[THE EPIDEMIOLOGICAL AND EPIZOOTIOLOGICAL COMPONENT OF TOXOCARIASIS FOCI AS AN ELEMENT OF THE ENVIRONMENTAL MANAGEMENT SYSTEM (IN CASE OF THE REPUBLIC OF ALTAI)].
The epidemiological and epizootiological features of toxocariasis foci were investigated in the Republic of Altai. The results of coproovoscopic examinations of dogs, those of serological screening for toxocariasis among different age and occupational groups and coniingents at risk for HIV infection, hepatitis B and C, patients with allergic and bronchopulmonary diseases, toxocariasis mortality rates in the Republic of Altai, and the materials of sanitary and parasitological studies of soil and other environmental constituents for Toxocara canis eggs provide support for the poor situation of toxocariasis in the region. Relying on the current standards and the findings of this study, the Republic of Altai may be referred to as a moderately dangerous area at medium risk for contamination in terms of epidemic, epizootic, and environmental hazards. The results of assessing the quality of laboratory diagnosis of zoonotic helminthisms call for further improvement of the professional knowledge, abilities, and skills of the employees from health care and veterinary facilities, as well as economic objects within production laboratory control, basing on the principles and requirements of the environmental management system and the food quality and safety management system.


Therapeutic biliary endoscopy.
Therapeutic biliary endoscopy is continuing to evolve; some small but important developments were seen during the last year. Competing techniques are continuing to develop.


Deficiency of BMAL1 promotes ROS generation and enhances IgE-dependent degranulation in mast cells.
Bmal1 (Brain and muscle arnt-like, or Arntl) is a bHLH/PAS domain transcription factor central to the transcription/translation feedback loop of the circadian clock. Mast cells are crucial for effector functions in allergic reaction and their activity follows a circadian rhythm. However, the functional roles of Bmal1 in mast cells remain to be determined. This study aimed to elucidate the specific roles of Bmal1 in IgE-dependent mast cell degranulation. IgE-dependent degranulation was enhanced in bone marrow-derived mast cells (BMMCs) derived from Bmal1-deficient mice (Bmal1-KO mice) compared to that in BMMCs derived from wild-type mice (WT mice) in the absence of 2-Mercaptoethanol (2-ME) in culture. Mast cell-deficient KitW-sh mice reconstituted with Bmal1-KO BMMCs showed more robust passive cutaneous anaphylactic (PCA) reactions, an in vivo model of IgE-dependent mast cell degranulation, than KitW-sh mice reconstituted with WT BMMCs. In the absence of 2-ME in culture, the mRNA expression of the anti-oxidative genes NF-E2-related factor 2 (Nrf2), superoxide dismutase 2 (SOD2), and heme oxygenase-1 (HO-1) was lower and reactive oxygen species (ROS) generation was higher in Bmal1-KO BMMCs than in WT BMMCs at steady state. The IgE-dependent ROS generation and degranulation were enhanced in Bmal1-KO BMMCs compared to WT BMMCs in the absence of 2-ME in culture. The addition of 2-ME into the culture abrogated or weakened the differences in anti-oxidative gene expression, ROS generation, and IgE-dependent degranulation between WT and Bmal1-KO BMMCs. The current findings suggest that Bmal1 controls the expression of anti-oxidative genes in mast cells and Bmal1 deficiency enhanced IgE-dependent degranulation associated with promotion of ROS generation. Thus, Bmal1 may function as a key molecule that integrates redox homeostasis and effector functions in mast cells.


Combined use of preoperative 18F FDG-PET imaging and intraoperative gamma probe detection for accurate assessment of tumor recurrence in patients with colorectal cancer.
The purpose of this study was to combine intraoperative gamma probe (GP) detection with preoperative fluorine 18-fluoro-2-deoxy-glucose positron emission tomography (18F FDG-PET) imaging in order to improve detection of tumor recurrence in colorectal cancer (CRC) patients. Twenty-one patients (12 females, 9 males) with a mean age of 54 years (range 31-78) were enrolled. Patients were suspected to have recurrent CRC by elevated CEA (n = 11), suspicious CT findings (n = 1), and clinically suspicious findings (n = 9). Preoperative FDG-PET scan and intraoperative GP study were performed in all patients. Mean time interval between preoperative FDG-PET scan and surgery was 16 days (range 1-41 days) in 19 patients. For intraoperative GP studies, 19 patients were injected with a dose of 10-15 mCi 18F FDG at approximately 30 minutes before the planned surgery time. In two patients, the intraoperative GP study was performed immediately after preoperative FDG-PET scan. Preoperative FDG-PET and intraoperative GP detected 48 and 45 lesions, respectively. A total of 50 presumed site of recurrent disease from 20 patients were resected. Thirty-seven of 50 presumed sites of recurrent disease were histological-proven tumor positive and 13 of 50 presumed sites of recurrent disease were histological-proven tumor negative. When correlated with final histopathology, the number of true positive lesions and false positive lesions by preoperative FDG-PET and intraoperative GP were 31/9 and 35/8, respectively. Both preoperative FDG-PET and intraoperative GP were true positive in 29 lesions. Intraoperative GP detected additional small lesions in the omentum and pelvis which were not seen on preoperative FDG-PET scan. FDG-PET scan demonstrated additional liver metastases which were not detected by intraoperative GP. Preoperative FDG-PET detected distant metastasis in the lung in one patient. The estimated radiation dose received by a surgeon during a single 18F FDG GP surgery was below the occupational limit. The combined use of preoperative FDG-PET and intraoperative GP is potentially helpful to the surgeon as a roadmap for accurately locating and determining the extent of tumor recurrence in patients with CRC. While intraoperative GP appears to be more sensitive in detecting the extent of abdominal and pelvic recurrence, preoperative FDG-PET appears to be more sensitive in detecting liver metastases. FDG-PET is also a valuable method in detecting distant metastases.


Frailty and associated prognosis among older emergency department patients with suspected infection: A prospective, observational cohort study.
Prognosis and disposition among older emergency department (ED) patients with suspected infection remains challenging. Frailty is increasingly recognized as a predictor of poor prognosis among critically ill patients; however, its association with clinical outcomes among older ED patients with suspected infection is unknown. We conducted a multicenter prospective cohort study at two tertiary care EDs. We included older ED patients (≥75 years) with suspected infection. Frailty at baseline (before index illness) was explicitly measured for all patients by the treating physicians using the Clinical Frailty Scale (CFS). We defined frailty as a CFS 5-8. The primary outcome was 30-day mortality. We used multivariable logistic regression to adjust for known confounders. We also compared the prognostic accuracy of frailty with the Systemic Inflammatory Response Syndrome (SIRS) and Quick Sequential Organ Failure Assessment (qSOFA) criteria. We enrolled 203 patients, of whom 117 (57.6%) were frail. Frail patients were more likely to develop septic shock (adjusted odds ratio [aOR], 1.83; 95% confidence interval [CI], 1.08-2.51) and more likely to die within 30 days of ED presentation (aOR 2.05; 95% CI, 1.02-5.24). Sensitivity for mortality was highest among the CFS (73.1%; 95% CI, 52.2-88.4), compared with SIRS ≥ 2 (65.4%; 95% CI, 44.3-82.8) or qSOFA ≥ 2 (38.4; 95% CI, 20.2-59.4). Frailty is a highly prevalent prognostic factor that can be used to risk-stratify older ED patients with suspected infection. ED clinicians should consider screening for frailty to optimize disposition in this population.


Symptomatic Sjögren's syndrome in mixed connective tissue disease.
Twelve of 25 patients with mixed connective tissue disease complained of xerostomia and/or ocular symptoms of keratoconjunctivitis sicca. In addition to the clinical features of mixed connective tissue disease, all 12 patients had high titers of antibody to the ribonuclease-sensitive component of the extractable nuclear antigen. Eight patients had both clinical xerostomia and keratoconjunctivitis sicca, one had keratoconjunctivitis sicca and salivary gland enlargement, while there had xerostomia but no ocular complaints. Sjörgren's syndrome was confirmed in all 12 patients by means of Schirmer's tests, Rose Bengal staining tests, salivary gland scintiscans, radionuclide excretion studies in saliva, parotid sialographies, and lip biopsies. At least three of these tests were abnormal in all patients.


Are immune complexes a factor in the pathogenesis of otitis media with effusion?
The authors investigated the presence of IgG-containing immune complexes in middle ear effusions as well as in middle ear mucosa and mastoid mucosa using the Raji cell radioimmunoassay (RIA), the inhibition of anti-antibody, and direct immunofluorescence tests. The Raji cell RIA showed positive results in two of 15 concentrated middle ear effusions but in none of 26 unconcentrated samples. The anti-antibody inhibition assay revealed immune complexes in two of 26 unconcentrated fluids. Thus, with two assays for soluble immune complexes, only four of 63 samples (6 per cent) were positive. Direct immunofluorescence of middle ear mucosa and mastoid mucosa resulted in localization of IgA and IgG in the plasma cells of the middle ear mucosa. A concomitant immunofluorescent staining for complement or immunoglobulin deposits along the basement membrane of the epithelium and/or blood vessels was not observed in 37 biopsy specimens. These findings do not support the concept that immune complexes are involved in the pathogenesis of otitis media with effusion.


Cloning of the chicken progesterone receptor.
Monospecific antibodies directed against the chicken progesterone receptor (PR) form B were used to screen a randomly primed phage lambda gt11 cDNA expression library prepared from size-fractionated chicken oviduct mRNA. Two independent immunoreactive clones, lambda cPR1 and lambda cPR2, were isolated. Antibodies selected from anti-PR form B antiserum on matrices of lambda cPR1 and lambda cPR2 fusion proteins detected two proteins on electrophoretic immunoblots of crude and purified PR preparations. These proteins had the same apparent molecular weights as did PR forms A and B crosslinked with the tritiated progestin R 5020. Thus, lambda cPR1 and lambda cPR2 fusion proteins contain epitopes present in both PR forms A and B. A cDNA clone, lambda cPR3, containing the inserts of both lambda cPR1 and lambda cPR2, was isolated from a randomly primed lambda gt10 oviduct cDNA library, indicating that both cDNA inserts were derived from the same oviduct mRNA. Additional evidence that these cDNAs correspond to PR mRNA was provided by sequencing the lambda cPR3 cDNA insert, since it was found to encode the sequence of three tryptic peptides prepared from purified PR form B. A fourth and a fifth cDNA clone, lambda cPR4 and lambda cPR5, were sequentially isolated from the same lambda gt10 cDNA library beginning with a probe derived from the 3' end of the lambda cPR3 insert. Partial DNA sequencing of lambda cPR4 and lambda cPR5 revealed the presence of a sequence coding for a cysteine-rich domain that is strikingly homologous to the amino acid sequences present in the putative DNA-binding domain of the human and chicken estrogen receptors, human glucocorticoid receptor, and v-erbA gene product of the avian erythroblastosis virus.


Approach to the patient with diffuse lung disease.
When evaluating diffuse lung infiltrates, the clinician should place special emphasis on the acuity of symptoms, nonpulmonary complaints and findings, environmental exposures, and risk factors for immunosuppressive diseases. Certain radiographic features, such as the distribution of opacities, hilar adenopathy, Kerley-B lines or pneumothorax, or pulmonary function tests demonstrating air flow limitation also narrow the differential diagnosis. One can direct the subsequent workup based on the narrowed differential diagnosis, the pace of disease, the activity of the ongoing inflammatory-immune process, and the age, overall medical condition, and wishes of the patient. Unless a specific diagnosis (for example, hypersensitivity pneumonitis, the treatment of which is withdrawal of the offending agent) can be made, therapy of noninfectious diffuse lung disease is quite unsatisfactory. Immunosuppressive therapy is indicated to arrest the active inflammatory process with the hope that objective signs of improvement will occur after a 3- to 12-month course. Important areas of basic research in pulmonary fibrosis include cell-cell and cell-matrix interactions in the lung interstitium and delineation of fibroblast biology and cytokine-mediated lung connective tissue pathology. More successful therapies will probably evolve from better understanding of the molecular and cellular biology of the lung fibrogenic process.


Interaction of human serum and neutrophils with Escherichia coli strains: differences between strains isolated from urine of patients with pyelonephritis or asymptomatic bacteriuria.
Strains of Escherichia coli isolated from the urine of children with pyelonephritis (n = 18) or asymptomatic bacteriuria (ABU) (n = 20) were serotyped and compared with respect to opsonic requirements, sensitivity to serum, amount of chemiluminescence produced by normal neutrophils during phagocytosis of the various strains, and amount of capsular antigen. Strains isolated from cases of ABU more often had the capacity to activate the alternative complement pathway than had strains causing pyelonephritis. The ABU strains were also better opsonized in fresh human serum and were more often serum sensitive than the pyelonephritic strains. There were individual variations in neutrophil chemiluminescence during phagocytosis of the various strains, but the two groups of strains did not differ significantly. The strains from pyelonephritis cases produced a greater amount of capsular antigens than the ABU strains. There was no correlation between presence of a particular O or K antigen and capacity to activate the alternative complement pathway. The observed differences between strains isolated from patients with ABU and those isolated from patients with pyelonephritis may be relevant for further studies on differences in bacterial virulence or host defense factors.


Critical elements of radical nephroureterectomy for pediatric unilateral renal tumor.
Children with renal masses require surgical management to provide accurate surgical staging and skilled resection of the tumor. This document includes evidence-based recommendations for pediatric surgeons regarding the resection, staging, and proper nodal basin evaluation.


Are Physical and Depressive Symptoms Different Between Women and Men With Heart Failure?: An Exploration Using Two Analytic Techniques.
Adults with heart failure (HF) experience a constellation of symptoms; however, understanding of gender differences in HF symptoms remain elusive. The aim of this study was to determine whether there are gender differences in physical and depressive symptoms and symptom patterns in HF using 2 different analytic techniques. We performed a secondary analysis of combined data from 6 studies of adults with HF. Physical symptoms were measured with the HF Somatic Perception Scale, and depressive symptoms were measured with the Patient Health Questionnaire-9. First, we performed propensity matching with the nearest neighbor to examine the average treatment effect for HF Somatic Perception Scale and Patient Health Questionnaire-9 in the matched sample of women and men. Next, we used the entire data set in a latent class mixture model to determine patterns of symptoms. Finally, we calculated predictors of class membership with multinomial logistic regression. The sample (n = 524, 86.5% systolic HF) was 37% women with a mean age of 58.3 ± 13.9 years and mean number of years with HF of 6.9 ± 6.9. Three hundred sixty-six participants were matched on propensity scores; there were no significant gender differences in symptom scores between matched women (n = 183) and men (n = 183). Among all 524 participants, 4 distinct latent classes of symptom patterns indicate that many patients with HF are fatigued, some have more depressive symptoms, and others have significantly more edema or cough. Gender did not predict membership to any symptom pattern. There were significant gender differences in sociodemographics, health behaviors, and clinical characteristics, but not HF symptoms or symptom patterns, using either analytic technique.


Continual conscious bioluminescent imaging in freely moving somatotransgenic mice.
Luciferase bioimaging in living animals is increasingly being applied in many fields of biomedical research. Rodent imaging usually involves anaesthetising the animal during data capture, however, the biological consequences of anaesthesia have been largely overlooked. We have evaluated luciferase bioimaging in conscious, unrestrained mice after neonatal intracranial or intravascular administration of lentiviral, luciferase reporter cassettes (biosensors); we present real-time analyses from the first day of life to adulthood. Anaesthetics have been shown to exert both neurotoxic and neuroprotective effects during development and in models of brain injury. Mice subjected to bioimaging after neonatal intracranial or intravascular administration of biosensors, targeting the brain and liver retrospectively showed no significant difference in luciferase expression when conscious or unconscious throughout development. We applied conscious bioimaging to the assessment of NFκB and STAT3 transcription factor activated reporters during the earliest stages of development in living, unrestrained pups. Our data showed unique longitudinal activities for NFκB and STAT3 in the brain of conscious mice. Conscious bioimaging was applied to a neonatal mouse model of cerebral palsy (Hypoxic-Ischaemic Encephalopathy). Imaging of NFκB reporter before and after surgery showed a significant increase in luciferase expression, coinciding with secondary energy failure, in lesioned mice compared to controls.


Class-Aware Sounding Objects Localization via Audiovisual Correspondence.
Audiovisual scenes are pervasive in our daily life. It is commonplace for humans to discriminatively localize different sounding objects but quite challenging for machines to achieve class-aware sounding objects localization without category annotations, i.e., localizing the sounding object and recognizing its category. To address this problem, we propose a two-stage step-by-step learning framework to localize and recognize sounding objects in complex audiovisual scenarios using only the correspondence between audio and vision. First, we propose to determine the sounding area via coarse-grained audiovisual correspondence in the single source cases. Then visual features in the sounding area are leveraged as candidate object representations to establish a category-representation object dictionary for expressive visual character extraction. We generate class-aware object localization maps in cocktail-party scenarios and use audiovisual correspondence to suppress silent areas by referring to this dictionary. Finally, we employ category-level audiovisual consistency as the supervision to achieve fine-grained audio and sounding object distribution alignment. Experiments on both realistic and synthesized videos show that our model is superior in localizing and recognizing objects as well as filtering out silent ones. We also transfer the learned audiovisual network into the unsupervised object detection task, obtaining reasonable performance.


Effects of the anthelmintics clorsulon, rafoxanide, mebendazole and arprinocid on Echinostoma caproni in ICR mice.
Female ICR mice, 5 to 6 weeks old, were exposed by stomach tube to 25 metacercarial cysts of Echinostoma caproni per mouse. At 14 days post-exposure, mice were fed by stomach tube clorsulon (1000 mg/kg, 500 mg/kg and 100 mg/ kg) or rafoxanide (50 mg/kg, 25 mg/kg and 5 mg/kg) dissolved in dimethylsulphoxide (DMSO) carrier and mebendazole (1000 mg/kg and 500 mg/ kg) or arprinocid (100 mg/kg and 50 mg/kg) suspended in a 2:1 polyethylene glycol (PEG)/DMSO carrier. All drugs were obtained from Merck Inc. (Rahway, New Jersey, USA) and only single dose regimes were used. Experimentally infected mice that served as controls received either DMSO or 2:1 PEG/DMSO carriers or were not given the carrier. Mice were necropsied 15, 16, 18 and 20 days postexposure to worms. Doses of 100 mg/kg of clorsulon and 50 mg/kg of rafoxanide were 100% effective in eliminating the echinostomes on day 1 post-administration of the anthelmintics. Mebendazole and arprinocid were ineffective in eliminating worms at 1 or 2 days post drug administration.


The role of the mitochondrial oxidative stress in the cytotoxic effects of the green tea catechin, (-)-epigallocatechin-3-gallate, in oral cells.
The tea catechin, (-)-epigallocatechin-3-gallate (EGCG), has potential cancer preventive effects. The prooxidant activity of EGCG may play a role in these effects. Here, we report that EGCG exerted cytotoxic effects against oral cancer cell lines (IC50 = 83-95 μM). EGCG treatment resulted in formation of extracellular reactive oxygen species (ROS), however, these ROS were rapidly cleared (half-life = 1.7 h). EGCG treatment increased the production of mitochondrial H2 O2 in SCC-25 cells (0-6 h) before the induction of apoptosis. Subsequently, an opening of the mitochondrial transition pore and a decrease in mitochondrial membrane potential were observed. The mitochondria-specific antioxidant, MitoTEMPO, reduced these effects. HGF-1 human gingival fibrobasts were resistant to EGCG (IC50 > 200 μM) and EGCG-induced ROS. EGCG induced differential expression of genes related to antioxidant defense in oral cancer cells and gingival fibroblasts: metallothionein 3, superoxide dismutase 2/3, and thioredoxin reductase 2 were downregulated in SCC-25 cells, but upregulated in HGF-1 cells. We conclude that induction of mitochondrial ROS and mitochondrial dysfunction by EGCG play a role in the inhibition of oral cancer, and that gingival fibroblasts are spared from these effects in part because of a selective induction of antioxidant responsive genes.


Cytokine Mediated Control of Muscle Stem Cell Function.
Skeletal muscle stem cells, known as satellite cells (SC), are an absolute requirement for muscle regeneration and contribute significantly to post-natal muscle growth. This stem cell population is governed by a network of transcription factors collectively referred to as the myogenic regulatory factors. These factors are responsible for the progression of a SC from the quiescent state through activation, proliferation and terminal differentiation in a process referred to as the myogenic programme. At each stage in this process, cytokines and growth factors have been shown to play a role in directing the myogenic response. The myogenic programme is complex and requires input from a host of factors that provide both stimulatory and inhibitory signals that regulate SC. Despite years of work in this field, there remains a paucity of information on the precise factors that drive the myogenic programme. In recent years, factors, such as IL-6, have been shown to be critical factors in promoting SC proliferation. In fact, a complete absence of IL-6 in skeletal muscle substantially impairs muscle SC proliferation. These observations highlight the potential importance of the inflammatory response and the cross-talk between inflammatory cells and SC in promoting muscle repair and growth. This chapter will focus on recent advances in cytokine (and some growth factors) regulation of SC. Work from cell, animal and human models will be discussed.


Coupled motion in proteins revealed by pressure perturbation.
The cooperative nature of protein substructure and internal motion is a critical aspect of their functional competence about which little is known experimentally. NMR relaxation is used here to monitor the effects of high pressure on fast internal motion in the protein ubiquitin. In contrast to the main chain, the motions of the methyl-bearing side chains have a large and variable pressure dependence. Within the core, this pressure sensitivity correlates with the magnitude of motion at ambient pressure. Spatial clustering of the dynamic response to applied hydrostatic pressure is also seen, indicating localized cooperativity of motion on the sub-nanosecond time scale and suggesting regions of variable compressibility. These and other features indicate that the native ensemble contains a significant fraction of members with characteristics ascribed to the recently postulated "dry molten globule". The accompanying variable side-chain conformational entropy helps complete our view of the thermodynamic architecture underlying protein stability, folding, and function.


Evaluation of the association between climate warming and the spread and proliferation of Ixodes scapularis in northern states in the Eastern United States.
Ixodes scapularis (the blacklegged tick) is widely distributed in forested areas across the eastern United States. The public health impact of I. scapularis is greatest in the north, where nymphal stage ticks commonly bite humans and serve as primary vectors for multiple human pathogens. There were dramatic increases in the tick's distribution and abundance over the last half-century in the northern part of the eastern US, and climate warming is commonly mentioned as a primary driver for these changes. In this review, we summarize the evidence for the observed spread and proliferation of I. scapularis being driven by climate warming. Although laboratory and small-scale field studies have provided insights into how temperature and humidity impact survival and reproduction of I. scapularis, using these associations to predict broad-scale distribution and abundance patterns is more challenging. Numerous efforts have been undertaken to model the distribution and abundance of I. scapularis at state, regional, and global scales based on climate and landscape variables, but outcomes have been ambiguous. Across the models, the functional relationships between seasonal or annual measures of heat, cold, precipitation, or humidity and tick presence or abundance were inconsistent. The contribution of climate relative to landscape variables was poorly defined. Over the last half-century, climate warming occurred in parallel with spread and population increase of the white-tailed deer, the most important reproductive host for I. scapularis adults, in the northern part of the eastern US. There is strong evidence for white-tailed deer playing a key role to facilitate spread and proliferation of I. scapularis in the US over the last century. However, due to a lack of spatially and temporally congruent data, climate, landscape, and host variables are rarely included in the same models, thus limiting the ability to evaluate their relative contributions or interactions in defining the geographic range and abundance patterns of ticks. We conclude that the role of climate change as a key driver for geographic expansion and population increase of I. scapularis in the northern part of the eastern US over the last half-century remains uncertain.


Analysis of oxygen/glucose-deprivation-induced changes in SUMO3 conjugation using SILAC-based quantitative proteomics.
Transient cerebral ischemia dramatically activates small ubiquitin-like modifier (SUMO2/3) conjugation. In cells exposed to 6 h of transient oxygen/glucose deprivation (OGD), a model of ischemia, SUMOylation increases profoundly between 0 and 30 min following re-oxygenation. To elucidate the effect of transient OGD on SUMO conjugation of target proteins, we exposed neuroblastoma B35 cells expressing HA-SUMO3 to transient OGD and used stable isotope labeling with amino acids in cell culture (SILAC) to quantify OGD-induced changes in levels of specific SUMOylated proteins. Lysates from control and OGD-treated cells were mixed equally, and HA-tagged proteins were immunoprecipitated and analyzed by 1D-SDS-PAGE-LC-MS/MS. We identified 188 putative SUMO3-conjugated proteins, including numerous transcription factors and coregulators, and PIAS2 and PIAS4 SUMO ligases, of which 22 were increased or decreased more than ±2-fold. In addition to SUMO3, the levels of protein-conjugated SUMO1 and SUMO2, as well as ubiquitin, were all increased. Importantly, protein ubiquitination induced by OGD was completely blocked by gene silencing of SUMO2/3. Collectively, these results suggest several mechanisms for OGD-modulated SUMOylation, point to a number of signaling pathways that may be targets of SUMO-based signaling and recovery from ischemic stress, and demonstrate a tightly controlled crosstalk between the SUMO and ubiquitin conjugation pathways.


Demonstration of an erbium-doped fiber with annular doping for low gain compression in cladding-pumped amplifiers.
We present the design and characterization of a cladding-pumped amplifier with erbium doping located in an annular region near the core. This erbium-doped fiber is proposed to reduce gain saturation, leading to smaller gain compression when compared to uniform core doping. Through numerical simulations, we first compare the performance of three fibers with different erbium doping profiles in the core or the cladding. When the doped fibers are operated at the optimum length, results show that the smaller overlap of the signal mode field with the annular erbium doping region leads to higher gain and lower saturation of the amplifier. A single-core erbium-doped fiber with an annular doping and a D-shaped cladding was fabricated. Measurements demonstrate less than 4 dB of gain compression over the C-band for input power ranging from -40 dBm to 3 dBm. Small gain compression EDFAs are of interest for applications that require input channel reconfiguration. Higher gain and saturation output power are also key issues in cladding-pumped multi-core amplifiers.


Electrocardiography in two subspecies of manatee (Trichechus manatus latirostris and T. m. manatus).
Electrocardiographic (ECG) measurements were recorded in two subspecies of awake, apparently healthy, wild manatees (Trichechus manatus latirostris and T. m. manatus) undergoing routine field examinations in Florida and Belize. Six unsedated juveniles (dependent and independent calves) and 6 adults were restrained in ventral recumbency for ECG measurements. Six lead ECGs were recorded for all manatees and the following parameters were determined: heart rate and rhythm; P, QRS, and T wave morphology, amplitude, and duration; and mean electrical axis (MEA). Statistical differences using a t-test for equality of means were determined. No statistical difference was seen based on sex or subspecies of manatees in the above measured criteria. Statistical differences existed in heart rate (P = 0.047), P wave duration (P = 0.019), PR interval (P = 0.025), and MEA (P = 0.021) between adult manatees and calves. Our findings revealed normal sinus rhythms, no detectable arrhythmias, prolonged PR and QT intervals, prolonged P wave duration, and small R wave amplitude as compared with cetacea and other marine mammals. This paper documents the techniques for and baseline recordings of ECGs in juvenile and adult free-living manatees. It also demonstrates that continual assessment of cardiac electrical activity in the awake manatee can be completed and can be used to aid veterinarians and biologists in routine health assessment, during procedures, and in detecting the presence of cardiac disease or dysfunction.


Return-to-play criteria after athletic concussion: a need for revision.
Management of a sport-related concussion, especially involving return-to-play decisions, is one of the most important challenges confronting sports medicine professionals. Current guidelines result from thoughtful consensus recommendations by expert committees but are chiefly based on the resolution of symptoms and the results of neuropsychological testing, if available. Adherence to this paradigm results in most injured athletes resuming competition in 1 to 2 weeks.


[Pseudocoarctation caused by a calcified intra-aortic mass].
Weak or absent lower limb pulses and a thoracic systolic murmur in a fifty-seven-year-old woman with hypertension suggested coarctation. Thoracic X-Ray showed a narrowing of the thoracic aorta over 10 cm due to an intraluminal calcified aortic mass. The remaining aorta and its branches were normal. Histologic examination of the operative specimen found atherosclerotic lesions with thrombosis. This very unusual condition seems to represent an individual entity of which a few cases have been reported in the literature.


Progressive impairment of developing neuroendocrine cell lineages in the hypothalamus of mice lacking the Orthopedia gene.
Development of the neuroendocrine hypothalamus is characterized by a precise series of morphogenetic milestones culminating in terminal differentiation of neurosecretory cell lineages. The homeobox-containing gene Orthopedia (Otp) is expressed in neurons giving rise to the paraventricular (PVN), supraoptic (SON), anterior periventricular (aPV), and arcuate (ARN) nuclei throughout their development. Homozygous Otp(-/-) mice die soon after birth and display progressive impairment of crucial neuroendocrine developmental events such as reduced cell proliferation, abnormal cell migration, and failure in terminal differentiation of the parvocellular and magnocellular neurons of the aPV, PVN, SON, and ARN. Moreover, our data provide evidence that Otp and Sim1, a bHLH-PAS transcription factor that directs terminal differentiation of the PVN, SON, and aPV, act in parallel and are both required to maintain Brn2 expression which, in turn, is required for neuronal cell lineages secreting oxytocin (OT), arginine vasopressin (AVP), and corticotropin-releasing hormone (CRH).


Ellipsometric determination of polarization-dependent transmission in resonant feedback systems.
The polarization-dependent transmission of a basic anisotropic feedback system (Fabry-Perot resonator) is mathematically modeled by means of the Jones-matrix formalism. Detailed numerical simulations of the resonance case are performed. Small phase anisotropies as well as small polarization-dependent losses of the resonator components can be extremely amplified by resonant feedback. The amplification factors depend on the magnitudes of amplitude and phase anisotropy and their mutual interactions as well as on the polarization-independent system parameters (forward transmission, system feedback). However, for higher phase anisotropies, saturation effects occur and, therefore, the anisotropy amplification factors decrease. Our experimental investigations applying anisotropic Fabry-Perot resonators in different ellipsometer systems confirm the predicted amplification of phase and loss anisotropies in resonance operation.


Sendai virus-based production of HIV type 1 subtype B and subtype E envelope glycoprotein 120 antigens and their use for highly sensitive detection of subtype-specific serum antibodies.
We previously described a Sendai virus (SeV)-based expression system for the recombinant gp120 of HIV-1 subtype B (rgp120-B), which has permitted the production of antigenetically and functionally authentic gp120 at a concentration as high as 6 microg/ml of culture supernatant (Yu D et al.: Genes Cells 1997;2:457-466). Here the same procedure was successfully applied to the production of HIV-1 subtype E gp120 (rgp120-E). The remarkable production of the proteins by the SeV expression system enabled us to use crude culture supernatants for serological and functional studies of gp120s. The immunological authenticity of rgp120-E was verified by patient sera and anti-V3 loop monoclonal antibodies specific for HIV-1 subtypes B and E. CD4-binding properties were corroborated by FACS analyses. The rgp120s were then used in an enzyme immunoassay (rgp120-EIA) to detect antibodies in the sera of HIV-1-infected individuals, and the performance was assessed in comparison with a conventional V3 loop peptide EIA (V3-EIA). The initial evaluation of a serum panel (n = 164) consisting of 76 subtype E and 88 subtype B sera revealed that the rgp120-EIA was nearly 1000-fold more sensitive than the V3-EIA and was able to detect subtype-specific antibody with 100% sensitivity and with a complete correlation with the genotypes, whereas the V3-EIA failed to detect 9 and 24% of the same subtype E and B sera, respectively. Furthermore, a study employing a panel of 28 international sera with known genotypes (HIV-1 subtypes A through F) confirmed the remarkable specificity of this method. An EIA reactivity higher than 1.0 was an unambiguous predictor of HIV-1 subtype E and B infections. The data imply the presence of strong subtype-specific epitopes for antibody bindings to these rgp120s.


Resource-rationality beyond individual minds: the case of interactive language use.
Resource-rational approaches offer much promise for understanding human cognition, especially if they can reach beyond the confines of individual minds. Language allows people to transcend individual resource limitations by augmenting computation and enabling distributed cognition. Interactive language use, an environment where social rational agents routinely deal with resource constraints together, offers a natural laboratory to test resource-rationality in the wild.


Understanding road surface pollutant wash-off and underlying physical processes using simulated rainfall.
Pollutant wash-off is one of the key pollutant processes that detailed knowledge is required in order to develop successful treatment design strategies for urban stormwater. Unfortunately, current knowledge relating to pollutant wash-off is limited. This paper presents the outcomes of a detailed investigation into pollutant wash-off on residential road surfaces. The investigations consisted of research methodologies formulated to overcome the physical constraints due to the heterogeneity of urban paved surfaces and the dependency on naturally occurring rainfall. This entailed the use of small road surface plots and artificially simulated rainfall. Road surfaces were selected due to its critical importance as an urban stormwater pollutant source. The study results showed that the influence of initially available pollutants on the wash-off process was limited. Furthermore, pollutant wash-off from road surfaces can be replicated using an exponential equation. However, the typical version of the exponential wash-off equation needs to be modified by introducing a non dimensional factor referred to as 'capacity factor' CF. Three rainfall intensity ranges were identified where the variation of CF can be defined. Furthermore, it was found that particulate density rather than size is the critical parameter that influences the process of pollutant wash-off.


Trigeminal neuralgia caused by venous angioma: case report.
A 34-year-old female presented with trigeminal neuralgia caused by a venous malformation in the right cerebello-pontine region. Computed tomography and magnetic resonance imaging demonstrated the abnormal draining veins from the venous malformation. The dilated vessels extended around the trigeminal nerve and compressed the root entry zone. Microvascular decompression (MVD) was performed, and her trigeminal neuralgia was completely relieved without neurological deficits. The offending vessel in most cases of trigeminal neuralgia is an arterial branch. Veins may also be associated with trigeminal neuralgia. The present rare case shows that MVD may be useful for the treatment of trigeminal neuralgia associated with venous malformation. Good outcome depends on decompression of the root entry zone without injury to the vessel. Surgical injury in this region can cause severe neurological deficits. Several treatment options should be prepared for the surgery, such as MVD or rhizotomy.


Lay understanding of familial risk of common chronic diseases: a systematic review and synthesis of qualitative research.
Although the family history is increasingly used for genetic risk assessment of common chronic diseases in primary care, evidence suggests that lay understanding about inheritance may conflict with medical models. This study systematically reviewed and synthesized the qualitative literature exploring understanding about familial risk held by persons with a family history of cancer, coronary artery disease, and diabetes mellitus. Twenty-two qualitative articles were found after a comprehensive literature search and were critically appraised; 11 were included. A meta-ethnographic approach was used to translate the studies across each other, synthesize the translation, and express the synthesis. A dynamic process emerged by which a personal sense of vulnerability included some features that mirror the medical factors used to assess risk, such as the number of affected relatives. Other features are more personal, such as experience of a relative's disease, sudden or premature death, perceived patterns of illness relating to gender or age at death, and comparisons between a person and an affected relative. The developing vulnerability is interpreted using personal mental models, including models of disease causation, inheritance, and fatalism. A person's sense of vulnerability affects how that person copes with, and attempts to control, any perceived familial risk. Persons with a family history of a common chronic disease develop a personal sense of vulnerability that is informed by the salience of their family history and interpreted within their personal models of disease causation and inheritance. Features that give meaning to familial risk may be perceived differently by patients and professionals. This review identifies key areas for health professionals to explore with patients that may improve the effectiveness of communication about disease risk and management.


Dose model for stent-based delivery of a radioactive compound for the treatment of restenosis in coronary arteries.
Radiolabeled drug-eluting stents have been proposed recently as a novel method to potentially reduce restenosis in coronary arteries. A P-32 labeled oligonucleotide (ODN) loaded on a polymer coated stent is slowly released in the arterial wall to deliver a therapeutic dose to the target tissue. However, the relatively low proportion of drugs transferred to the arterial wall (<2%-5% typically) raises questions about the degree to which radiolabeled drugs eluted from the stent can contribute to the total radiation dose delivered to tissues. A three-dimensional diffusion-convection transport model is used to model the transport of a hydrophilic drug released from the surface of a stent to the arterial media. Large drug concentration gradients are observed near the stent struts giving rise to a nonuniform radiation activity distribution for the drug in the tissues as a function of time. A voxel-based kernel convolution method is used to calculate the radiation dose rate resulting from this activity build-up in the arterial wall based on the medical internal radiation dose formalism. Measured residence time for the P-32 ODN in the arterial wall and at the stent surface obtained from animal studies are used to normalize the results in terms of absolute dose to tissue. The results indicate that radiation due to drug eluted from the stent contributes only a small fraction of the total radiation delivered to the arterial wall, the main contribution coming from the activity that remains embedded in the stent coating. For hydrophilic compounds with rapid transit times in arterial tissue and minimal binding interactions, the activity build-up in the arterial wall contributes only a small fraction to the total dose delivered by the P-32 ODN stent. For these compounds, it is concluded that radiolabeled drug-eluting stent will not likely improve the performance of radioactive stents for the treatment of restenosis. Also, variability in the delivery efficacy of drug delivery devices makes accurate dosimetry difficult and the drug washout in the systemic circulatory system may yield an unnecessary activity build-up and dose to healthy organs.


Living in a Paradox: How Older Single and Widowed Black Women Understand Their Sexuality.
The current phenomenological study explored how single and/or widowed older Black women understand their sexuality in the context of their Black matriarchal role and through their relational interactions with their children, families, friends, and their extended social networks. The women spoke about their sexuality in the contexts of Black matriarchy, concept of self, and communication. Black matriarchy was defined as the tenacity with which, as Black women and Black mothers, participants occupied a centralized role in their families, while concept of self reflected heavily on conflicting perceptions they held of their understanding of themselves as sexual beings. Regarding communication, many participants felt constrained in self-disclosing their sexual feelings and relationship status. Living in a paradox exemplified our interpretation of the women' struggles as they tried to balance the expectations of the roles they occupied in society with their own identity as a sexual being. Our findings offer a nuanced exploration of the various dimensions about how they understand themselves by providing invaluable insight into their world as older Black women. The implications for policy and practice pertain to assessing the fundamental historical and contemporary issues that older Black women face while simultaneously considering the convergence of race, gender, and sexuality.


Gene expression profiling with oligonucleotide microarrays distinguishes World Health Organization grade of oligodendrogliomas.
Oligodendrogliomas are the second most common type of glial neoplasm with distinct prognostic and therapeutic implications. Although refinements have led to improved clinical stratification, current grading schemes are still limited by subjective histopathological criteria. In this report, we have used oligonucleotide array technology to perform expression profiling in morphologically classic oligodendrogliomas. Expression information from approximately 1100 genes divided tumors into two molecularly distinct groups that corresponded exactly to their previously assigned histological grades. Subsequent gene clustering identified a subset of 196 transcripts showing a common, differential expression pattern between tumor grades. A number of these genes have been associated with the maintenance of cytoarchitecture, cellular differentiation and maturation, immunogenicity, and chemotherapeutic resistance. These results demonstrate the utility of gene expression profiling as an objective, ancillary tool for grading oligodendrogliomas and a potential approach for classifying diffuse gliomas where histological assessment may be difficult or ambiguous.


Serum metalloproteinase-9 is related to COPD severity and symptoms - cross-sectional data from a population based cohort-study.
Chronic obstructive pulmonary disease, COPD, is an increasing cause of morbidity and mortality worldwide, and an imbalance between proteases and antiproteases has been implicated to play a role in COPD pathogenesis. Matrix metalloproteinases (MMP) are important proteases that along with their inhibitors, tissue inhibitors of metalloproteinases (TIMP), affect homeostasis of elastin and collagen, of importance for the structural integrity of human airways. Small observational studies indicate that these biomarkers are involved in the pathogenesis of COPD. The aim of this study was to investigate serum levels of MMP-9 and TIMP-1 in a large Swedish population-based cohort, and their association with disease severity and important clinical symptoms of COPD such as productive cough. Spirometry was performed and peripheral blood samples were collected in a populations-based cohort (median age 67 years) comprising subjects with COPD (n = 594) and without COPD (n = 948), in total 1542 individuals. Serum MMP-9 and TIMP-1 concentrations were measured with enzyme linked immunosorbant assay (ELISA) and related to lung function data and symptoms. Median serum MMP-9 values were significantly higher in COPD compared with non-COPD 535 vs. 505 ng/ml (P = 0.017), without any significant differences in serum TIMP-1-levels or MMP-9/TIMP-1-ratio. In univariate analysis, productive cough and decreasing FEV1% predicted correlated significantly with increased MMP-9 among subjects with COPD (P = 0.004 and P = 0.001 respectively), and FEV1% predicted remained significantly associated to MMP-9 in a multivariate model adjusting for age, sex, pack years and productive cough (P = 0.033). Productive cough and decreasing FEV1 were each associated with MMP-9 in COPD, and decreasing FEV1 remained significantly associated with MMP-9 also after adjustment for common confounders in this population-based COPD cohort. The increased serum MMP-9 concentrations in COPD indicate an enhanced proteolytic activity that is related to disease severity, and further longitudinal studies are important for the understanding of MMP-9 in relation to the disease process and the pathogenesis of different COPD phenotypes.


5-Hydroxytryptamine1C/2 agonists in the thoracic spinal cord: cardiovascular effects and binding sites in the intermediolateral cell column.
The presence of 5-hydroxytryptamine (5-HT)1C/2 binding sites in autonomic regions of the thoracic spinal cord and their role in the regulation of sympathetic outflow to the cardiovascular system were examined. Light microscopic receptor autoradiography was used to visualize the binding of the 5-HT1C/2 ligand, [125I]-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane [( 125I]DOI). In thoracic spinal cord, a discrete and preferential localization of specific [125I]DOI binding sites was found in the intermediolateral cell column. To determine the mean arterial pressure (MAP) and heart rate (HR) effects resulting from activation of 5-HT1C/2 receptors in spinal cord, DOI and alpha-methyl-5-HT were administered intrathecally (i.t.) to anesthetized, artificially ventilated rats. DOI (1-100 micrograms) caused initial decreases followed by increases in MAP and HR, whereas alpha-methyl-5-HT (1-30 micrograms) only decreased MAP and HR. The distribution of [125I]DOI after i.t. administration and the effects of a peripherally administered 5-HT1C/2 antagonist 6-methyl-1-(1-methylethyl)-ergoline-8 beta-carboxylic acid, 2-hydroxyl-1-methyl propyl ester and maleate salt (LY53857) showed that the pressor effects of i.t. DOI were due to peripheral leakage and suggested that the depressor effects were due to a spinal site of action. The depressor effects of DOI were prevented by peripheral administration of phentolamine. Pretreatment with i.t. administration of 5-HT1C/2 antagonists (LY53857, ketanserin and mianserin) did not block the depressor or bradycardic effects of i.t. administration of DOI. Only LY53857 was effective in blocking the depressor effects of i.t. administration of alpha-methyl-5-HT.(ABSTRACT TRUNCATED AT 250 WORDS)


Factors relating to patient visit time with a physician.
This study sought to identify factors that increase or decrease patient time with a physician, determine which combinations of factors are associated with the shortest and longest visits to physicians, quantify how much physicians contribute to variation in the time they spend with patients, and assess how well patient time with a physician can be predicted. Data were acquired from a modified replication of the 1997-1998 National Ambulatory Medical Care Survey, administered by the Kentucky Ambulatory Network to 56 primary care clinicians at 24 practice sites in 2001 and 2002. A regression tree and a linear mixed model (LMM) were used to discover multivariate associations between patient time with a physician and 22 potentially predictive factors. Patient time with a physician was related to the number of diagnoses, whether non-illness care was received, and whether the patient had been seen before by the physician or someone at the practice. Approximately 38% of the variation in patient time with a physician was accounted for by predictive factors in the tree; roughly 33% was explained by predictive factors in the LMM, with another 12% linked to physicians. Knowledge of patient characteristics and needs could be used to schedule office visits, potentially improving patient flow through a clinic and reducing waiting times.


The association between high-grade varicocele and endothelial dysfunction.
Varicocele is determined as dilatation of veins in the pampiniform plexus of the spermatic cord. Although various factors have been implicated in the pathophysiology of varicocele, the underlying aetiological cause is not fully understood. Endothelial dysfunction is a precursor of vascular pathologies that may develop gradually and a substantial inducer in atherosclerosis aetiology. Brachial artery flow-mediated dilatation (FMD) measurement with sensitive brachial artery ultrasonography for assessing endothelial function is the most common noninvasive method. Similarly, carotid intima-media thickness (CIMT), measured using noninvasive ultrasonographic methods, is a tool for evaluating subclinical atherosclerosis and gives information on early changes in the vessel wall structure. Totally, 128 patients met the criteria were evaluated in this study. FMD was significantly lower in the varicocele group compared with the control group (9.16 ± 3.34 vs.7.96 ± 1.88, p = .013). CIMT measurements were similar between the groups (p = .091). Multivariate logistic regression revealed that FMD was independently associated with varicocele [odds ratio (OR): 0.814; 95% confidence interval (CI): 0.697-0.950; p = .009]. We suggest that endothelial dysfunction may have a role in the varicocele. Therefore, we recommend that every patient with symptomatic varicocele should be evaluated and followed up regularly for cardiovascular pathologies.


Lifestyle and Cardiac Structure and Function in Healthy Midlife Population.
The association between lifestyle and cardiac structure and function measures, such as global longitudinal strain and diastolic function in a healthy midlife general population, is not well known. A subpopulation of the Northern Finland Birth Cohort 1966 took part in follow-up, including echocardiography (n = 1,155) at the age of 46. All antihypertensive medication users (n = 164), patients with diabetes (n = 70), subjects with any cardiac diseases (n = 24), and subjects with echocardiography abnormalities (n = 21) were excluded. Moderate to vigorous physical activity (MVPA) was recorded with a wrist-worn accelerometer over 14 days and categorized into high, moderate, and low MVPA groups. Similarly, alcohol consumption was categorized as low, moderate, and high-dose users of alcohol and smoking as nonsmokers, former, and current smokers. The total number of healthy subjects included in the study was 715 (44% males). Left ventricular mass index and left atrial end-systolic volume index were significantly higher in the high MVPA group compared with the low MVPA group (adjusted main effect p = 0.002 and p <0.001, respectively). Cardiac function did not differ among the physical activity groups. High alcohol consumption was associated with impaired global longitudinal strain and diastolic function (adjusted main effect p = 0.002 and p = 0.004, respectively) but not with any cardiac structure variables. Smoking was not associated with cardiac structure or function. In healthy middle-aged adults, MVPA was independently associated with structural changes in the heart but not with cardiac function. High alcohol consumption was associated with impaired modern cardiac function measures but not with cardiac structure.


Does Epileptiform Activity Represent a Failure of Neuromodulation to Control Central Pattern Generator-Like Neocortical Behavior?
Rhythmic motor patterns in invertebrates are often driven by specialized "central pattern generators" (CPGs), containing small numbers of neurons, which are likely to be "identifiable" in one individual compared with another. The dynamics of any particular CPG lies under the control of modulatory substances, amines, or peptides, entering the CPG from outside it, or released by internal constituent neurons; consequently, a particular CPG can generate a given rhythm at different frequencies and amplitudes, and perhaps even generate a repertoire of distinctive patterns. The mechanisms exploited by neuromodulators in this respect are manifold: Intrinsic conductances (e.g., calcium, potassium channels), conductance state of postsynaptic receptors, degree of plasticity, and magnitude and kinetics of transmitter release can all be affected. The CPG concept has been generalized to vertebrate motor pattern generating circuits (e.g., for locomotion), which may contain large numbers of neurons - a construct that is sensible, if there is enough redundancy: that is, the large number of neurons consists of only a small number of classes, and the cells within any one class act stereotypically. Here we suggest that CPG and modulator ideas may also help to understand cortical oscillations, normal ones, and particularly transition to epileptiform pathology. Furthermore, in the case illustrated, the mechanism of the transition appears to be an exaggerated form of a normal modulatory action used to influence sensory processing.


Barrier Dysfunction in Eosinophilic Esophagitis.
Compelling evidence over the past decade supports the central role of epithelial barrier dysfunction in the pathophysiology of eosinophilic esophagitis (EoE). The purpose of this review is to summarize the genetic, environmental, and immunologic factors driving epithelial barrier dysfunction, and how this impaired barrier can further promote the inflammatory response in EoE. Common environmental exposures, such as detergents, may have a direct impact on the esophageal epithelial barrier. In addition, the effects of IL-13 on barrier dysfunction may be reduced by 17β-estradiol, Vitamin D, and the short chain fatty acids butyrate and propionate, suggesting novel therapeutic targets. There are many genetic, environmental, and immunologic factors that contribute to epithelial barrier dysfunction in EoE. This leads to further skewing of the immune response to a "Th2" phenotype, alterations in the esophageal microbiome, and penetration of relevant antigens into the esophageal mucosa, which are central to the pathophysiology of EoE.


A novel photoelectrochemical approach with "signal-off" pattern for anodic detection of sunset yellow in food samples based on Bi2WO6/TiO2 NTAs heterostructure nanocomposite.
A new and signal-off photoelectrochemical (PEC) sensing platform utilizing TiO2 nanotube arrays (NTAs) coated with Bi2WO6 nanoparticles (NPs) has been successfully developed for the highly sensitive detection of sunset yellow (SY). The interaction between SY and Bi2WO6 NPs leads to substantial steric hindrance, resulting in a noticeable decrease in the photocurrent signal. The proposed PEC sensor demonstrates quantitative detection capabilities for SY across a wide liner range of 10 fM to 100 µM with an ultralow detection limit (LOD) of 0.78 fM. Furthermore, the designed PEC sensor exhibits several notable advantages, including robust anti-interference properties, desirable repeatability, good reproducibility, and excellent stability. Finally, the designed PEC sensor was applied to determine SY in diverse real samples without any remarkable difference compared to the UV-Vis reference method.


Forward genetics by genome sequencing reveals that rapid cyanide release deters insect herbivory of Sorghum bicolor.
Whole genome sequencing has allowed rapid progress in the application of forward genetics in model species. In this study, we demonstrated an application of next-generation sequencing for forward genetics in a complex crop genome. We sequenced an ethyl methanesulfonate-induced mutant of Sorghum bicolor defective in hydrogen cyanide release and identified the causal mutation. A workflow identified the causal polymorphism relative to the reference BTx623 genome by integrating data from single nucleotide polymorphism identification, prior information about candidate gene(s) implicated in cyanogenesis, mutation spectra, and polymorphisms likely to affect phenotypic changes. A point mutation resulting in a premature stop codon in the coding sequence of dhurrinase2, which encodes a protein involved in the dhurrin catabolic pathway, was responsible for the acyanogenic phenotype. Cyanogenic glucosides are not cyanogenic compounds but their cyanohydrins derivatives do release cyanide. The mutant accumulated the glucoside, dhurrin, but failed to efficiently release cyanide upon tissue disruption. Thus, we tested the effects of cyanide release on insect herbivory in a genetic background in which accumulation of cyanogenic glucoside is unchanged. Insect preference choice experiments and herbivory measurements demonstrate a deterrent effect of cyanide release capacity, even in the presence of wild-type levels of cyanogenic glucoside accumulation. Our gene cloning method substantiates the value of (1) a sequenced genome, (2) a strongly penetrant and easily measurable phenotype, and (3) a workflow to pinpoint a causal mutation in crop genomes and accelerate in the discovery of gene function in the postgenomic era.


Crystal structure of the transcription activator BmrR bound to DNA and a drug.
The efflux of chemically diverse drugs by multidrug transporters that span the membrane is one mechanism of multidrug resistance in bacteria. The concentrations of many of these transporters are controlled by transcription regulators, such as BmrR in Bacillus subtilis, EmrR in Escherichia coli and QacR in Staphylococcus aureus. These proteins promote transporter gene expression when they bind toxic compounds. BmrR activates transcription of the multidrug transporter gene, bmr, in response to cellular invasion by certain lipophilic cationic compounds (drugs). BmrR belongs to the MerR family, which regulates response to stress such as exposure to toxic compounds or oxygen radicals in bacteria. MerR proteins have homologous amino-terminal DNA-binding domains but different carboxy-terminal domains, which enable them to bind specific 'coactivator' molecules. When bound to coactivator, MerR proteins upregulate transcription by reconfiguring the 19-base-pair spacer found between the -35 and -10 promoter elements to allow productive interaction with RNA polymerase. Here we report the 3.0 A resolution structure of BmrR in complex with the drug tetraphenylphosphonium (TPP) and a 22-base-pair oligodeoxynucleotide encompassing the bmr promoter. The structure reveals an unexpected mechanism for transcription activation that involves localized base-pair breaking, and base sliding and realignment of the -35 and -10 operator elements.


Contrast-enhanced ultrasonography of the thyroid gland in healthy dogs, hypothyroid dogs and dogs with non-thyroidal illness.
Diagnosis of canine hypothyroidism remains challenging, as non-thyroidal illness (NTI)-syndrome and medical treatment can influence thyroid hormone concentrations. Conventional ultrasound may give additional hints, however high interobserver variability has been described. Contrast-enhanced ultrasound (CEUS) allows detection of changes in tissue perfusion. The purpose of the present study was to assess the possible diagnostic value of CEUS regarding diagnosis of hypothyroidism. CEUS of the thyroid gland was performed in 52 healthy dogs, 16 hypothyroid dogs, and 20 NTI patients. The following perfusion parameters were calculated: Thyroid/carotid artery (TG/CA) ratios for peak enhancement (PE) and area under the curve (AUC), time to peak (TTP) and wash-in and wash-out rates (WiR, WoR) of the thyroid gland. Impact of sedation on perfusion parameters was investigated in 8 calm healthy dogs which were examined before and after sedation using midazolam and butorphanol. Significantly higher median TG/CA ratios for PE were detected for the left and right thyroid lobe in dogs with hypothyroidism (0.97/0.96) compared to healthy dogs (0.85/0.85) and dogs with NTI (0.84/0.84). AUCs were also significantly increased in hypothyroid dogs when compared to other groups. Dogs with NTI showed significantly lower WiR and WoR compared to other groups. Values for TTP were not significantly different between groups. Sedation had only impact on results of TTP which was significantly prolonged in sedated dogs. In conclusion, CEUS of the thyroid gland can provide an additional tool for diagnosis of hypothyroidism in dogs and support its differentiation from NTI. Sedation has limited impact on CEUS results.


Sumatriptan in the acute treatment of migraine without aura: efficacy of 50-mg dose.
We conducted an open study on the efficacy of 50 mg of sumatriptan as an acute treatment for migraine without aura. We recruited 200 consecutive patients, with an established history of migraine without aura, presenting at a headache center. The patients were instructed to take half a 100-mg sumatriptan tablet for their next migraine attack, and to record details of their headache in a diary. The primary outcome of the study was headache relief from one migraine attack. Attacks were moderately intense (46%), moderate to severe (7%), or severe (47%). Total or partial benefit at 2 hours from the 50-mg dose was reported by 140 of 200 patients (70%). Thirty-six patients received no benefit from half a tablet, and 24 did not take sumatriptan, preferring their habitual medication. Side effects were few, mild, and short lasting. We conclude that the 50-mg oral dose is generally effective for migraine without aura attacks of both moderate and severe intensity and recommend this dose for all such patients. If, however, sumatriptan is ineffective at that dose it can be increased to a maximum of 100 mg.


[Obtaining specific non-adsorbed sera to Haemophilus influenza for the agglutination test on glass].
Type-specific agglutinating sera to capsular antigenas of H. influenzae were recovered (from 1:3200 to 1:25600). With the given immunization scheme there formed mostly IgG immunoglobulins, and only insignificant amount of IgM (separation of G-200 Sephadex gel). IgG were found to be responsible for the type-specificity of the sera to bacteria, whereas the cross reactions within the H. influenzae genus were connected connected with the IgM. Use of the sera heated at various temperature regimens offered a possibility of obtaining highly specific agglutinating sera with the aid of which express serodiagnosis of the isolated H. influenzae strains was possible.


Comparative Safety and Effectiveness of Direct-Acting Oral Anticoagulants Versus Warfarin: a National Cohort Study of Nursing Home Residents.
Research comparing direct-acting oral anticoagulants (DOACs) to warfarin has excluded nursing home residents, a vulnerable and high-risk population. To compare the safety and effectiveness of DOACs versus warfarin. New-user cohort study (2011-2016). US nursing home residents aged > 65 years with non-valvular atrial fibrillation enrolled in fee-for-service Medicare for > 6 months. Initiators of DOACs (2881 apixaban, 1289 dabigatran, 3735 rivaroxaban) were 1:1 propensity matched to warfarin initiators. Outcomes included ischemic stroke or transient ischemic attack (i.e., ischemic cerebrovascular event), bleeding (extracranial or intracranial), other vascular events, death, and a composite of all outcomes. Absolute rate differences (RD) and cause-specific hazard ratios (HR) with 95% confidence intervals (CI) were estimated. Subgroup analyses were performed by alignment of DOAC dosing with labeling. Median age (84 years), CHA2DS2-Vasc (5), and ATRIA risk scores (3) were similar across medications. Clinical outcome rates were similar for dabigatran and rivaroxaban users versus warfarin users. However, ischemic cerebrovascular event rates were higher among dabigatran and rivaroxaban users that received reduced dosages without an indication. Overall, apixaban users had higher ischemic cerebrovascular event rates (HR 1.86; 95% CI 1.00-3.45) and lower bleeding rates (HR 0.66; 95% CI 0.49-0.88), but outcome rates varied by dosing alignment. Mortality rates (per 100 person-years) were lower for apixaban (RDs - 9.30; 95% CI - 13.18 to - 5.42), dabigatran (RDs - 10.79; 95% CI - 14.98 to - 6.60), and rivaroxaban (RDs - 8.92; 95% CI - 12.01 to - 5.83) versus warfarin; composite outcome findings were similar. Among US nursing home residents, the DOACs were each associated with lower mortality versus warfarin. Misaligned DOAC dosing was common in nursing homes and was associated with clinical and mortality outcomes. Overall, DOAC users had lower rates of adverse outcomes including mortality compared with warfarin users.


Assessment of speed distribution of red blood cells in the microvascular network in healthy volunteers and type 1 diabetes using laser Doppler spectra decomposition.
We applied a recently reported method of decomposition of laser Doppler power density spectra for in vivo monitoring of speed distributions of red blood cells (RBCs) in the microvascular network. The spectrum decomposition technique allows us to derive the distribution of RBC speed (in absolute units (mm s(-1))) versus RBC concentration (in arbitrary units). We carried out postocclusive reactive hyperaemia (PORH) test in 15 healthy volunteers and 21 diabetic patients in which the duration of type 1 diabetes was longer than 10 years. Measurements were carried out simultaneously with the use of a typical laser Doppler commercial instrument and speed resolved laser Doppler instrument utilizing the new technique based on decomposition of the laser Doppler spectra. We show that for the classical laser Doppler instrument, none of the PORH parameters revealed a statistical significance of difference between the groups analyzed. In contrast, the RBC speed distributions obtained from laser Doppler spectra during rest in the control group and type 1 diabetes are statistically significant. This result suggests that speed distribution measurements in the rest state (without any kind of stimulation test) allows for the assessment of microcirculation disorders. Measurements carried out in healthy subjects show that the first moment of speed distributions (mean speed of the distributions) is 2.32 ± 0.54 mm s(-1) and 2.57 ± 0.41 mm s(-1) for optodes located on the toe and finger of the hand, respectively. Respective values in type 1 diabetes were higher: 3.00 ± 0.36 mm s(-1) and 3.10 ± 0.48 mm s(-1).


[Allogeneic implantation of the tendon tissue sterilized with gaseous ethylene oxide in experiment].
The implantation of the allo-tendon tissue sterilized with gaseous ethylene oxide was carried out in 51 while rats. Results of histological investigations are described and a comparative estimation is given of durability of the properties of ethyleneoxide sterilized allotendons of the human with the anterior cruciate ligament and dermal tissue. A conclusion is made that it is possible to use the tendon allotransplants in clinical practice.


Health and greenhouse gas mitigation benefits of ambitious expansion of cycling, walking, and transit in California.
The purpose of this research was to quantify health co-benefits and carbon reductions of preferred scenarios of California regional transportation plans and alternatives with ambitious levels of active transport. The alternatives were designed to examine the efficacy of independent contributions of walking, bicycling, and transit at levels consistent with the U.S. Surgeon General recommendation for physical activity. Using data from travel and health surveys, vital statistics, collision databases, and outputs from regional and statewide travel models, the Integrated Transport and Health Impacts Model estimated the change in the population disease burden, as measured by deaths and disability adjusted life years (DALYs), due to a shift from a 2010 baseline travel pattern to an alternative. Health pathways modeled were physical activity and road traffic injuries. The preferred scenarios increased statewide active transport from 40.5 to 53.4 min person-1 w-1, which was associated with an annual decrease of 909 deaths and 16,089 DALYs. Sensitivity analyses that accounted for 2040 projected age- and sex-specific population characteristics and cause-specific mortality rates did not appreciably alter the annual change in deaths and DALYs on a population basis. The ambitious, maximal alternatives increased population mean travel duration to 283 min person-1 w-1 for walking, bicycling, or transit and were associated a reduction in deaths and DALYs from 2.5 to 12 times greater than the California preferred scenarios. The alternative with the largest health impact was bicycling 283 min person-1 w-1 which led to 8,543 fewer annual deaths and 194,003 fewer DALYs, despite an increase in bicyclist injuries. With anticipated population growth, no alternative achieved decreases in carbon emissions but bicycling had the greatest potential for slowing their growth. Alternatives that included transit similarly reduced carbon emissions, but with less health benefit. Aggressive expansion of active transport is an efficacious, but underutilized policy option with significant health co-benefits for mitigating greenhouse gases.


The Epidemiology and Economic Burden of Obesity and Related Cardiometabolic Disorders in the United Arab Emirates: A Systematic Review and Qualitative Synthesis.
Noncommunicable diseases (NCDs) are considered as a global health problem and considered as a public health priority with the more considerable increasing trend of obesity and cardiometabolic disorders rates in the Middle Eastern countries. This systematic review aims at assessing the prevalence, incidence rates, and trends, as well as the cost of obesity and related cardiometabolic disorders in the United Arab Emirates (UAE). A highly sensitive strategy was used to retrieve original observational studies, addressing the epidemiology and cost of obesity and related cardiometabolic disorders in the UAE, irrespective of nationality (nationals and expatriates). The search was conducted on April 4, 2017, within numerous electronic databases and the grey literature. Standardized and validated methods were used for data extraction and analysis as well as quality assessment. 6789 records were retrieved, of which 36 were deemed eligible. High prevalence rates were reported for obesity, diabetes, hypertension, and metabolic syndrome in all studies. However, the definitions and methods employed by the studies were highly variable. The risk of bias in the epidemiological studies ranged between low and medium. Only one study reported the cost of illness for diabetes. In this study, the estimated cost per patient was $2,015 (adjusted to the year 2015), and it became twofold and sixfold higher in patients with microvascular and macrovascular complications, respectively. Obesity and related cardiometabolic disorders are highly prevalent in the UAE, but quoting a precise prevalence for them is difficult given the methodological heterogeneity of the epidemiological studies addressing them. Nonetheless, we detected a 2-3-fold increase in the prevalence of overweight and obesity in the UAE between 1989 and 2017. It is hopeful that this systematic review will provide an insight into direct future studies, especially longitudinal studies exploring obesity and cardiometabolic risks and their costs.


Creative aging: functional brain networks associated with divergent thinking in older and younger adults.
Creative thinking is associated with connectivity between the default and executive control networks in the young brain. In aging, this pattern of functional coupling has been observed across multiple tasks. We have described this as the Default-Executive Coupling Hypothesis of Aging and suggest that this connectivity pattern may also be associated with creativity in older adulthood. However, age differences in brain networks implicated in creativity have yet to be investigated. The overarching goal of the present study was to examine age-related changes to functional brain networks associated with creativity. Specifically, we explored functional connectivity patterns among default and executive control brain regions associated with creative thoughts in older and younger adults. In a cross-sectional design, young (mean age = 21 y; n = 30) and older (mean age = 70 y; n = 25) participants completed a divergent thinking task during fMRI, which was examined using region of interest functional connectivity analyses. Consistent with predictions, analyses demonstrated that default and executive networks are more functionally coupled during creative thinking for older than younger adults. Critically, despite similar performance on an in-scanner creativity task, increased network efficiency was associated with creative ability for older adults only. These findings provide novel evidence of default-executive coupling as a putative mechanism associated with creative ability in later life.


Conserved steroid hormone homology converges on nuclear factor κB to modulate inflammation in asthma.
Asthma is a complex, multifactorial disease comprising multiple different subtypes, rather than a single disease entity, yet it has a consistent clinical phenotype: recurring episodes of chest tightness, wheezing, and difficulty breathing (Pediatr Pulmonol Suppl. 1997;15:9-12). Despite the complex pathogenesis of asthma, steroid hormones (eg, glucocorticoids) are ubiquitous in the short-term and long-term management of all types of asthma. Overall, steroid hormones are a class of widely relevant, biologically active compounds originating from cholesterol and altered in a stepwise fashion, but maintain a basic 17-carbon, 4-ring structure. Steroids are lipophilic molecules that diffuse readily through cell membranes to directly and/or indirectly affect gene transcription. In addition, they use rapid, nongenomic actions to affect cellular products. Steroid hormones comprise several groups (including glucocorticoids, sex steroid hormones, and secosteroids) with critical divergent biological and physiological functions relevant to health and disease. However, the conserved homology of steroid hormone molecules, receptors, and signaling pathways suggests that each of these is part of a dynamic system of hormone interaction, likely involving an overlap of downstream signaling mechanisms. Therefore, we will review the similarities and differences of these 3 groups of steroid hormones (ie, glucocorticoids, sex steroid hormones, and secosteroids), identifying nuclear factor κB as a common inflammatory mediator. Despite our understanding of the impact of individual steroids (eg, glucocorticoids, sex steroids and secosteroids) on asthma, research has yet to explain the interplay of the dynamic system in which these hormones function. To do so, there needs to be a better understanding of the interplay of classic, nonclassic, and nongenomic steroid hormone functions. However, clues from the conserved homology steroid hormone structure and function and signaling pathways offer insight into a possible model of steroid hormone regulation of inflammation in asthma through common nuclear factor κB-mediated downstream events.


Prodynorphin processing by proprotein convertase 2. Cleavage at single basic residues and enhanced processing in the presence of carboxypeptidase activity.
Endoproteolytic processing of the 26-kDa protein precursor prodynorphin (proDyn) at paired and single basic residues is most likely carried out by the proprotein convertases (PCs); however, the role of PCs at single basic residues is unclear. In previous studies we showed that limited proDyn processing by PC1/PC3 at both paired and single basic residues resulted in the formation of 8- and 10-kDa intermediates. Because PC2 is colocalized with proDyn, we examined the potential role of this convertase in cleaving proDyn. PC2 cleaved proDyn to produce dynorphin (Dyn) A 1-17, Dyn B 1-13, and alpha-neo-endorphin, without a previous requirement for PC1/PC3. PC2 also cleaved at single basic residues, resulting in the formation of the C-peptide and Dyn A 1-8. Only PC2, but not furin or PC1/PC3, could cleave the Arg-Pro bond to yield Dyn 1-8. Structure-activity studies with Dyn A 1-17 showed that a P4 Arg residue is important for single basic cleavage by PC2 and that the P1' Pro residue impedes processing. Conversion of Dyn A 1-17 or Dyn B 1-13 into leucine-enkephalin (Leu-Enk) by PC2 was never observed; however, Dyn AB 1-32 cleavage yielded small amounts of Leu-Enk, suggesting that Leu-Enk can be generated from the proDyn precursor only through a specific pathway. Finally, PC2 cleavages at single and paired basic residues were enhanced when carried out in the presence of carboxypeptidase (CP) E. Enhancement was blocked by GEMSA, a specific inhibitor of CPE activity, and could be duplicated by other carboxypeptidases, including CPD, CPB, or CPM. Our data suggest that carboxypeptidase activity enhances PC2 processing by the elimination of product inhibition caused by basic residue-extended peptides.


Colloidal aspects of digestion of Pickering emulsions: Experiments and theoretical models of lipid digestion kinetics.
Lipid digestion is a bio-interfacial process that is largely governed by the binding of the lipase-colipase-biosurfactant (bile salts) complex onto the surface of emulsified lipid droplets. Therefore, engineering oil-water interfaces that prevent competitive displacement by bile salts and/or delay the transportation of lipase to the lipidoidal substrate can be an effective strategy to modulate lipolysis in human physiology. In this review, we present the mechanistic role of Pickering emulsions i.e. emulsions stabilised by micron-to-nano sized particles in modulating the important fundamental biological process of lipid digestion by virtue of their distinctive stability against coalescence and resilience to desorption by intestinal biosurfactants. We provide a systematic summary of recent experimental investigations and mathematical models that have blossomed in the last decade in this domain. A strategic examination of the behavior and mechanism of lipid digestion of droplets stabilised by particles in simulated biophysical environments (oral, gastric, intestinal regimes) was conducted. Various particle-laden interfaces were considered, where the particles were derived from synthetic or biological sources. This allowed us to categorize these particles into two classes based on their mechanistic role in modifying lipid digestion. These are 'human enzyme-unresponsive particles' (e.g. silica, cellulose, chitin, flavonoids) i.e. the ones that cannot to be digested by human enzymes, such as amylase, protease and 'human enzyme-responsive particles' (e.g. protein microgels, starch granules), which can be readily digested by humans. We focused on the role of particle shape (spherical, anisotropic) on modifying both interfacial and bulk phases during lipolysis. Also, the techniques currently used to alter the kinetics of lipid digestion using intelligent physical or chemical treatments to control interfacial particle spacing were critically reviewed. A comparison of how various mathematical models reported in literature predict free fatty acid release kinetics during lipid digestion highlighted the importance of the clear statement of the underlying assumptions. We provide details of the initial first order kinetic models to the more recent models, which account for the rate of adsorption of lipase at the droplet surface and include the crucial aspect of interfacial dynamics. We provide a unique decision tree on model selection, which is appropriate to minimize the difference between experimental data of free fatty acid generation and model predictions based on precise assumptions of droplet shrinkage, lipase-binding rate, and nature of lipase transport process to the particle-laden interface. Greater insights into the mechanisms of controlling lipolysis using particle-laden interfaces with appropriate mathematical model fitting permit better understanding of the key lipid digestion processes. Future outlook on interfacial design parameters, such as particle shape, size, polydispersity, charge, fusion, material chemistry, loading and development of new mathematical models that provide closed-loop equations from early to later stages of kinetics are proposed. Such future experiments and models hold promise for the tailoring of particle-laden interfaces for delaying lipid digestion and/or site-dependent controlled release of lipidic active molecules in composite soft matter systems, such as food, personal care, pharmaceutical, healthcare and biotechnological applications.


Cardiovascular Manifestations of Human Monkeypox Virus: An Updated Review.
Cardiovascular manifestations in human monkeypox virus (MPXV) infection has gained increasing recognition as significant complications with both social and clinical implications. Myocarditis, viral pericarditis, heart failure, and arrhythmias can occur, leading to adverse effects on individuals' health and quality of life. Understanding the detailed pathophysiology of these cardiovascular manifestations is essential for improved diagnosis and management. The social implications of these cardiovascular complications are multifaceted, ranging from public health concerns and the impact on individuals' quality of life to psychological distress and social stigma. Clinically, diagnosing, and managing these complications present challenges, requiring a multidisciplinary approach and specialized care. The burden on healthcare resources necessitates preparedness and resource allocation to effectively address these complications. We delve into the pathophysiological mechanisms involved, including viral-induced cardiac damage, immune response, and inflammatory processes. Additionally, we explore the types of cardiovascular manifestations and their clinical presentations. Addressing cardiovascular manifestations' social and clinical implications in MPXV infection requires a comprehensive approach involving healthcare professionals, public health authorities, and communities. By prioritizing research, enhancing diagnosis and treatment strategies, and promoting preventive measures, we can mitigate the impact of these complications, improve patient care, and protect public health.


Trends, motivations and settings of recreational cocaine use by adolescents and young adults in the Netherlands.
In recent years the use of powder cocaine among socially integrated adolescents and young adults has normalised. It is no longer an extraordinary drug to use in trendy/innovative as well as mainstreams clubs. Not much research has been done on motivations for and settings in which this cocaine use takes place. To gain insight in normalisation and trends in cocaine use, we used quantitative data from the National Prevalence Study on Substance Use (NPS) 1997, 2001 and 2005. To gain insight in social settings and motivations (initiation and continuation), and in the combined use of cocaine with alcohol and/or other drugs, we analysed mostly qualitative data from in-depth interviews with 55 adolescents and young adults who used cocaine in the past year. The NPS studies show a rising trend in lifetime cocaine use, a fall in incidence, and a fall in continuation rates. From the interviews we learn that cocaine has further normalised. Cocaine is - and stays - attractive because of the ritual of snorting (the route of administration). Initiation is often planned. Effects play a role in the continuation of use, not in initiation. Motivations for use are divided into three categories: physical, mental and social. Cocaine is used in nightlife and home settings, together with friends, and it is often combined with alcohol (on the same occasion), because of feeling mentally clear and being able to drink more. About 5% of adolescents have used cocaine at least once in their lives. They feel it can be used in every setting, since it leaves a user in control. While acknowledging the negative side effects, young users try to regulate their cocaine use in order to regulate these effects. Although high frequent use is an exception in our sample, we cannot foretell how many might develop a pattern of problematic use.


Depressed cell-mediated immunity in chronic dermatophytic infections.
The immune response was studied in 10 patients with benign dermatophytosis and in 5 patients with a severe affection. At the humoral level no deficiencies were observed in both groups. However, all patients showed a marked and constant increase in IgE level. Skin test response in various concentrations of antigens as well as studies of activation of lymphocytes by specific and non-specific mitogens in vitro have demonstrated a depressed cell-mediated immunity. This anergy, however, is not an "all-or-one" phenomenon; it varies, and there seems to be a direct relationship between the state of anergy and the severity of the cases. Furthermore, certain discrepancies were observed between the in vivo and in vitro responses suggesting that defective cellular immune reactions in dermatophytosis may be symptomatic of a lack of some humoral factor and do not necessarily reflect an intrinsic cellular defect. Finally, among these 15 patients, 7 were brothers and sisters from 3 separate and unrelated families, suggesting an autosomal hereditary influence.


Fourier Transform vs Hadamard Transform Spectroscopy.
Recent articles have claimed a significant S/N advantage of Hadamard transform spectroscopy over Fourier transform spectroscopy. The scanty published data does not support this assertion, and the possibility that the claim is valid in theory is examined. Existing theory, as reported in the literature, is not consistent with the claims made for the technique. The advantages and drawbacks of Hadamard transform spectroscopy are examined in detail.


Dp-ucMGP as a Biomarker in Sarcopenia.
Sarcopenia is linked with an increased risk of falls, osteoporosis and mortality and is an increasing problem for healthcare systems. No satisfying biomarkers for sarcopenia diagnosis exist, connecting bone, fat and muscle. Matrix-GLA-protein (MGP) is an adipokine that regulates bone metabolism and is associated with decreased muscle strength. Associations of dp-ucMGP were analyzed in the BioPersMed cohort (58 ± 9 years), including 1022 asymptomatic subjects at moderate cardiovascular risk. Serum measurements of dp-ucMGP in 760 persons were performed with the InaKtif MGP Kit with the IDS-iSYS Multi-Discipline Automated System. DXA data (792 persons) measured with the Lunar iDXA system and physical performance data (786 persons) were available. Dp-ucMGP plasma levels correlate with sarcopenia parameters like gait speed (ρ = −0.192, p < 0.001), appendicular skeletal muscle mass (ρ = 0.102, p = 0.005) and appendicular skeletal muscle mass index (ρ = 0.112, p = 0.001). They are lower in persons with sarcopenia (p < 0.001) and higher in persons with reduced physical performance (p = 0.019). Persons in the lowest dp-ucMGP quartile have the highest risk for reduced muscle mass, decreasing with each quartile, whereas persons in the highest quartile have the highest risk of reduced muscle strength. Dp-ucMGP might be a good biomarker candidate in sarcopenia characterization.


Filtration and immunoprecipitation in the elimination of DNA polymerase activity associated with bacterial contamination of sera positive for hepatitis B e antigen and its corresponding antibody.
Samples of serum inoculated with Escherichia coli and serum that became contaminated with bacteria after exposure to a laboratory atmosphere demonstrated elevated DNA polymerase activity. The levels of activity were well within the range of values found in hepatitis B e antigen (HBeAg)-positive samples. The bacterial polymerase activity was markedly reduced by a single passage of serum samples through a 0.22-micron Millipore filter prior to analysis. Repeated filtration did not result in a substantial further decrease in polymerase activity. In sera that were heavily contamined with E. coli, however, filtration was not successful in reducing bacteria-associated polymerase activity to a base-line uncontaminated level. In such instances double antibody immunoprecipitation proved effective in elimination of bacterial activity. When bacterial contamination of serum samples is a possibility, specimens should be subjected to either Millipore filtration or immunoprecipitation prior to analysis, particularly when correlation of DNA polymerase activity with HBeAg and its corresponding antibody is attempted.


Frequency of use and preferences for information and communication technologies in patients with sleep apnea: A multicenter, multinational, observational cross-sectional survey study.
Obstructive sleep apnea (OSA) is a condition characterized by repeated episodes of partial or complete obstruction of the upper airway during sleep. An accessible method to facilitate self-management education is through information and communication technologies (ICTs). To assess the frequency of and preferences for ICT use in patients with sleep apnea. A multicenter, multinational, observational cross-sectional survey study was conducted between 2018 and 2019 in sleep units in different countries of Latin America, including patients of both genders older than 18 years with a diagnosis of sleep apnea. Participants were asked to complete 20 questions in a self-administered survey about the frequency of use of ICTs and their preferences for receiving disease-related information. A total of 435 patients participated in the study, with a mean age of 59.1 ± 14.0; 62.5% (n = 272) were males. Most patients had access to cellphones (92.4%, n = 402), smartphone (83.0%, n = 361) and an internet connection (82.3%, n = 358). One-to-one ICTs were regarded as the most frequently used ICT type, as 75.4% (n = 328) of participants reported using them daily (χ2(4) = 848.207, p =.000). With respect to categories of interest, one-to-one ICTs were also the best rated ICT type to receive (59.1%, n = 257; χ2(2) = 137.710, p =.000) and ask physicians (57.0%, n = 248; χ2(2) = 129.145, p =.000) information about OSA. Finally, older adults and those with lower educational levels were found to be less likely to use and be interested in ICTs. Most patients have access to different ICTs and often use them to seek and receive medical information. The preferred ICTs include those in the one-to-one category (WhatsApp, email) and the one-to-many category (web browsers) for general health and OSA-related information.


Parenteral Vancomycin in the Treatment of MRSA-Associated Diabetic Foot Infections: An Unnecessary Risk.
Diabetic foot infections (DFIs) are a common and costly complication of diabetes. Soft tissue and bone infections in DFIs frequently lead to amputation and/or sepsis which can be costly for both the patient and the healthcare system. Staphylococcus aureus is the most commonly identified causative agent in DFIs, and people with diabetes may have an increased risk of infection with methicillin-resistant Staphylococcus aureus (MRSA). In addition to increased susceptibility to severe infection, MRSA in DFIs is associated with high rates of treatment failure, morbidity, and hospitalization costs meaning appropriate treatment is a high priority. While hospitalized patients are usually treated with intravenous (IV) vancomycin, this can be costly in terms of inpatient stays, staffing costs, and adverse events. For example, vancomycin-associated acute kidney injury not only delays hospital discharge and increases costs but is also a particular concern for patients with diabetes who already have an increased risk of kidney problems. Vancomycin-resistant strains of S. aureus have also been identified, which means that alternative treatment options may need to be explored. Treatment alternatives to IV vancomycin, including oral antibiotics, have been shown to provide similar efficacy, with reduced costs, outpatient or home-based administration, and with fewer serious adverse effects. Although infectious disease specialists often use IV vancomycin alone, or in combination, as a first-line therapeutic option, they are increasingly seeing the value of outpatient or at-home oral antibiotics as an alternative. This manuscript reviews the evidence for true costs of vancomycin therapy for MRSA-associated DFIs and examines the alternatives.


Color opponent neurons in V1: a review and model reconciling results from imaging and single-unit recording.
The signals in visual cortex that ultimately give rise to color perception remain poorly understood. Controversy has particularly surrounded one aspect of color's encoding in the visual system-opponent processing in primary visual cortex. Early single-unit studies suggested that V1 contains relatively few color-opponent neurons. Neuroimaging measurements, however, have suggested that such neurons might be relatively numerous. Here, we reconcile these apparently discrepant results and conclude that V1 contains relatively large numbers of color-opponent neurons. We first review results from each method and find that most neuroimaging studies provide evidence of substantial color opponency in V1, and that despite apparent controversy, most single-unit studies agree that relatively large numbers of V1 neurons show some sort of color opponency. To reconcile the results from different techniques more formally, we used electrophysiological data to predict the outcomes of neuroimaging experiments. We simulated the expected fMRI response in V1 to spatial patterns of different color, based on the neurons' properties, as reported in Johnson, Hawken, and Shapley, (2001). The simulated responses to stimuli used in Engel, Zhang, and Wandell, (1997) agree well with the actually observed fMRI results. The model identifies several factors that led to the apparent discrepancy between techniques, and makes testable predictions about how these factors influence the magnitude of color-opponent signals. fMRI and single-unit data converge to show that large numbers of color-opponent neurons exist in V1.