates, as determined by immunoperoxidase labeling using monoclonal antibodies OX1 (pan leukocyte), W3/13 (pan T cell), W3/25 (T helper cell:Th), and OX8 (T cytotoxic-suppressor:Tc-s). The results suggest that: the intensity and relative distribution of rat hepatic allograft T cell infiltrates at a given time point do not necessarily correlate with eventual outcome; the intensities of W3/25 (Th) and OX1 (pan-leukocyte) cell infiltrates parallel each other in both high- and low-responder strain combinations; the relative ratio of T cells (W3/13) to non-T cells increases over time in low-responder strains but remains relatively constant in high-responder strains during active rejection; and the relative ratio of W3/25:OX8 (Th:Tc-s) decreases in high-responder strains but increases in low-responder strains.


Use of multiple imputation in the epidemiologic literature.
The authors attempted to catalog the use of procedures to impute missing data in the epidemiologic literature and to determine the degree to which imputed results differed in practice from unimputed results. The full text of articles published in 2005 and 2006 in four leading epidemiologic journals was searched for the text imput. Sixteen articles utilizing multiple imputation, inverse probability weighting, or the expectation-maximization algorithm to impute missing data were found. The small number of relevant manuscripts and diversity of detail provided precluded systematic analysis of the use of imputation procedures. To form a bridge between current and future practice, the authors suggest details that should be included in articles that utilize these procedures.


Correlation between clinical indication for treatment and liver histology in HBeAg-negative chronic hepatitis B: a novel role of alpha-fetoprotein.
It is unclear whether clinical indication for antiviral treatment is in agreement with histological indication in HBeAg-negative chronic hepatitis B (CHB). This study aimed to clarify this relationship and identify factors associated with liver histology. We investigated 152 consecutive, treatment-naïve, HBeAg-negative CHB patients who had undergone liver biopsies at a tertiary medical centre in Taiwan. Clinical indications for treatment included a serum alanine aminotransferase level more than twice the upper limit of normal and an hepatitis B virus DNA level > 2000 IU/ml. Factors associated with the histological indication (Ishak's grade > or = 7 and/or stage > or = 2) were analysed. The association between the clinical and the histological indications was significant (P=0.011). However, the agreement was poor (kappa value=0.197). In patients satisfying the clinical indication, age > 52 years [odds ratio (OR)=2.669, P=0.042], serum alpha-fetoprotein (AFP) level > 7 ng/ml (OR=7.070, P<0.001) and platelet count < 130 x 10(9)/L (OR=11.720, P=0.025) were identified to be independent factors associated with histological indication. In patients who did not satisfy the clinical indication, multivariate analysis revealed that only an AFP level > 7 ng/ml (OR=10.345, P=0.021) was independently associated with histological indication. Combining the clinical indication and/or AFP level > 7 ng/ml to predict liver histology, the sensitivity and the negative predictive value could improve from 86 to 94.4% and 66.7 to 81% respectively. AFP level is associated with liver histology in HBeAg-negative CHB. Serum AFP level can serve as a surrogate indicator to identify patients who need antiviral treatment.


[Elevated lipid levels during pregnancy--what to do?].
Based on a clinical case we discuss the physiological changes in the lipid metabolism during pregnancy. The changes are characterised by a marked elevation of the total plasma cholesterol and the triglyceride levels. Usually there is no need for a specific therapy.


National Emphysema Treatment Trial: the major outcomes of lung volume reduction surgery in severe emphysema.
The National Emphysema Treatment Trial (NETT) has published many articles reporting the various outcomes of lung volume reduction surgery versus medical treatment for patients with severe emphysema. However, long and complex clinical trials like NETT that involve both medical and surgical issues generate multiple manuscripts over a period of years and report an array of various outcomes. As a result, the essential findings of the trial may appear to be fragmented to the clinician or clinical researcher or be lost among the many medical reports published each year. In this review, we summarize in one publication the major medical and surgical outcomes of NETT.


Beyond communication: the development of a training program for hospital and hospice staff in the detection and management of psychological distress--preliminary results.
In the United Kingdom, a Four-Tier Model of Psychological Support has been recommended for all patients with cancer and their families. This model suggests that staff at Tier 2, such as nurses, doctors, and allied health professionals, should be proficient in screening for psychological distress and intervening with techniques such as psycho-education and problem solving. Research has suggested that although communication skills training is essential for staff working in cancer services, it does not necessarily improve the detection of specific psychological disorder or staff confidence in intervening with highly distressed patients. The objective was therefore to design a training program that addressed this deficit and was easily accessible to hospital staff. A training package was developed to train staff in the recommended skills. A literature review of teaching modalities and the effectiveness of different formats was conducted. A four-session program was developed, to be administered by staff at Tiers 3 and 4 of the model, such as clinical psychologists and counsellors. Over 3 years, 255 sets of data were collected from staff who attended the course. Precourse, postcourse, and 6-month follow-up data were collected through the use of confidence questionnaires, developed from the literature. The data show a significant improvement in staff confidence across all domains measured, including confidence in the detection and management of psychological distress (p =.0001). Although the results have limitations and the data are subjective, we can conclude that this course significantly improves staff confidence in dealing with psychological distress and that this increased confidence is maintained over a 6-month follow-up period.


Fungal xylanases-mediated synthesis of silver nanoparticles for catalytic and biomedical applications.
Green synthesis of nanoparticles has fuelled the use of biomaterials to synthesise a variety of metallic nanoparticles. The current study investigates the use of xylanases of Aspergillus niger L3 (NEA) and Trichoderma longibrachiatum L2 (TEA) to synthesise silver nanoparticles (AgNPs). Characterisation of AgNPs was carried out using UV-Vis spectroscopy, Fourier transform infrared spectroscopy (FTIR), and transmission electron microscopy, while their effectiveness as antimicrobial, antioxidant, catalytic, anticoagulant, and thrombolytic agents were determined. The colloidal AgNPs was brownish with surface plasmon resonance at 402.5 and 410 nm for NEA-AgNPs and TEA-AgNPs, respectively; while FTIR indicated that protein molecules were responsible for the capping and stabilisation of the nanoparticles. The spherical nanoparticles had size of 15.21-77.49 nm. The nanoparticles significantly inhibited the growth of tested bacteria (63.20-88.10%) and fungi (82.20-86.10%), and also scavenged DPPH (37.48-79.42%) and hydrogen peroxide (20.50-96.50%). In addition, the AgNPs degraded malachite green (78.97%) and methylene blue (25.30%). Furthermore, the AgNPs displayed excellent anticoagulant and thrombolytic activities using human blood. This study has demonstrated the potential of xylanases to synthesise AgNPs which is to the best of our knowledge the first record of such. The present study underscores the relevance of xylanases in nanobiotechnology.


Multiplexed single-cell 3D spatial gene expression analysis in plant tissue using PHYTOMap.
Retrieving the complex responses of individual cells in the native three-dimensional tissue context is crucial for a complete understanding of tissue functions. Here, we present PHYTOMap (plant hybridization-based targeted observation of gene expression map), a multiplexed fluorescence in situ hybridization method that enables single-cell and spatial analysis of gene expression in whole-mount plant tissue in a transgene-free manner and at low cost. We applied PHYTOMap to simultaneously analyse 28 cell-type marker genes in Arabidopsis roots and successfully identified major cell types, demonstrating that our method can substantially accelerate the spatial mapping of marker genes defined in single-cell RNA-sequencing datasets in complex plant tissue.


Determining optimal dosing regimen of oral administration of dicloxacillin using Monte Carlo simulation.
Dicloxacillin, a semisynthetic isoxazolyl penicillin, exhibits antimicrobial activity against a wide variety of Gram-positive bacteria, as well as stability against penicillinases and low level of toxicity. The objective of this study was to obtain optimal dosing regimen of oral administration of dicloxacillin by analyzing the pharmacokinetic (PK) index in healthy volunteers and in vitro antibacterial activity by using Monte Carlo simulation. A total of 867 clinical isolates from community-onset infections were collected from 31 secondary hospitals in People's Republic of China. The minimum inhibitory concentration (MIC) values of dicloxacillin were determined by the agar dilution method. Based on the MICs and the PK parameters of different dosage regimens, Monte Carlo simulation was performed to simulate the PK/pharmacodynamic indices of 250 mg once-daily (qd), 500 mg qd, 1,000 mg qd, 2,000 mg qd, 250 mg every 6 hours (q6h), and 500 mg q6h, respectively. The probability of target attainment was estimated at each MIC value, and the cumulative fraction of response (CFR) was calculated to evaluate the efficacy of these regimens. Dicloxacillin showed poor antibacterial activity against Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae. Resistance to dicloxacillin was observed in 7.5% of coagulase-negative Staphylococcus (CNS) isolates and 9.2% of other Streptococcus isolates, whereas 1.5% of methicillin-sensitive Staphylococcus aureus (MSSA) was resistant to dicloxacillin. Multiple-dose regimens could obtain higher CFR than single-dose regimens against H. influenza and S. pneumoniae. However, all dosing regimens against MSSA achieved CFR ≥$90%. Meanwhile, dosing regimen of 2,000 mg qd, 250 mg q6h, and 500 mg q6h could achieve >90% of CFR for CNS. For other Streptococcus isolates, multiple-dose regimens achieved CFR ≥90%. Dicloxacillin has a significant antibacterial activity against MSSA, CNS, and other Streptococcus isolates. The simulation results suggest that dicloxacillin 250 mg q6h and 500 mg q6h dosing regimens may be recommended for clinical applications, especially for community-onset infections.


Antagonist of nucleolin, N6L, inhibits neovascularization in mouse models of retinopathies.
Retinal vascular diseases (RVD) have been identified as a major cause of blindness worldwide. These pathologies, including the wet form of age-related macular degeneration, retinopathy of prematurity, and diabetic retinopathy are currently treated by intravitreal delivery of anti-vascular endothelial growth factor (VEGF) agents. However, repeated intravitreal injections can lead to ocular complications and resistance to these treatments. Thus, there is a need to find new targeted therapies. Nucleolin regulates the endothelial cell (EC) activation and angiogenesis. In previous studies, we designed a pseudopeptide, N6L, that binds the nucleolin and blocks the tumor angiogenesis. In this study, the effect of N6L was investigated in two experimental models of retinopathies including oxygen-induced retinopathy (OIR) and choroidal neovascularization (CNV). We found that in mouse OIR, intraperitoneal injection of N6L is delivered to activated ECs and induced a 50% reduction of pathological neovascularization. The anti-angiogenic effect of N6L has been tested in CNV model in which the systemic injection of N6L induced a 33% reduction of angiogenesis. This effect is comparable to those obtained with VEGF-trap, a standard of care drug for RVD. Interestingly, with preventive and curative treatments, neoangiogenesis is inhibited by 59%. Our results have potential interest in the development of new therapies targeting other molecules than VEGF for RVD.


Sleep apnoea and sleep breathing disorders.
Sleep apnoea and related sleep breathing disorders are a major cause of medical, social and occupational disability. Excessive sleepiness may be associated with respiratory failure, obesity, hypertension and insulin resistance in the cardiometabolic syndrome. This article reviews practical assessment and management.


Taekwondo coaches knowledge about prevention and management of dental trauma.
The aim of this study was to assess level of knowledge about prevention and dental trauma management among taekwondo coaches in Croatia. The questionnaire submitted to the taekwondo coaches contained 16 items about dental trauma prevention and management. The questionnaires were filled in by 131 taekwondo coaches; 28 females and 103 males. Descriptive statistics was used to describe and analyze the obtained data. The coaches were familiar with dental injuries in high percentage: 41 (31.3%) have observed dental injury and 36 (27.5%) have experienced a dental injury themselves. Eight of them had tooth avulsion, fourteen crown fracture, and eight had tooth luxation. About half of all interviewed coaches 68 (52.7%) were aware of the possibility of replanting avulsed teeth. Twenty six (19.8%) were familiar with the tooth rescue kit. Only 99 out of 131 coaches (75.6%) have used a mouthguard. The obtained results show low knowledge about possibilities for prevention of dental trauma. Insufficient use of mouthguards in this contact sport requires more attention of dentists and coaches education about dental trauma prevention.


Acetoin is a key odor for resource location in the giant robber crab Birgus latro.
The terrestrial and omnivorous robber crab Birgus latro inhabits islands of the Indian Ocean and the Pacific Ocean. The animals live solitarily but occasionally gather at freshly opened coconuts or fructiferous arenga palms. By analyzing volatiles of coconuts and arenga fruit, we identified five compounds, including acetoin, which are present in both food sources. In a behavioral screen performed in the crabs' habitat, a beach on Christmas Island, we found that of 15 tested fruit compounds, acetoin was the only volatile eliciting significant attraction. Hence, acetoin might play a key role in governing the crabs' aggregation behavior at both food sources.


Differences in Protein Expression between the U251 and U87 Cell Lines.
The U251 and U87 cell lines are commonly used as experimental models of glioblastoma. However, these cells exhibit significant differences in their proliferation, invasion, and migration. The aim of the present study was to compare the protein expression profiles of the U251 and U87 cell lines in order to provide a molecular basis for the observed phenotypic differences. Isobaric tags for relative and absolute quantitation (iTRAQ) and gene ontology (GO) analyses were performed to detect differentially expressed proteins and to predict protein functions, respectively. Two hundred and forty-four proteins were highly expressed, while 263 proteins exhibited lower levels of expression, in the U251 cells compared to the U87 cells. In particular, higher expression levels of the proteins, C10orf58, FLNC, PDLIM1, TPM4, and lower expression levels of MYH10, PSIP1, SYNM, SLC9A3R2, BCAM, were verified by qPCR in the U251 cell line versus the U87 cell line. When a GO analysis was applied to the iTRAQ results, the proteins that were highly expressed in the U251 cells were found to differ in their molecular functions, biological processes, cellular distribution, and cellular pathways associated with them compared with the highly expressed proteins detected in the U87 cells. Differentially expressed proteins between the U251 and U87 cell lines are associated with regulation of nicotinamide nucleotide metabolism, RNA splicing, glycolysis, and purine metabolism pathways. Further studies on these pathways may identify whether these various pathways account for the observed phenotype differences between the U87 and U251 GBM cell lines.


Overexpression of the mouse dishevelled-1 protein inhibits GSK-3beta-mediated phosphorylation of tau in transfected mammalian cells.
Tau is a neuronal microtubule-associated protein whose function is modulated by phosphorylation. GSK-3beta is a tau kinase. GSK-3beta is part of the wingless signalling pathway and stimulation by wingless is predicted to down-regulate GSK-3beta activity. In Drosophila imaginal disc cells, overexpression of dishevelled, a component of the wingless pathway, mimics the wingless signal. We have therefore studied the effect that overexpression of the murine dishevelled-1 protein has on GSK-3beta-mediated phosphorylation of tau in transfected CHO cells. We find that co-transfection with dishevelled-1 is inhibitory to GSK-3beta-mediated tau phosphorylation. Tau is hyperphosphorylated in Alzheimer's disease and the possible relevance of these findings to Alzheimer's disease pathogenesis are discussed.


Myeloid differentiated HL-60 cells display specific leukotriene B4 binding sites.
Exposure of HL-60 cells for 6 days to a combination of 1.25% (v/v) dimethyl sulfoxide (DMSO) and 10 microM dexamethasone (DEX) induces myeloid differentiation which results in a cell with many of the characteristics of a mature granulocyte. At 4 degrees C myeloid differentiated, but not undifferentiated, monocytic differentiated or eosinophilic differentiated HL-60 cells display marked specific leukotriene B4 binding. Leukotriene B4 binding at 4 degrees C reaches a maximum within 10 min, is readily reversed by unlabelled leukotriene B4, and is stereospecific. Only molecules with structural and biological similarity to leukotriene B4 can competitively inhibit leukotriene B4 binding. Scatchard analysis at 4 degrees C in differentiated cells shows two classes of binding sites. The high affinity sites have a Kd of 0.27 nM and a Bmax of 14.8 fmoles/10(7) cells; the low affinity sites have a Kd of 0.58 microM and a Bmax of 2453 fmoles/10(7) cells. The appearance of specific leukotriene B4 binding sites in the myeloid differentiated cells correlates with their ability to chemotax in response to leukotriene B4. Undifferentiated cells do not chemotax to leukotriene B4. At 37 degrees C leukotriene B4 is incorporated into phospholipid and triglyceride species in both undifferentiated and myeloid differentiated HL-60 cells making binding studies at 37 degrees C in intact cells impossible. Interestingly, incubation of the cells with cyclooxygenase inhibitors during differentiation enhances receptor density. No evidence of omega-hydroxylase activity was found in HL-60 cells. These data suggest that the HL-60 cell may be an excellent model system for the study of leukotriene B4 receptor binding, processing and gene expression.


Ordered kinetochore assembly in the human-pathogenic basidiomycetous yeast Cryptococcus neoformans.
Kinetochores facilitate interaction between chromosomes and the spindle apparatus. The formation of a metazoan trilayered kinetochore is an ordered event in which inner, middle, and outer layers assemble during disassembly of the nuclear envelope during mitosis. The existence of a similar strong correlation between kinetochore assembly and nuclear envelope breakdown in unicellular eukaryotes is unclear. Studies in the hemiascomycetous budding yeasts Saccharomyces cerevisiae and Candida albicans suggest that an ordered kinetochore assembly may not be evolutionarily conserved. Here, we utilized high-resolution time-lapse microscopy to analyze the localization patterns of a series of putative kinetochore proteins in the basidiomycetous budding yeast Cryptococcus neoformans, a human pathogen. Strikingly, similar to most metazoa but atypical of yeasts, the centromeres are not clustered but positioned adjacent to the nuclear envelope in premitotic C. neoformans cells. The centromeres gradually coalesce to a single cluster as cells progress toward mitosis. The mitotic clustering of centromeres seems to be dependent on the integrity of the mitotic spindle. To study the dynamics of the nuclear envelope, we followed the localization of two marker proteins, Ndc1 and Nup107. Fluorescence microscopy of the nuclear envelope and components of the kinetochore, along with ultrastructure analysis by transmission electron microscopy, reveal that in C. neoformans, the kinetochore assembles in an ordered manner prior to mitosis in concert with a partial opening of the nuclear envelope. Taken together, the results of this study demonstrate that kinetochore dynamics in C. neoformans is reminiscent of that of metazoans and shed new light on the evolution of mitosis in eukaryotes. Successful propagation of genetic material in progeny is essential for the survival of any organism. A proper kinetochore-microtubule interaction is crucial for high-fidelity chromosome segregation. An error in this process can lead to loss or gain of chromosomes, a common feature of most solid cancers. Several proteins assemble on centromere DNA to form a kinetochore. However, significant differences in the process of kinetochore assembly exist between unicellular yeasts and multicellular metaozoa. Here, we examined the key events that lead to formation of a proper kinetochore in a basidiomycetous budding yeast, Cryptococcus neoformans. We found that, during the progression of the cell cycle, nonclustered centromeres gradually clustered and kinetochores assembled in an ordered manner concomitant with partial opening of the nuclear envelope in this organism. These events have higher similarity to mitotic events of metazoans than to those previously described in other yeasts.


Drosophila Fezf coordinates laminar-specific connectivity through cell-intrinsic and cell-extrinsic mechanisms.
Laminar arrangement of neural connections is a fundamental feature of neural circuit organization. Identifying mechanisms that coordinate neural connections within correct layers is thus vital for understanding how neural circuits are assembled. In the medulla of the Drosophila visual system neurons form connections within ten parallel layers. The M3 layer receives input from two neuron types that sequentially innervate M3 during development. Here we show that M3-specific innervation by both neurons is coordinated by Drosophila Fezf (dFezf), a conserved transcription factor that is selectively expressed by the earlier targeting input neuron. In this cell, dFezf instructs layer specificity and activates the expression of a secreted molecule (Netrin) that regulates the layer specificity of the other input neuron. We propose that employment of transcriptional modules that cell-intrinsically target neurons to specific layers, and cell-extrinsically recruit other neurons is a general mechanism for building layered networks of neural connections.


Tissue-specific and developmentally regulated expression of a cluster of tandemly arrayed cell wall-associated kinase-like kinase genes in Arabidopsis.
The Arabidopsis cell wall-associated kinase (WAK) and WAK-like kinase (WAKL) family of receptor-like kinase genes encodes transmembrane proteins with a cytoplasmic serine/threonine kinase domain and an extracellular region containing epidermal growth factor-like repeats. Previous studies have suggested that some WAK members are involved in plant defense and heavy metal responses, whereas others are required for cell elongation and plant development. The WAK/WAKL gene family consists of 26 members in Arabidopsis and can be divided into four groups. Here, we describe the characterization of group 2 members that are composed of a cluster of seven tandemly arrayed WAKL genes. The predicted WAKL proteins are highly similar in their cytoplasmic region but are more divergent in their predicted extracellular ligand-binding region. WAKL7 encodes a truncated WAKL isoform that is predicted to be secreted from the cytoplasm. Ratios of nonsynonymous to synonymous substitutions suggest that the extracellular region is subject to diversifying selection. Comparison of the WAKL and WAK gene clusters suggests that they arose independently. Protein gel-blot and immunolocalization analyses suggest that WAKL6 is associated with the cell wall. Histochemical analyses of WAKL promoters fused with the beta-glucuronidase reporter gene have shown that the expressions of WAKL members are developmentally regulated and tissue specific. Unlike WAK members whose expressions were found predominately in green tissues, WAKL genes are highly expressed in roots and flowers. The expression of WAKL5 and WAKL7 can be induced by wounding stress and by the salicylic acid analog 2,6-dichloroisonicotinic acid in an nonexpressor of pathogenesis-related gene 1-dependent manner, suggesting that they, like some WAK members, are wound inducible and can be defined as pathogenesis-related genes.


Intraocular Pressure Measurements by Three Different Tonometers in Children with Aphakic Glaucoma and a Thick Cornea.
To evaluate the agreement in intraocular pressure (IOP) measurements by Ocular Response Analyzer (ORA) and Tono-Pen XL (TXL) with the Goldmann Applanation Tonometer (GAT) and to examine corneal biomechanical properties in aphakic glaucoma patients with a central corneal thickness (CCT) >600 µ. Thirty-six eyes of aphakic glaucoma patients (group 1) and 40 eyes of normal children (group 2) were studied. The mean ORA and TXL IOP values were compared with the GAT-IOP values. Regression analyses were used to evaluate the associations between IOP and CCT, corneal hysteresis (CH), and corneal resistance factor (CRF). Bland-Altman plots were used to evaluate the agreement between the tonometers. The mean±standard deviations of the age and male/female ratio were 16.58±5.44 and 15.75±5.04 years and 14/22 and 18/22 in group 1 and group 2, respectively. CCT in group 1 was 651.1±42 and in group 2 was 567.3±32.4. In group 1, the mean TXL (22.4, P=0.004), IOPcc (corneal compensated) (27.8, P=0.005), and IOPg (Goldmann correlated) values (28.1, P<0.0001) were greater than GAT-IOP (20.6). In group 2, only IOPg value (16.4) was higher than GAT-IOP (14.8, P=0.04). IOP reading of all the tonometers were positively and negatively associated with CRF and CH in the multiple regression analysis, respectively. The TXL had a greater agreement with the GAT, and the ORA overestimated IOP in aphakic glaucoma patients. The ORA and TXL seemed to be affected by CH and CRF.


Asian management of hypertension: Current status, home blood pressure, and specific concerns in Korea.
Hypertension is present in almost one-quarter of women and one-third of men in Korea. Although mortality rates from stroke and myocardial infarction (MI) appear to be decreasing, stroke is a more common cause of cardiovascular death than MI. This may be due to better control of hypertension, but national control rates have remained stable for more than a decade (at about 45%). Korean Society of Hypertension guidelines have recommended the use of home blood pressure monitoring (HBPM) since 2007, but a recent survey suggests that physicians have concerns about the accuracy of HBPM devices. Nevertheless, use of HBPM is indispensable to monitoring and achieving blood pressure (BP) control. Current diagnostic and treatment thresholds and recommendations are based on Asian consensus document guidance. Use of dual combination antihypertensive therapy is slightly more common than use of monotherapy in Korea, while triple combination therapy is used less often. Angiotensin receptor blockers and calcium channel blockers are the most popular choices for antihypertensive therapy and are the most widely used combination. HBPM plays an important role in evaluating and monitoring BP, particularly in Asians. Individualized cardiovascular risk assessment and better BP control are required to prevent cardiovascular diseases, but there is a need for local evidence relating to optimal BP thresholds and targets.


Limited root repair in acute type A aortic dissection is safe but results in increased risk of reoperation.
Management of the aortic root is a challenge for surgeons treating acute type A aortic dissection. We performed a retrospective review of the acute type A aortic dissection experience at Stanford Hospital between 2005 and 2015 and identified patients who underwent either limited root repair or aortic root replacement. Differences in baseline characteristics were balanced with inverse probability weighting to estimate the average treatment effect on the controls. Weighted logistic regression was used to evaluate in-hospital mortality. Weighted Cox proportional hazards regression was used to evaluate differences in the hazard for mid-term death. Reoperation was evaluated with death as a competing risk with the Fine-Gray subdistribution hazard. After we excluded patients managed either nonoperatively or with definitive endovascular repair, there were 293 patients without connective tissue disease who underwent either limited root repair or aortic root replacement. There was no difference in weighted perioperative mortality, odds ratio 0.89 (95% confidence interval [CI], 0.44-1.76, P = .7), and there was no difference in weighted survival, hazard ratio 1.12 (95% CI, 0.54-2.31, P = .8). Risk of reoperation was greater in limited root repair (11.8%, 95% CI, 0.0%-23.8%) than for root replacement (0%), P < .001. Limited root repair was associated with increased risk of late reoperation after repair of acute type A aortic dissection. Surgeons with adequate experience may consider aortic root replacement in well-selected patients. However, given good outcomes after limited root repair, surgeons should not feel compelled to perform this more-complex operation.


Identification and molecular modelling of a mutation in the motor head domain of myosin VIIA in a family with autosomal dominant hearing impairment (DFNA11).
Myosin VIIA is an unconventional myosin that has been implicated in Usher syndrome type 1B, atypical Usher syndrome, non-syndromic autosomal recessive hearing impairment (DFNB2) and autosomal dominant hearing impairment (DFNA11). Here, we present a family with non-syndromic autosomal dominant hearing impairment that clinically resembles the previously published DFNA11 family. The affected family members show a flat audiogram at young ages and only modest progression, most clearly at the high frequencies. In addition, they suffer from minor vestibular symptoms. Linkage analysis yielded a maximum two-point lodscore of 3.43 for marker D11S937 located within 1 cM of the myosin VIIA gene. The myosin VIIA gene was sequenced and 11 nucleotide variations were found. Ten nucleotide changes represent benign intronic variants, silent exon mutations or non-pathologic amino acid substitutions. One variant, a c.1373A-->T transversion that is heterozygously present in all affected family members and absent in 300 healthy individuals, is predicted to result in an Asn458Ile amino acid substitution. Asn458 is located in a region of the myosin VIIA motor domain that is highly conserved in different classes of myosins and in myosins of different species. To evaluate whether the Asn458Ile mutation was indeed responsible for the hearing impairment, a molecular model of myosin VIIA was built based on the known structure of the myosin II heavy chain from Dictyostelium discoideum. In this model, conformational changes in the protein caused by the amino acid substitution Asn458Ile are predicted to disrupt ATP/ADP binding and impair the myosin power-stroke, which would have a severe effect on the function of the myosin VIIA protein.


Lithium diisopropylamide-mediated lithiations of imines: insights into highly structure-dependent rates and selectivities.
Lithium diisopropylamide-mediated lithiations of N-alkyl ketimines derived from cyclohexanones reveal that simple substitutions on the N-alkyl side chain and the 2-position of the cyclohexyl moiety afford a 60,000-fold range of rates. Detailed rate studies implicate monosolvated monomers at the rate-limiting transition structures in all instances. Comparisons of experimentally derived regioselectivities and rates, taken in conjunction with density functional theory computational studies, reveal a number of factors that influence reactivities including: (a) axial versus equatorial disposition of the proton on the cyclohexane ring, (b) syn versus anti orientation of the lithiation relative to the N-alkyl group, (c) the presence or absence of a potentially chelating methoxy moiety on the N-alkyl group, (d) the presence of a 2-methyl substituent at the geminal or distal alpha-carbon, and (e) branching in the N-alkyl group. The isolated contributions are not large, yet they display a strong and predictable additivity leading to a kinetic resolution of imines derived from racemic 2-methylcyclohexanone.


The Landscape of Non-Coding RNA in an Adult Pig Model of Intrauterine Growth Restriction.
Intrauterine growth restriction (IUGR) is a risk factor for adult metabolic syndrome, but how this disease is regulated by lncRNAs and circRNAs remains elusive. Here, we employed adult IUGR and normal pigs as models to evaluate the expression of various global lncRNAs and circRNAs in pig livers using RNA-seq. In total, we obtained 1,162 million raw reads of approximately 104.54 Gb high quality data. After a strict five-step filtering process, 3,368 lncRNAs were identified, including 300 differentially expressed lncRNAs (p < 0.05) in the IUGR group relative to the control group. The cis-regulatory analysis identified target genes that were enriched in specific GO terms and pathways (p < 0.05), including amino acid metabolism, oxidoreductase activity, PPAR signaling pathway, and insulin signaling pathway. These are closely related to the observed phenotypes of increased gluconeogenesis and impaired mitochondrial oxidative phosphorylation in adulthood of the IUGR group. Additionally, we also identified 403 circRNAs, of which 44 were differentially expressed (p < 0.05). Interestingly, our results identified ATF4-miR214-circRNA7964 and TCF7-miR22-3p-circRNA16347 as two competing endogenous networks, which were closely associated with the observed increase in hepatic gluconeogenesis in the IUGR group. Together, this study reveals a multitude of candidate lncRNAs and circRNAs involved in the development of IUGR pigs, which could facilitate further researches on the molecular mechanisms of metabolic syndrome.


Interaction of tau with HNRNPA2B1 and N6-methyladenosine RNA mediates the progression of tauopathy.
The microtubule-associated protein tau oligomerizes, but the actions of oligomeric tau (oTau) are unknown. We have used Cry2-based optogenetics to induce tau oligomers (oTau-c). Optical induction of oTau-c elicits tau phosphorylation, aggregation, and a translational stress response that includes stress granules and reduced protein synthesis. Proteomic analysis identifies HNRNPA2B1 as a principle target of oTau-c. The association of HNRNPA2B1 with endogenous oTau was verified in neurons, animal models, and human Alzheimer brain tissues. Mechanistic studies demonstrate that HNRNPA2B1 functions as a linker, connecting oTau with N6-methyladenosine (m6A) modified RNA transcripts. Knockdown of HNRNPA2B1 prevents oTau or oTau-c from associating with m6A or from reducing protein synthesis and reduces oTau-induced neurodegeneration. Levels of m6A and the m6A-oTau-HNRNPA2B1 complex are increased up to 5-fold in the brains of Alzheimer subjects and P301S tau mice. These results reveal a complex containing oTau, HNRNPA2B1, and m6A that contributes to the integrated stress response of oTau.


[Effect of the unsaponifiables of the most common edible oils on the development of E. coli bacteria].
The writers within the context of the research on the biological actions of the unsaponificables in the most common edible oils, have tested the effects produced by such unsaponificables on the culture of E. Coli. The unsaponificables, and those of seed oils of peanuts and sunflowers in particular, aid the doubling of the E. Coli. Similar research on the culture of animal cells (in vitro) and unicellular algae, are at present outstanding.


Total laparoscopic hysterectomy: body mass index and outcomes.
This retrospective review of patients undergoing total laparoscopic hysterectomy examines whether differences in outcomes exist on the basis of body mass index (BMI). All cases of total laparoscopic hysterectomy performed from September 1996 to July 2002 for benign diagnoses, and microinvasive cervical, early endometrial, and occult ovarian carcinoma were reviewed. There were 330 patients analyzed by BMI category (range, 18.5-54.1): ideal (n = 150) less than 24.9 kg/m(2), overweight (n = 95) 25 to 29.9 kg/m(2), and obese (n = 78) 30 kg/m(2) or more. Seven patients were converted to laparotomy (four ideal BMI, two overweight, one obese) leaving 323 (98%) for analysis. Mean age (50 years), height (65 in.), and parity (1.2) were similar, with 39% nulligravidas in each group. Mean operating time (156 minutes), blood loss (160 mL), and length of hospital stay (1.9 days) did not vary by BMI group. Total complication rates (8.9%), and major (5.5%) and minor (3.4%) complication rates were similar in each BMI group. Urologic injury was observed in 3.1%, with two-thirds occurring in the first one-third of the patient series. Total laparoscopic hysterectomy is feasible and safe, resulting in short hospital stay, minimal blood loss, and minimal operating time for patients in all BMI groups. The laparoscopic approach may extend the benefits of minimally invasive hysterectomy to the very obese, for whom abdominal surgery poses serious risk.


Lattice dynamics of the icosahedral quasicrystals i-ZnMgSc and i-ZnAgSc and the cubic 1/1-approximant Zn6Sc.
A comparison of periodic approximants and their quasicrystalline counterparts offers the opportunity to better understand the structure, physical properties and stabilizing mechanisms of these complex phases. We present a combined experimental and computational study of the lattice dynamics of the icosahedral quasicrystals i-ZnMgSc and i-ZnAgSc and compare these to the lattice dynamics of the cubic 1/1-approximant Zn6Sc. The two phases, quasicrystal and approximant, are built up from the same atomic clusters, which are packed either quasiperiodically or on a body centered cubic lattice, respectively. Using inelastic neutron scattering and atomic scale simulations, we show that the vibrational spectra of these three systems are very similar, however, they contain a clear signature of the increasing structural complexity from approximant to quasicrystal.


Association between regional brain volumes and BMI z-score change over one year in children.
Associations between brain region volume and weight status have been observed in children cross-sectionally. However, it is unclear if differences in brain region volume precede weight gain. Two high-quality structural brain images were obtained approximately one year apart in 53 children aged 9-12 years old. Children's height and weight were also measured at each scan. Structural images were processed using the FreeSurfer software-package providing volume measures for regions of interest including the entorhinal cortex, nucleus accumbens, and hippocampus. Age- and sex-adjusted BMI z-scores (BMIz) were calculated at both timepoints. The association between brain region volume and BMIz was examined cross-sectionally using linear regression and longitudinally using structural equation modeling. All models were adjusted by estimated cranial volume to account for individual variation in head size and were corrected for multiple comparisons (pFDR<0.05). The sample of children was primarily healthy weight at baseline (79.78%). Cross-sectionally at the one-year follow-up, a positive relationship was observed between right hippocampal volume and BMIz (β = 0.43, 95% CI = (0.10, 0.77)). Longitudinally a negative relationship was observed between right entorhinal volume at baseline and BMIz at the one-year follow-up (β = -0.25, 95% CI = (-0.44, -0.07)). These results suggest that measured volumes from certain regions of the brain that have been associated with BMI in adults are associated with both concurrent BMIz and BMIz change over one-year in a primarily healthy weight sample of children. As the entorhinal cortex integrates signals from both reward and control regions, this region may be particularly important to weight management during child development.


Selection of CMV-specific CD8+ and CD4+ T cells by mini-EBV-transformed B cell lines.
Efficient protocols to generate cytomegalovirus (CMV)-specific T cells are required for adoptive immunotherapy. Recombinant Epstein-Barr virus (EBV) vectors called mini-EBV can be used to establish permanent B cell lines in a single step, which present the CMV antigen pp65 in a constitutive manner. These B cell lines, coined pp65 mini-LCL, were successfully used to reactivate and expand CMV-specific cytotoxic T cells. Here we evaluate this pp65 mini-EBV system in closer detail, focusing on (1) the quantification of T cells with specific effector function and (2) the identification of CMV-specific CD4(+) helper T cells. The co-expansion of various functional CMV epitope specificities was demonstrated by IFN-gamma enzyme-linked immunospot assay (ELISPOT) assays and HLA-peptide tetramer staining. Single-cell cloning resulted in both CD4(+) and CD8(+) T cell clones, the majority of which was CMV specific. Thus, mini-LCL present the pp65 antigen on HLA class I and II, mobilizing both arms of the T cell response. Using a peptide library covering the pp65 sequence for further analysis of T cell clones, we identified new pp65 CD8(+) and CD4(+) T cell epitopes.


The effect of pyrite on Escherichia coli in water: proof-of-concept for the elimination of waterborne bacteria by reactive minerals.
We present proof-of-concept results for the elimination of waterborne bacteria by reactive minerals. We exposed Escherichia coli MG1655 suspended in water to the reactive mineral pyrite (FeS₂) at room temperature and ambient light. This slurry eliminates 99.9% of bacteria in fewer than 4 hours. We also exposed Escherichia coli to pyrite leachate (supernatant liquid from slurry after 24 hours), which eliminates 99.99% of bacteria over the same time-scale. Unlike SOlar water DISinfection (SODIS), our results do not depend on the presence of ultraviolet (UV) light. We confirmed this by testing proposed SODIS additive and known photo-catalyst anatase (TiO₂) for antibacterial properties and found that, in contrast to pyrite, it does not eliminate E. coli under our experimental conditions. Previous investigations of naturally antibiotic minerals have focused on the medical applications of antibiotic clays, and thus have not been conducted under experimental conditions resembling those found in water purification. In our examination of the relevant literature, we have not found previously reported evidence for the use of reactive minerals in water sanitization. The results from this proof-of-concept experiment may have important implications for future directions in household water purification research.


Changes in motoneuron afterhyperpolarization duration in stroke survivors.
Hemispheric brain injury resulting from a stroke is often accompanied by muscle weakness in limbs contralateral to the lesion. In the present study, we investigated whether weakness in contralesional hand muscle in stroke survivors is partially attributable to alterations in motor unit activation, including alterations in firing rate modulation range. The afterhyperpolarization (AHP) potential of a motoneuron is a primary determinant of motoneuron firing rate. We examined differences in AHP duration in motoneurons innervating paretic and less impaired (contralateral) limb muscles of hemiparetic stroke survivors as well as in control subjects. A novel surface EMG (sEMG) electrode was used to record motor units from the first dorsal interosseous muscle. The sEMG data were subsequently decomposed to derive single-motor unit events, which were then utilized to produce interval (ISI) histograms of the motoneuron discharges. A modified version of interval death rate (IDR) analysis was used to estimate AHP duration. Results from data analyses performed on both arms of 11 stroke subjects and in 7 age-matched control subjects suggest that AHP duration is significantly longer for motor units innervating paretic muscle compared with units in contralateral muscles and in units of intact subjects. These results were supported by a coefficient of variation (CV) analysis showing that paretic motor unit discharges have a lower CV than either contralateral or control units. This study suggests that after stroke biophysical changes occur at the motoneuron level, potentially contributing to lower firing rates and potentially leading to less efficient force production in paretic muscles.