Cooling suits, physiological response, and task performance in hot environments for the power industry.
Heat stress on workers working outdoors in the power industry may result in fatigue and deterioration in task performance. This research collected and analyzed data on task performance of workers working indoors and outdoors with and without a cooling suit. The task performance was compared on the basis of heart rate, oxygen consumption, tympanic temperature, subjective responses, productivity, and error rates. Based on One-Way Analysis Of Variance (ANOVA) results, a significantly lower estimated working oxygen consumption was observed (p < .001) when the cooling suit was worn. The productivity was higher while workers wore the cooling suit as compared to no cooling suit (p = .011) whereas the error rates were significantly lower (p < .001). Also a significantly lower self-reported discomfort was observed in the neck and shoulders while working wearing the cooling suit (p = .004). This study concluded that wearing a cooling suit while working outdoors was associated with physiological benefits as well as improved task performance of the study participants.


Differential diagnosis and outcome of fetal intracranial hypoechoic lesions: report of 21 cases.
Our objective was to evaluate the diagnostic and prognostic value of sonography hypoechoic lesions. A retrospective study revealed revealed a total of 21 cases diagnosed over a period of 10 years. Most of the diagnosis were made in the third trimester. The presence fluid-filled lesions within the brain matter always predicted porencephaly and a poor outcome. In most of these cases (nine out of ten), the lesions were seen to communicate with the cavity of the lateral ventricles. Among the 11 cases of hypoechoic lesions that were external to the brain matter, Doppler ultrasound was always able to distinguish between arachnoid cysts (seven cases) and vein of Galen aneurysms (four cases). Arachnoid cysts were associated with a good outcome in four out of the five pregnancies that delivered at term. Three of the four cases of vein of Galen aneurysm were associated with distortion of the cerebral architecture and/or hydrops: one pregnancy was terminated and two resulted in early postnatal death. One pregnancy with vein of Galen aneurysm and normal cerebral structures, without signs of hydrops, had a good outcome. It is concluded that current antenatal ultrasound has the capability of accurate differentiation between different clinical entities resulting in fetal intracranial hypoechoic lesions, and that the sonographic findings have practical clinical implications.


Thromboembolic disease.
In 52 patients with pulmonary embolism, the deep venous circulation of the lower extremities and the pulmonary arterial blood flow were studied with albumin macroaggregates labeled with technetium-99m. A gamma camera with a data processor was used for this study. At the beginning, the perfusion lung scintigrams were abnormal in all the patients, 42 of them also had abnormal phlebograms and in half of them the perfusion by lung scintigram became normal when the phlebograms were obtained. These findings establish the high incidence of deep thrombophebitis in the legs of the patients with pulmonary embolism and indicate that the leg is of the most important 'thrombi factory' and that the deep venous circulation of the extremities should be studied to determine the primary cause of the pulmonary embolism.


A wireless, remote query glucose biosensor based on a pH-sensitive polymer.
This paper describes a wireless, remote query glucose biosensor using a ribbonlike, mass-sensitive magnetoelastic sensor as the transducer. The glucose biosensor is fabricated by first coating the magnetoelastic sensor with a pH-sensitive polymer and upon it a layer of glucose oxidase (GOx). The pH-responsive polymer swells or shrinks, thereby changing mass, respectively, in response to increasing or decreasing pH values. The GOx-catalyzed oxidation of glucose produces gluconic acid, inducing the pH-responsive polymer to shrink, which in turn decreases the polymer mass. In response to a time-varying magnetic field, a magnetoelastic sensor mechanically vibrates at a characteristic resonance frequency, the value of which inversely depends on sensor mass loading. As the magnetoelastic films are magnetostrictive, the vibrations launch magnetic flux that can be remotely detected using a pickup coil. Hence, changes in the resonance frequency of a passive magnetoelastic transducer are detected on a remote query basis, without the use of physical connections to the sensors.The sensitivity of the glucose biosensors decreases with increasing ionic strength; at physiological salt concentrations, 0.6 mmol/L of glucose can be measured. At glucose concentrations of 1-10 mmol/L, the biosensor response is reversible and linear, with the detection limit of 0.6 mmol/L corresponding to an error in resonance frequency determination of 20 Hz. Since no physical connections between the sensor and the monitoring instrument are required, this sensor can potentially be applied to in vivo and in situ measurement of glucose concentrations.


Congenitally transmitted visceral leishmaniasis: report of two Brazilian human cases.
Visceral leishmaniasis is a relevant public health problem worldwide. Most of the reported cases in Latin America are from Brazil. Herein we report two human cases of congenitally transmitted visceral leishmaniasis in two patients who developed symptoms during pregnancy. The diagnosis was made by visual examination of Leishmania parasites in bone marrow aspirates of the mothers and by detecting parasite kDNA in bone marrow samples of the newborn children using polymerase chain reaction.


The post-award effort of managing and reporting on funded research: a scoping review.
Reporting is a mechanism for funding organisations to monitor and manage the progress, outputs, outcomes, and impacts of the research they fund. Inconsistent approaches to reporting and post-award management, and a growing demand for research information, can lead to perception of unnecessary administrative effort that impacts on decision-making and research activity. Identifying this effort, and what stakeholders see as unmet need for improvement, is crucial if funders and Higher Education Institutions (HEIs) are to streamline their practices and provide better support with reporting activities. In this review, we summarise the processes in post-award management, compare current practices, and explore the purpose of collecting information on funded research. We also identify areas where unnecessary effort is perceived and improvement is needed, using previously reported solutions to inform recommendations for funders and HEIs. We conducted a scoping review of the relevant research and grey literature. Electronic searches of databases, and manual searches of journals and funder websites, resulted in inclusion of 52 records and 11 websites. Information on HEI and funder post-award management processes was extracted, catalogued, and summarised to inform discussion. Post-award management is a complex process that serves many purposes but requires considerable effort, particularly in the set up and reporting of research. Perceptions of unnecessary effort stem from inefficiencies in compliance, data management and reporting approaches, and there is evidence of needed improvement in mechanisms of administrative support, research impact assessment, monitoring, and evaluation. Solutions should focus on integrating digital systems to reduce duplication, streamlining reporting methods, and improving administrative resources in HEIs. Funders and HEIs should work together to support a more efficient post-award management process. The value of research information, and how it is collected and used, can be improved by aligning practices and addressing the specific issues highlighted in this review.


The self-regulation model of sexual offending: Relationship to risk and need.
In the present study, we evaluated the validity and utility of the self-regulation model in a sample of 275 adult male sexual offenders treated within the Correctional Service of Canada (CSC). Individuals following different self-regulation pathways, as delineated in the SRM, were compared on offence characteristics, static and dynamic risk measures, and various treatment targets. Multivariate analyses revealed that, in general, offenders guided by approach-motivated goals exhibited more problematic offence characteristics as well as greater risk and treatment need than individuals guided by inhibitory goals. However, several other important distinctions were noted across offenders with different goals and strategies toward offending. These findings highlight the main importance of utilizing a comprehensive and multidimensional offence process model that emphasizes multiple routes to offending in sexual offender treatment. Implications of these findings for the effective assessment and rehabilitation of sexual offenders are discussed.


Structural Characterization and Anti-complementary Activities of Two Polysaccharides from Houttuynia cordata.
In previous studies, crude Houttuynia cordata polysaccharides showed beneficial effects on acute lung injury in vivo, a syndrome in which anti-complementary activities played an important role. Anti-complementary activity-guided fractionation of H. cordata polysaccharides led to the isolation of two highly branched homogeneous polysaccharides, HC-PS1 and HC-PS3, with a molecular weight of 274 530 and 216 384 Da, respectively. The polysaccharides were purified by chromatography on DEAE-cellulose and Superdex columns. Their structural characterization was performed by IR, GC-MS, methylation, NMR, and SEM analysis. Both HC-PS1 and HC-PS3 are composed of eight types of monosaccharides, including rhamnose, arabinose, mannose, glucose, glucuronic acid, galactose, galacturonic acid, and xylose. The main linkages of the sugar residues in HC-PS1 include terminal Rhap, terminal and 1,5-linked Araf; 1,3,6-linked and 1,4,6-linked Manp; terminal, 1,4-linked, 1,3-linked, 1,3,6-linked and 1,4,6-linked and 1,3,4,6-linked Glcp; and terminal, 1,4-linked and 1,6-linked Galp. The main monosaccharide linkages in HC-PS3 are similar to that of HC-PS1, except the additional 1,3,4-linked Manp and the absence of 1,3,6-linked Glcp. HC-PS1 and HC-PS3 were found to inhibit complement activation through both the classical and alternative pathways with 50% inhibition concentrations of 0.272 - 0.318 mg/mL without interfering with the coagulation system. Preliminary mechanism studies indicated that both HC-PS1 and HC-PS3 inhibited the activation of the complement system by interacting with C2, C4, and C5. The results suggest that HC-PS1 and HC-PS3 could be valuable for the treatment of diseases associated with the excessive activation of the complement system.


Attachment of MAL32-encoded maltase on the outside of yeast cells improves maltotriose utilization.
The fermentation of maltotriose, the second most abundant fermentable sugar in wort, is often incomplete during high-gravity brewing. Poor maltotriose consumption is due to environmental stress conditions during high-gravity fermentation and especially to a low uptake of this sugar by some industrial strains. In this study we investigated whether the use of strains with an alpha-glucosidase attached to the outside of the cell might be a possible way to reduce residual maltotriose. To this end, the N-terminal leader sequence of Kre1 and the carboxy-terminal anchoring domain of either Cwp2 or Flo1 were used to target maltase encoded by MAL32 to the cell surface. We showed that Mal32 displayed on the cell surface of Saccharomyces cerevisiae laboratory strains was capable of hydrolysis of alpha-1,4-linkages, and that it increased the ability of a strain lacking a functional maltose permease to grow on maltotriose. Moreover, the enzyme was also expressed and found to be active in an industrial strain. These data show that expressing a suitable maltase on the cell surface might provide a means of modifying yeast for more complete maltotriose utilization in brewing and other fermentation applications.


Peripheral regulatory mechanisms in erection.
The most important pathway underlying the penile erection is the nonadrenergic/noncholinergic signalling, which through the release of nitric oxide (NO), leads to an intracellular increase of cyclic GMP (cGMP), the main secondary messenger mediating tumescence in the penis. Interestingly, both cGMP formation and degradation are affected by testosterone (T). In fact, beyond the well-known role of T in regulating sexual desire and NO release, recent experimental evidences from our group showed that T also regulates the expression of phosphodiesterase type 5 (PDE5), the hydrolytic enzyme involved in cGMP breakdown. This antithetic role of T seems to be the main way through which the peripheral hormonal regulation of penile erections occurs, allowing an important synchronization between erectile processes and sexual desire. Hence, erections are still possible in hypogonadal conditions where a decreased cGMP formation, because of impaired NO production, is counterbalanced by a reduced cGMP hydrolysis. The purpose of this review is to describe evidences about the peripheral role of T in regulating penile erection and to justify the importance to test T plasma levels in those patients with erectile dysfunction who do not respond to PDE5 inhibitors.


Architecture as animate landscape: circular shrines in the ancient Maya lowlands.
In this study, I develop a theory of landscape archaeology that incorporates the concept of "animism" as a cognitive approach. Current trends in anthropology are placing greater emphasis on indigenous perspectives, and in recent decades animism has seen a resurgence in anthropological theory. As a means of relating in (not to) one's world, animism is a mode of thought that has direct bearing on landscape archaeology. Yet, Americanist archaeologists have been slow to incorporate this concept as a component of landscape theory. I consider animism and Nurit Bird-David's (1999) theory of "relatedness" and how such perspectives might be expressed archaeologically in Mesoamerica. I examine the distribution of marine shells and cave formations that appear incorporated as architectural elements on ancient Maya circular shrine architecture. More than just "symbols" of sacred geography, I suggest these materials represent living entities that animate shrines through their ongoing relationships with human and other-than-human agents in the world.


Advances on diagnosis of Helicobacter pylori infections.
The association of Helicobacter pylori to several gastric diseases, such as chronic gastritis, peptic ulcer disease, and gastric cancer, and its high prevalence worldwide, raised the necessity to use methods for a proper and fast diagnosis and monitoring the pathogen eradication. Available diagnostic methods can be classified as invasive or non-invasive, and the selection of the best relies on the clinical condition of the patient, as well as on the sensitivity, specificity, and accessibility of the diagnostic test. This review summarises all diagnostic methods currently available, including the invasive methods: endoscopy, histology, culture, and molecular methods, and the rapid urease test (RUT), as well as the non-invasive methods urea breath test (UBT), serological assays, biosensors, and microfluidic devices and the stool antigen test (SAT). Moreover, it lists the diagnostic advantages and limitations, as well as the main advances for each methodology. In the end, research on the development of new diagnostic methods, such as bacteriophage-based H. pylori diagnostic tools, is also discussed.


Clinical risk factors for osteoporosis are common among elderly people in Nuuk, Greenland.
Osteoporosis is a debilitating condition characterized by fractures, pain and premature death. Risk factors for osteoporosis predict the risk of fragility fractures. To describe the occurrence of risk factors for osteoporosis among populations in Nuuk, the capital of Greenland. A random sample of women born in 1934-42, 1945-47, 1956, and men born in 1956 were selected from the national civil registry. A questionnaire was sent out in Greenlandic and Danish on risk factors for osteoporosis: family history, smoking habits, alcohol intake, presence of disease, sun exposure, intake of dairy products, age at menopause (women) and number of falls. Additional questions included the frequency of back pain, previous fractures, intake of vitamin D and calcium supplements, use of anti-osteoporotic drugs, steroids and other drugs. The questionnaire was sent to 317 subjects confirmed to be living at an address in Nuuk and 181 (57.1%) responded. More young women than older women were smokers (60.6% vs. 35.0%; p=0.022) while limited sun exposure was reported by more of the old women (37.2% vs. 5.6%; p=0.003). Family history of osteoporosis was reported by 15.0%, without difference between groups. Alcohol and milk intake did not differ between groups. Premature menopause was reported by 17.9% of the women. Falls within the last year were reported by 42.4% with fewer falls in the oldest age group (21.9% vs. 50.0%; p=0.005). Frequency of fragility fractures increased with age (5.7% vs. 24.3% vs. 30.4%; p=0.02) and the risk of a fragility fracture increased with age (p=0.004; OR, 95% CI: 4.5, 1.6-12.2, reference: below 70 years), when adjusted for smoking, gender and falls. The use of anti-osteoporotic drugs was low (3.4%) while 28.8% took calcium and vitamin D supplements. Age is a dominating risk factor for fragility fractures in Greenland. The use of anti-osteoporotic drugs is low in Greenland, even if osteoporotic fractures are common in old age.


Synergistic effects of encoding strategy and context salience on associative memory in older adults.
Older adults' deficits in memory for context and memory for inter-item associations are often assumed to be related, yet typically are examined in separate experiments. The present study combined associative recognition and list discrimination into a single task with conditions that varied in terms of item, pair, and context information, and independently manipulated context salience and encoding strategy between subjects in order to examine their effects on memory for associative information in young and older adults. Older adults' memory for pairs was found to be less affected than that of young adults by manipulations of context and associative information, but the age difference in context effects on pair memory was influenced by an interaction of encoding strategy and context salience. The results provide novel evidence that older adults' deficits in associative memory involve interactions between context and inter-item associations.


Analytical performance of a venturi-assisted array of micromachined ultrasonic electrosprays coupled to ion trap mass spectrometry for the analysis of peptides and proteins.
The analytical characterization of a novel ion source for mass spectrometry named array of micromachined ultrasonic electrosprays (AMUSE) is presented here. This is a fundamentally different type of ion generation device, consisting of three major components: (1) a piezoelectric transducer that creates ultrasonic waves at one of the resonant frequencies of the sample-filled device, (2) an array of pyramidally shaped nozzles micromachined on a silicon wafer, and (3) a spacer which prevents contact between the array and transducer ensuring the transfer of acoustic energy to the sample. A high-pressure gradient generated at the apexes of the nozzle pyramids forces the periodic ejection of multiple droplet streams from the device. With this device, the processes of droplet formation and droplet charging are separated; hence, the limitations of conventional electrospray-type ion sources, including the need for high charging potentials and the addition of organic solvent to decrease surface tension, can be avoided. In this work, a Venturi device is coupled with AMUSE in order to increase desolvation, droplet focusing, and signal stability. Results show that ionization of model peptides and small tuning molecules is possible with dc charging potentials of 100 Vdc or less. Ionization in rf-only mode (without dc biasing) was also possible. It was observed that, when combined with AMUSE, the Venturi device provides a 10-fold gain in signal-to-noise ratio for 90% aqueous sample solutions. Further reduction in the diameter of the orifices of the micromachined arrays led to an additional signal gain of at least 3 orders of magnitude, a 2-10-fold gain in the signal-to-noise ratio and an improvement in signal stability from 47% to 8.5% RSD. The effectiveness of this device for the soft ionization of model proteins in aqueous media, such as cytochrome c, was also examined, yielding spectra with an average charge state of 8.8 when analyzed with a 100 Vdc charging potential. Ionization of model proteins was also possible in rf-only mode.


Area-based socioeconomic factors and Human Papillomavirus (HPV) vaccination among teen boys in the United States.
This study is the first to examine associations between several area-based socioeconomic factors and human papillomavirus (HPV) vaccine uptake among boys in the United States (U.S.). Data from the 2012-2013 National Immunization Survey-Teen restricted-use data were analyzed to examine associations of HPV vaccination initiation (receipt of ≥1 dose) and series completion (receipt of three doses) among boys aged 13-17 years (N = 19,518) with several individual-level and ZIP Code Tabulation Area (ZCTA) census measures. Multivariable logistic regression was used to estimate the odds of HPV vaccination initiation and series completion separately. In 2012-2013 approximately 27.9% (95% CI 26.6%-29.2%) of boys initiated and 10.38% (95% CI 9.48%-11.29%) completed the HPV vaccine series. Area-based poverty was not statistically significantly associated with HPV vaccination initiation. It was, however, associated with series completion, with boys living in high-poverty areas (≥20% of residents living below poverty) having higher odds of completing the series (AOR 1.22, 95% CI 1.01-1.48) than boys in low-poverty areas (0-4.99%). Interactions between race/ethnicity and ZIP code-level poverty indicated that Hispanic boys living in high-poverty areas had a statistically significantly higher odds of HPV vaccine initiation (AOR 1.43, 95% CI 1.03-1.97) and series completion (AOR 1.56, 95% CI 1.05-2.32) than Hispanic boys in low-poverty areas. Non-Hispanic Black boys in high poverty areas had higher odds of initiation (AOR 2.23, 95% CI 1.33-3.75) and completion (AOR 2.61, 95% CI 1.06-6.44) than non-Hispanic Black boys in low-poverty areas. Rural/urban residence and population density were also significant factors, with boys from urban or densely populated areas having higher odds of initiation and completion compared to boys living in non-urban, less densely populated areas. Higher HPV vaccination coverage in urban areas and among racial/ethnic minorities in areas with high poverty may be attributable to factors such as vaccine acceptance, health-care practices, and their access to HPV vaccines through the Vaccines for Children Program, which provides free vaccines to uninsured and under-insured children. Given the low HPV vaccination rates among boys in the U.S., these results provide important evidence to inform public health interventions to increase HPV vaccination.


Acute nonlymphocytic leukemia, preleukemia, and acute myeloproliferative syndrome secondary to treatment of other malignant diseases. II. Bone marrow cytology, cytogenetics, results of HLA typing, response to antileukemic chemotherapy, and survival in a total series of 55 patients.
Secondary acute nonlymphocytic leukemia or its earlier stages, preleukemia or an acute myeloproliferative syndrome with refractory cytopenia and clonal cytogenetic abnormalities of the bone marrow, was diagnosed in 55 patients previously treated for other malignant diseases. In patients with overt leukemia, cytologic, and cytochemical studies showed predominance of the French-American-British (FAB) type M2. Cytogenetic examination demonstrated a normal karyotype in 11 cases, whereas clonal abnormalities were observed in 44 patients. Defects of chromosome 7 were observed in 24 cases, most often -7, and defects of chromosome 5 in 14 cases, most often 5q-. In addition, chromosomes 3 and 17 were possibly nonrandomly involved. Other abnormalities commonly observed in de novo acute nonlymphocytic leukemia as t(8;21) and t(15;17) were not observed and +8 rarely seen in secondary leukemia. The survival from the leukemic complication was short for the whole group of 55 patients (median, 7 months). However, a significantly longer survival was observed in a subgroup of 11 patients with a normal karyotype (P less than 0.01), due to a favorable response to antileukemic chemotherapy, and in a subgroup of 11 patients with -7 or -C as the only cytogenetic abnormality (P less than 0.01), due to a prolonged preleukemic phase, compared with the remaining 33 cases with mostly multiple karyotypic abnormalities. Three preleukemic patients with -7 who were studied during transformation to overt leukemia all developed additional cytogenetic abnormalities. According to the two-step or multistep hypothesis for malignant transformation, the prolonged preleukemic course in patients with -7 as the only abnormality could represent a premalignant stage, in which further evolution is required for development of overt leukemia. The patients showed a random distribution of blood groups and HLA types.


[Serum tumor markers at exocrine adenocarcinoma of pancreas].
Pancreatic cancer represents a group of cancers with the worst prognosis. There exists only one method of successful therapy--radical surgery, i.e. the complete resection of the tumor. However, only 5% of cases are diagnosed in the early stage. More than 60% are recognised in the period of advanced disease. For those patients only palliative treatment can be used. Only early diagnosis can ensure better therapy results. Possibility of early diagnosis based on imaging and endoscope methods is at present very limited due to the anatomical location of pancreas. Serum tumor markers assessment might represent one of the possibilities of early detection of the pancreatic cancer. Review summarizes current knowledge on the use of tumor markers for diagnosis, prognosis and therapy monitoring of pancreatic exocrine adenocarcinomas with respect to the clinical use at the daily routine practice.


σ-1 receptor stimulation protects against pressure-induced damage through InsR-MAPK signaling in human trabecular meshwork cells.
The purpose of the present study was to investigate the protective effect of the σ-1 receptor (Sig-1R) agonist (+)‑pentazocin (PTZ) on pressure-induced apoptosis and death of human trabecular meshwork cells (hTMCs). The expression levels of Sig‑1R and insulin receptor (InsR) were examined in hTMCs. Cells were cultured under a pressure of 0, 20, 40, 60 and 80 mmHg for 48 h, and under 80 mmHg for 44 h, after which the cells were treated with (+)‑PTZ (20 µM), N-(2-(3,4-dichlorophenyl)ethyl)-N‑methyl-2‑(dimethylamino) ethylamine (BD‑1063; 20 µM) administered 30 min prior to (+)‑PTZ, or BD‑1063 (20 µM) and then exposed to 80 mmHg again until the 48 h time‑point. The changes of the cells were observed by optical and electron microscopy, the apoptosis and death of hTMCs were detected by ethidium bromide/acridine orange dual staining assay and the expression of Sig‑1R and InsR by reverse transcription‑quantitative polymerase chain reaction and western blot analysis. The phosphorylation of extracellular signal‑regulated kinase (ERK), an important downstream protein of the InsR‑mitogen‑activated protein kinases (MAPK) signaling pathway, was also detected by western blot analysis when (+)‑PTZ and BD‑1063 were added to the 80 mmHg‑treated cells. Sig‑1Rs and InsRs were expressed in hTMCs. The apoptosis and death of hTMCs increased from 40 mmHg with 50% cell death when the pressure was at 80 mmHg and the structure of the cells noticeably changed. The expression of Sig‑1R and InsR increased along with the elevation of pressure. (+)‑PTZ decreased the apoptosis and death of hTMCs and increased the expression of Sig‑1R and InsR, and the phosphorylation of ERK. Such effects were blocked by BD‑1063. The present study suggested that Sig‑1R agonist (+)‑PTZ can protect hTMCs from pressure‑induced apoptosis and death by activating InsR and the MAPK signal pathway.


Synthesis of a functional C2-symmetrical bidentate diphenylphosphonite DIOP derivative and its conversion into the corresponding pi-acidic bis(pentafluorophenyl) and bis(p-tetrafluoropyridyl) compounds.
The reaction of a C2-symmetric diiodo compound, 1,4-dideoxy-1,4-diiodo-2,3,-O-isopropyliden-L-threitole, with [K([18]crown-6)]P(CN)2 led to the generation of a corresponding bidentate dicyanophosphorus derivative. The in situ reaction with excess methanol and phenol yielded the corresponding bidentate dimethyl- and diphenylphosphonites, respectively. The isolated liquids were characterized by multinuclear NMR spectroscopy, elemental analysis, and mass spectrometry. The bidentate diphenylphosphonite ligand (a diphenoxyphosphane derivative) represents one of the very few functional bidentate phosphane derivatives: a DIOP [(2,2-dimethyl-1,3-dioxolane-4,5-diyl)bis(methylene)]bis(diphenylphosphane) modification, in which the phenyl groups at the phosphorus atoms are replaced by functional phenoxy groups. Treatment of the bidentate diphenylphosphonite derivative with C6F5MgBr and p-C5NF4MgBr allowed the isolation and full characterization of the comparable bidentate bis(pentafluorophenyl) and bis(p-tetrafluoropyridyl)phosphanes. The ligand properties of the novel bidentate ligand systems were evaluated through the synthesis and vibrational investigation of their tetracarbonyl-molybdenum and cyclopentadienyl-iron complexes. The pi acidity of the synthesized ligands increases in the order methoxy-<phenoxy-<pentafluorophenyl-<p-tetrafluoropyridyl phosphane.


Novel biomarker-based score (SAD-60) for predicting mortality in patients with COVID-19 pneumonia: a multicenter retrospective cohort of 1013 patients.
Background: The aim was to explore a novel risk score to predict mortality in hospitalized patients with COVID-19 pneumonia. Methods: This was a retrospective, multicenter study. Results: A total of 1013 patients with COVID-19 were included. The mean age was 60.5 ± 14.4 years, and 581 (57.4%) patients were male. In-hospital death occurred in 124 (12.2%) patients. Multivariate analysis revealed peripheral capillary oxygen saturation (SpO2), albumin, D-dimer and age as independent predictors. The mortality score model was given the acronym SAD-60, representing SpO2, Albumin, D-dimer, age ≥60 years. The SAD-60 score (0.776) had the highest area under the curve compared with CURB-65 (0.753), NEWS2 (0.686) and qSOFA (0.628) scores. Conclusion: The SAD-60 score has a promising predictive capacity for mortality in hospitalized patients with COVID-19.


Effect of Comedication With Conventional Synthetic Disease-Modifying Antirheumatic Drugs on Retention of Tumor Necrosis Factor Inhibitors in Patients With Spondyloarthritis: A Prospective Cohort Study.
To evaluate whether use of comedication with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) influences the retention of tumor necrosis factor inhibitors (TNFi) in patients with spondyloarthritis (SpA). Patients with SpA from the Rheumatic Diseases Portuguese Register who started treatment with their first TNFi between 2001 and 2014 were included in this study. Cox regression analysis was used to estimate the effect of comedication with csDMARDs on TNFi retention in 2 types of models: a model in which baseline (time-fixed) variables were included, and a second model incorporating time-varying variables, including sociodemographic features, measures of disease activity, measures of physical function, and cotreatment with other drugs (nonsteroidal antiinflammatory drugs and oral steroids). To control for possible confounding by indication, the effect of csDMARD comedication on TNFi retention was also tested after adjustment for the treatment propensity score. In total, 954 patients were included in the study, of whom 289 (30.3%) discontinued treatment with their first TNFi after a median follow-up time of 2.5 years (range 0.08-13 years). Inefficacy was the most common reason for TNFi discontinuation (55.7% of patients). In the multivariable analyses, comedication with csDMARDs had no measurable effect on TNFi retention, neither in the baseline model (hazard ratio [HR] 0.83, 95% confidence interval [95% CI] 0.59-1.16) nor during follow-up in the model adjusted for time-varying covariates (HR 1.07, 95% CI 0.68-1.68). The effect of csDMARD comedication remained nonsignificant after propensity score adjustment. Comedication with csDMARDs does not prolong TNFi retention in patients with SpA in clinical practice, suggesting that there is no benefit conferred by the concomitant use of these drugs.


A Perspective on Designing Chiral Organic Magnetic Molecules with Unusual Behavior in Magnetic Exchange Coupling.
A total of nine diradical-based organic chiral magnetic molecules with allene and cumulene couplers have been theoretically designed, and subsequently, their magnetic property has been studied by density functional theory. It is found that with an increase in length of the coupler, a remarkable increase in spin density within the coupler takes place. An increase in the length of the coupler reduces the energy of LUMO, and a smaller HOMO-LUMO gap facilitates stronger magnetic coupling and thereby a higher magnetic exchange coupling constant (J). This observation is supported by the occupation number of natural orbitals.


The 24 h pattern of arterial pressure in mice is determined mainly by heart rate-driven variation in cardiac output.
Few studies have systematically investigated whether daily patterns of arterial blood pressure over 24 h are mediated by changes in cardiac output, peripheral resistance, or both. Understanding the hemodynamic mechanisms that determine the 24 h patterns of blood pressure may lead to a better understanding of how such patterns become disturbed in hypertension and influence risk for cardiovascular events. In conscious, unrestrained C57BL/6J mice, we investigated whether the 24 h pattern of arterial blood pressure is determined by variation in cardiac output, systemic vascular resistance, or both and also whether variations in cardiac output are mediated by variations in heart rate and or stroke volume. As expected, arterial pressure and locomotor activity were significantly (P < 0.05) higher during the nighttime period compared with the daytime period when mice are typically sleeping (+12.5 ± 1.0 mmHg, [13%] and +7.7 ± 1.3 activity counts, [254%], respectively). The higher arterial pressure during the nighttime period was mediated by higher cardiac output (+2.6 ± 0.3 mL/min, [26%], P < 0.05) in association with lower peripheral resistance (-1.5 ± 0.3 mmHg/mL/min, [-13%] P < 0.05). The increased cardiac output during the nighttime was mainly mediated by increased heart rate (+80.0 ± 16.5 beats/min, [18%] P < 0.05), as stroke volume increased minimally at night (+1.6 ± 0.5 μL per beat, [6%] P < 0.05). These results indicate that in C57BL/6J mice, the 24 h pattern of blood pressure is hemodynamically mediated primarily by the 24 h pattern of cardiac output which is almost entirely determined by the 24 h pattern of heart rate. These findings suggest that the differences in blood pressure between nighttime and daytime are mainly driven by differences in heart rate which are strongly correlated with differences in locomotor activity.


Rapid, large-scale purification and characterization of 'Ada protein' (O6 methylguanine-DNA methyltransferase) of E. coli.
The E. coli Ada protein (O6-methylguanine-DNA methyltransferase) has been purified using a high-level expression vector with a yield of about 3 mg per liter of E. coli culture. The 39-kDa protein has an extinction coefficient (E280 nm (1%)) of 5.3. Its isoelectric point of 7.1 is lower than that predicted from the amino acid content. The homogeneous Ada protein is fully active as a methyl acceptor from O6-methylguanine in DNA. Its reaction with O6-methylguanine in a synthetic DNA has a second-order rate constant of 1.1 x 10(9) M-1 min-1 at O degree C. Both the native form and the protein methylated at Cys-69 are monomeric. The CD spectrum suggests a low alpha-helical content and the radius of gyration of 23 A indicates a compact, globular shape. The middle region of the protein is sensitive to a variety of proteases, including an endogenous activity in E. coli, suggesting that the protein is composed of N-terminal and C-terminal domains connected by a hinge region. E. coli B has a higher level of this protease than does K12.


Anticoagulants for acute ischaemic stroke.
Most ischaemic strokes are caused by blood clots blocking an artery in the brain. Clot prevention with anticoagulant therapy could have a significant impact on patient survival, disability and stroke recurrence. The objective of this review was to assess the effect of anticoagulant therapy versus control in the early treatment of patients with acute ischaemic stroke. We searched the Cochrane Stroke Group trials register (last searched 30 October 2003). For previous updates of this review, we searched the register of the Antithrombotic Trialists' (ATT) Collaboration, consulted MedStrategy (1995), and contacted relevant drug companies. Randomised trials comparing early anticoagulant therapy (started within two weeks of stroke onset) with control in patients with acute presumed or confirmed ischaemic stroke. Two reviewers independently selected trials for inclusion, assessed trial quality and extracted the data. Twenty-two trials involving 23,547 patients were included. The quality of the trials varied considerably. The anticoagulants tested were standard unfractionated heparin, low-molecular-weight heparins, heparinoids, oral anticoagulants, and thrombin inhibitors. Based on nine trials (22,570 patients) there was no evidence that anticoagulant therapy reduced the odds of death from all causes (odds ratio (OR) = 1.05, 95% confidence interval (CI) 0.98 to 1.12) at the end of follow-up. Similarly, based on six trials (21,966 patients), there was no evidence that anticoagulants reduced the odds of being dead or dependent at the end of follow-up (OR = 0.99; 95% CI 0.93 to 1.04). Although anticoagulant therapy was associated with about 9 fewer recurrent ischaemic strokes per 1000 patients treated (OR = 0.76; 95% CI 0.65 to 0.88), it was also associated with a similar sized 9 per 1000 increase in symptomatic intracranial haemorrhages (OR = 2.52; 95% CI 1.92 to 3.30). Similarly, anticoagulants avoided about 4 pulmonary emboli per 1000 (OR = 0.60, 95% CI 0.44 to 0.81), but this benefit was offset by an extra 9 major extracranial haemorrhages per 1000 (OR = 2.99; 95% CI 2.24 to 3.99). Sensitivity analyses did not identify a particular type of anticoagulant regimen or patient characteristic associated with net benefit. Immediate anticoagulant therapy in patients with acute ischaemic stroke is not associated with net short- or long-term benefit. The data from this review do not support the routine use of any type of anticoagulant in acute ischaemic stroke. People treated with anticoagulants had less chance of developing deep vein thrombosis (DVT) and pulmonary embolism (PE) following their stroke, but these sorts of blood clots are not very common, and may be prevented in other ways.


[Psychotherapy and pharmacotherapy of anxiety disorders].
Anxiety disorders are highly prevalent in the general population, their course of illness is often chronic with many relapses, and is associated with a pronounced psychiatric comorbidity and psychosocial disability. Therefore, anxiety disorders are a major challenge to any mental health delivery system. From a perspective of treatment both differential psychopharmacological and psychotherapeutic interventions can be outlined which are well based in empirical terms. In psychiatric care biological and psychological approaches are often combined although the empirical basement of combined treatments still requires further validation.


Mercury distribution in fish organs sampled along the Mauritanian Atlantic coast and their potential human health risks.
This paper aimed at assessing total mercury concentration in seven common fish species (Auxis rochei, Caranx rhonchus, Sardina pilchardus, Sardinella aurita, Sardinella maderensis, Scomber colias and Trachurus trecae) and a relationship between Hg organotropism and food regimes along the Mauritanian Atlantic coast. Results show that total mercury concentration in fish collected along five sites ranged from 0.027 to 0.533 mg/kg dry weight. Significant differences were observed among species depending on feeding behavior. Muscle tissues of carnivorous fish presented significantly higher levels of total mercury than that of omnivorous fish, except for Scomber colias, suggesting mercury biomagnification through the food chain. Significant differences in mercury concentrations were observed between muscle tissues and liver, for Auxis rochei, Trachurus trecae, and Caranx rhonchus. The mean concentrations in the different species are however low and none of the concentration values exceed the World Health Organization's threshold for human consumption.


[A Projection of the Need for Rehabilitation in Germany Till 2040 Based on Demographic Factors].
The demographic changes in Germany leads to a significant shift in the composition of the population and the workforce, this affecting the future need for medical rehabilitation. This paper estimates the future change in rehabilitation demand based on a forecast for demographic changes till 2040. First, the sensitivity of the rehabilitation demand with respect to demographic factors is estimated. Second, the demographic factors are projected by stochastic methods, resulting in forecasts for the future need for medical rehabilitation. The projections show that the short-term demand is likely to rise. Theoretically, yearly wage increases of about 2.2% are needed for covering the increasing medical rehabilitation costs from 2010 till 2017. For the mid-term demand, the model predicts a slight decline in rehabilitation cases. Considering all these facts, the budget for rehabilitation will probably not cover the future costs for rehabilitation. However, the long-term forecast is subject to considerable uncertainty.


Expression Pattern and Function Analysis of AtPPRT1, a Novel Negative Regulator in ABA and Drought Stress Responses in Arabidopsis.
Abscisic acid (ABA) plays a fundamental role in plant growth and development, as well as in the responses to abiotic stresses. Previous studies have revealed that many components in ABA and drought stress signaling pathways are ubiquitinated by E3 ligases. In this study, AtPPRT1, a putative C3HC4 zinc-finger ubiquitin E3 ligase, was explored for its role in abiotic stress response in Arabidopsis thaliana. The expression of AtPPRT1 was induced by ABA. In addition, the β-glucuronidase (GUS) gene driven by the AtPPRT1 promoter was more active in the root hair zone and root tips of primary and major lateral roots of young seedlings in the presence of ABA. The assays for seed germination, stomatal aperture, root length, and water deficit demonstrated that the AtPPRT1-overexpressing Arabidopsis was insensitive to ABA and sensitive to drought stress compared with wild-type (WT) plants. The analysis by quantitative real-time PCR (qRT-PCR) revealed that the expression of three stress-inducible genes (AtRAB18, AtERD10, and AtKIN1) were upregulated in the atpprt1 mutant and downregulated in AtPPRT1-overexpressing plants, while two ABA hydrolysis genes (AtCYP707A1 and AtCYP707A3) were downregulated in the atpprt1 mutant and upregulated in AtPPRT1-overexpressing plants in the presence of ABA. AtPPRT1 was localized in the mitochondria. Our findings indicate that AtPPRT1 plays a negative role in ABA and drought stress responses.


Not by (Good) Microbes Alone: Towards Immunocommensal Therapies.
Commensal bacteria have been identified as critical drivers of host resilience to pathogen invasion. The resulting 'competitive exclusion' of pathogens by commensals can arise via multiple mechanisms, including direct competition for sites of colonization, production of metabolic products that inhibit pathogen growth, and modulation of host immune responses (including differential targeting of pathogens). Nonetheless, suppression of pathogens through the combined action of commensals and host immunity is far from inevitable. Here, we utilize a simple, within-host ecosystem model to explore the microbiological and immunological conditions that govern the fate of pathogen colonization. Model analysis leads to the hypothesis that robust elimination of pathogens requires a synergy between host immune defense and commensal bacteria. That is, pathogens can proliferate and establish persistent infections if either the state of the microbiota or the host immune defense falls below critical levels. Leveraging these findings, we advocate for improved integration of nonlinear dynamic models in efforts to understand infection dynamics in an immunological context. Doing so may provide new opportunities to establish baseline indicators for healthy microbiomes and to develop improved therapeutics through targeted modification of feedback amongst commensals and between commensals and the immune system.


Transfer Dysphagia Due to Focal Dystonia.
The inability to propel a bolus of food successfully from the posterior part of the oral cavity to the oropharynx is defined as transfer dysphagia. The present case series describes the varied presentation of transfer dysphagia due to focal dystonia and highlights the importance of early detection by following up on strong suspicions. We describe seven cases of transfer dysphagia due to focal dystonia. Transfer dysphagia as a form of focal dystonia may appear as the sole presenting complaint or may present with other forms of focal dystonia. Four out of seven patients had pure transfer dysphagia and had previously been treated for functional dysphagia. A high index of suspicion, barium swallow including videofluoroscopy, associated dystonia in other parts of the body and response to drug therapy with trihexyphenidyl/tetrabenazine helped to confirm the diagnosis. Awareness of these clinical presentations among neurologists and non-neurologists can facilitate an early diagnosis and prevent unnecessary investigations.


Is percutaneous cholecystostomy the optimal treatment for acute cholecystitis in the very elderly?
In elderly patients emergent cholecystectomy for acute cholecystitis is a high risk procedure. We prospectively assessed the value of percutaneous cholecystostomy for acute cholecystitis in 38 consecutive elderly (> or = 80 years) patients. All 38 underwent percutaneous transhepatic cholecystostomy under ultrasonographic and fluoroscopic guidance for acute cholecystitis (25 calculous, 13 acalculous). Eight (21%) patients had acute severe medical problems, such as shock and respiratory distress. Thirty-one (82%) patients had chronic severe underlying diseases, including cardiovascular and neurologic diseases. Cholecystostomy was successful in all 38 patients. Prompt clinical improvement was obtained in 36 (95%) patients. Morbidity and mortality rates were 3% and 3%, respectively. After cholecystostomy, 10 patients with cholelithiasis underwent elective cholecystectomy without serious complications. Two patients underwent percutaneous cholecystolithotomy, which produced complete resolution of symptoms. Four of 12 patients with and none of 12 without cholelithiasis had recurrent cholecystitis after catheter removal during a mean follow-up of 1.8 years. A second cholecystostomy was successful in these four patients. Elderly patients are often poor surgical candidates because of severe cholecystitis or concomitant medical problems. Percutaneous cholecystostomy is a safe, effective treatment for acute cholecystitis even in elderly patients. For calculous cholecystitis, cholecystostomy can be followed by elective surgery, if possible, or by nonsurgical treatment or expectant conservative management in high-risk patients. Cholecystostomy may be a definitive treatment for acalculous cholecystitis.


Association of Arm Position and Playing Time with Prevalence of Complaints of the Arm, Neck, and/or Shoulder (CANS) in Amateur Musicians: A Cross-Sectional Pilot Study Among University Students.
In addition to known risk factors for musculoskeletal complaints in the general population, playing a musical instrument is an additional risk factor. In this pilot study, the prevalence of musculoskeletal complaints in student amateur musicians and their relation with playing posture and playing time were evaluated. A cross-sectional web-based survey among amateur musicians studying at a Dutch university. 162 amateur musicians were included in this pilot study (response rate 17.6%). 46.9% of these amateur musicians played with an elevated arm position. Presence of complaints of the arm, neck and/or shoulder (CANS) was not statistically significantly related to arm position, except for complaints in the left shoulder with an elevated left arm position compared to neutral left arm position (OR 6.7, CI 95% 2.2-20.8) The number of hours playing per week did not significantly contribute to CANS (OR 1.0, CI 95% 0.95-1.17). In this pilot study among student amateur musicians, the occurrence of CANS was not significantly related to arm position, except for musicians playing with an elevated left arm position, which was associated with complaints of the left shoulder (OR 6.7). The number of hours playing per week did not significantly contribute to CANS in this group of musicians.


Treatment of extra-articular proximal and middle phalangeal fractures of the hand: a systematic review.
The aim of the study was to systematically review the patient reported and functional outcomes of treatment for extra-articular proximal or middle phalangeal fractures of the hand in order to determine the best treatment options. The review methodology was registered with PROSPERO. A systematic literature search was conducted in electronic bibliographic databases. Two independent reviewers performed screening and data extraction. The evaluation of quality of the included studies was performed using the Structured Effectiveness Quality Evaluation scale. The initial search yielded 2354 studies. The full text manuscripts of 79 studies were evaluated of which 16 studies met the inclusion criteria. In total, 513 extra-articular proximal and middle phalangeal fractures of the hand were included of which 118 (23%) were treated non-operatively, 188 (37%) were treated by closed reduction internal fixation (CRIF) and 207 (40%) by open reduction internal fixation. It can be recommended that closed displaced extra-articular phalangeal fractures can be treated non-operatively, even fractures with an oblique or complex pattern, provided that closed reduction is possible and maintained. Conservative treatment is preferably performed with a cast/brace allowing free mobilization of the wrist. No definite conclusion could be drawn upon whether closed reduction with extra-articular K-wire pinning or transarticular pinning is superior; however, it might be suggested that extra-articular K-wire pinning is favoured. When open reduction is necessary for oblique or spiral extra-articular fractures, lag screw fixation is preferable to plate and screw fixation. But, similar recovery and functional results are achieved with transversally inserted K-wires compared to lag screw fixation. therapeutic III.


Knowledge towards Strabismus and Associated Factors among Adults in Gondar Town, Northwest Ethiopia.
Strabismus/squint is an ocular misalignment in which the eyes are not properly aligned with each other. It is an avoidable cause of blindness and has a global prevalence which ranges from 2% to 6%. Knowledge of eye diseases is important in encouraging people to seek early treatment, which further helps in reducing the burden of visual impairment. Studies in Ethiopia showed that the level of good knowledge was 37%. There is a lack of information regarding knowledge and related factors of strabismus in the study area and limited in Ethiopia at large. The aim of this study was to asses knowledge about strabismus and associated factors among adults in Gondar town, Northwest Ethiopia. Community-based cross-sectional study was conducted using a pretested structured questionnaire through face to face interview from April 17 to May 01, 2019. Using multistage random sampling, 553 participants were included. Data from the entire questionnaire were coded, entered into Epi info version 7, and exported to SPSS version 20 for processing and analysis. Binary logistic regression was fitted, and variables with P value <0.05 in the multivariable logistic regression were considered as statistically significant. A total of 553 adults with a response rate of 93.25% participated in the study. The median age was 33 (IQR = 14) years. Among the participants, 52.3% (95% CI: 47.9-56.4) had good knowledge towards strabismus. Being a student (AOR = 2.15, (95% CI: 1.11-4.13) was positively associated, while monthly income >5000 birrs (AOR = 0.44, 95% CI: 0.26-0.76) was negatively associated with good knowledge about strabismus. Almost half of the participants had good knowledge. Occupation and monthly income had a significant association with knowledge about strabismus. Since the source of information (TV/radio and Internet) was extremely important for the reliability and the level of knowledge, it is better to have sufficient media coverage.


Short latency cerebellar modulation of the basal ganglia.
The graceful, purposeful motion of our body is an engineering feat that remains unparalleled in robotic devices using advanced artificial intelligence. Much of the information required for complex movements is generated by the cerebellum and the basal ganglia in conjunction with the cortex. Cerebellum and basal ganglia have been thought to communicate with each other only through slow, multi-synaptic cortical loops, begging the question as to how they coordinate their outputs in real time. We found that the cerebellum rapidly modulates the activity of the striatum via a disynaptic pathway in mice. Under physiological conditions, this short latency pathway was capable of facilitating optimal motor control by allowing the basal ganglia to incorporate time-sensitive cerebellar information and by guiding the sign of cortico-striatal plasticity. Conversely, under pathological condition, this pathway relayed aberrant cerebellar activity to the basal ganglia to cause dystonia.


Long-Term Prophylactic Antibiotic Treatment: Effects on Survival, Immunocompetence and Reproduction Success of Parasemia plantaginis (Lepidoptera: Erebidae).
Hundreds of insect species are nowadays reared under laboratory conditions. Rearing of insects always implicates the risk of diseases, among which microbial infections are the most frequent and difficult problems. Although there are effective prophylactic treatments, the side effects of applied antibiotics are not well understood. We examined the effect of prophylactic antibiotic treatment on the overwintering success of wood tiger moth (Parasemia plantaginis) larvae, and the postdiapause effect on their life-history traits. Four weeks before hibernation larvae were treated with a widely used antibiotic (fumagillin). We monitored moths' survival and life-history traits during the following 10 mo, and compared them to those of untreated control larvae. Prophylactic antibiotic treatment had no effect on survival but we show effects on some life-history traits by decreasing the developmental time of treated larvae. However, we also revealed relevant negative effects, as antibiotic treated individuals show a decreased number of laid eggs and also furthermore a suppressed immunocompetence. These results implicate, that a prophylactic medication can also lead to negative effects on life-history traits and reproductive success, which should be seriously taken in consideration when applying a prophylactic treatment to laboratory reared insect populations.


Should high BMI be a reason for IVF treatment denial?
Our aim was to examine the influence of BMI on the live-birth rate following IVF/ICSI and evaluate its specific contribution among other factors thus enabling accurate reproductive policy development. All patients that underwent IVF/ICSI at our center during January 2012-July 2015 were included in this retrospective study. A total of 1654 ICSI cycles were divided into four groups according to the patient's BMI (kg/m2): group I (normal weight): <25 (943 cycles); group II (overweight): 25-30 (403 cycles); group III (obese): 30-35 (212 cycles); group IV (morbid obesity): >35 (96 cycles). Comparing the four groups of BMI, mean age and number of previous ART cycles was significantly lower in group I compared to groups II, III and IV. Length of treatment was significantly shorter in group I compared to groups II, III and IV. Ovarian response to COH was comparable in terms of mean estradiol and progesterone levels on the day of hCG administration mean number of oocytes retrieved, fertilized and number of embryos transferred. Endometrial thickness was significantly lower in group IV. Outcome measures, such as implantation rate, clinical pregnancy rate (CPR) per cycle and per ET, as well as live-birth rates did not differ significantly between the groups, although in group IV LBR per cycle and per ET was lower. Multivariate logistic regression stepwise analysis found a significant correlation between age and BMI but did not find correlation between BMI and clinical pregnancy (p = 0.436) or LB (p = 0.206). The results of our relatively large retrospective study did not demonstrate a significant impact of BMI on the ART cycle outcome. Therefore, BMI should not be a basis for IVF treatment denial.


Arabidopsis thaliana subcellular responses to compatible Erysiphe cichoracearum infections.
Subcellular events of Erysiphe cichoracearum infections of epidermal cells were visualized in living tissues of Arabidopsis plants carrying various green fluorescent protein (GFP)-tagged organelles via laser scanning confocal microscopy. Early in the infection sequence, cytoplasm and organelles moved towards penetration sites and accumulated near penetration pegs. Peroxisomes appeared to accumulate preferentially relative to the cytoplasm at penetration sites. Another early event, which preceded haustorium formation, was the aggregation of some GFP-tagged plasma membrane marker proteins into rings around penetration sites, which extended across cell-wall boundaries into neighboring cells. This feature localized to sites where papillae were deposited. The extrahaustorial membrane (EHM) encases the fungal feeding structure, the haustorium, separating it from the host cytoplasm. Eight plasma membrane markers were excluded from the EHM and remained in a collar-like formation around the haustorial neck. These observations support the suggestions that the EHM is a unique, specialized membrane and is different from the plasma membrane. Our results suggested two possibilities for the origin of the EHM: invagination of the plasma membrane coupled with membrane differentiation; or de novo synthesis of the EHM by targeted vesicle trafficking.


The effect of breeding system on polymorphism in mitochondrial genes of Silene.
Gynodioecy is a breeding system characterized by the co-occurrence of hermaphrodite and female individuals, generally as the result of nuclear-cytoplasmic interactions. The question remains whether the genetic factors controlling gynodioecy are maintained in species over long evolutionary timescales by balancing selection or are continually arising and being replaced in epidemic sweeps. If balancing selection maintains these factors, then neutral cytoplasmic diversity should be greater in gynodioecious than hermaphroditic species. In contrast, epidemic sweeps of factors controlling gynodioecy should decrease cytoplasmic diversity in gynodioecious relative to hermaphroditic species. We took a comparative approach in which we sequenced two mitochondrial genes, cytochrome b (cob) and cytochrome oxidase (cox1), for multiple populations of several hermaphroditic, gynodioecious, and dioecious species in the genus Silene. Breeding system was predictive of polymorphism. Gynodioecious species harbor many old haplotypes while hermaphroditic and dioecious species have little to no nucleotide diversity. The genealogical structure of neither gene departed from neutral expectations. Taken together, our results suggest that balancing selection acts on cytoplasmic male-sterility factors in several gynodioecious species in the genus.


Cardiovascular disease and ANCA-associated vasculitis: are we missing a beat?
The association between cardiovascular (CV) disease and anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is well documented. The recent work by Massicotte-Azarniouch et al. confirms the risk and adds to the existing evidence by describing the highest risk in the first 3 months after diagnosis. In this review, we aim to put their findings into perspective and formulate implications for the care of AAV patients. We discuss mechanisms for increased CV disease in AAV, including the impact of traditional risk factors and disease-related risks such as renal impairment and anti-myeloperoxidase (MPO) ANCA serotype. We also provide a brief primer on the impact of inflammatory-driven endothelial dysfunction and platelet activation on accelerated atherosclerosis in AAV patients. These features alongside the impact of disease activity and systemic inflammation provide potential explanations to why the incidence of CV events is highest in the first 3 months from diagnosis. We suggest future avenues of research, provide some suggestions to address and treat CV risk based on current evidence, and highlight the importance of addressing this topic early on. Addressing modifiable risk factors, dialogue with patients, patient information and a structured approach overall will be key to improve CV outcomes in AAV.


Psoriasis treatment patterns with etanercept and adalimumab in a United States health plan population.
A retrospective study utilizing administrative claims from a US commercial health plan was performed to examine etanercept and adalimumab treatment patterns among patients with psoriasis (PSO). Biologic-naïve PSO patients initiating etanercept or adalimumab therapy between 18 January 2008 and 31 December 2008 were identified. Patients continuously enrolled in the health plan for 6 months before and ≥12 months after therapy initiation were followed until disenrollment from the plan or 31 December 2009. Persistence was defined as continuous use of index TNF blocker without a gap in therapy ≥60 days. Patients with gaps in index therapy ≥60 days were classified as discontinuing, switching, or restarting the index therapy. In total, 497 patients initiated etanercept and 330 the adalimumab therapy. Mean age for both groups was 43 years. Approximately 40-42% of patients were persistent on their index TNF blocker for 1 year. Among patients with a ≥60-day gap in therapy, discontinuation without restart or switch occurred in 37% of etanercept and 45% of adalimumab patients (p = 0.04). Differences in therapy restart or switching between the groups were not statistically significant. TNF-blocker therapy persistence is low among PSO patients in this health plan. More than one-third of patients restarted their index TNF blocker after a gap in therapy.


Prolonged interval immunotherapy of Hymenoptera sting allergy.
Sixty-six patients receiving hyposensitizing allergy injections for hymenoptera sting allergy had the interval between these injections prolonged to eight weeks or longer. Thirty of these patients received 67 subsequent stings without difficulty. The author concludes that this method of treatment is an effective safe method of managing insect sting allergy.


Verruciform xanthoma of the oral cavity: clinicopathological study relating to pathogenesis. Report of three cases.
Verruciform xanthoma is a rare condition that was first reported in the oral cavity in 1971. Its histopathology is distinctive on account of the presence of foamy histiocytes within elongated dermal papillae. Three cases of oral mucosal verruciform xanthoma were studied. Immunohistochemical staining by streptavidin-peroxidase and in situ hybridization to detect human papillomavirus (HPV types 6, 11, 16, 18) DNA and matrix metalloproteinase (MMP-2, -9) RNA were performed to investigate the pathogenesis of verruciform xanthoma. This study showed that the foam cells were strongly positive for CD68 (KP1) and vimentin. Cytokeratin, PCNA and S-100 stained focally negative in foam cells. In situ hybridization failed to detect HPV (types 6, 11, 16, 18) in any of the three cases. Based on our findings we conclude that verruciform xanthoma is most likely not a human papillomavirus-associated lesion; the foam cells, as a histological hallmark of the lesion, are most likely derived from the monocyte-macrophage lineage, and verruciform xanthoma is, at least partly, mediated by an immune mechanism. MMPs degrade basilar membrane that promotes the reciprocal induction between epithelium and mesenchyme. However, as yet unrecognized factors may play a role in the development of epithelium-mesenchyme reciprocal induction.


[Anxiety disease: decreased of functional connectivity in left superior temporal gyrus (GTs) and right GTs].
Neuronal circuits involved in the pathophysiology of anxiety are not yet fully understood. We used functional connectivity MRI to explore the characteristic of functional connectivity in anxiety disorders patient and the neural mechanism of this disease. This work was selected as an oral presentation in 2006 ISMRM. Twenty right-handed subjects were included in this study, and were divided into two groups. The anxiety (P) group (n = 10; 7 male, mean age 42 years) consisted of patients meeting DSM-IV criteria for a principal diagnosis of anxiety disorder. The control (C) group consisted of volunteers free of psychiatric symptoms, and was matched on age and gender (n = 10; 7 male) with the panic patients. The subjects underwent noninvasive functional magnetic resonance imaging while listening actively to (1): emotionally neutral word alternating with no word as the control condition (CN, PN), and (2): threat-related words alternating with emotionally neutral word as the experimental condition (CT, PT). Each word was presented in pseudorandom order in each 16 s block of 12 words of the same type. Eight alternating blocks of neutral words were presented for about 256 s. The subject was only asked to passively listen to each word. All MRI data were obtained on a 1.5-Tesla scanner Data analysis was performed with SPM99 to find significant activations in two tasks for two groups. Based on group t-test, we chose two anatomically defined regions: left superior temporal gyrus (GTs) and right GTs. Then, based on individual t-map, the voxel with the largest t-value within two regions was taken as the subject-specific peak voxel. We define clusters based on faces and edges, but not corners, so each voxel has 18 neighbors. Subject-specific averaged time series were extracted by averaging the time series of 19 voxels. Since healthy control subjects showed no significant activation (corrected, P < 0.05) during processing of anxiety word to neutral word, region of interest during processing of neutral word to no word was used as substitution. The connectivity degree eta(i j) between the node i and the node j is used to identify the change of the functional connectivity associated with differential tasks, which calculated by using the methods that have developed by ourselves. Moreover, we just consider coherence in low-frequency (0-0.15 Hz). The activation brain regions have been reported in our previous work. Patients were significant different from normal controls on two experiments. The connectivity degree of left Gts and right Gts in two tasks across all subjects was calculated. Comparing during processing neutral word to blank, a significant decrease (P < 0.001) in functional degree was observed during processing of threaten word to neutral word (eta = 0.5636 for CN, eta = 0.555 for CT, eta = 0.5616 for PN, eta = 0.4926 for PT). Especially, the greater decrease connectivity degree was identified for patient group compared with normal control during threat-related words alternating with emotionally neutral word condition. The connectivity degree identifies that functional interactions change with differential task. This result suggests decreased functional connectivity among left superior temporal gyrus and right GTs during processing of anxiety word to neutral word in anxiety patients. This dysfunction may mediate the neural mechanism of this sort of disease.


ATAF2 integrates Arabidopsis brassinosteroid inactivation and seedling photomorphogenesis.
The Arabidopsis thaliana hypocotyl is a robust system for studying the interplay of light and plant hormones, such as brassinosteroids (BRs), in the regulation of plant growth and development. Since BRs cannot be transported between plant tissues, their cellular levels must be appropriate for given developmental fates. BR homeostasis is maintained in part by transcriptional feedback regulation loops that control the expression of key metabolic enzymes, including the BR-inactivating enzymes BAS1 (CYP734A1, formerly CYP72B1) and SOB7 (CYP72C1). Here, we find that the NAC transcription factor (TF) ATAF2 binds the promoters of BAS1 and SOB7 to suppress their expression. ATAF2 restricts the tissue-specific expression of BAS1 and SOB7 in planta. ATAF2 loss- and gain-of-function seedlings have opposite BR-response phenotypes for hypocotyl elongation. ATAF2 modulates hypocotyl growth in a light-dependent manner, with the photoreceptor phytochrome A playing a major role. The photomorphogenic phenotypes of ATAF2 loss- and gain-of-function seedlings are suppressed by treatment with the BR biosynthesis inhibitor brassinazole. Moreover, the disruption of BAS1 and SOB7 abolishes the short-hypocotyl phenotype of ATAF2 loss-of-function seedlings in low fluence rate white light, demonstrating an ATAF2-mediated connection between BR catabolism and photomorphogenesis. ATAF2 expression is suppressed by both BRs and light, which demonstrates the existence of an ATAF2-BAS1/SOB7-BR-ATAF2 feedback regulation loop, as well as a light-ATAF2-BAS1/SOB7-BR-photomorphogenesis pathway. ATAF2 also modulates root growth by regulating BR catabolism. As it is known to regulate plant defense and auxin biosynthesis, ATAF2 therefore acts as a central regulator of plant defense, hormone metabolism and light-mediated seedling development.


Extracellular matrix protein-1 secretory isoform promotes ovarian cancer through increasing alternative mRNA splicing and stemness.
Extracellular matrix protein-1 (ECM1) promotes tumorigenesis in multiple organs but the mechanisms associated to ECM1 isoform subtypes have yet to be clarified. We report in this study that the secretory ECM1a isoform induces tumorigenesis through the GPR motif binding to integrin αXβ2 and the activation of AKT/FAK/Rho/cytoskeleton signaling. The ATP binding cassette subfamily G member 1 (ABCG1) transduces the ECM1a-integrin αXβ2 interactive signaling to facilitate the phosphorylation of AKT/FAK/Rho/cytoskeletal molecules and to confer cancer cell cisplatin resistance through up-regulation of the CD326-mediated cell stemness. On the contrary, the non-secretory ECM1b isoform binds myosin and blocks its phosphorylation, impairing cytoskeleton-mediated signaling and tumorigenesis. Moreover, ECM1a induces the expression of the heterogeneous nuclear ribonucleoprotein L like (hnRNPLL) protein to favor the alternative mRNA splicing generating ECM1a. ECM1a, αXβ2, ABCG1 and hnRNPLL higher expression associates with poor survival, while ECM1b higher expression associates with good survival. These results highlight ECM1a, integrin αXβ2, hnRNPLL and ABCG1 as potential targets for treating cancers associated with ECM1-activated signaling.


Endovenous laser ablation of the great saphenous vein with a 980-nm diode laser in continuous mode: early treatment failures and successful repeat treatments.
To investigate the efficacy of lower-energy endovenous laser treatment for great saphenous vein (GSV) incompetence and treatment parameters associated with early treatment failure. Sixty consecutive endovenous laser treatments (32 left, 28 right; 57 initial treatments, three repeat treatments) in 48 patients (13 men, 35 women; mean age, 55.2 +/- 12.9 years), with bilateral treatments in nine patients, were studied. Preprocedural clinical signs, etiology, anatomy, and physiologic classifications demonstrated class 2 limbs in 11.7% of cases, class 3 limbs in 25.0%, class 4 limbs in 48.3%, and class 5 limbs in 15.0%. All initial and repeat treatments were performed with lower-energy with use of a 980-nm diode endovenous laser at 11 W in continuous mode. Patients wore class II compression stockings for 2 weeks and were followed up at 1, 3, and 6 months with clinical and duplex ultrasound examinations. Treatment failures were diagnosed at 3 months on the basis of GSV patency or lack of clinical improvement. Diameter and length of GSV treated, treatment energy parameters, and clinical outcomes were prospectively measured and compared between successful and failed treatments. The initial treatment success rate was 94.7% (54 of 57). The mean maximum diameter of successfully treated GSVs was 1.12 +/- 0.52 cm, and the mean maximum diameter of GSVs in which treatment failure occurred was 2.05 +/- 0.23 cm (P = .008). Mean total energy applied for successful treatments was 1,131.3 +/- 248.1 J, and mean total energy applied for failed treatments was 1,439.6 +/- 425.0 J (P = 0.053). Mean unit energy applied for successful treatments was 32.7 +/- 7.5 J/cm, and that for failed treatments was 32.8 +/- 4.9 J/cm (P = .986). All patients in whom treatment failed were successfully treated again with a mean total energy of 1,393.0 +/- 81.0 J and a mean unit energy of 29.4 +/- 4.9 J/cm. There were no significant differences in mean total energy or unit energy applied among successful, failed, and repeat treatments (P > .05). Mean follow-up duration was 6.8 months. Endovenous laser treatment with lower energy appears to be safe and effective. Larger GSV diameter is associated with early treatment failures.


Characterization of Simbu serogroup virus infections in type I interferon receptor knock-out mice.
In late 2011, Schmallenberg virus (SBV), a novel, arthropod-borne, teratogenic orthobunyavirus, emerged near the German/Dutch border and thereafter spread rapidly throughout the continent thereby causing great economic losses in European livestock. SBV mainly infects ruminants and closely related viruses such as Sabo virus (SABOV), Simbu virus (SIMBUV) and Sathuperi virus (SATV) have been isolated from their insect-vectors or putative ruminant hosts. However, information about their pathogenesis and in vivo studies with SABOV, SIMBUV, and SATV are scarce. As experimental infections of ruminants are comprehensive and time-consuming, an SBV small animal model was assessed regarding its suitability for studying Simbu viruses. Adult type I interferon deficient mice (IFNAR-/-) were subcutaneously infected with the Simbu serogroup members SABOV, SIMV and SATV, respectively, and compared to SBV-infected mice. All animals were clinically, virologically, serologically, and pathologically examined. The clinical signs were mainly characterised by the loss of body weight and by paralysis. In blood, and samples from the spleen and brain, high loads of viral genome were detected using newly developed real-time PCR assays. The most common histologic lesions included meningo-encephalomyelitis, perivascular cuffing of lymphocytes and macrophages, neuronal degeneration and gliosis. These lesions have also been described in foetuses after transplacental infection with SBV. In-situ hybridisation signals were widely distributed in multiple neurons of the brain and spinal cord in all examined, inoculated mice. In conclusion, IFNAR-/- mice are a suitable animal model for pathogenesis studies of a broad range of Simbu serogroup viruses since all the viruses examined displayed a common pattern of viral organ and tissue distribution in this mouse model.


The Drosophila melanogaster genome sequencing and annotation projects: a status report.
The sequence and genome annotations of Drosophila melanogaster were initially published in late 1999 and early 2000. Since then, the Berkeley Drosophila Genome Project (BDGP) and FlyBase have improved the quality of the sequence and reviewed the annotations by hand, respectively, to produce an account of the fruit fly genome that is of the highest quality. This review discusses the main features of this process, both from the point of view of the biology revealed in the end result and in the development of software that has been central to this genome sequencing and annotation project.


All polymer microfluidic chips-A fixed target sample delivery workhorse for serial crystallography.
The development of x-ray free electron laser (XFEL) light sources and serial crystallography methodologies has led to a revolution in protein crystallography, enabling the determination of previously unobtainable protein structures and near-atomic resolution of otherwise poorly diffracting protein crystals. However, to utilize XFEL sources efficiently demands the continuous, rapid delivery of a large number of difficult-to-handle microcrystals to the x-ray beam. A recently developed fixed-target system, in which crystals of interest are enclosed within a sample holder, which is rastered through the x-ray beam, is discussed in detail in this Perspective. The fixed target is easy to use, maintains sample hydration, and can be readily modified to allow a broad range of sample types and different beamline requirements. Recent innovations demonstrate the potential of such microfluidic-based fixed targets to be an all-around "workhorse" for serial crystallography measurements. This Perspective will summarize recent advancements in microfluidic fixed targets for serial crystallography, examine needs for future development, and guide users in designing, choosing, and utilizing a fixed-target sample delivery device for their system.


[Effects of atorvastatin on LPS-induced PGE2 and IL-6 secretions in human pulmonary epithelial cells].
To investigate the effects of atorvastatin on LPS-induced PGE2 and IL-6 secretions in human pulmonary epithelial cells (A549). The supernates of LPS-induced cultured human pulmonary epithelial cells from different intervention groups were collected to measure the concentrations of PGE2 and IL-6 by enzyme-linked immunosorbent assay. The concentrations of PGE2 and IL-6 in supernates of LPS-induced human pulmonary epithelial cells were significantly higher than those in the control group (P < 0.05) at different time-points. The concentrations of PGE2 and IL-6 in supernates of atorvastatin intervention groups at different levels were significantly lower than those in non-intervention group (P < 0.05). Atorvastatin decreased LPS-induced PGE2 and IL-6 secretions in human pulmonary epithelial cells (A549), which suggests that statins have anti-inflammatory properties on human pulmonary epithelial cells.


The gaussian curvature elastic modulus of N-monomethylated dioleoylphosphatidylethanolamine: relevance to membrane fusion and lipid phase behavior.
The energy of intermediates in fusion of phospholipid bilayers is sensitive to kappa(m), the saddle splay (Gaussian curvature) elastic modulus of the lipid monolayers. The value kappa(m) is also important in understanding the stability of inverted cubic (Q(II)) and rhombohedral (R) phases relative to the lamellar (L(alpha)) and inverted hexagonal (H(II)) phases in phospholipids. However, kappa(m) cannot be measured directly. It was previously measured by observing changes in Q(II) phase lattice dimensions as a function of water content. Here we use observations of the phase behavior of N-mono-methylated dioleoylphosphatidylethanolamine (DOPE-Me) to determine kappa(m). At the temperature of the L(alpha)/Q(II) phase transition, T(Q), the partial energies of the two phases are equal, and we can express kappa(m) in terms of known lipid monolayer parameters: the spontaneous curvature of DOPE-Me, the monolayer bending modulus kappa(m), and the distance of the monolayer neutral surface from the bilayer midplane, delta. The calculated ratio kappa(m)/kappa(m) is -0.83 +/- 0.08 at T(Q) approximately 55 degrees C. The uncertainty is due primarily to uncertainty in the value of delta for the L(alpha) phase. This value of kappa(m)/kappa(m) is in accord with theoretical expectations, including recent estimates of the value required to rationalize observations of rhombohedral (R) phase stability in phospholipids. The value kappa(m) substantially affects the free energy of formation of fusion intermediates: more energy (tens of k(B)T) is required to form stalks and fusion pores (ILAs) than estimated solely on the basis of the bending elastic energy. In particular, ILAs are much higher in energy than previously estimated. This rationalizes the action of fusion-catalyzing proteins in stabilizing nascent fusion pores in biomembranes; a function inferred from recent experiments in viral systems. These results change predictions of earlier work on ILA and Q(II) phase stability and L(alpha)/Q(II) phase transition mechanisms. To our knowledge, this is the first determination of the saddle splay (Gaussian) modulus in a lipid system consisting only of phospholipids.


Tear Film Stability Affects Visual Acuity After Implantations of Monofocal and Multifocal Intraocular Lenses: An Evaluation by Objective Scatter Index.
To assess the impact of tear film on postoperative visual acuity after cataract surgery to implant an intraocular lens (IOL). Tear break-up time (TBUT), Schirmer I test, objective scatter index (OSI), and uncorrected distance visual acuity (UCDVA), intermediate visual acuity (UCIVA), and near visual acuity (UCNVA) were collected 6 months after cataract surgery. Fifteen eyes with monofocal (Mo-) IOLs and 15 eyes with multifocal (Mu-) IOLs from 30 subjects were included. The Mu-IOL group exhibited higher baseline OSI (1.92 ± 0.69, P < 0.001). Negative correlations-both groups: tear film-related OSI (TF-OSI) and TBUT/Schirmer I test; Mo-IOL: TBUT and logMAR UCDVA-and positive correlations-both groups: TF-OSI and baseline OSI, baseline OSI/TF-OSI and logMAR UCDVA; Mu-IOL: baseline OSI/TF-OSI and logMAR UCIVA/UCNVA-were found. Linear regression showed associations between TF-OSI and TBUT (Mo-IOL: R2 = 0.455, P = 0.006; Mu-IOL: R2 = 0.454, P = 0.006)/Schirmer I test (Mo-IOL: R2 = 0.527, P = 0.002; Mu-IOL: R2 = 0.266, P = 0.049). Multiple regression showed associations between baseline OSI (Mo-IOL: R2 = 0.309, P = 0.032; Mu-IOL: R2 = 0.305, P = 0.033)/TF-OSI (Mo-IOL: R2 = 0.332, P = 0.025; Mu-IOL: R2 = 0.523, P = 0.002)/TBUT (Mo-IOL only: R2 = 0.315, P = 0.029) and logMAR UCDVA. TF-OSI reflects the UCDVA performance in eyes with IOLs and facilitates a better understanding of the effects of the tear film. TF-OSI offers a developmental and objective approach to assessing the changing visual performance caused by tear film after cataract surgery and IOL implantation in clinical practices.


HLA Epitopes and Shared Molecular Eplet Characterization and Their Implication on Transplant Outcome: The Experience of One Center.
We report three interesting cases concerning antibody-mediated rejection (AMR), associated or not with anti-donor-specific antibodies, and detection of implicated molecular epitopes. The first report presents a case of intra-allele sensitization. The second case presents an interesting case concerning Luminex mean fluorescence intensity (MFI) levels considered to be low risk antibodies (<1000), but producing AMR. The third case occurred after a second kidney transplantation mediated by antibodies directed against HLA-C antigens (MFI<1000) in the previous transplantation (which was considered to be an indicator of low-risk of AMR).


Orexins modulate the growth of cultured rat adrenocortical cells, acting through type 1 and type 2 receptors coupled to the MAPK p42/p44- and p38-dependent cascades.
Orexin A and B are hypothalamic peptides that act through two subtypes of receptors named OX1-R and OX2-R. The OX1-R almost exclusively binds orexin-A, whereas OX2-R is non-selective for both orexins. We previously found that rat adrenocortical cells express both orexin-receptor subtypes, and orexin-A stimulates corticosterone secretion from dispersed adrenocortical cells acting via the OX1-R. Here, we examined the possibility that orexins, acting through both their receptor subtypes, modulate the growth of adrenocortical cells. Reverse transcription-polymerase chain reaction showed that rat adrenocortical cells cultured in vitro for four days expressed OX1-R and OX2-R mRNAs. Orexin-A increased the proliferation rate (PR) of cultured cells, while orexin-B lowered it. Using selective antibodies, we demonstrated that OX1-R immuno-blockade reversed the proliferogenic action of orexin-A, causing a sizeable decrease in PR. In contrast, OX2-R immuno-blockade magnified the proliferogenic effect of orexin-A and annulled the antiproliferogenic action of orexin-B. The proliferogenic effect of orexin-A in the presence of OX2-R immuno-blockade was abrogated by the MAPK p42/p44 inhibitor PD-98059, while the antiproliferogenic effect of orexin-A in the presence of OX1-R immuno-blockade was annulled by the MAPK p38 inhibitor SB-203580. Neither inhibitor altered per se the basal PR of cultured cells. Taken together, our present findings allow us to conclude that i) orexins modulate the growth of rat adrenocortical cells cultured in vitro, by exerting both proliferogenic and antiproliferogenic effects, which are mediated by OX1-Rs and OX2-Rs, respectively; and ii) OX1-R and OX2-R growth effects involve the activation of the MAPK p42/p44 and p38 signaling cascades, respectively.


Pyrrolidine dithiocarbamate and zinc inhibit proteasome-dependent proteolysis.
Proteasomes play important roles in a variety of cellular processes such as cell cycle progression, signal transduction and immune responses. Proteasome activity is important in maintaining rapid turnover of short-lived proteins, as well as preventing accumulation of misfolded or damaged proteins. Alteration in ubiquitin-proteasome function may be detrimental to its crucial role in maintaining cellular homeostasis. Here, we have found that treatment of pyrrolidine dithiocarbamate (PDTC), a zinc ionophore, resulted in the accumulation of several proteasome substrates including p53 and p21 in HeLa cells. The PDTC effect was due to an extended half-life of these proteins through the mobilization of zinc. PDTC and/or zinc also increased fluorescence intensity of Ub(G76V)-GFP fusion protein that is degraded rapidly by the ubiquitin-proteasome system. Treatment of cells with zinc induced formation of ubiquitinated inclusions in the centrosome, a histological marker of proteasome inhibition. Western blotting showed zinc-induced increase in laddering bands of polyubiquitin-conjugated proteins. In vitro study, zinc inhibited the ubiquitin-independent proteasomal degradations of p21 and alpha-synuclein. These results suggest that zinc may modulate cell functions through its action on the turnover of proteins that are susceptible to proteasome-dependent proteolysis.


The application of the tie-down suture to the excision of cutaneous tumors.
We describe a surgical procedure that acts as a compressive dressing and contributes to eliminate dead spaces. Because of its similarity to a tie-down dressing, this technique is called the "tie-down suture." It is especially indicated after excision of mass lesions--epidermoid and dermoid cysts, steatocystomas, lipomas, hibernomas, etc.--where there are real or virtual dead spaces; in high-movement or hairy areas where compressive dressings or adhesive tapes are difficult to hold in place; and in particular, in anatomic sites such as behind the auricle, armpit, or eyebrow.


Bacillary characteristics in Whipple's disease: an electron microscopic study.
Extensive electron microscopic observations of 19 intestinal biopsies obtained from 13 patients with untreated Whipple's disease are reported. The outstanding feature is the profuse presence of bacilli free within the lamina propria of the intestinal mucosa and the presence of numerous macrophages containing ingested bacilli. Intestinal epithelial cell invasion by bacilli is identified in 11 patients, and evidence of bacillary invasion is identified within the lymphatic endothelium of 4 patients, within capillary endothelium of 3 patients, within polymorphonuclear leukocytes of 5 patients, and within plasma cells of 2 patients. Reported for the first time is the presence of bacilli within intrinsic smooth muscle of the lamina propria of 2 patients, within intraepithelial lymphocytes of 1 patient, and in mast cells of 1 patient. These observations suggest that the Whipple bacillus is an intracellular pathogen. Intracellular pathogens, unlike pyogenic bacteria, may survive within macrophages. The morphologic appearance of the Whipple bacillus is reviewed. Emphasis is placed upon the unique nature of an outer "membrane" external to the cell wall of Whipple bacilli, a feature that is one of the identifying characteristics of the Whipple bacillus and that may explain the inability to culture the bacillus in vitro.


A survivor following repair of laryngotracheo-esophageal cleft: lessons learned.
A survivor, following successful repair of laryngotracheo-esophageal cleft extending up to cervical trachea, is being described. The cleft was repaired with anterior laryngofissure approach, using no interposition of tissue between trachea and esophagus. The patient had an uneventful recovery, short hospitalization, and satisfactory outcome on follow-up for over 1-1/2 years, as of now. Optimum ventilation was achieved intra-operatively via an endotracheal tube passed through operative field, following visualization of the cleft. Postoperatively, mechanical ventilation was given via nasotracheal tube left indwelling in trachea following completion of tracheal repair. Early nutrition through enteral route was started 72 hours postoperatively by drip feeds (using infusion pump) through a soft nasogastric tube that was left indwelling following esophageal repair. This maneuver, along with positional and medical therapy, helped us to gain control over gastro-esophageal reflux that is known to be incapacitating in these patients. The authors recommend a reexamination of existing management strategies for patients with laryngotracheo-esophageal clefts and suggest that conservative approach in dealing with associated problems can help decrease morbidity in these patients.


The effects of exercise using an ergometer with swaying saddle on chronic lower back pain.
[Purpose] This study aims to investigate the effects of exercise using an ergometer with swaying saddle on chronic lower back pain. [Subjects and Methods] Thirty-three normal adults (university students) with chronic lower back pain were randomly recruited. The flexibility and strength of muscles were measured before and after an 8-week intervention. Belly-bike, an ergometer with a swaying saddle, was used. The duration of intervention was 30 minutes a day, 3 times a week. To measure the level of pain, visual analogue scale (VAS) and Korean Oswestry Disability Index were used. In addition, flexibility tests such as straight leg raising and forward reaching test in the long sitting posture were used to confirm back muscle shortness. Activations of the erector spinae muscle, gluteus medius muscle, rectus femoris muscle, and vastus lateralis muscle were also measured by electromyography before and after the intervention. Electromyography of muscles around the pelvis was performed and functional tests were conducted. [Results] The flexibility and strength of the muscles significantly increased post-intervention. Functional test scores for the forward reaching test and straight leg raising test significantly improved in the Belly-bike group. [Conclusion] The results show that exercise using the Belly-bike could be effective in reducing lower back pain.


Analysis of the genes responsible for steroid-resistant nephrotic syndrome and/or focal segmental glomerulosclerosis in Japanese patients by whole-exome sequencing analysis.
Steroid-resistant nephrotic syndrome (SRNS) represents glomerular disease resulting from a number of different etiologies leading to focal segmental glomerulosclerosis (FSGS). Recently, many genes causing SRNS/FSGS have been identified. These genes encode the proteins associated with the formation and/or maintenance of glomerular filtration barrier. Next-generation sequencing is used to analyze large numbers of genes at lower costs. To identify the genetic background of Japanese patients, we studied 26 disease-causing genes using whole-exome sequencing analysis in 24 patients with SRNS and/or FSGS from 22 different Japanese families. We finally found eight causative gene mutations, four recessive and four dominant gene mutations, including three novel mutations, in six patients from five different families, and one novel predisposing mutation in two patients from two different families. Causative gene mutations have only been identified in ~20% of families and further analysis is necessary to identify the unknown disease-causing gene. Identification of the disease-causing gene would support clinical practices, including the diagnosis, understanding of pathogenesis and treatment.


Repeated rotation of a toric implantable collamer lens: A case report.
Implantable collamer lens have been used widely worldwide, and have been accepted by more and more doctors and patients due to good safety, stability, and effectiveness. However, there is still a problem of crystal rotation. The large angle rotation (over 10°) would weaken the original astigmatism correction effect and even induce irregular astigmatism, seriously affecting the visual quality of patients. Herein, we reported a case who had 2 times of crystal rotations after toric implantable collamer lens (TICL) implantation. The patient was a 38-year-old man who underwent TICL implantation for the correction of high myopic astigmatism in eyes. He presented a sudden decrease in the visual acuity (VA) of the left eye 4 months after the TICL implantation. The uncorrected visual acuity (UCVA) was 8/20 (refraction, +2.25 -5.25 × 68). Rotation of TICL was diagnosed. The toric marks with a rotation of 75° counter-clockwise from the original position were observed. The TICL was re-set to the original position, leading to the UCVA of 12/20 in the left eye (refraction, -0.00 -0.75 × 131), with the vaulting of 589 μm. Ten months after the TICL relocation, the patient again presented a sudden decrease in the VA of the left eye, with the UCVA of 2/20 (refraction, +2.25 -5.00 × 66). Again, the toric marks with a rotation of 75° counter-clockwise from the original position was observed, just at the same position as the last rotation. This time, the TICL was removed. The axis and power were recalculated, and a new TICL was implanted, with the rotation of 73° counter-clockwise from the horizontal line of the temporal side. The patient obtained a final UCVA of 12/20 in the left eye (refraction, +0.50 -0.50 × 26), which remained stable in the 6-month follow-up period, with the vaulting of 602 μm. Rotation is a common complication after TICL surgery. Relocation or replacement of TICL are safe and efficient ways to recover VA due to TICL rotation.


Prevalence of hepatitis B markers among hospital workers in Senegal.
A total of 775 serum samples from men and women working in hospitals in Dakar, Senegal, were tested for serological markers of hepatitis B virus (HBV). HBsAg was detected in 17.8% of the subjects, and 79.2% of the subjects were anti-HBc positive. Among HBsAg carriers 0.04% (5) subjects were HBeAg positive, 0.03% (4) were HBV-DNA positive, and 5.8% (8) were also anti-Delta positive. HBsAg seropositivity was independent of sex and inversely related to age. Duration of service in the hospital was an important predictor of HBsAg seropositivity and the prevalence of seropositive subjects peaked between 2 and 3 years of employment (OR = 1.9; 95% confidence interval [Cl] = 1.1-3.3, when compared to subjects who worked 1 year of less). This peak was critical in the Department of Dentistry, where subjects who worked for 2-3 years experienced a fourfold increase in the risk of HBV infection (OR = 4.0; 95% Cl = 1.8-9.0). Adjusting for age and sex did not modify the results. Within the Department of Dentistry, 15 subjects were HBsAg positive but anti-HBc negative; 12 subjects were retested 1 year later and did not present any markers of past or current HBV infection. These results confirm the increased risk of HBV infection among hospital workers and suggest the presence of HBV variant(s) in Senegal.