Leafhopper genus Kolla Distant (Hemiptera: Cicadellidae: Cicadellinae) with descriptions of four new species from China.
Four new species of the genus Kolla from China, Kolla emphysematosa, K. prolongata, K. procerula and K. petalina spp. nov. are described and illustrated. A key to the males of Chinese species and a checklist of the known species worldwide are provided.


Segmentation of brain tissue from magnetic resonance images.
Segmentation of medical imagery is a challenging problem due to the complexity of the images, as well as to the absence of models of the anatomy that fully capture the possible deformations in each structure. The brain is a particularly complex structure, and its segmentation is an important step for many problems, including studies in temporal change detection of morphology, and 3-D visualizations for surgical planning. We present a method for segmentation of brain tissue from magnetic resonance images that is a combination of three existing techniques from the computer vision literature: expectation/maximization segmentation, binary mathematical morphology, and active contour models. Each of these techniques has been customized for the problem of brain tissue segmentation such that the resultant method is more robust than its components. Finally, we present the results of a parallel implementation of this method on IBM's supercomputer Power Visualization System for a database of 20 brain scans each with 256 x 256 x 124 voxels and validate those results against segmentations generated by neuroanatomy experts.


Isolation and amino acid sequence of COOH-terminal fragments from the beta subunit of human choriogonadotropin.
The amino acid sequence of the unique COOH-terminal region of the beta subunit of human choriogonadotropin has been reinvestigated. The desialylated subunit was digested with thermolysin and a 27-residue peptide from positions 115 through 141 isolated in a high yield. Quantitative Edman sequence degradation of this peptide, of another peptide produced by thermolysin digestion containing residues 142 to 145, and of two tryptic peptides (residues 123 to 145, 134 to 145) has established that the amino acid sequence of this region is: (formula: see text). In addition, the positions of attachment of the carbohydrate moieties to serine residues was established by a direct procedure using alkaline elimination and 35S-labeled sulfite addition, which yields [35S]-cysteic acid residues at the site of a substituted serine. Carbohydrate side chains in the COOH-terminal region have been shown to exist at residues 121, 127, 132, and 138. These studies have also resulted in the development of improved methods for the purification of COOH-terminal peptides of the human choriogonadotropin beta subunit.


No evidence of cardiovascular toxicity in workers exposed below 5 ppm carbon disulfide.
Carbon disulfide (CS2), used in the viscose process, is well known for having multiple health effects, including on the cardiovascular system, in workers with long-term exposure higher than 10 ppm. The mechanisms of those effects are, however, not precisely defined, and it remains uncertain whether cardiovascular toxicity may occur at exposure levels lower than 10 ppm. Therefore, the purpose of this study is to explore the health impact of low CS2 exposure levels using an array of preclinical biomarkers of cardiovascular risk. Exposure intensity was determined by measuring urinary 2-thiothiazolidine-4-carboxylic acid (TTCA) in 117 workers from two plants using the viscose process, sampled in multiples phases (2003, 2006 and 2013). A cumulative exposure index (CEI) and a recent exposure index (REI) were calculated for each worker, and shiftwork was documented to account for potential confounding. Cardiovascular parameters included blood pressure, total, LDL and HDL cholesterol, triglycerides, C-reactive protein dosed in serum with high sensitivity (HsCRP), N-terminal pro-brain natriuretic peptide, and albuminuria/creatininuria ratio (UACR). Potential biological confounders were fasting blood glucose and serum creatinine. Bivariate and multivariate regression analyses were used to trace relationships between cardiovascular risk biomarkers and other variables, including CEI, REI and shiftwork duration. Median REI and CEI were 0.05 mg TTCA/g creat and 21.5 mg TTCA/g creat*months, respectively. While expected associations, such as between HsCRP and LDL Cholesterol, were found, significant associations between cardiovascular risk markers and CS2 exposure indexes (CEI or REI) were not detected. Shiftwork duration was positively associated with UACR in workers with elevated fasting blood glucose. In practice, when CS2 exposure levels are kept below 5 ppm (TTCA < 2.2 mg/g creat), it does not appear useful to perform a systematic monitoring of total serum cholesterol or its subfractions, or of the new biomarkers of cardiovascular risk (NTproBNP, HsCRP, UACR) investigated in the present study. It appears important to carefully monitor the existence of diabetes that may justify avoiding shiftwork.


Nucleosome-restricted antibodies are detected before anti-dsDNA and/or antihistone antibodies in serum of MRL-Mp lpr/lpr and +/+ mice, and are present in kidney eluates of lupus mice with proteinuria.
To compare the humoral response to nucleosomes with the response to their individual components (double-stranded DNA [dsDNA] and histones) and to assess the involvement of antinucleosome antibodies in immune deposits in the kidney of MRL mice. We used enzyme-linked immunosorbent assays of sera and kidney eluates for antibody activity against purified nucleosomes, dsDNA, and histones. Antinucleosome antibodies emerged before anti-dsDNA and antihistone antibodies. A fraction of antinucleosome antibodies reacted exclusively with nucleosomes and not with their components, dsDNA and histones. These nucleosome-restricted antibodies were detected in the proteinuric MRL mouse kidney eluate. Our findings support the notion that nucleosomes play a major role in the emergence of antinuclear autoantibodies and that antinucleosome antibodies might be involved in the nephritogenic process in murine lupus.


Infectivity of symptomatic Plasmodium vivax cases to different generations of wild-caught and laboratory-adapted Anopheles arabiensis using a membrane feeding assay, Ethiopia.
When measuring human to mosquito transmission of Plasmodium spp., laboratory-adapted (colony) mosquitoes can be utilized. To connect transmission studies to the local epidemiology, it can be important to comprehend the relationship between infectivity in laboratory-adapted (colony) and wild-caught (wild) mosquitoes of the same species. Microscopically confirmed Plasmodium vivax cases were recruited from health facilities in Arba Minch town, and a nested polymerase chain reaction (nPCR) was used for subsequent confirmation. We performed paired membrane-feeding assays using colony An. arabiensis and three generations of wild origin An. arabiensis. Anopheles arabiensis aged 3-6 days were fed after being starved for 8-14 h. Microscopically, the oocyst development was evaluated at day 7 after feeding. Circumsporozoite proteins (CSPs) assay was carried out by enzyme-linked immunosorbent assay (ELISA). In 19 paired feeding experiments, the feeding efficiency was more than doubled in colony (median: 62.5%; interquartile range, IQR: 35-78%) than in wild mosquitoes (median: 28.5%; IQR: 17.5-40%; P < 0.001). Among the 19 P. vivax gametocyte-positive blood samples, 63.2% (n = 12) were infective to wild An. arabiensis and 73.7% (n = 14) were infective to colony An. arabiensis. The median infection rate was twice as high (26%) in the colony than in the wild (13%) An. arabiensis, although the difference was marginally insignificant (P = 0.06). Although the observed difference was not statistically significant (P = 0.19), the median number of oocysts per midgut was more than twice as high (17.8/midgut) in colony than in wild (7.2/midgut) An. arabiensis. The median feeding efficiency was 26.5% (IQR: 18-37%) in F1, 29.3% (IQR: 28-40%) in F2 and 31.2% (IQR: 30-37%) in F3 generations of wild An. arabiensis. Also, no significant difference was observed in oocyst infection rate and load between generations of wild An. arabiensis. CSP rate of P. vivax was 3.1% (3/97; 95% CI: 0.6-8.8%) in wild and 3.6% (3/84; 95% CI: 0.7-10.1%) in colony An. arabiensis. The results of the present study revealed that oocyst infection and load/midgut, and CSP rate were roughly comparable, indicating that colony mosquitoes can be employed for infectivity studies, while larger sample sizes may be necessary in future studies.


Blood Clotting Dissolution in the Presence of a Magnetic Field and Preliminary Study with MG63 Osteoblast-like Cells-Further Developments for Guided Bone Regeneration?
The influence of a magnetic field on the activation of bone cells and remodelling of alveolar bone is known to incite bone regeneration. Guided Bone Regeneration (GBR) aims to develop biomimetic scaffolds to allow for the functioning of the barrier and the precise succession of wound healing steps, including haemostasis. The effect of a magnetic field on blood clot dissolution has not been studied yet. We conducted a methodological study on the clot stability in the presence of a static magnetic field (SMF). Preformed whole blood (WB) clots were treated with either a broad proteolytic enzyme (trypsin) or a specific fibrinolytic agent, i.e., tissue-type plasminogen activator (t-PA). MG63 osteoblast-like cells were added to preformed WB clots to assess cell proliferation. After having experienced a number of clotting and dissolution protocols, we obtained clot stability exerted by SMF when tissue factor (for clotting) and t-PA + plasminogen (for fibrinolysis) were used. WB clots allowed osteoblast-like cells to survive and proliferate, however no obvious effects of the magnetic field were noted. Paramagnetic properties of erythrocytes may have influenced the reduction in clot dissolution. Future studies are warranted to fully exploit the combination of magnetic forces, WB clot and cells in GBR applied to orthodontics and prosthodontics.


The stability of cerebrovascular CO2 reactivity following attainment of physiological steady-state.
What is the central question of this study? During a steady-state cerebrovascular CO2 reactivity test, do different data extraction time points change the outcome for cerebrovascular CO2 reactivity? What is the main finding and its importance? Once steady-state end-tidal pressure of CO2 and haemodynamics were achieved, cerebral blood flow was stable, and so cerebrovascular CO2 reactivity values remained unchanged regardless of data extraction length (30 vs. 60 s) and time point (at 2-5 min). This study assessed cerebrovascular CO2 reactivity (CVR) and examined data extraction time points and durations with the hypotheses that: (1) there would be no difference in CVR values when calculated with cerebral blood flow (CBF) measures at different time points following the attainment of physiological steady-state, (2) once steady-state was achieved there would be no difference in CVR values derived from 60 to 30 s extracted means, and (3) that changes in V̇E would not be associated with any changes in CVR. We conducted a single step iso-oxic hypercapnic CVR test using dynamic end-tidal forcing (end-tidal PCO2 , +9.4 ± 0.7 mmHg), and transcranial Doppler and Duplex ultrasound of middle cerebral artery (MCA) and internal carotid artery (ICA), respectively. From the second minute of hypercapnia onwards, physiological steady-state was apparent, with no subsequent changes in end-tidal PCO2 , PO2 or mean arterial pressure. Therefore, CVR measured in the ICA and MCA was stable following the second minute of hypercapnia onwards. Data extraction durations of 30 or 60 s did not give statistically different CVR values. No differences in CVR were detected following the second minute of hypercapnia after accounting for mean arterial pressure via calculated conductance or covariation of mean arterial pressure. These findings demonstrate that, provided the PCO2 stimulus remains in a steady-state, data extracted from any minute of a CVR test during physiological steady-state conditions produce equivalent CVR values; any change in the CVR value would represent a failure of CVR mechanisms, a change in the magnitude of the stimulus, or measurement error.


The influence of duckweed species diversity on ecophysiological tolerance to copper exposure.
In excess, copper is toxic to plants. In the plants, Landoltia punctata and Lemna minor grown in mixed and monoculture, the effects of exposure to varying concentrations of copper (0.01, 0.1, 0.5 and 1mgL(-1) Cu) for seven days were assessed by measuring changes in the chlorophyll, protein and malondialdehyde (MDA) content, catalase (CAT), superoxide dismutase (SOD) and ascorbate peroxidase (APX) activity. According to results, Cu levels in plants increased with increasing Cu concentration. The level of photosynthetic pigments and crude proteins decreased only upon exposure to high Cu concentrations. However, the starch and malondialdehyde (MDA) content increased. These results suggested a stress alleviation that was possibly the result of antioxidants such as CAT and SOD, the activities of which increased with increasing Cu levels. APX activity increased in L. punctata, but decreased in L. minor, under monoculture or mixed culture conditions. In addition, the duckweed in mixed culture exhibited increased antioxidant enzyme activities which provide increased resistance to copper in moderate copper concentrations. As the copper concentration increased, the duckweed in the mixed culture limited the uptake of copper to avoid toxicity.


Positive association of a Sirt1 variant and parameters of oxidative stress on Alzheimer's disease.
Alzheimer's disease (AD) is a complex neurodegenerative disorder and the most common type of dementia in the elderly. Although its cause is not completely known, several studies suggest that oxidative stress plays an important role in the etiology of this disease. The SIRT1 and SOD2 proteins are linked to pathways that may impair oxidative stress. In this study, we analyzed the association between polymorphisms in these genes and in the APOE gene, through RT-PCR, as well as between environmental factors and the risk of AD. Additionally, the thiobarbituric acid reactive substance assay was performed to estimate the plasma level of malondialdehyde (MDA), a biomarker of lipid peroxidation. Furthermore, some cytogenetic studies indicate that cells of AD patients show increased chromosomal damage; thus, we performed the micronucleus cytome assay to assess cytogenetic damage in AD patients. As expected, the APOE polymorphisms were found to be highly associated with AD. Additionally, the CT genotype of the SIRT1 gene showed a positive association with the disease. The frequencies of genomic damage (micronucleus, buds, nucleoplasmic bridges and binucleated cells), the presence of cell death biomarkers (condensed chromatin, karyorrhexis and pyknosis), and the plasma level of MDA were significantly greater in AD patients than in controls. Our results support the hypothesis that AD is a condition with increased oxidative stress and genomic instability, which may contribute to the neurodegeneration in AD.


Chemoreception and asphyxia-induced arousal.
Arousal protects against the adverse and potentially fatal effects of asphyxia during sleep. Asphyxia stimulates the carotid bodies and central chemoreceptors but the sequence of events leading to arousal is uncertain. In this review, the theoretical mechanisms leading to arousal from sleep are briefly summarized and the issue of whether central respiratory chemoreceptors (CRCs) or other types of CO2-responsive CNS neurons contribute to asphyxia-induced arousal is discussed. We focus on the role of the retrotrapezoid nucleus, the raphe and the locus coeruleus and emphasize the anatomical and neurophysiological evidence which suggests that these putative central chemoreceptors could contribute to arousal independently of their effects on breathing. Finally, we describe recent attempts to test the contribution of specific brainstem pathways to asphyxia-induced arousal using optogenetic and other tools and the possible contribution of a group of hypoxia-sensitive brainstem neurons (the C1 cells) to breathing and arousal.


Anatomy and physiology of feeding and swallowing: normal and abnormal.
Eating and swallowing are complex behaviors involving volitional and reflexive activities of more than 30 nerves and muscles. They have two crucial biologic features: food passage from the oral cavity to stomach and airway protection. The swallowing process is commonly divided into oral, pharyngeal, and esophageal stages, according to the location of the bolus. The movement of the food in the oral cavity and to the oropharynx differs depending on the type of food (eating solid food versus drinking liquid). Dysphagia can result from a wide variety of functional or structural deficits of the oral cavity, pharynx, larynx, or esophagus. The goal of dysphagia rehabilitation is to identify and treat abnormalities of feeding and swallowing while maintaining safe and efficient alimentation and hydration.


Medicated-related burden and adherence in patients with co-morbid type 2 diabetes mellitus and hypertension.
Medication adherence is an integral component in the management of patients with co-morbid type 2 diabetes mellitus (T2DM) and hypertension. However due to their combined conditions, there is likelihood of polypharmacy and medication-related burden, which could negatively impact adherence to therapy. This study aimed to assess the perceived medication-related burden among patients with co-morbid T2DM and hypertension and to evaluate the association between the perceived burden and adherence to medication therapy. A cross-sectional study was conducted among adult patients with co-morbid T2DM and hypertension attending a primary health facility. The living with medicines questionnaire and the medication adherence report scale were used to assess extent of medication-related burden and adherence respectively. Binary logistic regression model was used to estimate the adjusted odds and their corresponding 95% confidence interval for medication-related burden and adherence outcomes. All observed categorical variables were considered for the multivariable binary logistic regression model. The total number of participants was 329 with a median age of 57.5 ± 13.2 years. The median score for the overall burden was 99 (IQR: 93-113), and this significantly varied by sex (p = 0.012), monthly income (p = 0.025), monthly expenditure on medications (p = 0.012), frequency of daily dose of medications (p = 0.020) and family history of T2DM (p < 0.001). About 30.7% and 36.8% of participants reported moderate/high burden and medication adherence respectively. Uncontrolled diastolic blood pressure (AOR: 2.46, 95% CI: 1.20-5.05, p = 0.014), high glucose (AOR: 4.24, 95% CI: 2.13-8.46, p < 0.001) and no family history of T2DM (AOR: 2.14, 95% CI: 1.14-4.02, p = 0.026) were associated with moderate/high medication burden. Uncontrolled diastolic blood pressure (AOR: 0.48, 95% CI: 0.25-0.94, p = 0.031), at least 5 years since hypertension diagnosis (AOR: 0.55, 95% CI: 0.30-0.99, p = 0.045) and moderate/high medication-related burden (AOR: 0.33, 95% CI: 0.16-0.69, p = 0.003) were associated with lower odds of medication adherence. These findings suggest that to improve the preventive and optimal care of patients with T2DM and hypertension, interventions that aim to reduce medication-related burden and morbidity are recommended. The study proposes that health stakeholders such as clinicians, pharmacists, and policy makers, develop multidisciplinary clinical and pharmaceutical care interventions to include provision of counselling to patients on adherence. In addition, developing policies and sensitization activities on deprescribing and fixed-dose drug combinations aimed at reducing medication-related burden, while promoting better adherence, blood pressure and blood glucose outcomes are recommended.


HLA-DR7 association with African Burkitt's lymphoma.
Association between HLA-DR7 and Burkitt's lymphoma previously reported has been confirmed by a second study. Analysis of additional data from a second study of 33 Ghanaian patients with African Burkitt's lymphoma and 54 Ghanaian controls matched for age and ethnic origin showed that 39.4% of cases, but only 14.8% of controls, had HLA-DR7 (p less than 0.01). The relative risk of 3.7 is similar to that observed in the earlier study (3.3). Combining the earlier and present studies, analysis of clinical data from 94 patients with Burkitt's lymphoma and 116 controls shows the relative risk of Burkitt's lymphoma among individuals with HLA-DR7 was 3.4 (p less than 0.001). There was an increased relative risk of the disease associated with HLA-DR7 in: patients under 10 years of age; and patients with advanced stages of disease (Stage III or IV). However, comparison of relative risks by sequential analysis of 2 X 2 tables showed that these differences by age and stage were not statistically significant.


Deep brain stimulation does not change neurovascular coupling in non-motor visual cortex: an autonomic and visual evoked blood flow velocity response study.
In Parkinson's disease (PD) subthalamic nucleus deep brain stimulation (STN-DBS) improves motor function. Also an effect on the neurovascular coupling in motor cortex was reported due to a parallel activation of a subthalamic vasodilator area (SVA). To address this issue further we analysed neurovascular coupling in a non-motor area. Twenty PD patients selected for bilateral STN-DBS were investigated with functional transcranial Doppler (f-TCD) before and after surgery. Hemodynamic responses to visual stimulation were registered in left posterior cerebral artery (PCA) and analysed with a control-system approach (parameters gain, rate time, attenuation and natural frequency). To exclude autonomic effects of STN-DBS, we also addressed spectrum analysis of heart rate and of systolic arterial blood pressure variability, and baroreceptor gain. Findings in the PD group were compared with healthy age-matched controls. PD patients showed no neurovascular coupling changes in PCA territory, compared to controls, and STN-DBS changed neither blood flow regulatory parameters nor autonomic function. Improvement of vasoregulation in some motor cortical areas after STN-DBS might be related to an improved neuronal functional rather than indicating an effect on the neurovascular coupling or autonomic function.


Advances in gut microbiome in metabonomics perspective: based on bibliometrics methods and visualization analysis.
Gastrointestinal microbial metabolomics is closely related to the state of the organism and has significant interaction with the pathogenesis of many diseases. Based on the publications in Web of Science Core Collection(WoSCC) from 2004 to 2022, this study conducted a bibliometric analysis of this field, aiming to understand its development trend and frontier, and provide basic information and potential points for in-depth exploration of this field. All articles on gastrointestinal flora and metabolism published from 2004 to 2022 were collected and identified in WoCSS. CiteSpace v.6.1 and VOSviewer v.22.214.171.124 were used to calculate bibliometric indicators, including number of publications and citations, study categories, countries/institutions, authors/co-cited authors, journals/co-cited journals, co-cited references, and keywords. A map was drawn to visualize the data based on the analysis results for a more intuitive view. There were 3811 articles in WoSCC that met our criteria. Analysis results show that the number of publications and citations in this field are increasing year by year. China is the country with the highest number of publications and USA owns the highest total link strength and citations. Chinese Acad Sci rank first for the number of institutional publications and total link strength. Journal of Proteome Research has the most publications. Nicholson, Jeremy K. is one of the most important scholars in this field. The most cited reference is "Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease". Burst detection indicates that Urine, spectroscopy, metabonomic and gut microflora are long-standing hot topics in this field, while autism spectrum disorder and omics are likely to be at the forefront of research. The study of related metabolic small molecules and the application of gastrointestinal microbiome metabolomics in various diseases are currently emerging research directions and frontier in this field. This study is the first to make a bibliometric analysis of the studies related to gastrointestinal microbial metabolomics and reveal the development trends and current research hotspots in this field. This can contribute to the development of the field by providing relevant scholars with valuable and effective information about the current state of the field.


Bilateral aniridia with Marfan's syndrome and dental anomalies--a new association.
A unique case of bilateral aniridia, partial anodontia, bilateral cervical ribs and Marfan's syndrome is presented. This is the first report in the literature of the established association of all these four entities in the same patient. The etiological possibilities and clinical significance are discussed.


Regulation of T cell differentiation and function by long noncoding RNAs in homeostasis and cancer.
Long noncoding RNAs (lncRNAs) increase in genomes of complex organisms and represent the largest group of RNA genes transcribed in mammalian cells. Previously considered only transcriptional noise, lncRNAs comprise a heterogeneous class of transcripts that are emerging as critical regulators of T cell-mediated immunity. Here we summarize the lncRNA expression landscape of different T cell subsets and highlight recent advances in the role of lncRNAs in regulating T cell differentiation, function and exhaustion during homeostasis and cancer. We discuss the different molecular mechanisms of lncRNAs and highlight lncRNAs that can serve as novel targets to modulate T cell function or to improve the response to cancer immunotherapies by modulating the immunosuppressive tumor microenvironment.


Developmental instability in a stem-mining sawfly: can fluctuating asymmetry detect plant host stress in a model system?
Fluctuating asymmetry (FA) may be a sensitive indicator of the stress experienced by organisms during their development. Its use in this manner is an intuitively appealing, frequently proposed, and potentially powerful tool but remains controversial partially because its underlying premise rarely has been critically tested. Such tests should include direct comparisons among individuals for which levels of FA, stress and fitness have been unambiguously quantified. We assessed the use of FA as a bioindicator of the stress experienced during egg-to-adult development by the stem-mining sawfly, Cephus cinctus Norton. Sawflies were reared in a common garden from seven different wheat cultivars, which were selected to represent a gradient of stem solidness, a key factor imposing stress on sawflies during development. In this model system, stress was quantified by the weight of emergent adults. Fitness was quantified by counting the number of eggs in dissected females, which emerge with their full lifetime complement. FA was measured for wing length, three wing cells, and three wing veins using image analyses. The greatest amount of stress was induced by solid-stemmed cultivars from which the adults were significantly smaller than those developing in hollow-stemmed hosts. In turn, adult weight was positively correlated with fitness. The net effect was a 25-fold variation in sawfly fitness, which gave a reasonable expectation that FA levels would differ across cultivars. However, FA levels of all the traits were similar among cultivars and there was no negative relationship between FA and fitness. These results: (1) document the failure of FA as an indicator of stress in this model system, (2) identify adult weight as a satisfactory indicator of plant-induced stress and sawfly fitness, and (3) add to the growing body of literature questioning the value of FA as a biomonitor tool of developmental stress.


Clinical performance of four immunoassays for antibodies to SARS-CoV-2, including a prospective analysis for the diagnosis of COVID-19 in a real-life routine care setting.
The aim of the present study was to evaluate the clinical performance of four SARS-CoV-2 immunoassays and their contribution in routine care for the diagnosis of COVID-19, in order to benefit of robust data before their extensive use. The clinical performance of Euroimmun ELISA SARS-CoV-2 IgG, Abbott SARS-CoV-2 IgG, Wantai SARS-CoV-2 Ab ELISA, and DiaPro COVID-19 IgG confirmation were evaluated in the context of both a retrospective and a prospective analysis of COVID-19 patients. The retrospective analysis included plasma samples from 63 COVID-19 patients and 89 control (pre-pandemic) patients. The prospective study included 203 patients who tested either negative (n = 181) or positive (n = 22) by RT-PCR before serology sampling. The specificity was 92.1 %, 98.9 %, 100 % and 98.9 % and the sensitivity 14 days after onset of symptoms was 95.6 %, 95.6 %, 97.8 % and 95.6 % for Euroimmun IgG, Abbott IgG, Wantai Ab, and DiaPro IgG confirmation SARS-CoV-2 immunoassays, respectively. The low specificity of Euroimmun IgG (for ratio <5) was not confirmed in routine care setting (98.5 % negative agreement). Serology was complementary to RT-PCR in routine care and lead to identification of false positive (Ct>38, <2 targets detected) and false negative RT-PCR results (>1 month post onset of symptoms). Serology was complementary to RT-PCR for the diagnosis of COVID-19 at least 14 days after onset of symptoms. First line serology testing can be performed with Wantai Ab or Abbott IgG assays, while DiaPro IgG confirmation assay can be used as an efficient confirmation assay.


Current Aspects of the Endocannabinoid System and Targeted THC and CBD Phytocannabinoids as Potential Therapeutics for Parkinson's and Alzheimer's Diseases: a Review.
Neurodegeneration leading to Parkinson's disease (PD) and Alzheimer's disease (AD) has become a major health burden globally. Current treatments mainly target controlling symptoms and there are no therapeutics available in clinical practice to preventing the neurodegeneration or inducing neuronal repairing. Thus, the demand of novel research for the two disorders is imperative. This literature review aims to provide a collection of published work on PD and AD and current uses of endocannabinoid system (ECS) as a potential drug target for neurodegeneration. PD is frequently treated with L-DOPA and deep brain stimulation. Recent gene modification and remodelling techniques, such as CRISPR through human embryonic stem cells and induced pluripotent stem cells, have shown promising strategy for personalised medicine. AD characterised by extracellular deposits of amyloid β-senile plaques and neurofibrillary tangles of tau protein commonly uses choline acetyltransferase enhancers as therapeutics. The ECS is currently being studied as PD and AD drug targets where overexpression of ECS receptors exerted neuroprotection against PD and reduced neuroinflammation in AD. The delta-9-tetrahydrocannabinoid (Δ9-THC) and cannabidiol (CBD) cannabinoids of plant Cannabis sativa have shown neuroprotection upon PD and AD animal models yet triggered toxic effects on patients when administered directly. Therefore, understanding the precise molecular cascade following cannabinoid treatment is suggested, focusing especially on gene expression to identify drug targets for preventing and repairing neurodegeneration.


Hypertension and other risk factors in coronary heart disease.
Whether systolic or diastolic, labile or fixed, at any age in either sex, hypertension is dangerous. Adiposity, heart rate, alcohol intake, hematocrit, blood sugar, serum cholesterol, and triglycerides are all related to the occurrence of hypertension in one or both sexes. These factors also contribute to the occurrence of the cardiovascular sequelae of hypertension. The influence of blood pressure on the incidence of cardiovascular disease is independent of other predisposing cofactors but is greatly affected by them. Elevated pressures are often accompanied by hyperlipidemia, hyperglycemia, elevated fibrinogen, and ECG abnormalities, all of which augment the risk. Coronary disease is now the most common sequela of hypertension, and the excess risk is concentrated in those with an increased low-density lipoprotein/high density lipoprotein ratio, impaired glucose tolerance, and ECG abnormalities, and in cigarette smokers. Hypertension is only a component of a multifactorial coronary risk profile which must be considered when implementing optimal therapy. Both the urgency for treatment and judgment of efficacy should be guided by the multivariate risk profile.


Regression of a meningioma during paclitaxel and bevacizumab therapy for breast cancer.
Meningiomas often are not amenable to total resection, and subtotally resected meningiomas often recur. Recurrent meningiomas present a clinical dilemma, particularly when surgical and radiotherapy options are exhausted, as there are no chemotherapeutic options that demonstrate consistent, significant efficacy. We report a patient with the regression of a recurrent World Health Organization grade I meningioma during combination chemotherapy with bevacizumab and paclitaxel for breast cancer. This chemotherapy regimen has never been explored for recurrent meningiomas. While further data are necessary, we suggest that combination chemotherapy with bevacizumab and paclitaxel may be an option for treatment of recurrent meningiomas when no further surgical or radiotherapy options exist.


Erosion and sedimentation pattern of fine sediments and its physical characteristics in a macrotidal estuary.
The seasonal and fortnightly erosion and sedimentation pattern as well as the bonding characteristics of the mud deposit at the estuarine turbidity maximum (ETM) zone of the macrotidal Chikugo River estuarine channel were studied during 2005-2008 using the periodical topographic surveys and mud sampling along with continuous monitoring of water level, turbidity and flow velocity. The results revealed that the estuary was influenced by the tidal forcing during the dry season. This tidal forcing accelerated the net landward sediment transport and sedimentation takes place in the estuarine channel. On the contrary, the river discharge dominated the estuary during the rainy season which eroded those mud deposit in the estuarine channel and exported to the downstream and the sandy base layer appeared at the bottom. During the dry season, a mud deposit of 1.5-1.8 m thick was formed which was characterized by 90% of mud (fine silt and clay) and 10% of fine sand. The high viscosity ratio and loss on ignition of this mud deposit revealed that its consolidation begins at the early stages of deposition due to thixotropy and the presence of organic matter. This consolidation process in the natural environment will be several times higher than that of the disturbed mud, which will help the sediment surface to maintain stability against erosion even at high velocities. Moreover, the consolidation of the mud deposit has a strong impact on the seasonal changes in estuarine morphology other than external forcing such as river discharge, tides, wind and availability of sediments.


Gender differences in the association between self-reported stress and cigarette smoking in Korean adolescents.
The aim of this study was to examine the relationship between stress and smoking among Korean adolescents, as well as the influence of gender on this relationship. A cross-sectional study was conducted using data from 3930 adolescents aged 12-18 years, collected in the 2007-2012 Korea National Health and Nutrition Examination Surveys. An increased level of self-reported stress was positively associated with increasing levels of smoking in both girls and boys (p for trend < 0.001). After adjusting for age, the odds ratios of smoking among girls and boys reporting very high levels of stress were 15.99 (95 % confidence interval (CI), 4.17-61.30) and 2.34 (95 % CI, 1.07-5.11), respectively, compared with those who reported low levels of stress. This study found a statistically significant association between stress and smoking among Korean adolescents and this association was stronger in girls than boys. Further research is needed to understand more fully the link between stress and smoking in adolescents, with particular attention to sex differences.


[Platelet morphology and physical stress (author's transl)].
The morphology of thrombocytes of 45 volunteers in varying conditions of training was analysed under physical stress. The probands were divided in three groups of 15 each. Group X (aged 20-26 years) had occasional gymnastics training. Group Y (aged 44-52 years) was without any physical training, and Group Z consisted of athletes (aged 22-25 years) in good training condition. By means of the platelet aggregation test (PAT), thrombocyte changes were classified in 5 stages: solitary stage (I), accumulation stage (II), degranulation stage (III), fibrin forming stage (IV), irreversible aggregation stage (V). The probands were subjected to ergometer stress in exact dosage. With the exception of the athletes, all blood smears showed a decrease in stage I (solitary), and considerable increase in stages II-V. 5, 30, or 60 min after stress, the return of irreversible aggregates (PAT V), of platelet changes in the fibrin-forming stage (PAT IV), and in the degranulation stage (PAT III), was markedly delayed in Group Y (untrained older persons) when compared with the group of well-trained athletes. The observation may offer an explanation for some cases of acute thrombotic cardiac death among trained athletes. On the other hand, it may prove the better adaptation of the thrombocytic system during physical stress when athletes are in good physical condition.


Synthesis and 5 alpha-reductase inhibitory activity of 8-substituted benzo[f]quinolinones derived from palladium mediated coupling reactions.
Benzoquinolinones have been shown to be potent, selective inhibitors of the Type I 5 alpha-reductase enzyme, which is responsible for the production of dihydrotestosterone from testosterone localized in the scalp. In an effort to identify compounds that demonstrate inhibition of both 5 alpha-reductase isozymes, we have employed 8-bromobenzoquinolinone as an advanced intermediate for participation in a variety of palladium mediated carbon-carbon bond forming reactions. By varying the 8-substituent it is possible to alter the selectivity profile of the series.


Induction of apoptosis by c9, t11-CLA in human endometrial cancer RL 95-2 cells via ERα-mediated pathway.
Numerous studies have shown that conjugated linoleic acid (CLA) can inhibit cancer cells growth and induce apoptosis in vitro and in vivo. The aim of the present study was to investigate the effects of CLA, including cis9, trans11-conjugated linoleic acid (c9, t11-CLA) and trans10, cis12-conjugated linoleic acid (t10, c12-CLA), on apoptosis of human endometrial cancer RL 95-2 cells and its related mechanisms. The MTT analysis was used to evaluate the effect of CLA isomers on the viability of endometrial cancer RL 95-2 cells. We then estimated the apoptosis by Morphological observation and Annexin V-FITC/PI staining and flow cytometry. We also used Western blot analysis to assess the expression of caspase-3, Bax, Bcl-2 proteins and the activation of Akt/p-Akt and ERα/p-ERα. Propylpyrazole-triol (PPT), a selective ERα agonist was used to confirm the induction of apoptosis by c9, t11 CLA may relate to ERα-mediated pathway. In CLA-treated RL 95-2 cells, we found that c9, t11-CLA inhibited viability and trigged apoptosis, as judged from nuclear morphology and flow cytometric analysis. The expression of caspase-3 and the ratio of Bax/Bcl-2 were significant increased, but no obvious change was observed about Akt and p-Akt in c9, t11-CLA-treated cells. However, the expression of total ERα level in RL 95-2 cells-treated with c9, t11-CLA was unchanged, while in the concentration of 80 mM, c9, t11-CLA down-regulated the protein expression level of p-ERα. Then PPT has the antagonistic action on growth inhibitory effect in RL 95-2 cells incubated with c9, t11-CLA. This study demonstrated that c9, t11- CLA could induce apoptosis in RL 95-2 cells, and may involve in ERα-mediated pathway. These results indicated that c9, t11- CLA could induce apoptosis of endometrial cancer cells and may be potential agents for the treatment of endometrial cancer.


[The effect of troxevasin on the aggregation capability of thrombocytes in children under 3 years of age with various forms of acute suppurative destructive pneumonia].
In children at the age under 3 years with different forms of acute purulent destructive pneumonia, the positive effect of troxevasin on the platelet aggregation correlating with the pronounced positive clinical effect was revealed.


Differentiation of the cardiac and pulmonary toxicity of monocrotaline, a pyrrolizidine alkaloid.
Monocrotaline, given to rats as a 20 mg/l solution in drinking water for 3 weeks, doubled the mass of the right heart and lung. The rise in lung mass preceded that of the heart. These increases were accompanied by increases in the absolute protein content of the two organs, together with increases in the rates of both protein and RNA syntheses. The increase in lung mass was not accompanied by a change in total collagen content, as measured by two independent methods: 4-hydroxyproline content and detergent fractionation. In contrast, the right ventricle showed more than a 4-fold increase in total collagen content. Total pulmonary lipids increased by 86%, but the lipid: protein ratio was unchanged. Right ventricular lipids were unchanged in amount but the lipid: protein ratio fell by 29%. Lung DNA:RNA ratio decreased 49% and right ventricle DNA:RNA ratio decreased 69%, indicating that both of these organs were responding to monocrotaline with hypertrophy. These results suggest that the processes of hypertrophy differ in the two organs: in the lung, there was no fibrosis despite a marked increase in dry weight, while right ventricular hypertrophy was characterized by increased collagen deposition. There was no alteration in the left ventricle in any of the parameters investigated.


Neighborhood environment, sexual risk behaviors and acquisition of sexually transmitted infections among adolescents diagnosed with psychological disorders.
The association between neighborhood environment and prevalence of STIs, sexual partner variables and condom use among adolescents with psychological disorders was examined. Cross-sectional data in three urban areas of the US (Southeast, Northeast and Midwest) were obtained from 384 sexually active male and female participants who provided urine samples for laboratory-confirmed testing of Neisseria gonorrhoeae, Chlamydia trachomatis and Trichomonas vaginalis. A total of 15.4% of participants tested positive for one of the three STIs. Results indicated that relative to adolescents living in low risk neighborhood environments, those living in high risk environments were significantly more likely to have a STI and to report having casual partners. Findings suggest that in high risk neighborhoods, STI acquisition may be less dependent on condom use and more dependent on other contextual factors. The importance of expanding public health research to include assessment of neighborhood context as a determinant of sexual risk-taking is emphasized.


Quantum error correction of a qubit encoded in grid states of an oscillator.
The accuracy of logical operations on quantum bits (qubits) must be improved for quantum computers to outperform classical ones in useful tasks. One method to achieve this is quantum error correction (QEC), which prevents noise in the underlying system from causing logical errors. This approach derives from the reasonable assumption that noise is local, that is, it does not act in a coordinated way on different parts of the physical system. Therefore, if a logical qubit is encoded non-locally, we can-for a limited time-detect and correct noise-induced evolution before it corrupts the encoded information1. In 2001, Gottesman, Kitaev and Preskill (GKP) proposed a hardware-efficient instance of such a non-local qubit: a superposition of position eigenstates that forms grid states of a single oscillator2. However, the implementation of measurements that reveal this noise-induced evolution of the oscillator while preserving the encoded information3-7 has proved to be experimentally challenging, and the only realization reported so far relied on post-selection8,9, which is incompatible with QEC. Here we experimentally prepare square and hexagonal GKP code states through a feedback protocol that incorporates non-destructive measurements that are implemented with a superconducting microwave cavity having the role of the oscillator. We demonstrate QEC of an encoded qubit with suppression of all logical errors, in quantitative agreement with a theoretical estimate based on the measured imperfections of the experiment. Our protocol is applicable to other continuous-variable systems and, in contrast to previous implementations of QEC10-14, can mitigate all logical errors generated by a wide variety of noise processes and facilitate fault-tolerant quantum computation.


Autonomic measures and behavioral indices of pain sensitivity.
Autonomic measures (skin conductance and heart rate) were obtained from subjects before (warning period), during (immersion period), and after (resting state) the performance of the Cold Pressor task under tolerance instructions. The Autonomic Perception Questionnaire was administered shortly before the Cold Pressor task. Skin conductance and heart rate during the warning period proved to be significant predictors of pain tolerance behaviorally measured. The Autonomic Perception Questionnaire did not reveal any relationship between awareness of autonomic arousal and pain tolerance nor between actual level of arousal and subjective awareness of this arousal.


Natural occurrence of mycotoxins other than aflatoxin in Africa, Asia and South America.
This is a compilation of data on the occurrence of mycotoxins other than aflatoxin in foods and feeds from Africa, Asia and South America with 75 references.


Serum leptin level positively correlates with metabolic syndrome among elderly Taiwanese.
Leptin is an adipocyte-derived hormone and has shown positive correlation with obesity and metabolic syndrome (MetS) in many studies. However, there are few studies investigating this relation in elderly people. Therefore, we aimed to investigate the correlation between the fasting serum leptin level and MetS among older Taiwanese. The fasting serum leptin level was obtained from 62 Taiwanese participants over 65 years old and was measured using a commercially available enzyme immunoassay kit. MetS and its components were defined using diagnostic criteria from the International Diabetes Federation. Thirty elderly participants (48.4%) had MetS. The serum leptin level was positively correlated with MetS (P < 0.001). Multivariate logistic regression analysis of the factors significantly associated with MetS showed that logarithmically transformed leptin (log-leptin, each increase 0.1 ng/mL log-leptin, odds ratio: 1.276, 95% confidence interval: 1.015-1.603, P = 0.037) was still an independent predictor of MetS in elderly persons. Univariable linear analysis showed that body weight (r = 0280, P = 0.028), body mass index (r = 0.417, P = 0.001), waist circumference (r = 0.419, P = 0.001), blood urea nitrogen (r = 0255, P = 0.046), log-insulin (r = 0436, P < 0.001), and logarithmically transformed homeostasis model assessment of insulin resistance (r = 0359, P = 0.004) positively correlated with fasting serum log-leptin levels. Multivariate forward stepwise linear regression analysis of the factors significantly associated with fasting serum log-leptin levels revealed that waist circumference (adjusted R2 = 0.083, P = 0.002), statin use (adjusted R2 = 0.058, P = 0.016), and female gender (adjusted R2 = 0.041, P = 0.034) were independent predictors of fasting serum log-leptin levels among elderly participants. In elderly Taiwanese, the serum leptin level was positively correlated with MetS. Waist circumference, statin use, and female gender were independent predictors of the fasting serum leptin level in elderly participants.


Impacts of biogenic emissions of VOC and NOx on tropospheric ozone during summertime in eastern China.
This study is intended to understand and quantify the impacts of biogenic emissions of volatile organic compounds (VOC) and nitrogen oxides (NO(x)) on the formation of tropospheric ozone during summertime in eastern China. The model system consists of the non-hydrostatic mesoscale meteorological model (MM5) and a tropospheric chemical and transport model (TCTM) with the updated carbon-bond chemical reaction mechanism (CBM-IV). The spatial resolution of the system domain is 30 km x 30 km. The impacts of biogenic emissions are investigated by performing simulations (36 h) with and without biogenic emissions, while anthropogenic emissions are constant. The results indicate that biogenic emissions have remarkable impacts on surface ozone in eastern China. In big cities and their surrounding areas, surface ozone formation tends to be VOC-limited. The increase in ozone concentration by biogenic VOC is generally 5 ppbv or less, but could be more than 10 ppbv or even 30 ppbv in some local places. The impacts of biogenic NO(x) are different or even contrary in different regions, depending on the relative availability of NO(x) and VOC. The surface ozone concentrations reduced or increased by the biogenic NO(x) could be as much as 10 ppbv or 20 ppbv, respectively. The impacts of biogenic emissions on ozone aloft are generally restricted to the boundary layer and generally more obvious during the daytime than during the nighttime. This study is useful for understanding the role of biogenic emissions and for planning strategies for surface ozone abatement in eastern China. Due to limitations of the emission inventories used and the highly non-linear nature of zone formation, however, some uncertainties remain in the results.


Analysis of cell-free fetal DNA in 16,843 pregnant women from a single center in China using targeted sequencing approach.
Non-invasive prenatal testing (NIPT) using cell-free fetal DNA (cffDNA) has been widely accepted for detecting common fetal chromosome aneuploidies, but few large-scale studies have reported the kinetics of cffDNA concentration during gestation. This study examines cffDNA kinetics spanning gestational periods. In this retrospective cohort study, cffDNA concentration from maternal plasma of 16,843 pregnant women between 4 and 39 weeks of pregnancy were determined by SNP-based targeted deep sequencing. Maternal plasma cffDNA could be detected as early as the fourth gestational week. After detection, cffDNA concentration begun to increase to the 39th week showing three conspicuous inflection points characterized by growth and stabilization phases. The rapid increase in cffDNA (∼1.19% per week) from the 4th to 9th week represents the first growth stage. The first plateau phase spanned from the 10th to 19th week (∼0.03% increase per week). cffDNA begun to rise dramatically (∼0.85% per week) from the 19th to 29th week, stabilizing at week 30 and onwards with only 0.27% increase per week representing the second plateau period. The proportion of cases with cffDNA ≥4% increased rapidly before the 10th gestational week with no significant increase from the 10th week onwards. About 92.00% of all the maternal plasma had a cffDNA greater than 4% from 10 weeks. We indicate that cffDNA had 3 inflection points at the 10th, 19th and 30th week of gestation, an observation not yet reported. Moreover, we show that cffDNA concentration has met the NIPT requirements after 9 weeks gestational age.


Crossover Randomized Study of Pharmacologic Effects of Ripasudil-Brimonidine Fixed-Dose Combination Versus Ripasudil or Brimonidine.
Multidrug regimens for glaucoma treatment often result in adherence issues due to inconvenience; these issues may be improved with fixed-dose combination drugs. The ophthalmic solution of ripasudil-brimonidine fixed-dose combination (RBFC; K-232) is the first treatment combining a Rho kinase inhibitor and an α2-adrenoceptor agonist, and has demonstrated ability to lower intraocular pressure (IOP) and have various effects on conjunctival hyperemia and corneal endothelial cell morphology. This study evaluates the pharmacologic effects of RBFC treatment versus its separate components-ripasudil or brimonidine. This single-center, prospective, randomized, open-label, blinded endpoint study with 3 × 3 crossover design randomly assigned healthy adult men to three groups (1:1:1) to undergo consecutive 8-day administration phases (with drug-free intervals of at least 5 days). Subjects received twice-daily instillation of RBFC → ripasudil → brimonidine (group A), ripasudil → brimonidine → RBFC (group B), or brimonidine → RBFC → ripasudil (group C). Endpoints included change in IOP, severity of conjunctival hyperemia, corneal endothelial cell morphology, pupil diameter, and pharmacokinetics. Eighteen subjects were assigned in total (six to each group). RBFC significantly reduced IOP from baseline at 1 h post-instillation on days 1 and 8 (12.7 vs. 9.1 and 9.0 mmHg, respectively; both P < 0.001), and provided significantly greater IOP reductions than ripasudil or brimonidine at several time points. The most common adverse drug reaction with all three treatments was mild conjunctival hyperemia, which transiently increased in severity with RBFC or ripasudil, peaking at 15 min post-instillation. In post hoc analyses, conjunctival hyperemia scores were lower with RBFC than with ripasudil at several time points. Transient morphologic changes in corneal endothelial cells occurred for up to several hours with RBFC or ripasudil, but not with brimonidine. Pupil diameter did not change with RBFC. RBFC significantly reduced IOP compared with each agent alone. A combination of each agent's pharmacologic profile was observed in that of RBFC. Japan Registry of Clinical Trials; Registration No. jRCT2080225220.


Diagnosing breast lesions with contrast-enhanced 3-dimensional power Doppler imaging.
To compare mammography with contrast-enhanced 2- and 3-dimensional power Doppler imaging for the diagnosis of breast cancer. Fifty-five patients, who underwent breast biopsies with histopathologic assessment, participated in a study of mammography and contrast-enhanced sonography. Levovist (Berlex Laboratories, Montville, NJ) and Optison (Mallinckrodt, St Louis, MO) were administrated to 22 and 33 patients, respectively. Precontrast and postcontrast 2-dimensional power Doppler data of the lesion were obtained with an HDI 3000 system (Philips Medical Systems, Bothell, WA), and 3-dimensional data were acquired with an LIS 6000A system (Life Imaging Systems Inc, London, Ontario, Canada). Two independent and blinded readers assessed diagnosis. Receiver operating characteristic curves were computed individually and in combination for mammography and 2- and 3-dimensional sonography (before and after contrast). Histopathologic and imaging parameters were compared by Mann-Whitney statistics. Mammographic findings were available for 50 patients, biopsy for 54, and 2- and 3-dimensional sonographic images for 53 and 52, respectively. Of the 50 patients who had all 4 measures, 15 (30%) had malignancies. The areas under the receiver operating characteristic curve for the diagnosis of breast cancer were 0.51 for 2-dimensional contrast-enhanced imaging, 0.60 for 3-dimensional power Doppler imaging, and 0.76 for 3-dimensional contrast-enhanced imaging (P < .01). Mammography produced an area of 0.86, which increased when combined with 3-dimensional contrast-enhanced imaging to 0.90 and with all sonographic modalities to 0.96 (P < .001). The histopathologic diagnosis of benign or malignant correlated with the presence or absence of anastomoses and with the degree of vascularity assessed with contrast-enhanced 3-dimensional power Doppler imaging (P = .007 and .02). Contrast-enhanced 3-dimensional power Doppler imaging increases the ability to diagnose breast cancer relative to conventional 2- and 3-dimensional sonographic imaging.


MRI as an Alternative to Second Look Mastoid Surgery.
The main goal of surgery of cholesteatoma is eradication of the disease and revision surgery is indicated when a dry and safe ear has not been achieved. Residual cholesteatoma usually occurs at the sites that are difficult to reach with an operating microscope, such as posterior tympanum and anterior epitympanic recess. Computed tomography can be performed to delineate the extent of disease. High-resolution computed tomography scanning is important for planning for surgery and is indicated for all revision mastoid operations. Magnetic resonance imaging is superior to computed tomography in tissue characterization for diagnosis of recurrent cholesteatoma. To evaluate the cases of recurrent cholesteatoma comparing the intraoperative surgical findings with the preoperative MRI radiological findings and if the preoperative MRI can replace the second look surgery for cholesteatoma. This study was applied on 60 patients that have a recurrent cholesteatoma after previous mastoid surgery. A preoperative radiological evaluation was done by Magnetic resonance, surgical management was done by canal wall up or canal wall down mastoidectomy to exclude residual disease. Then, radiological, and surgical findings correlation was done. Diffusion-weighted MRI successfully detected 42 cases out of the 45 cases of surgically proved cholesteatoma, it has accuracy 95%, sensitivity 93.33%, specificity 100%, PPV 100% and NPV 83.33%. MRI is better than CT in tissue characterization for diagnosis of recurrent cholesteatoma, and can replace the unnecessary second look surgery of cholesteatoma.


Foley catheter balloon tamponade for life-threatening hemorrhage in penetrating neck trauma.
Foley catheter (FC) balloon tamponade is a well-recognized technique employed to arrest hemorrhage from penetrating wounds. The aim of this study was to review our experience with this technique in penetrating neck wounds and to propose a management algorithm for patients with successful FC tamponade. A retrospective chart review (July 2004-June 2005 inclusive) was performed of patients identified from a prospectively collected penetrating neck injury computer database in whom FC balloon tamponade was used. The units' policy for penetrating neck injuries is one of selective nonoperative management. All patients with successful FC tamponade underwent angiography. A venous injury was diagnosed if angiography was normal. Ancillary tests were performed as indicated. Removal of the FC was performed in the OR. During the study period, 220 patients with penetrating neck injuries were admitted to our unit. Foley catheter balloon tamponade was used in 18 patients and was successful in 17 patients. Angiography was positive in 3 patients, all of whom underwent surgery. The FC was successfully removed in 13 patients at a mean of 72 (range 48-96) hours. One patient bled after removal of the catheter, mandating emergency surgery. Foley catheter balloon tamponade remains a useful adjunct in the management of selective patients with penetrating, bleeding neck wounds.


[AUTOIMMUNE REACTIONS IN PATIENTS WITH DISEASES OF A THYROID GLAND].
A state of autoimmunity was studied in 25 patients, suffering diffuse toxic goiter (DTG), and in 20--in nodular euthyroid goiter (NEG) before and after the operation. The level of circulating immune complexes, quantity of cytotoxic lymphocytes, the subpopulation index, the apoptosis marker were determined. There was established, that in NEG autoimmune disorders have occurred rarer and were less severe, than in DTG.


Profiling of cAMP and cGMP phosphodiesterases in isolated ventricular cardiomyocytes from human hearts: comparison with rat and guinea pig.
Phosphodiesterases (PDEs) are key enzymes controlling cAMP and cGMP levels and spatial distribution within cardiomyocytes. Despite the clinical importance of several classes of PDE inhibitor there has not been a complete characterization of the PDE profile within the human cardiomyocyte, and no attempt to assess which species might best be used to model this for drug evaluation in heart disease. Ventricular cardiomyocytes were isolated from failing human hearts of patients with various etiologies of disease, and from rat and guinea pig hearts. Expression of PDE isoforms was determined using RT-PCR. cAMP- and cGMP-PDE hydrolytic activity was determined by scintillation proximity assay, before and after treatment with PDE inhibitors for PDEs 1, 2, 3, 4, 5 and 7. Functional effects of cAMP PDEi were determined on the contraction of single human, rat and guinea pig cardiomyocytes. The presence and activity of PDE5 were confirmed in ventricular cardiomyocytes from failing and hypertrophied human heart, as well as PDE3, with ventricle-specific results for PDE4 and a surprisingly large contribution from PDE1 for hydrolysis of both cAMP and cGMP. The total PDE activity of human cardiomyocytes, and the profile of inhibition by PDE1, 3, 4, and 5 inhibitors, was modelled well in guinea pig but not rat cardiomyocytes. Our results provide the first full characterisation of human cardiomyocyte PDE isoforms, and suggest that guinea pig myocytes provide a better model than rat for PDE levels and activity.


On the question of dose-dependent chloroquine elimination of a single oral dose.
Subjects (n = 45) were randomly given single oral doses of 2 (n = 11), 3 (n = 9), 5 (n = 8), 10 (n = 10), or 15 mg/kg (n = 7) chloroquine base. Chloroquine was analyzed by HPLC in serum samples taken at 3 to 168 hr after dosing. AUCs, calculated for the time period of 0 to 168 hr were proportional to the doses. Mean AUC value increased 6.7 times when the dose was increased 7.5 times (from 2 to 15 mg/kg). These data do not support the existence of significant capacity-limited chloroquine elimination within the dose range studied.


The nature of tryptophan radicals involved in the long-range electron transfer of lignin peroxidase and lignin peroxidase-like systems: Insights from quantum mechanical/molecular mechanics simulations.
A catalytically active tryptophan radical has been demonstrated to be involved in the long-range electron transfer to the heme cofactor of lignin peroxidase (LiP) from Phanerochaete chrysosporium although no direct detection by EPR spectroscopy of the tryptophan radical intermediate has been reported to date. An engineering-based approach has been used to manipulate the microenvironment of the redox-active tryptophan site in LiP and Coprinus cinereus Peroxidase (CiP), allowing the direct evidence of the tryptophan radical species. In light of the newly available EPR experimental data, we performed a quantum mechanical/molecular mechanics computational study to characterize the tryptophan radicals in the above protein matrices as well as in pristine LiP. The nature of the tryptophan radicals is discussed together with the analysis of their environment with the aim of understanding the different behavior of pristine LiP in comparison with that of LiP and CiP variants.


I-bands of striated muscle contain lateral struts.
In electron micrographs of striated muscle, the I-band often shows a distinct cross-striation. The periodicity of this striation is near 40 nm and has been attributed to troponin, which is localized along the thin filament. However, the cross-striation is often so prominent as to be suggestive of physical structures running transversely across the I-band. We examined I-band ultrastructure using three independent methods: thin sections of chemically fixed specimens; freeze-fracture; and freeze-substitution. With all three methods we found transverse structures distributed throughout the I-band, many of which bridged the gap between neighboring filaments. Such structures were observed in each of the several species studied. In fish muscle in particular, which has a highly regular lattice, it was obvious that these structures gave rise to the observed periodicity.


Teaching an Experienced Multidisciplinary Team About Postpartum Hemorrhage: Comparison of Two Different Methods.
Morbidity from postpartum hemorrhage (PPH) affects 20% of pregnancies worldwide and remains a significant cause of maternal mortality. This study compared the impressions of experienced clinicians on the effect of two methods of educational interventions in a MoreOB training program designed to improve recognition and management of PPH. Participants were exposed to a traditional didactic lecture and an interactive clinical intervention exercise incorporating video simulation of a PPH event with opportunities for feedback and discussion of how to proceed. They were then invited to respond to a questionnaire regarding their impressions of both methods. Of 150 participants, 110 completed the questionnaire. Respondents considered the interactive format to be more effective (55%) and enjoyable (72%) than the traditional didactic format. The majority (81%), however, still recommended a mixture of both interactive and didactic formats in future events, supported by a multidisciplinary drill. Clinical learners value interactivity and mutual reinforcement among varied learning exercises in their educational experiences. Future educational programs may consider incorporating similar methods in order to maximize participants' receptiveness.


Dietary Intake of Competitive Bodybuilders.
Competitive bodybuilders are well known for extreme physique traits and extremes in diet and training manipulation to optimize lean mass and achieve a low body fat. Although many of the dietary dogmas in bodybuilding lack scientific scrutiny, a number, including timing and dosing of high biological value proteins across the day, have more recently been confirmed as effective by empirical research studies. A more comprehensive understanding of the dietary intakes of bodybuilders has the potential to uncover other dietary approaches, deserving of scientific investigation, with application to the wider sporting, and potential health contexts, where manipulation of physique traits is desired. Our objective was to conduct a systematic review of dietary intake practices of competitive bodybuilders, evaluate the quality and currency of the existing literature, and identify research gaps to inform future studies. A systematic search of electronic databases was conducted from the earliest record until March 2014. The search combined permutations of the terms 'bodybuilding', 'dietary intake', and 'dietary supplement'. Included studies needed to report quantitative data (energy and macronutrients at a minimum) on habitual dietary intake of competitive bodybuilders. The 18 manuscripts meeting eligibility criteria reported on 385 participants (n = 62 women). Most studies were published in the 1980-1990s, with three published in the past 5 years. Study methodological quality was evaluated as poor. Energy intake ranged from 10 to 24 MJ/day for men and from 4 to 14 MJ/day for women. Protein intake ranged from 1.9 to 4.3 g/kg for men and from 0.8 to 2.8 g/kg for women. Intake of carbohydrate and fat was <6 g/kg/day and below 30% of energy, respectively. Carbohydrate intakes were below, and protein (in men) intakes were higher than, the current recommendations for strength athletes, with no consideration for exploration of macronutrient quality or distribution over the day. Energy intakes varied over different phases of preparation, typically being highest in the non-competition (>6 months from competition) or immediate post-competition period and lowest during competition preparation (≤6 months from competition) or competition week. The most commonly reported dietary supplements were protein powders/liquids and amino acids. The studies failed to provide details on rationale for different dietary intakes. The contribution of diet supplements was also often not reported. When supplements were reported, intakes of some micronutrients were excessive (~1000% of US Recommended Dietary Allowance) and above the tolerable upper limit. This review demonstrates that literature describing the dietary intake practices of competitive bodybuilders is dated and often of poor quality. Intake reporting required better specificity and details of the rationale underpinning the use. The review suggests that high-quality contemporary research is needed in this area, with the potential to uncover dietary strategies worthy of scientific exploration.


Reasons for admission to an adolescent unit.
Three years admissions to a regional adolescent unit are analyzed to obtain information on the referral, the adolescent and family, and the behaviours leading to admission. The findings are discussed with particular relevance to the N.H.S. Health Advisory Service report on services for disturbed adolescents. Possible implications of the report which are not described by the H.A.S. are described.


Randomized, Double-Blind, Placebo-Controlled, Phase 2 Trial of BMS-986020, a Lysophosphatidic Acid Receptor Antagonist for the Treatment of Idiopathic Pulmonary Fibrosis.
Idiopathic pulmonary fibrosis (IPF) causes irreversible loss of lung function. The lysophosphatidic acid receptor 1 (LPA1) pathway is implicated in IPF etiology. Safety and efficacy of BMS-986020, a high-affinity LPA1 antagonist, was assessed vs placebo in a phase 2 study in patients with IPF. IM136003 was a phase 2, parallel-arm, multicenter, randomized, double-blind, placebo-controlled trial. Adults with IPF (FVC, 45%-90%; diffusing capacity for carbon monoxide, 30%-80%) were randomized to receive placebo or 600 mg BMS-986020 (once daily [qd] or bid) for 26 weeks. The primary end point was rate of change in FVC from baseline to week 26. Of 143 randomized patients, 108 completed the 26-week dosing phase. Thirty-five patients discontinued prematurely. Patient baseline characteristics were similar between treatment groups (placebo: n = 47; 600 mg qd: n = 48; 600 mg bid: n = 48). Patients treated with BMS-986020 bid experienced a significantly slower rate of decline in FVC vs placebo (-0.042 L; 95% CI, -0.106 to -0.022 vs -0.134 L; 95% CI, -0.201 to -0.068, respectively; P = .049). Dose-related elevations in hepatic enzymes were observed in both BMS-986020 treatment groups. The study was terminated early because of three cases of cholecystitis that were determined to be related to BMS-986020 after unblinding. BMS-986020 600 mg bid treatment for 26 weeks vs placebo significantly slowed the rate of FVC decline. Both regimens of BMS-986020 were associated with elevations in hepatic enzymes. ClinicalTrials.gov; No.: NCT01766817; URL: www.clinicaltrials.gov.


To see or not to see: imaging surfactant coated nano-particles using HIM and SEM.
Nano-particles are of great interest in fundamental and applied research. However, their accurate visualization is often difficult and the interpretation of the obtained images can be complicated. We present a comparative scanning electron microscopy and helium ion microscopy study of cetyltrimethylammonium-bromide (CTAB) coated gold nano-rods. Using both methods we show how the gold core as well as the surrounding thin CTAB shell can selectively be visualized. This allows for a quantitative determination of the dimensions of the gold core or the CTAB shell. The obtained CTAB shell thickness of 1.0 nm-1.5 nm is in excellent agreement with earlier results using more demanding and reciprocal space techniques.


Efficacy of combination treatment with anti-IgE plus specific immunotherapy in polysensitized children and adolescents with seasonal allergic rhinitis.
Specific immunotherapy (SIT) and treatment with monoclonal anti-IgE antibody have complementary modes of action. The purpose of this study was to determine whether combined therapy could provide better efficacy than either treatment alone. We conducted a randomized, double-blinded trial to assess the efficacy and safety of subcutaneously administered anti-IgE (omalizumab) or placebo in children and adolescents with seasonal allergic rhinitis in both a birch pollen season and a grass pollen season (sequential seasons together lasting an average of 84 days). There were 4 treatment arms. Each subject was started on SIT-birch or SIT-grass, and anti-IgE or placebo was started before and maintained during the anticipated pollen seasons (a total of 24 weeks). The primary efficacy variable was symptom load, the sum of daily symptom severity score plus rescue medication use. A total of 221 subjects (intent-to-treat population) aged 6 to 17 years were analyzed for efficacy. Combination therapy reduced symptom load over the 2 pollen seasons by 48% (P <.001) over SIT alone. When analyzed separately by season, the 2 groups receiving unrelated SIT were considered placebo controls. In the grass season, symptom loads were as follows: unrelated (birch) SIT + placebo, 0.89 (reference value); unrelated (birch) SIT + anti-IgE, 0.49 (-45%); SIT-grass + placebo, 0.61 (-32%); SIT-grass + anti-IgE, 0.26 (-71%). Anti-IgE therapy conferred a protective effect independent of the type of allergen. Additional clinical benefit was demonstrated in both pollen seasons, whether there was coverage by SIT or not. This combination might prove useful for the treatment of allergic rhinitis, particularly for polysensitized patients.


The role of drug treatment in children with strabismus and amblyopia.
Strabismus, or misalignment of the eyes, is a common ophthalmic problem in childhood, affecting 2 to 5% of the preschool population. Amblyopia is an important cause of visual morbidity frequently associated with strabismus, and both conditions should be treated simultaneously. Pharmacological means for treating strabismus and amblyopia can be divided into 3 categories: paralytic agents (botulinum toxin) used directly on the extraocular muscles to affect eye movements; autonomic agents (atropine, miotics) used topically to manipulate the refractive status of the eye and thereby affect alignment, focus and amblyopia; and centrally acting agents, including levodopa and citicoline, which affect the central visual system abnormalities in amblyopia. Botulinum toxin, the paralytic agent that causes the clinical symptoms of botulism poisoning, can be injected in minute quantities to achieve controlled paralysis of the extraocular muscles. Although the role of botulinum toxin is established in adults with paralytic strabismus, its usefulness in the treatment of comitant childhood strabismus (primary esotropia and exotropia) is not universally accepted. Botulinum injections tend to be more effective with smaller degrees of strabismus, in patients with good binocular fusion, and in managing overcorrections or undercorrections after traditional muscle surgery. Inadvertent ptosis and paralysis of adjacent muscles, unpredictable responses and technical constraints of the injections limit its use in children. Miotic therapy, by altering the refractive state of the treated eye, offers an alternative to optical correction with bifocals in treating esotropia due to excessive accommodative convergence. It is also effective in treating residual esotropia following surgery. The ease of use of glasses restricts the wide application of miotics in these common strabismus syndromes. Atropine, an anticholinergic agent, paralyses the ability of the eye to focus or accommodate. In amblyopia therapy, atropine is used to blur vision in the non-amblyopic eye and offers a useful alternative to traditional occlusion therapy with patching, especially in older children who are not compliant with patching. The neurotransmitter precursor levodopa and the related compound citicoline have been demonstrated to improve vision in amblyopic eyes. The therapeutic role of these centrally acting agents in the clinical management of amblyopia remains unproven.


Structure and dynamics of the excited states of 1,3-diarylisobenzofurans: an experimental and theoretical study.
The emission properties of a series of substituted 1,3-diarylisobenzofurans have been studied. Most compounds exhibit very intense emission in the nanosecond timescale at room temperature as well as at 77 K. The room temperature emission is attributed to the deactivation of a twisted intramolecular charge transfer excited state, based on its energy, shape and solvent dependence. The experimental results are strongly supported by a theoretical study on one representative compound. The DFT/TD-DFT calculations demonstrate that the initial excited state relaxes toward a twisted structure.


Hydroarylations by cobalt-catalyzed C-H activation.
As an earth-abundant first-row transition metal, cobalt catalysts offer a broad range of economical methods for organic transformations via C-H activation. One of the transformations is the addition of C-H to C-X multiple bonds to afford alkylation, alkenation, amidation, and cyclization products using low- or high-valent cobalt catalysts. This hydroarylation is an efficient approach to build new C-C bonds in a 100% atom-economical manner. In this review, the recent developments of Co-catalyzed hydroarylation reactions and their mechanistic studies are summarized.


Fecal microbiota transplantation from patients with rheumatoid arthritis causes depression-like behaviors in mice through abnormal T cells activation.
Depression is common in patients with rheumatoid arthritis (RA); however, the precise mechanisms underlying a link between depression and RA remain unclear. Accumulating evidence suggests the role of gut-microbiota-brain axis in depression. In this study, we investigated whether collagen-induced arthritis (CIA) mice produce depression-like behaviors and abnormal composition of gut microbiota. Furthermore, we investigated whether fecal microbiota transplantation (FMT) from RA patients causes depression-like phenotypes in antibiotic cocktail (ABX)-treated mice. CIA mice displayed depression-like behaviors, increased blood levels of pro-inflammatory cytokine interleukin-6 (IL-6), decreased expression of synaptic proteins in the prefrontal cortex (PFC), and abnormal composition of gut microbiota. Furthermore, FMT from RA patients caused depression-like phenotypes, alterations of gut microbiota composition, increased levels of IL-6 and tumor necrosis factor-α (TNF-α), and downregulation of synaptic proteins in the PFC compared to FMT from healthy controls. There were correlations between relative abundance of microbiota and plasma cytokines, expression of synaptic proteins in the PFC or depression-like behaviors. Interestingly, FMT from RA patients induced T cells differentiation in Peyer's patches and spleen. Reduced percentage of Treg cells with an increase of Th1/Th2 index was observed in the mice after FMT from RA patients. These findings suggest that CIA mice exhibit depression-like behaviors, systemic inflammation, and abnormal composition of gut microbiota, and that FMT from RA patients produces depression-like behaviors in ABX-treated mice via T cells differentiation. Therefore, abnormalities in gut microbiota in RA patients may contribute to depression via gut-microbiota-brain axis.


Glucose metabolism: A link between traumatic brain injury and Alzheimer's disease.
Traumatic brain injury (TBI), a growing public health problem, is a leading cause of death and disability worldwide, although its prevention measures and clinical cares are substantially improved. Increasing evidence shows that TBI may increase the risk of mood disorders and neurodegenerative diseases, including Alzheimer's disease (AD). However, the complex relationship between TBI and AD remains elusive. Metabolic dysfunction has been the common pathology in both TBI and AD. On the one hand, TBI perturbs the glucose metabolism of the brain, and causes energy crisis and subsequent hyperglycolysis. On the other hand, glucose deprivation promotes amyloidogenesis via β-site APP cleaving enzyme-1 dependent mechanism, and triggers tau pathology and synaptic function. Recent findings suggest that TBI might facilitate Alzheimer's pathogenesis by altering metabolism, which provides clues to metabolic link between TBI and AD. In this review, we will explore how TBI-induced metabolic changes contribute to the development of AD.


Impact of consensus statements and reimbursement on vena cava filter utilization.
Pulmonary embolism is the third most common cause of death in hospitalized patients. Vena cava filters (VCFs) are indicated in patients with venous thromboembolism with a contraindication to anticoagulation. Prophylactic indications are still controversial. However, the utilization of VCFs during the past 15 years may have been affected by societal recommendations and reimbursement rates. The aim of this study was to evaluate the impact of societal guidelines and reimbursement on national trends in VCF placement from 1998 to 2012. The National Inpatient Sample was used to identify patients who underwent VCF placement between 1998 and 2012. VCF placement yearly rates were evaluated. Societal guidelines and consensus statements were identified using a PubMed search. Reimbursement rates for VCF were determined on the basis of published Medicare reports. Statistical analysis was completed using descriptive statistics, Fisher exact test, and trend analysis using the Mann-Kendall test and considered significant for P < .05. The use of VCFs increased 350% between January 1998 and January 2008. Consensus statements in favor of VCFs published by the Eastern Association for the Surgery of Trauma (July 2002) and the Society of Interventional Radiology (March 2006) were temporally associated with a significant 138% and 122% increase in the use of VCFs, respectively (P = .014 and P = .023, respectively). The American College of Chest Physicians guidelines (February 2008 and 2012) discouraging the use of VCFs were preceded by an initial stabilization in the use of VCFs between 2008 and 2012, followed by a 16% decrease in use starting in March 2012 (P = .38). Changes in Medicare reimbursement were not followed by a change in VCF implantation rates. There is a temporal association between the societal guidelines' recommendations regarding VCF placement and the actual rates of insertion. More uniform consensus statements from multiple societies along with the use of level I evidence may be required to lead to a definitive change in practice.


Kangaroo Mother Care in reducing pain in preterm neonates on heel prick.
To determine the effect of Kangaroo Mother Care (KMC) of small duration of 15 min in decreasing pain in preterm neonates between 32-36 wk 6 d on heel prick by a 26 gauge needle. Randomized controlled double masked crossover trial involving 50 neonates, between 32 wk and 36 wk 6 d gestation and weighing less than 2500 g, within 10 d of birth, vitally stable, breathing without assistance or on Continuous positive airway pressure (CPAP), without any clinically evident neurological signs, not having received analgesics/sedatives within last 24 h and not fed within last 30 min and requiring heel pricking were eligible. Outcome measured was the Premature Infant Pain Profile (PIPP). Analysis was done using independent sample t test, with Bonferroni correction applied for comparing individual components of PIPP score. The heart rate, behaviour and facial scores were statistically significant and lower in KMC group. But there was no statistically significant difference in oxygen saturation (SpO(2)). The difference(4.85) in PIPP score was clinically and statistically significant (p < 0.0001). The findings suggest that short duration KMC (15 min) has stress reducing benefits. Preterm neonates above 32 wk gestational age can benefit from KMC to decrease pain from heel prick procedure.


Clozapine-induced cardiotoxicity in rats: Involvement of tumour necrosis factor alpha, NF-κβ and caspase-3.
Clozapine, an ideal antipsychotic drug for the treatment of resistant schizophrenia, is considered the most underutilised treatment for schizophrenia. However, safety concerns have been raised about clozapine-induced cardiotoxicity, which may lead to sudden death, particularly in young patients. The exact mechanism of clozapine cardiotoxicity has not yet been thoroughly studied. This study aimed to investigate the possible mechanisms of clozapine-induced cardiotoxicity in a rat model. Young male Wistar rats were treated with clozapine (10, 15 and 25 mg/kg/day, i.p.) for 21 days. Haemodynamic and echocardiographic studies were performed for assessment of cardiac functions. Heart sections were studied histopathologically and immunohistochemically. Serum and cardiac markers of cardiotoxicity, oxidative stress, inflammation and apoptosis were evaluated. Heart sections of CLZ-treated animals showed increased cardiac inflammation that correlated with the clozapine dose. Serum levels of CK-MB and LDH levels increased, as did cardiac levels of TNF-α, MDA, NO, myeloperoxidase (MPO), 8-OHdG, caspase-3 and NF-κB p65. In contrast, GSH levels and GSH-Px activity decreased. Furthermore, immunohistochemical examination of the heart sections showed positive immunostaining for both 3-nitrotyrosine and caspase-3 in all clozapine-treated groups. Clozapine, particularly in relatively high doses, has a clear cardiotoxic effect. This cardiotoxicity is accompanied by increased myocardial oxidative stress, inflammatory cytokines, DNA damage and apoptosis with attenuation in antioxidant defences, thus explaining the previously reported myocarditis and pericarditis during clozapine therapy in clinical studies.


Instability and rotation of silver silicone penile prosthesis.
Four cases of a similar complication in patients who have had the Jonas silver silicone prosthesis implanted are reported. The patients complain of instability and rotation of the prosthesis to a position that stands out from the body, no matter what the initial position of the prosthesis. The rotation causes difficulty with coitus. The explanation is one of a manufacturing and not a surgical defect.


Efficacy and safety of an adsorbent and anti-oxidative vaginal gel on CIN1 and 2, on high-risk HPV, and on p16/Ki-67: a randomized controlled trial.
The effect of SAM vaginal gel, a medical device containing adsorptive silicon dioxide and antioxidative sodium selenite and citric acid, on histologically-proven cervical intraepithelial neoplasia type 2 (CIN2) as well as p16 positive CIN1, and on the presence of the onco-marker p16 was investigated. 216 women aged 25-60 years were randomized to either receive an intravaginal daily dose of SAM gel for three 28-day periods, or be followed-up without intervention. The primary endpoint was efficacy, defined as a combined histological and cytological regression. At baseline and after 3 months participants had: a guided biopsy including p16 immunohistochemical (IHC) staining, only if a lesion was visible at colposcopy; a cervical smear for cytology, high-risk human papillomavirus (hr-HPV) and a p16/Ki-67 test. At 6 months a further cytology and p16/Ki-67 test was performed. Regression of CIN lesions was observed in 78 out of 108 patients (72.2%) in the SAM gel arm and in 27 out of 108 patients (25.0%) in the control arm. Similarly, the change in the p16/Ki-67 cytological test status was significantly in favor of the treatment arm. The prevalence of hr-HPV decreased significantly (p < 0.001) in the treatment arm, from 87.0% to 39.8%, while it slightly increased in the control arm, from 78.7% to 83.3%. At 6 months the cytological regression in the treatment group and the highly significant effect on p16/Ki-67 was still present. SAM vaginal gel enhances the regression of cervical lesions and clears hr-HPV and p16/Ki-67 in smears significantly, thus offering an active non-destructive management to prevent cervical cancer. ISRCTN11009040, date of registration: 10/12/2019; https://doi.org/10.1186/ISRCTN11009040 ; retrospectively registered.


[Use of an anti-B monoclonal antibody of mouse origin with the Groupamatic (MG 50) apparatus].
This study refers to the use of a monoclonal anti-B antibody of murine origin on Groupamatic MG 50. The monoclonal antibody produces results similar to those obtained with human immune antibodies.


Persistent clot anuria complicating renal transplant biopsy.
Serious morbidity from renal transplant biopsy is reported to be infrequent. However, 4 of 43 patients who had renal transplant biopsy between July, 1981, and March, 1984, experienced anuria from upper urinary tract obstruction by blood clots. Although these clots usually dissolve, 3 patients (7%) experienced persistent clot anuria and deterioration of renal function. Awareness of this complication is important. Retrograde pyelography and ureteral catheterization are preferred primarily for diagnosis and treatment. Percutaneous techniques are reserved for those cases in which the ureter cannot be catheterized cystoscopically.


Insights into the European rabbit (Oryctolagus cuniculus) innate immune system: genetic diversity of the toll-like receptor 3 (TLR3) in wild populations and domestic breeds.
Toll-like receptors (TLRs) belong to the innate immune system and are a major class of pattern recognition receptors representing the first line of the innate immune response. The TLR molecule is structurally composed by an ectodomain that contains leucine rich repeats (LRRs) that interact with pathogen associated molecular patterns (PAMPs), a transmembrane domain and a conserved cytoplasmic domain designated TIR (Toll-IL1 receptor) that is responsible for the intracellular signaling. TLR3 has been associated with the direct recognition of double-stranded viral RNA resulting from viral replication, while TLR7 and TLR8 target single-stranded viral RNA. In the European rabbit (Oryctolagus cuniculus), TLR7 and TLR8 were reported to be absent and pseudogenised, respectively, making TLR3 the only available TLR for the recognition of viral RNA. Thus, the levels of diversity of TLR3 were evaluated in the European rabbit by analysing different genetic backgrounds and exposure to pathogen pressures. We detected 41 single nucleotide polymorphisms (SNPs) in the coding sequence of TLR3. The highest diversity was observed in the wild populations of Iberian Peninsula, between 22-33 polymorphic positions. In the French population, 18 SNPs were observed and only 4 polymorphic positions were detected in the domestic breeds. 14 non-synonymous substitutions were observed, most of them in the LRR molecules. The remaining were scattered across the transmembrane and TIR domains. The study of TLR3 in European rabbit populations might be relevant to understand the interplay between RNA viruses and innate immunity. Wild rabbit populations presented more diversity than domestic breeds and other mammals previously studied. This might be linked to the absence of population bottlenecks during their evolution and to the almost inexistence of man-mediated selection. The observed variability might have also been potentiated by the contact of the wild populations with various pathogens. The study of these patterns of variability might reveal scenarios of host-pathogen interaction and identify TLR3 polymorphisms' that arose due to viral pathogens affecting wild populations.


Centrifugal enhancement of human immunodeficiency virus type 1 infection and human cytomegalovirus gene expression in human primary monocyte/macrophages in vitro.
In an effort to facilitate the efficiency of human immunodeficiency virus type 1 (HIV-1) and/or human cytomegalovirus (HCMV) infection in primary monocyte/macrophages in vitro, the effect of low-speed centrifugation was studied. The infectivity of three strains (Bal, Ada-M, and IIIB) of HIV-1 tested was significantly enhanced by centrifugal inoculation at a force of 1500g for 60 min. Reverse transcriptase activity and HIV-1 p24 antigen in primary monocyte/macrophages infected by a centrifugal inoculation technique were detectable 3-7 days earlier and were more than 10-fold greater in magnitude (at an early stage of the infection) than those of control cells infected by the conventional inoculation technique. Examination of the cells by indirect immunofluorescence revealed higher expression of HIV-1 p24 protein in the monocyte/macrophages infected by the centrifugal inoculation technique. These differences were directly related to centrifugal inoculation and were evident up to 3 weeks after infection. Enhancement was not observed when centrifugation was carried out before or after HIV-1 infection. Centrifugal inoculation of HCMV also enhanced its immediate-early and early gene expression up to 30- to 50-fold, although neither late nuclear antigens and glycoproteins of HCMV nor infectious virus was detected in HCMV-infected monocyte/macrophage cultures. These results show that centrifugal inoculation is a useful technique for improving the efficiency of HCMV and HIV-1 infection in vitro.


Homology modeling, vasorelaxant and bradykinin-potentiating activities of a novel hypotensin found in the scorpion venom from Tityus stigmurus.
In a recent work by our group involving a transcriptomics approach applied to the venom glands from Tityus stigmurus we identified a new family of peptides called Hypotensins (TSTI0006C) (Almeida et al., 2012). The cluster TSTI0006C was analyzed in the main 25 amino acid residues and named T. stigmurus Hypotensin (TistH), showing a molecular mass of 2.7 kDa, an absence of cysteines and the presence of two C-terminal proline residues, which are a bradykinin-potentiating peptide (BPP) signature. Here, we describe the homology modeling of the three-dimensional structure of TistH. In addition, we evaluated the cardiovascular effects elicited by TistH in normotensive rats. Firstly, TistH showed no cytotoxic effect on horse erythrocyte. Furthermore, in normotensive rats TistH was able to potentiate the hypotensive action of bradykinin (BK) and induced a vasorelaxant effect in mesenteric artery rings by endothelium-dependent release of nitric oxide (NO) and demonstrated independent inhibition of angiotensin converting enzyme (ACE). Our data can contribute to a better understanding of the structural and functional characteristics of TistH and suggest its potential use in cardiovascular diseases.


Responsiveness of plasma aldosterone: dependency upon basal secretory activity.
The responsiveness of plasma aldosterone levels to various stimuli was evaluated in 44 normal subjects, 17 patients with mild to moderate renal failure, 30 patients with terminal renal failure, and 13 anephric subjects. Plasma aldosterone, renin activity (PRA), cortisol, sodium, and potassium levels were measured before and after one hour of upright posture (N = 191); ACTH infusions (N = 76); and angiotensin II infusion (N = 36). Plasma aldosterone responses correlated (r greater than or equal to 0.53; p less than 0.02) with basal plasma aldosterone levels during upright posture in all four groups, with ACTH infusion in all groups except anephric subjects, and with angiotensin II administration in patients with mild to moderate renal failure or patients combined. These relationships were consistently closer than those between aldosterone responses and changes in PRA or basal PRA. However, postural aldosterone responsiveness at any given basal aldosterone level was significantly lower in patients with renal disease than in normal subjects, and this was associated with a parallel impairment in renin responsiveness. In contrast, when related to basal levels aldosterone responsiveness to ACTH or angiotensin II appreared to be comparable in normal subjects and patients with renal disease. Aldosterone responses to posture, ACTH, or angiotensin II did not correlate with associated changes in plasma cortisol, sodium, or potassium levels. These data suggest that basal adrenal secretory activity is a major factor conditioning aldosterone responsiveness to various stimuli in normal subjects as well as in patients with renal disease.


The transcriptome of NaCl-treated Limonium bicolor leaves reveals the genes controlling salt secretion of salt gland.
Limonium bicolor, a typical recretohalophyte that lives in saline environments, excretes excessive salt to the environment through epidermal salt glands to avoid salt stress. The aim of this study was to screen for L. bicolor genes involved in salt secretion by high-throughput RNA sequencing. We established the experimental procedure of salt secretion using detached mature leaves, in which the optimal salt concentration was determined as 200 mM NaCl. The detached salt secretion system combined with Illumina deep sequencing were applied. In total, 27,311 genes were annotated using an L. bicolor database, and 2040 of these genes were differentially expressed, of which 744 were up-regulated and 1260 were down-regulated with the NaCl versus the control treatment. A gene ontology enrichment analysis indicated that genes related to ion transport, vesicles, reactive oxygen species scavenging, the abscisic acid-dependent signaling pathway and transcription factors were found to be highly expressed under NaCl treatment. We found that 102 of these genes were likely to be involved in salt secretion, which was confirmed using salt-secretion mutants. The present study identifies the candidate genes in the L. bicolor salt gland that are highly associated with salt secretion. In addition, a salt-transporting pathway is presented to explain how Na(+) is excreted by the salt gland in L. bicolor. These findings will shed light on the molecular mechanism of salt secretion from the salt glands of plants.