Tai Chi and vestibular rehabilitation improve vestibulopathic gait via different neuromuscular mechanisms: preliminary report.
Vestibular rehabilitation (VR) is a well-accepted exercise program intended to remedy balance impairment caused by damage to the peripheral vestibular system. Alternative therapies, such as Tai Chi (TC), have recently gained popularity as a treatment for balance impairment. Although VR and TC can benefit people with vestibulopathy, the degree to which gait improvements may be related to neuromuscular adaptations of the lower extremities for the two different therapies are unknown. We examined the relationship between lower extremity neuromuscular function and trunk control in 36 older adults with vestibulopathy, randomized to 10 weeks of either VR or TC exercise. Time-distance measures (gait speed, step length, stance duration and step width), lower extremity sagittal plane mechanical energy expenditures (MEE), and trunk sagittal and frontal plane kinematics (peak and range of linear and angular velocity), were measured. Although gait time-distance measures were improved in both groups following treatment, no significant between-groups differences were observed for the MEE and trunk kinematic measures. Significant within groups changes, however, were observed. The TC group significantly increased ankle MEE contribution and decreased hip MEE contribution to total leg MEE, while no significant changes were found within the VR group. The TC group exhibited a positive relationship between change in leg MEE and change in trunk velocity peak and range, while the VR group exhibited a negative relationship. Gait function improved in both groups consistent with expectations of the interventions. Differences in each group's response to therapy appear to suggest that improved gait function may be due to different neuromuscular adaptations resulting from the different interventions. The TC group's improvements were associated with reorganized lower extremity neuromuscular patterns, which appear to promote a faster gait and reduced excessive hip compensation. The VR group's improvements, however, were not the result of lower extremity neuromuscular pattern changes. Lower-extremity MEE increases corresponded to attenuated forward trunk linear and angular movement in the VR group, suggesting better control of upper body motion to minimize loss of balance. These data support a growing body of evidence that Tai Chi may be a valuable complementary treatment for vestibular disorders.


Gender differences in cognitive function of patients with chronic schizophrenia.
Schizophrenic patients have cognitive impairments, but gender differences in these cognitive deficits have had limited study. This study assessed cognitive functioning in 471 subjects including 122 male and 78 female schizophrenic patients and 141 male and 130 female healthy controls. We found that immediate memory, language, delayed memory and total RBANS scores were significantly decreased in schizophrenia compared with healthy controls for both genders. Male patients had significant lower immediate memory, delayed memory and total RBANS scores than female patients, and healthy controls showed a similar gender difference. The RBANS showed modest correlations with PANSS scores, duration of illness and antipsychotic dose (chlorpromazine equivalents). Almost all RBANS scores in the schizophrenics and healthy controls showed significant positive correlations with education. Thus, patients of both sexes with schizophrenia experienced more deteriorated performance than healthy controls on cognitive domains of immediate memory, language and delayed memory. Furthermore, male schizophrenic patients had more serious cognitive deficits than female patients in immediate and delayed memory, but not in language, visuospatial and attention indices.


Five Fatty Aldehyde Dehydrogenase Enzymes from Marinobacter and Acinetobacter spp. and Structural Insights into the Aldehyde Binding Pocket.
Enzymes involved in lipid biosynthesis and metabolism play an important role in energy conversion and storage and in the function of structural components such as cell membranes. The fatty aldehyde dehydrogenase (FAldDH) plays a central function in the metabolism of lipid intermediates, oxidizing fatty aldehydes to the corresponding fatty acid and competing with pathways that would further reduce the fatty aldehydes to fatty alcohols or require the fatty aldehydes to produce alkanes. In this report, the genes for four putative FAldDH enzymes from Marinobacter aquaeolei VT8 and an additional enzyme from Acinetobacter baylyi were heterologously expressed in Escherichia coli and shown to display FAldDH activity. Five enzymes (Maqu_0438, Maqu_3316, Maqu_3410, Maqu_3572, and the enzyme reported under RefSeq accession no. WP_004927398) were found to act on aldehydes ranging from acetaldehyde to hexadecanal and also acted on the unsaturated long-chain palmitoleyl and oleyl aldehydes. A comparison of the specificities of these enzymes with various aldehydes is presented. Crystallization trials yielded diffraction-quality crystals of one particular FAldDH (Maqu_3316) from M. aquaeolei VT8. Crystals were independently treated with both the NAD+ cofactor and the aldehyde substrate decanal, revealing specific details of the likely substrate binding pocket for this class of enzymes. A likely model for how catalysis by the enzyme is accomplished is also provided.IMPORTANCE This study provides a comparison of multiple enzymes with the ability to oxidize fatty aldehydes to fatty acids and provides a likely picture of how the fatty aldehyde and NAD+ are bound to the enzyme to facilitate catalysis. Based on the information obtained from this structural analysis and comparisons of specificities for the five enzymes that were characterized, correlations to the potential roles played by specific residues within the structure may be drawn.


Helicobacter pylori associated phospholipase A2 activity: a factor in peptic ulcer production?
To examine the potential role of the lipolytic enzyme phospholipase A2, produced by Helicobacter pylori in ulcer formation. Phospholipase A2 activity in H pylori was compared with that in 10 commonly occurring pathogenic bacteria. Phospholipase A2 activity and its cytotoxic metabolite, lysolecithin, in the basal gastric aspirates of 12 patients infected with H pylori were compared with those in 12 subjects not infected with H pylori. The phospholipase A2 activity in H pylori was substantially higher than that in most of the other bacteria tested, and the activities of phospholipase A2 and lysolecithin in the basal gastric aspirates of those infected with H pylori were significantly higher than the activities found in the basal gastric aspirates of subjects who were not infected. The lysolecithin proportion of total phospholipids in the gastric aspirates was also much higher in the infected than the non-infected group and a weak positive correlation (0.415) was found between phospholipase A2 and lysolecithin in the infected group. H pylori has clinically important concentrations of phospholipase A2, an enzyme capable of hydrolysing gastric mucosal phospholipids. The high values of phospholipase A2 and lysolecithin in gastric fluid from subjects with H pylori infections supports the notion that phospholipase A2 is involved in the inflammation and mucosal damage associated with peptic ulcer formation.


Cancellation of bending-induced birefringence in single-mode fibers: application to faraday sensors.
We demonstrate that one can cancel the bending-induced linear birefringence in single-mode fibers by inducing a controlled anisotropy in a direction orthogonal to the bending plane. In particular, the controlled anisotropy can be generated by application of a lateral compressive stress on the fiber. This effect can be applied for the construction of birefringence-free fiber coils in Faraday sensor heads (e.g., in current sensors) to improve their sensitivity.


Construction of an improved Aspergillus niger platform for enhanced glucoamylase secretion.
The lifestyle of filamentous fungi depends on the secretion of hydrolytic enzymes into the surrounding medium, which degrade polymeric substances into monomers that are then taken up to sustain metabolism. This feature has been exploited in biotechnology to establish platform strains with high secretory capacity including Aspergillus niger. The accepted paradigm is that proteins become mainly secreted at the tips of fungal hyphae. However, it is still a matter of debate if the amount of growing hyphal tips in filamentous fungi correlates with an increase in secretion, with previous studies showing either a positive or no correlation. Here, we followed a systematic approach to study protein secretion in A. niger. First, we put the glaA gene encoding for glucoamylase (GlaA), the most abundant secreted protein of A. niger, under control of the tunable Tet-on system. Regulation of glaA gene expression by omitting or adding the inducer doxycycline to cultivation media allowed us to study the effect of glaA under- or overexpression in the same isolate. By inducing glaA expression in a fluorescently tagged v-SNARE reporter strain expressing GFP-SncA, we could demonstrate that the amount of post-Golgi carriers indeed depends on and correlates with glaA gene expression. By deleting the racA gene, encoding the Rho-GTPase RacA in this isolate, we generated a strain which is identical to the parental strain with respect to biomass formation but produces about 20% more hyphal tips. This hyperbranching phenotype caused a more compact macromorphology in shake flask cultivations. When ensuring continuous high-level expression of glaA by repeated addition of doxycycline, this hyperbranching strain secreted up to four times more GlaA into the culture medium compared to its parental strain. The data obtained in this study strongly indicate that A. niger responds to forced transcription of secretory enzymes with increased formation of post-Golgi carriers to efficiently accommodate the incoming cargo load. This physiological adaptation can be rationally exploited to generate hypersecretion platforms based on a hyperbranching phenotype. We propose that a racA deletion background serves as an excellent chassis for such hypersecretion strains.


Stratification of diabetes in the context of comorbidities, using representation learning and topological data analysis.
Diabetes is a heterogenous, multimorbid disorder with a large variation in manifestations, trajectories, and outcomes. The aim of this study is to validate a novel machine learning method for the phenotyping of diabetes in the context of comorbidities. Data from 9967 multimorbid patients with a new diagnosis of diabetes were extracted from Clinical Practice Research Datalink. First, using BEHRT (a transformer-based deep learning architecture), the embeddings corresponding to diabetes were learned. Next, topological data analysis (TDA) was carried out to test how different areas in high-dimensional manifold correspond to different risk profiles. The following endpoints were considered when profiling risk trajectories: major adverse cardiovascular events (MACE), coronary artery disease (CAD), stroke (CVA), heart failure (HF), renal failure (RF), diabetic neuropathy, peripheral arterial disease, reduced visual acuity and all-cause mortality. Kaplan Meier curves were plotted for each derived phenotype. Finally, we tested the performance of an established risk prediction model (QRISK) by adding TDA-derived features. We identified four subgroups of patients with diabetes and divergent comorbidity patterns differing in their risk of future cardiovascular, renal, and other microvascular outcomes. Phenotype 1 (young with chronic inflammatory conditions) and phenotype 2 (young with CAD) included relatively younger patients with diabetes compared to phenotypes 3 (older with hypertension and renal disease) and 4 (older with previous CVA), and those subgroups had a higher frequency of pre-existing cardio-renal diseases. Within ten years of follow-up, 2592 patients (26%) experienced MACE, 2515 patients (25%) died, and 2020 patients (20%) suffered RF. QRISK3 model's AUC was augmented from 67.26% (CI 67.25-67.28%) to 67.67% (CI 67.66-67.69%) by adding specific TDA-derived phenotype and the distances to both extremities of the TDA graph improving its performance in the prediction of CV outcomes. We confirmed the importance of accounting for multimorbidity when risk stratifying heterogenous cohort of patients with new diagnosis of diabetes. Our unsupervised machine learning method improved the prediction of clinical outcomes.


The researcher as experimental subject: using self-experimentation to access experiences, understand social phenomena, and stimulate reflexivity.
The current article argues that researcher-as-subject self-experimentation can provide valuable insight and systematic knowledge to social psychologists. This approach, the modus operandi of experimental psychology when the field was in its infancy, has been largely eclipsed by an almost exclusive focus on participant-as-subject other-experimentation. Drawing from the non-experimental first-person traditions of autoethnography, participant observation, and phenomenology, we argue that participating as both observer and subject within one's own social psychological experiment affords researchers at least three potential benefits: (1) access to "social qualia," that is, the subjective experience of social phenomena; (2) improved mental models of social phenomena, potentially stimulating new research questions; and (3) an enhanced ability to be reflexive about the given experiment. To support our position, we provide first-person self-reflections from researchers who have self-experimented with transformed social interactions involving Milgram's cyranoid method. We close by offering guidelines on how one might approach self-experimentation, and discuss a variety of first-person perspective ethnographic technologies that can be incorporated into the practice.


Parabens as urinary biomarkers of exposure in humans.
Parabens appear frequently as antimicrobial preservatives in cosmetic products, in pharmaceuticals, and in food and beverage processing. In vivo and in vitro studies have revealed weak estrogenic activity of some parabens. Widespread use has raised concerns about the potential human health risks associated with paraben exposure. Assessing human exposure to parabens usually involves measuring in urine the conjugated or free species of parabens or their metabolites. In animals, parabens are mostly hydrolyzed to p-hydroxybenzoic acid and excreted in the urine as conjugates. Still, monitoring urinary concentrations of p-hydroxybenzoic acid is not necessarily the best way to assess exposure to parabens. p-hydroxybenzoic acid is a nonspecific biomarker, and the varying estrogenic bioactivities of parabens require specific biomarkers. Therefore, we evaluated the use of free and conjugated parent parabens as new biomarkers for human exposure to these compounds. We measured the urinary concentrations of methyl, ethyl, n-propyl, butyl (n- and iso-), and benzyl parabens in a demographically diverse group of 100 anonymous adults. We detected methyl and n-propyl parabens at the highest median concentrations (43.9 ng/mL and 9.05 ng/mL, respectively) in nearly all (> 96%) of the samples. We also detected other parabens in more than half of the samples (ethyl, 58%; butyl, 69%). Most important, however, we found that parabens in urine appear predominantly in their conjugated forms. The results, demonstrating the presence of urinary conjugates of parabens in humans, suggest that such conjugated parabens could be used as exposure biomarkers. Additionally, the fact that conjugates appear to be the main urinary products of parabens may be important for risk assessment.


Appropriateness of diagnostic coronary angiography as a measure of cardiac ischemia testing in non-emergency patients - a retrospective cross-sectional analysis.
Adequate application of guidelines concerning non-invasive ischemia testing (NIIT) could avoid inappropriate invasive testing in non-emergency situations. Hardly any data exists regarding frequency and appropriateness of diagnostic coronary angiography (CA). The aim of this study was to evaluate the proportion and predictors of patients without NIIT prior to elective purely diagnostic CA without therapeutic intervention. Retrospective cross-sectional analysis of insurance claims data from 2012 and 2013. Patients <18 years, acute cardiac ischemia and emergency procedures and patients insured in a managed care model were excluded from analysis. The proportion of patients with NIIT procedures (stress-ECG, transthoracic echocardiography, stress echocardiography, scintigraphy, computer tomography, heart MRI) undertaken within two months before diagnostic CA was assessed. Multiple logistic regression analysis was applied to investigate independent determinants for receiving NIIT. 2714 patients were included for analysis. 37.5% (1018) did not receive any NIIT before CA. When high risk patients (patients having received therapeutic cardiac intervention within one month after or 18 months prior to diagnostic CA, n = 766) were excluded 34.3% (669) did not receive NIIT before CA. High risk status as well as >6 chronic comorbidities were independently associated with a lower proportion of NIIT (p<0.0001, OR 0.607 and p = 0.0041, OR 0.648), when additionally controlled for age, sex, language area, insurance coverage, inpatient treatment, cardiovascular medication and lower number of chronic comorbidities. Age (p<0.05, OR 1.009) and intake of oral antiplatelet therapy (p<0.0001, OR 1.914) were independently associated with a higher proportion of NIIT when controlled for the mentioned cofactors. Our data show that despite the existence of guidelines a substantial overuse of a potentially harmful and inappropriate diagnostic intervention is performed suggesting the need for improvement of diagnostic pathways prior to invasive testing.


Capturing the Complex Relationship Between Internal and External Training Load: A Data-Driven Approach.
Training load is typically described in terms of internal and external load. Investigating the coupling of internal and external training load is relevant to many sports. Here, continuous kernel-density estimation (KDE) may be a valuable tool to capture and visualize this coupling. Using training load data in speed skating, we evaluated how well bivariate KDE plots describe the coupling of internal and external load and differentiate between specific training sessions, compared to training impulse scores or intensity distribution into training zones. On-ice training sessions of 18 young (sub)elite speed skaters were monitored for velocity and heart rate during 2 consecutive seasons. Training session types were obtained from the coach's training scheme, including endurance, interval, tempo, and sprint sessions. Differences in training load between session types were assessed using Kruskal-Wallis or Kolmogorov-Smirnov tests for training impulse and KDE scores, respectively. Training impulse scores were not different between training session types, except for extensive endurance sessions. However, all training session types differed when comparing KDEs for heart rate and velocity (both P < .001). In addition, 2D KDE plots of heart rate and velocity provide detailed insights into the (subtle differences in) coupling of internal and external training load that could not be obtained by 2D plots using training zones. 2D KDE plots provide a valuable tool to visualize and inform coaches on the (subtle differences in) coupling of internal and external training load for training sessions. This will help coaches design better training schemes aiming at desired training adaptations.


Sexual behaviors and other risk factors for oral human papillomavirus infections in young women.
Oral human papillomavirus (HPV) is associated with a rising incidence of certain head and neck cancers, and oral sex has been associated with oral HPV. This study sought to identify more specific patterns of oral sexual activity, including self-inoculation, that are associated with oral HPV infections in young women. A total of 1010 women attending a large university completed a computer-based questionnaire and provided oral specimens that were tested for any oral HPV using a Linear Array assay that detects any HPV as well as 37 HPV genotypes. Twenty-seven women provided additional samples up to 12 months after enrollment. Bivariable and multivariable analyses were conducted to identify oral sexual patterns and other risk factors associated with prevalent oral HPV. Nineteen women had prevalent oral HPV (1.9%), with 10 women (1%) having a type-specific infection. Oral HPV was significantly associated with lifetime coital sex partnership numbers (P = 0.03), lifetime and yearly oral sex partnership numbers (P < 0.01), and hand and/or sex toy transfer from genitals to mouth (P < 0.001). Oral HPV was also associated with greater use of alcohol, cigarettes, marijuana, and sharing of smoking devices, lipstick, or toothbrushes (P < 0.05 for each), with an apparent dose-response for alcohol use and smoking behavior, stratified by number of sexual partners. Of 7 women with prevalent HPV who provided follow-up samples, none had evidence of a persistent type-specific infection. These data provide additional evidence of transmission of oral HPV from oral sexual activity and also suggest possible transmission from self-inoculation or sharing of oral products.


Detection of Fetal Sex, Aneuploidy and a Microdeletion from Single Placental Syncytial Nuclear Aggregates.
A key problem in prenatal screening using extra-embryonic cells is the feasibility of extracting usable DNA from a small number of cells. Syncytial nuclear aggregates (SNAs) are multinucleated structures shed from the placenta. This study assesses the potential of SNAs as a source of fetal DNA for the detection of genetic abnormalities. SNAs were collected in vitro. Whole-genome amplification was used to amplify DNA from single SNAs, and DNA quality and quantity was assessed by spectrophotometry and PCR. Confocal microscopy was used to count nuclei within SNAs, determine metabolic activity and investigate DNA damage. Fetal sex and chromosomal/genetic abnormalities were investigated with array-comparative genomic hybridization (aCGH). DNA was amplified from 81% of the individual SNAs. A mean of 61 ± 43 nuclei were found per SNA. DNA strand breaks were found in 76% of the SNAs. Seventy-five percent of SNAs yielded whole-genome-amplified DNA of sufficient quality for aCGH after storage and shipping. Individual SNAs from the same pregnancy reliably gave the same chromosomal profile, and fetal sex and trisomies could be detected. A microdeletion was detected in one pregnancy. SNAs could provide a source of extra-embryonic DNA for the prenatal screening/diagnosis of fetal sex and chromosomal and sub-chromosomal genetic abnormalities.


Streptomycin and gentamicin have no immediate effect on outer hair cell electromotility.
The cochlear outer hair cell (OHC), which plays a crucial role in mammalian hearing through its unique voltage-dependent motility, has been established as a primary target of the ototoxicity of aminoglycoside antibiotics. These polycationic drugs are also known to block a wide variety of ion channels, purinergic ionotropic channels, and nicotinic ACh receptors in hair cells in vitro. The OHC motor protein, prestin, is a voltage-sensitive transmembrane protein containing several negatively charged residues on both intra- and extracellular surface. The acidic sites may be susceptible to polycationic-charged aminoglycoside binding, which may result in disruption of motility. We attempted to examine whether aminoglycosides such as streptomycin and gentamicin could affect OHC motility and its electrical signature, the nonlinear capacitance (NLC) in adult gerbil OHCs. Somatic motility and NLC were measured under the whole-cell voltage-clamp mode. Streptomycin and gentamicin were applied extracellularly or intracellularly. Results show that streptomycin and gentamicin did not change either the magnitude of motility or the NLC. Theses results suggest that, although streptomycin and gentamicin can block mechanotransduction channels as well as ACh receptors in hair cells, they have no direct affect on OHC somatic motility.


Lobular neoplasia: frequency and association with other breast lesions.
Using new molecular biology techniques, recent studies have implicated a common evolutionary pathway between lobular neoplasia, lobular carcinomas, and columnar cell lesions. Our aims were to assess the frequency of lobular neoplasia in a series of breast biopsies that were performed and examined in the same institution and to analyze the association between subtypes of lobular neoplasia and benign and malignant breast lesions. Cases were selected after reviewing archived pathological reports in the Breast Pathology Laboratory, School of Medicine of Federal University of Minas Gerais (1999-2008). Cases of lobular neoplasia were reviewed and classified as atypical lobular hyperplasia, ductal involvement by cells of atypical lobular hyperplasia, lobular carcinoma in situ, and pleomorphic lobular carcinoma in situ. Coexistence of lobular neoplasia with other breast lesions, including columnar cell lesions, invasive ductal carcinoma and invasive lobular carcinoma, was evaluated. The association between lobular neoplasia and breast lesions was analyzed by Fisher's exact test and chi-square test for linear trend. We analyzed 5650 breast specimens, selecting 135 breast specimens (2.4%) that had a diagnosis of lobular neoplasia, corresponding to 106 patients. Hematoxylin and eosin-stained slides were available for 84 cases, 5 of which were excluded because they contained only "indeterminate" in situ lesions. Of the 79 remaining cases, columnar cell lesions were present in 78.5%, primarily with columnar cell changes without atypia (67.7%). Invasive carcinoma was present in 45.6% of cases of lobular neoplasia--a similar frequency (47.2%) as invasive ductal carcinoma and invasive lobular carcinoma. We noted a significant linear trend (p < 0.03) of a higher frequency of invasive carcinomas that were concomitant with lobular carcinoma in situ compared with atypical lobular hyperplasia. Invasive lobular carcinomas were associated with lobular carcinoma in situ in 33% of cases, compared with 2.8% of atypical lobular hyperplasia cases. Our findings confirm a frequent association between lobular neoplasia and columnar cell lesions, the majority of which lacked atypia. We also observed a greater frequency of invasive carcinoma, more commonly invasive lobular carcinoma, associated with more developed forms of lobular neoplasia (lobular carcinoma in situ).


Genome-scale identification of cellular pathways required for cell surface recognition.
Interactions mediated by cell surface receptors initiate important instructive signaling cues but can be difficult to detect in biochemical assays because they are often highly transient and membrane-embedded receptors are difficult to solubilize in their native conformation. Here, we address these biochemical challenges by using a genome-scale, cell-based genetic screening approach using CRISPR gene knockout technology to identify cellular pathways required for specific cell surface recognition events. By using high-affinity monoclonal antibodies and low-affinity ligands, we determined the necessary screening parameters, including the importance of establishing binding contributions from the glycocalyx, that permitted the unequivocal identification of genes encoding directly interacting membrane-embedded receptors with high statistical confidence. Importantly, we show that this genome-wide screening approach additionally identified receptor-specific pathways that are required for functional display of receptors on the cell surface that included chaperones, enzymes that add post-translational modifications, trafficking proteins, and transcription factors. Finally, we demonstrate the utility of the approach by identifying IGF2R (insulin like growth factor 2 receptor) as a binding partner for the R2 subunit of GABAB receptors. We show that this interaction is direct and is critically dependent on mannose-6-phosphate, providing a mechanism for the internalization and regulation of GABAB receptor signaling. We conclude that this single approach can reveal both the molecular nature and the genetic pathways required for functional cell surface display of receptors recognized by antibodies, secreted proteins, and membrane-embedded ligands without the need to make any prior assumptions regarding their biochemical properties.


Proximal junctional kyphosis and clinical outcomes in adult spinal deformity surgery with fusion from the thoracic spine to the sacrum: a comparison of proximal and distal upper instrumented vertebrae.
Proximal junctional kyphosis (PJK) is a common and significant complication after corrective spinal deformity surgery. The object of this study was to compare-based on clinical outcomes, postoperative proximal junctional kyphosis rates, and prevalence of revision surgery-proximal thoracic (PT) and distal thoracic (DT) upper instrumented vertebra (UIV) in adults who underwent spine fusion to the sacrum for the treatment of spinal deformity. In this retrospective study the authors evaluated clinical and radiographic data from consecutive adults (age > 21 years) with a deformity treated using long instrumented posterior spinal fusion to the sacrum in the period from 2007 to 2009. The PT group included patients in whom the UIV was between T-2 and T-5, whereas the DT group included patients in whom the UIV level was between T-9 and L-1. Perioperative surgical data were compared between the PT and DT groups. Additionally, segmental, regional, and global spinal alignments, as well as the sagittal Cobb angle at the proximal junction, were analyzed on preoperative, early postoperative, and final standing 36-in. radiographs. Patient-reported outcome measurements (visual analog scale, Scoliosis Research Society Patient Questionnaire-22, Oswestry Disability Index, and the 36-Item Short-Form Health Survey) were compared. Eighty-nine patients, 22 males and 67 females, had a minimum follow-up of 2 years, and thus were eligible for participation in this study. Sixty-seven patients were in the DT group and 22 were in the PT group. Operative time (p = 0.387) and estimated blood loss (p < 0.05) were slightly higher in the PT group. The overall rate of revision surgery was 48.0% and 54.5% in the DT and PT groups, respectively (p = 0.629). The prevalence of PJK according to radiological criteria was 34% in the DT group and 27% in the PT group (p = 0.609). The percent of patients with PJK that required surgical correction (surgical PJK) was 11.9% (8 of 67) in the DT group and 9.1% (2 of 22) in the PT group (p = 1.0). The onset of surgical PJK was significantly earlier than radiological PJK in the DT group (p < 0.01). The types of PJK were different in the PT and DT groups. Compression fracture at the UIV was more prevalent in the DT group, whereas subluxation was more prevalent in the PT group. Postoperatively, the PT group had less thoracic kyphosis (p = 0.02), less sagittal imbalance (p < 0.01), and less pelvic tilt (p = 0.04). In the DT group, early postoperative radiographs demonstrated that the proximal junctional angle of patients with surgical PJK was greater than in those without PJK and those with radiological PJK (p < 0.01). Clinical outcomes were significantly improved in both groups, and there was no significant difference between the groups. Both PT and DT UIVs improve segmental and global sagittal plane alignment as well as patient-reported quality of life in those treated for adult spinal deformity. The prevalence of PJK was not different in the PT and DT groups. However, compression fracture was the mechanism more frequently observed with DT PJK, and subluxation was the mechanism more frequently observed in PT PJK. Strategies to avoid PJK may include vertebral augmentation to prevent fracture at the DT spine and mechanical means to prevent vertebral subluxation at the PT spine.


A pre-initiation complex at the 3'-end of genes drives antisense transcription independent of divergent sense transcription.
The precise nature of antisense transcripts in eukaryotes such as Saccharomyces cerevisiae remains elusive. Here we show that the 3' regions of genes possess a promoter architecture, including a pre-initiation complex (PIC), which mirrors that at the 5' region and which is much more pronounced at genes with a defined antisense transcript. Remarkably, for genes with an antisense transcript, average levels of PIC components at the 3' region are ∼60% of those at the 5' region. Moreover, at these genes, average levels of nascent antisense transcription are ∼45% of sense transcription. We find that this 3' promoter architecture persists for highly transcribed antisense transcripts where there are only low levels of transcription in the divergent sense direction, suggesting that the 3' regions of genes can drive antisense transcription independent of divergent sense transcription. To validate this, we insert short 3' regions into the middle of other genes and find that they are capable of both initiating antisense transcripts and terminating sense transcripts. Our results suggest that antisense transcription can be regulated independently of divergent sense transcription in a PIC-dependent manner and we propose that regulated production of antisense transcripts represents a fundamental and widespread component of gene regulation.


Research on the provider contribution to race/ethnicity disparities in medical care.
Little is known about why black patients and other ethnic/racial minorities are less likely to receive the best treatments independent of clinical appropriateness, payer, and treatment site. Although both provider and patient behavior have been suggested as possible explanatory factors, the potential role of provider behavior has remained largely unexplored. Does provider behavior contribute to systematic inequities? If so, why? The purpose of this paper is to build on existing evidence to provide an integrated, coherent, and sound approach to future research on the provider contribution to race/ethnicity disparities in medical care. First, the existing evidence suggestive of a provider contribution to race/ethnicity variance in medical care is discussed. Second, a proposed causal model, based on a review of the social cognition and provider behavior literature, representing an integrated set of hypothesized mechanisms through which physician behavior may contribute to race/ethnicity disparities in care is presented. There is sufficient evidence for the hypothesis that provider behavior contributes to race/ethnicity disparities in care to warrant further study. Although there is some evidence of support of the hypotheses that both provider beliefs about of patients and provider behavior during encounters are independently influenced by patient race/ethnicity further systematic rigorous study is needed and is proposed as a major immediate research priority. These mechanisms deserve intensive research focus as they may prove to be the most promising targets for interventions intended to ameliorate the provider contribution to disparities in care.


Chitosan microparticles loaded with yeast-derived PCV2 virus-like particles elicit antigen-specific cellular immune response in mice after oral administration.
Porcine circovirus type 2 (PCV2)-associated diseases are a major problem for the swine industry worldwide. In addition to improved management and husbandry practices, the availability of several anti-PCV2 vaccines provides an efficient immunological option for reducing the impact of these diseases. Most anti-PCV2 vaccines are marketed as injectable formulations. Although these are effective, there are problems associated with the use of injectable products, including laborious and time-consuming procedures, the induction of inflammatory responses at the injection site, and treatment-associated stress to the animals. Oral vaccines represent an improvement in antigen delivery technology; they overcome the problems associated with injection management and facilitate antigen boosting when an animals' immunity falls outside the protective window. Chitosan microparticles were used as both a vehicle and mucosal adjuvant to deliver yeast-derived PCV2 virus-like particles (VLPs) in an attempt to develop an oral vaccine. The physical characteristics of the microparticles, including size, Zeta potential, and polydispersity, were examined along with the potential to induce PCV2-specific cellular immune responses in mice after oral delivery. Feeding mice with PCV2 VLP-loaded, positively-charged chitosan microparticles with an average size of 2.5 μm induced the proliferation of PCV2-specific splenic CD4+/CD8+ lymphocytes and the subsequent production of IFN-γ to levels comparable with those induced by an injectable commercial formulation. Chitosan microparticles appear to be a safe, simple system on which to base PCV2 oral vaccines. Oral chitosan-mediated antigen delivery is a novel strategy that efficiently induces anti-PCV2 cellular responses in a mouse model. Further studies in swine are warranted.


Anti-mosquito plants as an alternative or incremental method for malaria vector control among rural communities of Bagamoyo District, Tanzania.
Plants represent one of the most accessible resources available for mosquito control by communities in Tanzania. However, no documented statistics exist for their contribution in the management of mosquitoes and other insects except through verbal and some publications. This study aimed at assessing communities' knowledge, attitudes and practices of using plants as an alternative method for mosquito control among selected communities in a malaria-prone area in Tanzania. Questionnaires were administered to 202 respondents from four villages of Bagamoyo District, Pwani Region, in Tanzania followed by participatory rural appraisal with village health workers. Secondary data collection for plants mentioned by the communities was undertaken using different search engines such as googlescholar, PubMED and NAPRALERT. Results showed about 40.3% of respondents used plants to manage insects, including mosquitoes. A broad profile of plants are used, including "mwarobaini" (Azadirachta indica) (22.5%), "mtopetope" (Annona spp) (20.8%), "mchungwa/mlimau" (Citrus spp) (8.3%), "mvumbashi/uvumbati" (Ocimum spp) (7.4%), "mkorosho" (Anacadium occidentale) (7.1%), "mwembe" (5.4%) (Mangifera indica), "mpera" (4.1%) (Psidium spp) and "maganda ya nazi" (4.1%) (Cocos nucifera). Majority of respondents collected these plants from the wild (54.2%), farms (28.9%) and/or home gardens (6%). The roles played by these plants in fighting mosquitoes is reflected by the majority that deploy them with or without bed-nets (p > 0.55) or insecticidal sprays (p >0.22). Most respondents were aware that mosquitoes transmit malaria (90.6%) while few respondents associated elephantiasis/hydrocele (46.5%) and yellow fever (24.3%) with mosquitoes. Most of the ethnobotanical uses mentioned by the communities were consistent with scientific information gathered from the literature, except for Psidium guajava, which is reported for the first time in insect control. This survey has indicated some knowledge gap among community members in managing mosquito vectors using plant. The communities need a basic health education and sensitization for effective exploitation of this valuable tool for reducing mosquitoes and associated disease burdens. On the other hand, the government of Tanzania should strengthen advocacy of botanical pesticides development, registration and regulation for public health benefits because they are source of pest control tools people rely on them.


The inflammatory bowel disease live interinstitutional and interdisciplinary videoconference education (IBD LIVE) series.
Managing patients with inflammatory bowel disease requires multidisciplinary coordination. Technological advances have enhanced access to care for patients and improved physician interactions. The primary aim of our project was to convene diverse institutions and specialties through a multisite virtual conferencing platform to discuss complex patient management. The case conference is designed to include multiple institutions to exchange ideas, review evidence-based data, and provide input on the management of patients with Crohn's disease and ulcerative colitis. Technology is supplied and coordinated by an information technology specialist and Chorus Call, Inc., an international teleconferencing service provider. The Inflammatory Bowel Disease Live Interinstitutional Interdisciplinary Videoconference Education (IBD LIVE) initiative is accredited by the University of Pittsburgh Medical Center (UPMC) Center for Continuing Education in the Health Sciences for 1 AMA PRA Category 1 Credit per weekly session. IBD LIVE began in 2009 comprising only adult gastroenterology and pediatric gastroenterology from UPMC Presbyterian and Children's Hospitals. Participation steadily increased from 5 sites in 2010 to 11 sites in 2014. Maximum attendance for a single conference was 73 participants with a median of 48. The Continuing Medical Education scores (1 = worst to 5 = best) have a high median overall score (4.6, range 3.2-5.0) with positive responses with regard to the degree to which the conference changed practice. IBD LIVE has been successful and continues to grow. Implementation of the Crohn's and Colitis Foundation of America Virtual Preceptor Program using the IBD LIVE platform will provide expanded national physician access to this professional education activity.


Interleukin 1 plus interleukin 3 plus colony-stimulating factor 1 are essential for clonal proliferation of primitive myeloid bone marrow cells.
The clonal growth in nutrient agar at low cell densities of high-proliferative potential colony-forming cells (HPP-CFC) of bone marrow obtained from mice treated 2 days earlier with 5-fluorouracil (FU) (FU2dBM) has been shown to require a combination of three growth factors, interleukin 1 (IL-1), interleukin 3 (IL-3), and macrophage colony-stimulating factor (CSF-1). These HPP-CFC have been enriched 140-fold from FU2dBM by fluorescence-activated cell sorting of 7/4-, B220-, and L3T4-negative cells. The mean of the plating efficiencies of these enriched populations was 4.4% and no growth was observed when the factors were used singly. Similarly, enrichments of 16-fold were obtained from FU2dBM using immunomagnetic Dynabeads with anti-7/4 plus anti-B220 (meaning plating efficiency 0.5%). The further additions of human granulocyte CSF or mouse granulocyte-macrophage CSF or both to IL-1 plus IL-3 plus CSF-1 did not increase HPP-CFC colony formation, but both augmented the small colony formation with IL-1 plus IL-3, IL-3 plus CSF-1, or IL-1 plus CSF-1.


What Is Intensity and How Can It Benefit Exercise Intervention in People With Stroke? A Rapid Review.
Background: Stroke is one of the major causes of chronic physical disability in the United Kingdom, typically characterized by unilateral weakness and a loss of muscle power and movement coordination. When combined with pre-existing comorbidities such as cardiac disease and diabetes, it results in reductions in cardiovascular (CV) fitness, physical activity levels, functional capacity, and levels of independent living. High-intensity training protocols have shown promising improvements in fitness and function for people with stroke (PwS). However, it remains unclear how intensity is defined, measured, and prescribed in this population. Further, we do not know what the optimal outcome measures are to capture the benefits of intensive exercise. Aim: To understand how intensity is defined and calibrated in the stroke exercise literature to date and how the benefits of high-intensity training in PwS are measured. Methods: A rapid review of the literature was undertaken to provide an evidence synthesis that would provide more timely information for decision-making (compared with a standard systematic review). Electronic databases were searched (including Medline, PubMed, CINAHL, and Embase for studies from 2015 to 2020). These were screened by title and abstract for inclusion if they: (a) were specific to adult PwS; and (b) were high-intensity exercise interventions. Eligible studies were critically appraised using the Mixed Method Appraisal Tool (MMAT). The data extraction tool recorded the definition of intensity, methods used to measure and progress intensity within sessions, and the outcomes measure used to capture the effects of the exercise intervention. Results: Seventeen studies were selected for review, 15 primary research studies and two literature reviews. Sixteen of the 17 studies were of high quality. Nine of the primary research studies used bodyweight-supported treadmills to achieve the high-intensity training threshold, four used static exercise bikes, and two used isometric arm strengthening. Five of the primary research studies had the aim of increasing walking speed, five aimed to increase CV fitness, three aimed to improve electroencephalogram (EEG) measured cortical evoked potentials and corticospinal excitability, and two investigated any changes in muscle strength. Although only one study gave a clear definition of intensity, all studies clearly defined the high-intensity protocol used, with most (15 out of 17 studies) clearly describing threshold periods of high-intensity activity, followed by rest or active recovery periods (of varying times). All of the studies reviewed used outcomes specific to body structure and function (International Classification of Functioning, Disability, and Health (ICF) constructs), with fewer including outcomes relating to activity and only three outcomes relating to participation. The reported effect of high-intensity training on PwS was promising, however, the underlying impact on neurological, musculoskeletal, and CV systems was not clearly specified. Conclusions: There is a clear lack of definition and understanding about intensity and how thresholds of intensity in this population are used as an intervention. There is also an inconsistency about the most appropriate methods to assess and provide a training protocol based on that assessment. It remains unclear if high-intensity training impacts the desired body system, given the diverse presentation of PwS, from a neuromuscular, CV, functional, and psychosocial perspective. Future work needs to establish a clearer understanding of intensity and the impact of exercise training on multiple body systems in PwS. Further understanding into the appropriate assessment tools to enable appropriate prescription of intensity in exercise intervention is required. Outcomes need to capture measures specific not only to the body system, but also level of function and desired goals of individuals.


Placental growth factor and its potential role in diabetic retinopathy and other ocular neovascular diseases.
The role of vascular endothelial growth factor (VEGF), including in retinal vascular diseases, has been well studied, and pharmacological blockade of VEGF is the gold standard of treatment for neovascular age-related macular degeneration, retinal vein occlusion and diabetic macular oedema. Placental growth factor (PGF, previously known as PlGF), a homologue of VEGF, is a multifunctional peptide associated with angiogenesis-dependent pathologies in the eye and non-ocular conditions. Animal studies using genetic modification and pharmacological treatment have demonstrated a mechanistic role for PGF in pathological angiogenesis. Inhibition decreases neovascularization and microvascular abnormalities across different models, including oxygen-induced retinopathy, laser-induced choroidal neovascularization and in diabetic mice exhibiting retinopathies. High levels of PGF have been found in the vitreous of patients with diabetic retinopathy. Despite these strong animal data, the exact role of PGF in pathological angiogenesis in retinal vascular diseases remains to be defined, and the benefits of PGF-specific inhibition in humans with retinal neovascular diseases and macular oedema remain controversial. Comparative effectiveness research studies in patients with diabetic retinal disease have shown that treatment that inhibits both VEGF and PGF may provide superior outcomes in certain patients compared with treatment that inhibits only VEGF. This review summarizes current knowledge of PGF, including its relationship to VEGF and its role in pathological angiogenesis in retinal diseases, and identifies some key unanswered questions about PGF that can serve as a pathway for future basic, translational and clinical research.


Isolation of Listeria monocytogenes small-plaque mutants defective for intracellular growth and cell-to-cell spread.
To dissect the regulatory and structural requirements for Listeria monocytogenes intracellular growth and cell-to-cell spread, we designed a protocol based on transposon mutagenesis and the isolation of mutants which form small plaques in monolayers of mouse L2 cell fibroblasts. Two different transposable elements were used to generate libraries of insertion mutants: Tn916 and a derivative of Tn917-lac, Tn917-LTV3. Ten classes of mutants were isolated and evaluated for growth and cell-to-cell spread in J774 mouse macrophagelike cells, Henle 407 human epithelial cells, and mouse bone marrow-derived macrophages. Mutants were also evaluated for secretion of hemolysin and phospholipase (assayed by egg yolk opacity) and association with F-actin in the cytoplasm of cells, using NBD-phallacidin staining. The ten classes of mutants included (i) mutants showing abortive intracellular and extracellular growth; (ii) mutants showing abortive intracellular growth; (iii) rough mutants; (iv) mutants showing greatly reduced hemolysin and phospholipase secretion but showing normal growth in cells and little or no association with F-actin; (v) mutants with mutations mapping to an open reading frame (ORF) adjacent to hlyA and referred to as ORF U, lacking phospholipase activity, and with 50% normal hemolysin activity; (vi) mutants with reduced secretion of both hemolysin and phospholipase; (vii) nonhemolytic mutants with mutations mapping to the structural gene, hlyA; (viii) mutants with 25% normal hemolysin secretion and absolutely no association with F-actin; (ix) mutants with mutations mapping to ORF U, lacking phospholipase activity, and with normal hemolysin activity; and (x) mutants showing a mixed-plaque morphology but normal for all other parameters.


A behavioral model for mapping the genetic architecture of gut-microbiota networks.
The gut microbiota may play an important role in affecting human health. To explore the genetic mechanisms underlying microbiota-host relationships, many genome-wide association studies have begun to identify host genes that shape the microbial composition of the gut. It is becoming increasingly clear that the gut microbiota impacts host processes not only through the action of individual microbes but also their interaction networks. However, a systematic characterization of microbial interactions that occur in densely packed aggregates of the gut bacteria has proven to be extremely difficult. We develop a computational rule of thumb for addressing this issue by integrating ecological behavioral theory and genetic mapping theory. We introduce behavioral ecology theory to derive mathematical descriptors of how each microbe interacts with every other microbe through a web of cooperation and competition. We estimate the emergent properties of gut-microbiota networks reconstructed from these descriptors and map host-driven mutualism, antagonism, aggression, and altruism QTLs. We further integrate path analysis and mapping theory to detect and visualize how host genetic variants affect human diseases by perturbing the internal workings of the gut microbiota. As the proof of concept, we apply our model to analyze a published dataset of the gut microbiota, showing its usefulness and potential to gain new insight into how microbes are organized in human guts. The new model provides an analytical tool for revealing the "endophenotype" role of microbial networks in linking genotype to end-point phenotypes.


Edentulous persons, United States-1971.
There were an estimated 22.6 million edentulous persons in the United States according to the Health Interview Survey conducted in 1971. The Ju1y 1957-June 1958 survey estimate of the number of persons who were edentulous (had lost all their natural teeth) was 21.9 million. Since in most instances it takes many years of dental neglect for an individual to lose all his teeth, persons with no teeth are heavily concentrated in the older age groups. For example, in 1971,86.3 percent (19.5 million) of the edentulous population were in the age group 45 years of age and older, while in 1957-58 the comparable figure was 85.2 percent. Virtually every American will be affected during his or her lifetime by dental decay or periodontal disease. Reports previously published in the Vital and Health Statistics series contain national estimates of the prevalence, severity, and effects of dental disease among U.S. adults. Based on dental examinations conducted during 1960-62, it was estimated that approximately 20 million adults had lost all their natural teeth. Of the remaining adults with at least one natural tooth (approximately 90 million), about haIf had 18 or more decayed, missing, or filled teeth. In addition, about three out of four of those with natural teeth had periodontal disease, and about one out of four had an advanced form of periodontal disease with pocket formations. The result of neglected dental caries and advanced periodontal disease is the loss of teeth. Persons using artificial dentures are considerably less efficient at chewing than persons with healthy natural teeth. For the aged, artificial dentures mean a decrease in masticator function at a time when an efficient dental function is increasingly desirable due to changes in nutritional requirements. While the ultimate dental health goaI is the eradication of dental disease, an important immediate goal is the reduction of tooth Ioss. Tooth loss can usualIy be obviated by diagnosing and treating dental disease in its early stages and by utilizing the preventive measures now available.


A Novel G16B09-Like Effector From Heterodera avenae Suppresses Plant Defenses and Promotes Parasitism.
Plant parasitic nematodes secrete effectors into host plant tissues to facilitate parasitism. In this study, we identified a G16B09-like effector protein family from the transcriptome of Heterodera avenae, and then verified that most of the members could suppress programmed cell death triggered by BAX in Nicotiana benthamiana. Ha18764, the most homologous to G16B09, was further characterized for its function. Our experimental evidence suggested that Ha18764 was specifically expressed in the dorsal gland and was dramatically upregulated in the J4 stage of nematode development. A Magnaporthe oryzae secretion system in barley showed that the signal peptide of Ha18764 had secretion activity to deliver mCherry into plant cells. Arabidopsis thaliana overexpressing Ha18764 or Hs18764 was more susceptible to Heterodera schachtii. In contrast, BSMV-based host-induced gene silencing (HIGS) targeting Ha18764 attenuated H. avenae parasitism and its reproduction in wheat plants. Transient expression of Ha18764 suppressed PsojNIP, Avr3a/R3a, RBP-1/Gpa2, and MAPK kinases (MKK1 and NPK1Nt)-related cell death in Nicotiana benthamiana. Co-expression assays indicated that Ha18764 also suppressed cell death triggered by four H. avenae putative cell-death-inducing effectors. Moreover, Ha18764 was also shown strong PTI suppression such as reducing the expression of plant defense-related genes, the burst of reactive oxygen species, and the deposition of cell wall callose. Together, our results indicate that Ha18764 promotes parasitism, probably by suppressing plant PTI and ETI signaling in the parasitic stages of H. avenae.


Purification and characterization of a keratinolytic serine proteinase from Streptomyces albidoflavus.
Streptomyces strain K1-02, which was identified as a strain of Streptomyces albidoflavus, secreted at least six extracellular proteases when it was cultured on feather meal-based medium. The major keratinolytic serine proteinase was purified to homogeneity by a two-step procedure. This enzyme had a molecular weight of 18,000 and was optimally active at pH values ranging from 6 to 9.5 and at temperatures ranging from 40 to 70 degrees C. Its sensitivity to protease inhibitors, its specificity on synthetic substrates, and its remarkably high level of NH2-terminal sequence homology with Streptomyces griseus protease B (SGPB) showed that the new enzyme, designated SAKase, was homologous to SGPB. We tested the activity of SAKase with soluble and fibrous substrates (elastin, keratin, and type I collagen) and found that it was very specific for keratinous substrates compared to SGPB and proteinase K.


Separable pupillary signatures of perception and action during perceptual multistability.
The pupil provides a rich, non-invasive measure of the neural bases of perception and cognition and has been of particular value in uncovering the role of arousal-linked neuromodulation, which alters both cortical processing and pupil size. But pupil size is subject to a multitude of influences, which complicates unique interpretation. We measured pupils of observers experiencing perceptual multistability-an ever-changing subjective percept in the face of unchanging but inconclusive sensory input. In separate conditions, the endogenously generated perceptual changes were either task-relevant or not, allowing a separation between perception-related and task-related pupil signals. Perceptual changes were marked by a complex pupil response that could be decomposed into two components: a dilation tied to task execution and plausibly indicative of an arousal-linked noradrenaline surge, and an overlapping constriction tied to the perceptual transient and plausibly a marker of altered visual cortical representation. Constriction, but not dilation, amplitude systematically depended on the time interval between perceptual changes, possibly providing an overt index of neural adaptation. These results show that the pupil provides a simultaneous reading on interacting but dissociable neural processes during perceptual multistability, and suggest that arousal-linked neuromodulator release shapes action but not perception in these circumstances.


Head and neck squamous cell carcinomas in HIV-positive patients: a preliminary investigation of viral associations.
Oncogenic human papillomaviruses (HPVs) are associated with oropharyngeal squamous cell carcinoma (SCC). Infection with human immunodeficiency virus (HIV) increases susceptibility to opportunistic infections and viral-promoted cancers. The prevalences of HPV, herpes simplex virus (HSV), Epstein-Barr virus (EBV), and human herpesvirus-8 (HHV-8) have not been established for head and neck squamous cell carcinoma in HIV-positive patients (HIV+ HNSCC). We have observed that HIV+ HNSCC tend to contain numerous multinucleated tumor giant cells, this finding has not been described previously. The goal of this study is to test for these oncogenic viruses in a small cohort of retrospectively identified patients with HIV infection, and to compare histologically these cancers to a control group of HNSCC patients. Tumors were reviewed histologically and compared to a control group of 102 patients with HNSCC (serologically untyped or HIV negative). Polymerase chain reaction (PCR) was performed on formalin-fixed, paraffin-embedded HIV+ HNSCC samples from combined 25 patients in two institutions. In situ hybridization was performed to identify EBV (EBER) and immunohistochemistry was performed to detect HSV-1, HSV-2, HHV-8, and HIV-related proteins (Nef, p24). The study sample consisted of 34 HIV+ patients with HNSCC from Montefiore Medical Center, and six HIV+ HNSCC patients from Hospital Clinic, University of Barcelona; 24 (60%) men and 16 (40%) women. The larynx was most commonly involved (65%, n = 26); followed by the oropharynx (22.5%, n = 9). Four carcinomas arose from the oral cavity (10%) and one from the nasal cavity (2.5%). Histologically, multinucleated tumor giant cells were more common in the HIV+ group (39/40, 97.5%) than the control group (27/102, 26%, p 0.001, chi-square). HPV was detected in 6 of 25 (24%) HNSCC tumors by PCR, five were typed as HPV 16 and one as HPV 26/69; five of these tumors (83%) were located in the oropharynx. EBV, HSV-1, HSV-2, and HHV-8 were detected only infrequently in tumor cells. Nef protein was detected in tumor cells in 7 of 21 (33.3%) cases; p24 was not detectable in 6 tumors studied. There were no significant associations between HPV positive tumors and co-infections with other viruses. This study is consistent with other reports that suggest an increased incidence of laryngeal carcinoma for HIV+ patients. HPV was detected in 24% of HIV+ HNSCC, however, the number of tumors with amplifiable DNA (n = 25) is too small to allow for conclusions. EBV, HSV-1, HSV-2, and HHV-8 are uncommon in HIV+ HNSCC; it is unlikely that these viruses have a promoting effect. MNTCG are significantly common in HIV+ HNSCC, but there is overlap in MNTCG counts with the control group and therefore this finding cannot be used as a biomarker of HIV infection.


Low albumin-to-globulin ratio associated with cancer incidence and mortality in generally healthy adults.
Chronic inflammation is known to be one of the main steps in carcinogenesis. Identification of those with chronic inflammation may help identify subjects at risk of cancer. Previous studies have reported low albumin-to-globulin ratio (AGR) to be associated with increased cancer mortality in cancer patients, but there has been no study based on healthy populations. Our retrospective cohort study involved 26 974 generally healthy adults aged 30 or older who visited Seoul National University Hospital Health Promotion Center for self-referred health checkup. National medical service claims data were used to determine cancer incidence, and Korean death registry data was used to determine mortality. Median follow-up time for survival was 5.9 years (interquartile range 4.1 years). Compared with subjects with AGR ≥ 1.5, subjects with 1.1 > AGR ≥ 1.0 and 1.0 > AGR showed adjusted hazard ratio (aHR) 2.69 (95% confidence interval, CI, 1.54-4.72) and aHR 6.71 (95% CI 3.56-12.66) for all-cause mortality, aHR 2.95 (95% CI 1.42-6.11) and aHR 4.38 (95% CI 1.57-12.25) for cancer mortality, and aHR 2.07 (95% CI 1.28-3.36) and aHR 3.99 (95% CI 2.10-7.58) for cancer incidence, respectively. When cancer incidence events after 2 years from baseline were separately analyzed, subjects with 1.1 > AGR ≥ 1.0 and 1.0 > AGR were associated with aHR 1.88 (95% CI 1.01-3.48) and aHR 2.55 (95% CI 1.03-7.11) for cancer incidence, respectively. Cancer events were increased in all types of cancer, but especially in liver and hematologic malignancies. Low AGR is a risk factor for cancer incidence and mortality, both short- and long terms, in a generally healthy screened population. The results of this study need to be replicated in larger studies, along with the determination of the sensitivity and other diagnostic values of low AGR.


A cohort study of regional migration and the risks of attempted suicide and violent assault injury.
We study the association between changing residence and risks of attempted suicide and violent assault injury in Alberta, Canada. Our primary objective is to understand whether a change in residence between urban, rural and semiurban areas is associated with increased risk of intentional injury. Study subjects are a cohort of residents linked to data on emergency department and inpatient hospital admissions between 1999 and 2010. We used generalised estimating equations to model the effects of changing residence on risk of intentional injury while controlling for the influence of age, sex, socio-economic status, Aboriginal status and history of intentional injury. Changing residence is associated with an increase in the risk of both attempted suicide and violent assault injury. In the case of attempted suicide, this effect is strongest for persons between 20 and 35 years of age. For violent assault injuries, persons from rural regions that have recently moved to urban regions have higher risk of injuries, and women of rural origin are at higher risk of violent assault injury than women of urban origin. Our findings reveal an association between risk of intentional injuries and change of residence adjusting for geographical differences in injury risk. These findings suggest that intentional injury risk is associated with change in community at intraregional scales and that these populations may benefit from support that helps integrate them into their new communities.


Breastfeeding, the use of docosahexaenoic acid-fortified formulas in infancy and neuropsychological function in childhood.
To investigate the relation between breastfeeding, use of docosahexaenoic acid (DHA)-fortified formula and neuropsychological function in children. Prospective cohort study. Southampton, UK. 241 children aged 4 years followed up from birth. IQ measured by the Wechsler Pre-School and Primary Scale of Intelligence (3rd edn), visual attention, visuomotor precision, sentence repetition and verbal fluency measured by the NEPSY, and visual form-constancy measured by the Test of Visual-Perceptual Skills (Non-Motor). In unadjusted analyses, children for whom breast milk or DHA-fortified formula was the main method of feeding throughout the first 6 months of life had higher mean full-scale and verbal IQ scores at age 4 years than those fed mainly unfortified formula. After adjustment for potential confounding factors, particularly maternal IQ and educational attainment, the differences in IQ between children in the breast milk and unfortified formula groups were severely attenuated, but children who were fed DHA-fortified formula had full-scale and verbal IQ scores that were respectively 5.62 (0.98 to 10.2) and 7.02 (1.56 to 12.4) points higher than children fed unfortified formula. However, estimated total intake of DHA in milk up to age 6 months was not associated with subsequent IQ or with score on any other test. Differences in children's intelligence according to type of milk fed in infancy may be due more to confounding by maternal or family characteristics than to the amount of long-chain polyunsaturated fatty acids they receive in milk.


Effect of Body Temperature on Cerebral Autoregulation in Acutely Comatose Neurocritically Ill Patients.
Impaired cerebral autoregulation following neurologic injury is a predictor of poor clinical outcome. We aimed to assess the relationship between body temperature and cerebral autoregulation in comatose patients. Retrospective analysis of prospectively collected data. Neurocritical care unit of the Johns Hopkins Hospital. Eighty-five acutely comatose patients (Glasgow Coma Scale score of ≤ 8) admitted between 2013 and 2017. None. Cerebral autoregulation was monitored using multimodal monitoring with near-infrared spectroscopy-derived cerebral oximetry index. Cerebral oximetry index was calculated as a Pearson correlation coefficient between low-frequency changes in regional cerebral oxygenation saturation and mean arterial pressure. Patients were initially analyzed together, then stratified by temperature pattern over the monitoring period: no change (< 1°C difference between highest and lowest temperatures; n = 11), increasing (≥ 1°C; n = 9), decreasing (≥ 1°C; n = 9), and fluctuating (≥ 1°C difference but no sustained direction of change; n = 56). Mixed random effects models with random intercept and multivariable logistic regression analysis were used to assess the association between hourly temperature and cerebral oximetry index, as well as between temperature and clinical outcomes. Cerebral oximetry index showed a positive linear relationship with temperature (β = 0.04 ± 0.10; p = 0.29). In patients where a continual increase or decrease in temperature was seen during the monitoring period, every 1°C change in temperature resulted in a cerebral oximetry index change in the same direction by 0.04 ± 0.01 (p < 0.001) and 0.02 ± 0.01 (p = 0.12), respectively, after adjusting for PaCO2, hemoglobin, mean arterial pressure, vasopressor and sedation use, and temperature probe location. There was no significant difference in mortality or poor outcome (modified Rankin Scale score of 4-6) between temperature pattern groups at discharge, 3, or 6 months. In acute coma patients, increasing body temperature is associated with worsening cerebral autoregulation as measured by cerebral oximetry index. More studies are needed to clarify the impact of increasing temperature on cerebral autoregulation in patients with acute brain injury.


Consumption of dairy products and the risk of breast cancer: a review of the literature.
Differences in eating patterns and breast cancer rates across countries suggest that several dietary components, including dairy products, could affect breast cancer risk. However, dairy products are a diverse food group in terms of the factors that could potentially influence risk. Some dairy products, such as whole milk and many types of cheese, have a relatively high saturated fat content, which may increase risk. Moreover, milk products may contain contaminants such as pesticides, which have carcinogenic potential, and growth factors such as insulin-like growth factor I, which have been shown to promote breast cancer cell growth. In contrast, the calcium and vitamin D contents of dairy products have been hypothesized to reduce breast cancer risk. We reviewed the current epidemiologic literature on the relation between dairy product intakes and breast cancer risk, focusing primarily on the results of cohort and case-control studies. Most of the studies reviewed showed no consistent pattern of increased or decreased breast cancer risk with a high consumption of dairy products as a whole or when broken down into high-fat and low-fat dairy products, milk, cheese, or butter. Measurement error may have attenuated any modest association with dairy products. The available epidemiologic evidence does not support a strong association between the consumption of milk or other dairy products and breast cancer risk.


Maximum intensity projection images in the detection of simulated pulmonary nodules by spiral CT.
This study was undertaken to investigate the use of maximum intensity projection (MIP) images in the detection of pulmonary nodules by spiral CT (SCT). 40 pulmonary nodules of high density were created by endobronchial deployment of 2 and 4 mm beads in the peripheral airways of five anesthetized dogs. Standard SCT was performed with 5 mm collimation, pitch 2 and reconstruction of contiguous slices. MIP images were generated from overlapped slabs of seven consecutive 3 mm slices, reconstructed at 2 mm intervals and acquired at pitch 2. Scans were reviewed by six radiologists. The data were modelled using ordinal logistic regression for repeated measures, and the Wald chi 2 statistic used to test if there was a difference in nodule detection and reader confidence level between the two techniques. MIP imaging increased the odds of nodule detection by 2.18 (p = 0.0002). Reader confidence level for nodule detection was significantly higher with MIP images (p < 0.00001). MIP images improve the detection rate for small high density pulmonary nodules and increase reader confidence level, when compared with standard SCT.


Vitamin A supplementation for postpartum women.
In vitamin A deficient populations, the amount of vitamin A may be insufficient for maintenance of maternal health and levels in breast milk may be insufficient for breastfeeding infants' needs. To assess the effects of postpartum maternal vitamin A supplementation on maternal and infant health. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 July 2010), LILACS (1982 to July 2010), Web of Science (1945 to July 2010) and Biological Abstracts (1998 to July 2010). Randomised controlled trials evaluating the effects of postpartum maternal vitamin A supplementation. Two review authors assessed the studies independently. We included 12 trials at moderate risk of bias, enrolling 25,465 mother-baby pairs and comparing several postpartum doses (200,000-400,000 IU) of vitamin A or 7.8 mg daily beta-carotene, with placebo, iron or no supplement; or higher (400,000 IU) versus lower dose (200,000 IU). The majority of infants in all studies were at least partially breastfed for six months.Maternal: we observed no impact of vitamin A on maternal mortality (two trials of 9,126 women), morbidity (one trial of 50 women) or adverse effects (subset of 786 women in one trial). Vitamin A enhanced serum and breast milk retinol at three months in five trials, but these improvements were generally not sustained.Infant: we observed no significant differences for infant mortality RR 1.14 95% CI 0.84 to 1.57 (five trials (6,170 infants) or morbidity (three trials) except for fewer episodes of fever with vitamin A in one small trial. No significant differences in infant vitamin A status were seen with maternal vitamin A supplementation (five trials).No beneficial effects for maternal or infant health were associated with higher compared to lower doses of vitamin A in two trials. The lack of effect on maternal and infant mortality and morbidity, with exception of some improved infant morbidity in one small study, and the improvement in maternal vitamin A status, suggest that maternal postpartum vitamin A supplementation offers limited benefits.


Combined electrical stimulation and exercise for swallow rehabilitation post-stroke: a pilot randomized control trial.
Dysphagia is common after stroke, affecting up to 50% of patients initially. It can lead to post-stroke pneumonia, which causes 30% of stroke-related deaths, a longer hospital stay and poorer health outcomes. Dysphagia care post-stroke generally focuses on the management of symptoms, via modified oral intake textures and adapted posture, rather than direct physical rehabilitation of the swallowing function. Transcutaneous neuromuscular electrical stimulation (NMES) is a promising rehabilitation technology that can be used to stimulate swallowing; however, findings regarding efficacy have been conflicting. This pilot randomized controlled study involving three UK sites compared the efficacy of the Ampcare Effective Swallowing Protocol (ESP), combining NMES with swallow-strengthening exercises, with usual care in order to clarify evidence on NMES in the treatment of dysphagia post-stroke. A further objective was to pilot recruitment procedures and outcome measures in order to inform the design of a full-scale trial. Thirty patients were recruited and randomized into either (1) usual speech and language therapy dysphagia care; or (2) Ampcare ESP, receiving treatment 5 days/week for 4 weeks. Outcome measures included: the Functional Oral Intake Scale (FOIS), the Rosenbek Penetration-Aspiration Scale (PAS) and patient-reported outcomes (Swallow Related Quality of Life-SWAL-QOL). Thirty patients were recruited; 15 were randomized to the Ampcare ESP intervention arm and 15 to usual care. A greater proportion (75%, or 9/12) of patients receiving Ampcare ESP improved compared with 57% (or 8/14) of the usual-care group. Patients receiving Ampcare ESP also made clinically meaningful change (a comparative benefit of 1.5 on the FOIS, and on the PAS: 1.35 for diet and 0.3 for fluids) compared with usual care. The intervention group also reported much better outcome satisfaction. The pilot demonstrated successful recruitment, treatment safety and tolerability and clinically meaningful outcome improvements, justifying progression to a fully powered study. It also showed clinically meaningful treatment trends for the Ampcare ESP intervention.


Effects of antihypertensive treatment after acute stroke in the Continue or Stop Post-Stroke Antihypertensives Collaborative Study (COSSACS): a prospective, randomised, open, blinded-endpoint trial.
Up to 50% of patients with acute stroke are taking antihypertensive drugs on hospital admission. However, whether such treatment should be continued during the immediate post-stroke period is unclear. We therefore aimed to assess the efficacy and safety of continuing or stopping pre-existing antihypertensive drugs in patients who had recently had a stroke. The Continue or Stop Post-Stroke Antihypertensives Collaborative Study (COSSACS) was a UK multicentre, prospective, randomised, open, blinded-endpoint trial. Patients were recruited at 49 UK National Institute for Health Research Stroke Research Network centres from January 1, 2003, to March 31, 2009. Patients aged over 18 years who were taking antihypertensive drugs were enrolled within 48 h of stroke and the last dose of antihypertensive drug. Patients were randomly assigned (1:1) by secure internet central randomisation to either continue or stop pre-existing antihypertensive drugs for 2 weeks. Patients and clinicians who randomly assigned patients were unmasked to group allocation. Clinicians who assessed 2-week outcomes and 6-month outcomes were masked to group allocation. The primary endpoint was death or dependency at 2 weeks, with dependency defined as a modified Rankin scale score greater than 3 points. Analysis was by intention to treat. This trial is registered with the International Standard Randomised Controlled Trial Register, number ISRCTN89712435. 763 patients were assigned to continue (n=379) or stop (n=384) pre-existing antihypertensive drugs. 72 of 379 patients in the continue group and 82 of 384 patients in the stop group reached the primary endpoint (relative risk 0.86, 95% CI 0.65-1.14; p=0.3). The difference in systolic blood pressure at 2 weeks between the continue group and the stop group was 13 mm Hg (95% CI 10-17) and the difference in diastolic blood pressure was 8 mm Hg (6-10; difference between groups p<0.0001). No substantial differences were observed between groups in rates of serious adverse events, 6-month mortality, or major cardiovascular events. Continuation of antihypertensive drugs did not reduce 2-week death or dependency, cardiovascular event rate, or mortality at 6 months. Lower blood pressure levels in those who continued antihypertensive treatment after acute mild stroke were not associated with an increase in adverse events. These neutral results might be because COSSACS was underpowered owing to early termination of the trial, and support the continuation of ongoing research trials. The Health Foundation and The Stroke Association.


'We are the bridge': an implementation research study of SEWA Shakti Kendras to improve community engagement in publicly funded health insurance in Gujarat, India.
India's efforts towards universal health coverage include a national health insurance scheme that aims to protect the most vulnerable from catastrophic health expenditure. However, emerging evidence on publicly funded health insurance, as well as experience from community-based schemes, indicates that women face specific barriers to access and utilisation. Community engagement interventions have been shown to improve equitable utilisation of public health services, but there is limited research specific to health insurance. We examined how existing community-based resource centres implemented by a women's organisation could improve women's access to, and utilisation of, health insurance. We conducted an implementation research study in Gujarat, India to examine how SEWA Shakti Kendras, established by the Self-Employed Women's Association, worked to improve community engagement in health insurance. SEWA organises women in the informal sector and provides social protection through health, insurance and childcare services. We examined administrative data, programme reports and conducted 30 in-depth qualitative interviews with users and staff. Data were analysed thematically to examine intervention content, context, and implementation processes and to identify enablers and barriers to improving women's access to health insurance through SEWA's community engagement approach. The centres worked through multiple channels-doorstep services, centre-based support and health system navigation-to strengthen women's capability to access health insurance. Each centre's approach varied by contextual factors, such as women's digital literacy levels and rural-urban settings. Effective community engagement required local leadership, strong government partnerships and the flexibility to address a range of public services, with implementation by trusted local health workers. SEWA Shakti Kendras demonstrate how a local, flexible and community-based model can serve as a bridge to improve utilisation of health insurance, by engaging women and their households through multiple channels. Scaling up this approach will require investing in partnerships with community-based organisations as part of strategies towards universal health coverage.


QT interval in normal infants during sleep with concurrent evaluation of QT correction formulae.
Physiological changes in the QT interval caused by sleep are important in the evaluation of the normal QT interval. Traditionally, Bazett's formula is used for correcting the QT interval for heart rate in childhood. We set out to establish the QT-RR relationship in infants during sleep and concurrently test the performance of four QT correction formulae to determine their comparability and clinical utility. 130 healthy term born infants undergoing routine 8-hour polysomnography were enrolled. Continuous EKG limb lead II recording, saturation monitoring, and electroencephalography were conducted. QT intervals and heart rate were measured manually digitally on-screen at hourly intervals. The QT-RR relationship was plotted and QTc calculated using the Bazett, Hodges, Fridericia and Framingham formulae. QTc values for each formula were plotted against age and RR interval. Analysis of variance and regression analysis were used to compare the four formulae and the QT-RR relationship. Mean age was 17.7 weeks (range 4-72) and mean weight 6.3 kg (range 2.68-12.7). The QT-RR relationship during sleep is curvilinear and appears to be slightly shifted. With increasing heart rate and younger age the Bazett and Hodges formulae overcorrect the QTc whereas the Fridericia and Framingham formulae undercorrect. The Hodges formula correlated best with the RR interval. These formulae are strongly dependent on heart rate. In the setting of a borderline QTc Bazett prolongation, Hodges formula may be a useful adjunct. Normal infants may have a slightly longer QTc Bazett during sleep.


An analysis of the genetics of alcohol intoxication in inbred mice.
We compared the behaviors of eight inbred mouse strains across 18 variables, using 11 behavioral assays, and gave ethanol (EtOH) as an intoxicant. Genetic influences on behavior and sensitivity to EtOH were pronounced, but strain sensitivities were generally only modestly correlated across tasks. Certain well-correlated clusters of responses suggested that some genes affect similar neurobiological substrates. No strains of mice were generally sensitive or resistant to intoxication across tasks. Anthropomorphically appealing concepts like 'muscle strength' had little explanatory power across tasks. A battery of selected tests was proposed for future studies. Overall, the results show that each mouse behavioral assay captures only a portion of ataxia, a genetically complex behavioral domain. Conversely, multiple behavioral capacities are apparently required for performance in each specific assay. Thus, if only one or two tests are used to evaluate motor function in genetically engineered mutant mice, only a small portion of the domain will be assessed and results may be misleading. This caveat likely extends to many behavioral domains (e.g. learning and memory, anxiety).


HIV prevention in southern Africa: why we must reassess our strategies?
Southern Africa continues to shoulder a disproportionate burden of the HIV epidemic with the number of new infections outstripping treatment initiation two- to threefold. Current prevention strategies have had a limited impact on the trajectory of the epidemic so far. The history of HIV prevention research is dominated by failed approaches, but recent developments have provided reason for hope. These include the successful male circumcision outcomes in trials in South Africa, Kenya and Uganda, the recent protective outcome of a tenofovir vaginal gel trial in South Africa and the proof that pre-exposure prophylaxis with oral combination tenofovir/emtricitabine can work in men. The latter positive outcome has however been shattered by the early closure of FEM-PrEP for futility. The challenge now is on how to best integrate emerging prevention methods with established strategies, recognising that some of the older methods have never been scaled up to saturation level.


Aductive laser iridoplasty and laser goniopuncture after non-perforating trabeculectomy.
Successful non-perforating trabeculectomy (NPT) results in filtration of aqueous humor out of the anterior chamber and into a filtration bleb, without surgical excision of tissue from the anterior chamber angle, and without penetration into the anterior chamber. The complications of perforating trabeculectomy, due to early postoperative hypotony (shallow anterior chamber, hyphema, macular folds, suprachoroidal effusion, and ciliochoroidal hemorrhage) (3, 4, 5, 6, 7, 8, 9) are regarded by many surgeons as significant risks. Nonperforating surgery has been reported to reduce the incidence of early hypotony-related complications (10), because it has the advantage of creating gradual filtration of aqueous humor, through a thin trabeculodescemetic membrane (TDM), which markedly reduces postoperative complications seen after a conventional trabeculectomy (11), and also has been reported to provide better long-term intraocular pressure (IOP) control (12, 13). NPT is reported to be a procedure with a significant learning curve, sometimes necessitating conversion to perforating trabeculectomy, and requiring careful postoperative monitoring (14, 15, 16, 17). Zimmerman et al. reported filtration of aqueous humor under a filtering bleb, by resecting the roof of Schlemms canal and removing corneal stroma overlying the trabecular meshwork (18) Mermoud et al. reported filtration of aqueous humor under a filtering, bleb by unroofing Schlemms canal and removing corneal stroma overlying the trabecular meshwork as well Descemets membrane (19); he found that resistance across the TDM sometimes increased with time. When this resistance to aqueous humor outflow occurred, Mermoud found TDM resistance could be eliminated by performance of goniopuncture (ab interno Nd:YAG laser membranotomy via gonioprism), to enhance aqueous humor outflow into the filtration bleb. Failure to filter adequately through the TDM is a potential complication following NPT which can result in a rise in intraocular pressure (IOP). In this paper we examine the effectiveness of adjunctive Nd:YAG laser goniopuncture (YGP) in patients who underwent NPT, to reduce post-operative IOP rise, secondary to scarring at or poor aqueous outflow through the TDM. Iris prolapse (IP) is another potential complication following NPT which can result in a rise in IOP. In this paper we examine the effectiveness of adjunctive argon laser peripheral iridoplasty (ALPI) in patients who underwent NPT, to reduce post-operative IOP rise, secondary to IP obstructing outflow across the TDM. Nd:YAG laser goniopuncture consists of placing several laser shots on the undersurface of the trabeculodescemetic membrane. The result is a microperforation in this membrane, with flow of aqueous into the filtration bleb, which converts a non-perforating filtration procedure into a partial thickness filtration procedure. In this technique, several high power, multi-burst shots are applied, ab interno, by a Nd:YAG laser via a gonioprism, to the underside of the TDM, to facilitate aqueous outflow out from the anterior chamber. YGP can be effective when increased aqueous outflow is desired postoperatively. After this procedure, patent perforation in the TDM is usually observed gonioscopically, generally accompanied with reduction in IOP, and increase in bleb elevation (in height and in circumferential extent). Argon laser peripheral iridoplasty consists of placing several laser burns on the surface of the peripheral iris to contract the iris stroma, in a centripetal fashion, between the site of the burn and the anterior chamber angle. The result is iris stromal tissue contraction and compaction, movement of IP away from the angle and toward the pupil, which physically widens the angle and clears the synechial apposition of the peripheral iris against the TDM. In this technique, a series of low power, long duration, and large size burns is applied to the iris periphery to contract the iris stroma, to open the angle, and to clear IP causing synechial obstruction of the TDM after successful NPT. Used previously in acute angle closure glaucoma, ALPI may be effective in controlling IOP and clearing corneal edema when systemic and topical anti-glaucoma treatments fail to control high IOP, and when laser peripheral iridotomy (LPI) is not possible (e.g. in cases of severe corneal edema). Additionally, ALPI can be effective in permanently reopening the anterior chamber angle of iridectomized eyes with plateau iris syndrome; in this technique a full 360 degrees ring of spots is often applied, but a more limited area of treatment may also be effective. When a post-operative elevation in IOP was detected in a patients eye which had undergone NPT, careful indentation gonioscopy was performed to examine the TDM at the surgical site. If the peripheral iris was flat, the anterior chamber angle was open, and the TDM did not appear obstructed by IP, YGP was performed. First, the eyes were pre-treated with aproclonodine 1% and pilocarpine 2% (if needed to allow visualization of the TDM). Next, a Nd:YAG laser was set on triple burst mode and shots were applied to the underside of the TDM at the NPT site, using a Goldman 3-mirror lens in the following manner: Energy - 3-5 mJ; Mode - Triple burst. The power and amount of spots were titrated in order to achieve partial or microperforation of TDM at the NPT surgical site, thus resulting in restoration of aqueous outflow into the filtration bleb. When a post-operative elevation in IOP was detected in a patients eye which had undergone NPT and or YGP, careful indentation gonioscopy was performed to examine the TDM at the surgical site. If irreducible synechial IP were detected, which obstructed filtration through the TDM at the NPT surgical site, ALPI was performed. First, the eyes were pre-treated with aproclonodine 1% and pilocarpine 2%. Next, an argon laser was set on blue-green mode and shots were applied to the IP adherent to cornea or to the TDM at the NPT site, using a Goldman 3-mirror lens in the following manner: Spot Size - 500 mM; Duration - 0.5 s; Power - 200 to 400 mW. The power and amount of burns were titrated in order to achieve partial or complete centripetal retraction of the IP from the TDM at the NPT surgical site, causing a clearance of the obstruction to the TDM, thus resulting in restoration of aqueous outflow into the filtration bleb.


Measurement of flow harmonics with multi-particle cumulants in Pb+Pb collisions at [Formula: see text] TeV with the ATLAS detector.
ATLAS measurements of the azimuthal anisotropy in lead-lead collisions at [Formula: see text] TeV are shown using a dataset of approximately 7 [Formula: see text]b[Formula: see text] collected at the LHC in 2010. The measurements are performed for charged particles with transverse momenta [Formula: see text] GeV and in the pseudorapidity range [Formula: see text]. The anisotropy is characterized by the Fourier coefficients, [Formula: see text], of the charged-particle azimuthal angle distribution for [Formula: see text]-4. The Fourier coefficients are evaluated using multi-particle cumulants calculated with the generating function method. Results on the transverse momentum, pseudorapidity and centrality dependence of the [Formula: see text] coefficients are presented. The elliptic flow, [Formula: see text], is obtained from the two-, four-, six- and eight-particle cumulants while higher-order coefficients, [Formula: see text] and [Formula: see text], are determined with two- and four-particle cumulants. Flow harmonics [Formula: see text] measured with four-particle cumulants are significantly reduced compared to the measurement involving two-particle cumulants. A comparison to [Formula: see text] measurements obtained using different analysis methods and previously reported by the LHC experiments is also shown. Results of measurements of flow fluctuations evaluated with multi-particle cumulants are shown as a function of transverse momentum and the collision centrality. Models of the initial spatial geometry and its fluctuations fail to describe the flow fluctuations measurements.


Surface roughness of dental implants and treatment time using six different implantoplasty procedures.
To test whether or not one of six implantoplasty procedures is superior to the others rendering a minimal final implant surface roughness and a short treatment time. Forty-two one-piece implants were embedded in epoxy resin blocks with 6-mm rough implant surface exposed. The following implantoplasty polishing sequences were applied: Brownie(®) , Greenie(®) sequence (BG) (diamond rotary instruments 106-, 40-, 15-μm grit, Brownie(®) , Greenie(®) silicone polishers); Arkansas stone sequence (AS) (diamond 106-, 40-, 15-μm grit, Arkansas stone torpedo-shaped bur); Short diamond sequence (SD) (diamond 106-, 40-, 4-μm grit); Short diamond sequence with Greenie(®) (SDG) (diamond 106-, 40-, 4-μm grit, Greenie(®) ); Complete diamond sequence (CD) (diamond 106-, 40-, 15-, 8-, 4-μm grit); Complete diamond sequence with Greenie(®) (CDG) (106-, 40-, 15-, 8-, 4-μm grit, Greenie(®) ). The polished neck portion served as a positive control, the untreated sandblasted and acid-etched surface as negative control. Each implant was scanned with a contact profilometer rendering Ra values and Rz values as a measure of surface roughness. The time needed to polish the implant surface for each group was recorded. Simultaneous comparisons between more than two groups were done performing Kruskal-Wallis tests. Comparisons between two groups were analysed using Wilcoxon rank-sum tests. Mean Ra values amounted to 0.32 ± 0.14 μm (BG), 0.39 ± 0.13 μm (AS), 0.59 ± 0.19 μm (SDG), 0.71 ± 0.22 μm (SD), 0.75 ± 0.26 μm (CDG), 0.98 ± 0.30 μm (CD), 0.10 ± 0.01 μm (PC) and 1.94 ± 0.47 μm (NC). Pairwise one-sided comparisons between the test group revealed statistically significant differences (P < 0.05). The shortest treatment time was recorded for group AS (13 ± 2 min) and the longest for CDG (21 ± 2 min) and BG (21 ± 4 min). Considering final surface roughness and treatment duration, the use of rotary diamond burs in decreasing roughness, followed by an arkansas stone (group AS), appears to be an optimal treatment option.


The Potential of Current Noninvasive Wearable Technology for the Monitoring of Physiological Signals in the Management of Type 1 Diabetes: Literature Survey.
Monitoring glucose and other parameters in persons with type 1 diabetes (T1D) can enhance acute glycemic management and the diagnosis of long-term complications of the disease. For most persons living with T1D, the determination of insulin delivery is based on a single measured parameter-glucose. To date, wearable sensors exist that enable the seamless, noninvasive, and low-cost monitoring of multiple physiological parameters. The objective of this literature survey is to explore whether some of the physiological parameters that can be monitored with noninvasive, wearable sensors may be used to enhance T1D management. A list of physiological parameters, which can be monitored by using wearable sensors available in 2020, was compiled by a thorough review of the devices available in the market. A literature survey was performed using search terms related to T1D combined with the identified physiological parameters. The selected publications were restricted to human studies, which had at least their abstracts available. The PubMed and Scopus databases were interrogated. In total, 77 articles were retained and analyzed based on the following two axes: the reported relations between these parameters and T1D, which were found by comparing persons with T1D and healthy control participants, and the potential areas for T1D enhancement via the further analysis of the found relationships in studies working within T1D cohorts. On the basis of our search methodology, 626 articles were returned, and after applying our exclusion criteria, 77 (12.3%) articles were retained. Physiological parameters with potential for monitoring by using noninvasive wearable devices in persons with T1D included those related to cardiac autonomic function, cardiorespiratory control balance and fitness, sudomotor function, and skin temperature. Cardiac autonomic function measures, particularly the indices of heart rate and heart rate variability, have been shown to be valuable in diagnosing and monitoring cardiac autonomic neuropathy and, potentially, predicting and detecting hypoglycemia. All identified physiological parameters were shown to be associated with some aspects of diabetes complications, such as retinopathy, neuropathy, and nephropathy, as well as macrovascular disease, with capacity for early risk prediction. However, although they can be monitored by available wearable sensors, most studies have yet to adopt them, as opposed to using more conventional devices. Wearable sensors have the potential to augment T1D sensing with additional, informative biomarkers, which can be monitored noninvasively, seamlessly, and continuously. However, significant challenges associated with measurement accuracy, removal of noise and motion artifacts, and smart decision-making exist. Consequently, research should focus on harvesting the information hidden in the complex data generated by wearable sensors and on developing models and smart decision strategies to optimize the incorporation of these novel inputs into T1D interventions.