Harmonic imaging of the brain parenchyma in a dog model following NC100100 (Sonazoid) bolus injection.
NC100100 (Sonazoid) is a new perfluorocarbon-based ultrasound contrast agent (UCA) that has not been introduced to transcranial harmonic imaging. In an animal study on 6 beagle dogs, the authors performed harmonic power Doppler and gray-scale imaging (SONOS 5500, S4 probe) after bolus injection of 2 different doses of Sonazoid. Time intensity curves for brain parenchyma, masticatory muscle, and contralateral skull were generated, and the peak increase from baseline was computed. With harmonic gray-scale imaging, a dose-dependent homogeneous increase in acoustic intensity of the brain parenchyma was observed. Evaluation of the contralateral base of the skull showed a moderate signal decrease. In harmonic power Doppler sonography, signal increase was dose dependent also, but the signal pattern was inhomogeneous, with stronger enhancement in the anterior part of the brain. The new UCA Sonazoid is suitable for displaying brain perfusion. As already observed for other UCAs, gray-scale harmonic imaging with Sonazoid leads to a more homogeneous contrast increase in cerebral parenchyma compared to harmonic power Doppler imaging. Sonazoid produces a moderate shadowing effect, with signal attenuation in the underlying deeper regions of interest.


Emergency surgical treatment of complicated acute pancreatitis after kidney transplantation with acute rejection: Case report and literature review.
Acute pancreatitis is a rare but frequently fatal complication in patients following kidney transplantation. The first case of acute pancreatitis in patients following a kidney transplant was described by Starzl in 1964. The incidence of acute pancreatitis is stated at between 1 and 5%. The mortality rate amongst these patients reaches as high as 50-100%. Here we present a case of acute pancreatic abscess in a caucasian female - shortly following a kidney transplant complicated by the development of acute rejection, in which immunosuppressant therapy is a potential etiological agent. Emergency surgical treatment was indicated, which included drainage of the abscesses irrigation of the abdominal cavity. Immunosuppressive medication was considered a possible etiological factor, and as a result administration of tacrolimus and mycophenolate mofetil was discontinued. This was successful and three months later, diagnostic rebiopsy of the graft was performed without signs of rejection. The etiology of this illness is multifactorial. The clinical manifestation of acute pancreatitis in patients following kidney transplantation is the same as in the remainder of the population. However, in patients following transplantation with long-term immunosuppression, it usually manifests a more rapid development and a more severe, frequently fatal course. With regard to the patient's comorbidities, early surgical therapy was indicated - drainage and closed lavage and immunosuppressive medication as a suspected tobe ethiological factor was discontinued. This course of treatment led to a complete recovery with preservation of good function of the cadaverous kidney.


Rate laws and kinetic modeling of N-ethyl perfluorooctane sulfonamidoethanol (N-EtFOSE) transformation by hydroxyl radical in aqueous solution.
The degradation of perfluorochemicals (PFCs) by hydroxyl radical ((·)OH) follows complex pathways resulting in stable products. Kinetic models are needed to predict the product distribution of (·)OH-initiated PFC degradation under environmental and treatment conditions. The bimolecular rate constants were measured in water for the reaction of (·)OH and N-ethyl perfluorooctane sulfonamidoethanol (N-EtFOSE), and intermediates, N-ethyl perfluorooctane sulfonamidoacetate (N-EtFOSAA), N-ethyl perfluorooctane sulfonamide (N-EtFOSA) and perfluorooctane sulfonamidoacetate (FOSAA). Under standard conditions (pH = 6, 25 ± 2 °C, Co PFC = 5-10 μg L(-1), Co H2O2 = 10 mM, irradiation intensity = 765 W m(-2)), the measured constants for N-EtFOSE, N-EtFOSAA, N-EtFOSA and FOSAA were (1.05 ± 0.12) × 10(9) M(-1) s(-1), (0.68 ± 0.05) × 10(9) M(-1) s(-1), (0.68 ± 0.05) × 10(9) M(-1) s(-1) and (0.53 ± 0.05) × 10(9) M(-1) s(-1), respectively. Constants in the pH range from 1 to 10 varied within a factor of 2-4 for most compounds. Over a period of 2-days, N-EtFOSE reacted directly (without forming long-lived intermediates) to perfluorooctane sulfonamide (FOSA) (18.8%) and perfluorooctanoic acid (PFOA) (39.1%). N-EtFOSE reacted via oxidation of the ethanolic hydroxyl group to N-EtFOSAA (12.4%) and N-dealkylation to N-EtFOSA (13.3%) and FOSAA (0.2%) and unknown intermediates. In sunlit surface waters, the (·)OH-induced transformation of N-substituted sulfonamide compounds to photostable products occurs on a time scale of days to weeks by model prediction.


Bicarbonate-dependence of responses to ethylenediamine in the guinea-pig isolated ileum: involvement of ethylenediamine-monocarbamate.
gamma-Aminobutyric-acid (GABA)-mimetic responses were induced by ethylenediamine (EDA) in the isolated ileum of the guinea-pig maintained in bicarbonate buffered Krebs-Henseleit (KBC) solution, pH 7.4, 37 degrees C, the responses consisting of a contraction followed by a relaxation. There were no such responses to EDA in bicarbonate-free phosphate buffered (KPO) or HEPES buffered (KHO) Krebs solution, gassed with 100% O2, pH 7.4, 37 degrees C, yet the ileum responded to GABA in bicarbonate-free Krebs solution. Similar GABA-mimetic responses were induced by EDA in the isolated ileum maintained in bicarbonate-free KPO or KHO modified Krebs solution, gassed with O2, if HCO3- (5mM) was first added immediately before the test dose of EDA (0.1-1 mM), the threshold [HCO3-]being 2 mM for EDA-induced responses in these preparations. However, ileal GABA-mimetic responses were induced in bicarbonate-free KPO or KHO solutions by EDA that had been pretreated with carbon dioxide, where the final [HCO3-]in the bath did not exceed 25 microM. Ethylenediamine monocarbamate (synthetic EDAC) released [3H]-GABA from preloaded segments of ileum maintained in bicarbonate-free KPO or KHO solution containing amino-oxyacetic acid and beta-alanine, the release being sensitive to 3-mercaptopropionic acid which prevents GABA release. EDA itself did not evoke any such release in the absence of bicarbonate, but released [3H]-GABA from segments maintained in KBC solution. 4 GABA-mimetic responses were induced by EDAC in the isolated ileum maintained in bicarbonate-free KPO solution, as was a delta-aminovalerate-sensitive depression of ileal twitch responses elicited by transmural stimulation, all of which were also sensitive to 3-mercaptopropionic acid. 5 It is concluded that GABA-mimetic responses to EDA in the isolated ileum of the guinea-pig, maintained in normal Krebs bicarbonate medium, result from the release of endogenous GABA by ethylenediamine monocarbamate formed through the rapid reaction of EDA with the carbon dioxide of bicarbonate buffered Krebs solution. Furthermore, in the ileum, HCO3 ions per se are not necessary for this GABA-releasing property of EDA if the latter is first converted to the monocarbamate, since syntheticethylenediamine monocarbamate elicits ileal GABA-mimetic responses in the total absence of bicarbonate.


Characterization of hawthorn pectin gained via different ethanol concentrations.
Pectin is identified as an effective delivery material due to its excellent gel-forming ability, low immunogenic properties, biocompatibility, and biodegradability. These excellent properties depend on the preparation method of pectin. In the study, four pectin fractions (named: CAHP30, CAHP40, CAHP50, and CAHP60, respectively) were obtained by different ethanol precipitations (30%, 40%, 50%, and 60%). Physicochemical properties, antioxidant activity, and emulsifying ability of HP were investigated and analyzed. Results showed that the surface structure of pectin was changed by ethanol fractional precipitation, and four fractions were low methoxy pectin. They had different monosaccharide compositions, but all rich in GalA. The Mw/Mn of CAHP30, CAHP40, CAHP50, and CAHP60 were 3.29, 2.57, 2.66, and 2.77, respectively. CAHP30 and CAHP60 had excellent emulsifying ability; moreover, CAHP60 was endowed with additional lipid antioxidant capacity and had the best thermal stability. E-CAHP40 exhibited a property between the entangled network structure. Overall, pectin with specific properties could be obtained by different ethanol concentrations.


Writing tips for authors.
Writing an article for publication may seem intimidating to you at first, but believe it or not, it can be exciting and fun. When you initially accept a writing assignment, research a clinical "gut feeling," or describe a nursing scenario, it may seem like a gargantuan task, but when you break it into small segments or steps you may be surprised how quickly you will complete your project. This article will offer some helpful hints or tips to get you started. Many of the tips will apply specifically for submission of an article to insight; absorb all clues that might be helpful and disregard anything that won't help you. Remember, you can get your article published, and the insight editorial board and peer reviewers only want to facilitate your success!


Fourteen composite probiotics alleviate type 2 diabetes through modulating gut microbiota and modifying M1/M2 phenotype macrophage in db/db mice.
Dysregulation of intestinal microbiota accelerates the development of type 2 diabetes. Probiotics are potential adjunctive therapy in the treatment of diabetes. This study investigated the anti-diabetic mechanism of 14 composite probiotics. Results showed that treatment with 14 composite probiotics improved intestinal microbiota equilibrium by increasing the population of short-chain fatty acids (SCFAs)-producing bacteria and decreasing the number of harmful bacteria. Further, the probiotics significantly improved blood glucose metabolism by promoting glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) secretion. These effects were ascribed to the activation of GPR43/41, restoration of the pancreatic structure, the elevation of insulin secretion and balancing of blood glucose-related parameters. Additionally, the 14 composite probiotics markedly restored gut barrier function via activating antioxidant enzymes, promoting tight junction protein expression, inhibiting the activity of pro-inflammatory factors and improving the morphology of the colon. Furthermore, the 14 composite probiotics upregulated M2 polarization factors and downregulated M1 polarization factors, possibly through TLRs/MyD88/NF-κB signaling pathway. These results indicate that the 14 composite probiotics can potentially improve diabetes prognosis.


Nomogram and Artificial Neural Network for Prognostic Performance on the Albumin-Bilirubin Grade for Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization.
To construct the albumin-bilirubin (ALBI) grade and the Child-Turcotte-Pugh (CTP) score based on nomograms, as well as to develop an artificial neural network (ANN) to compare the prognostic performance of the 2 scores for hepatocellular carcinoma (HCC) that has undergone transarterial chemoembolization. This multicentric retrospective study included patients with HCC who underwent transarterial chemoembolization monotherapy as an initial treatment at 4 institutions between January 2008 and December 2016. In the training cohort, significant risk factors associated with overall survival (OS) were identified by univariate and multivariate analyses. The prognostic nomograms and ANN were established and then validated in 2 validation cohorts. A total of 838 patients (548, 115, and 175 in the training cohort and validation cohorts 1 and 2, respectively) were included. The median OS was 10.4, 15.7, and 9.2 months in the training cohort and validation cohorts 1 and 2, respectively. In the training cohort, both ALBI grade and CTP score were identified as significant risk factors. The ALBI grade and CTP score based on nomograms were established separately and showed similar prognostic performance when assessed externally in validation cohorts (C-index in validation cohort 1: 0.823 vs 0.802, P = .417; in validation cohort 2: 0.716 vs 0.729, P = .793). ANN showed that ALBI grade had higher importance on survival prediction than CTP score. ALBI grade performs at least no worse than CTP score regarding survival prediction for HCC receiving transarterial chemoembolization. Considering the easy application, ALBI grade has the potential to be regarded as an alternative to CTP score.


MRI measures of neurodegeneration in multiple sclerosis: implications for disability, disease monitoring, and treatment.
Magnetic resonance imaging (MRI) techniques, such as T2-weighted and gadolinium-enhanced T1-weighted sequences, have long been used to diagnose multiple sclerosis (MS). However, these methods are limited in their ability to depict underlying disease pathology. A PubMed literature search was conducted to identify the publications discussing MRI in MS from 2010 to 2013, using the medical subject heading terms: "multiple sclerosis" and "grey/gray matter", "brain atrophy", "grey/gray matter atrophy", "normal appearing white matter," and "cortical lesions." Recent proceedings of conferences on MRI were also used to identify emerging techniques. MRI-derived metrics can assess the microstructural, metabolic, and functional changes that occur in newly formed lesions and allow further characterization of diffuse degeneration in different central nervous system compartments across MS phenotypes. Advanced imaging techniques aim to complement our understanding of MS disease pathophysiology, which may facilitate the identification of markers that could be used to predict the clinical outcomes of agents in development.


Extraction of large intracoronary thrombus in acute myocardial infarction by percutaneous Fogarty maneuver: intentional abuse of a novel interventional device.
Intracoronary thrombus in the infarct-related artery remains a challenge for interventional catheter-based techniques in acute myocardial infarction and may result in severe complications due to distal embolization. We describe a patient with acute myocardial infarction in whom a large intracoronary thrombus of the left anterior descending coronary artery was successfully removed by percutaneous Fogarty maneuver using an expanded filter protection device.


A Mathematical Method to Adjust MLC Leaf End Position for Accurate Dose Calculation in Carbon Ion Beam Radiation Therapy Treatment Planning System.
We present a mathematical method to adjust the leaf end position for dose calculation correction in the carbon ion radiation therapy treatment planning system. A straggling range algorism of 400 MeV/n carbon ion beam in nine different multileaf collimator (MLC) materials was conducted to calculate the dose 50% point to derive the offset corrections in the carbon ion treatment planning system (ciPlan). The visualized light field edge position in the treatment planning system is denoted as X tang.p, and MLC position (X mlc.p) is defined as the source to leaf end midpoint projection on axis for monitor unit calculation. The virtual source position of energy at 400 MeV/n and straggling range in MLC at different field sizes were used to calculate the dose 50% position on axis. On-axis MLC offset (correction) could then be obtained from the position corresponding to 50% of the central axis dose minus the X mlc.p. The exact MLC position in the carbon ion treatment planning system can be used as an offset to do the correction. The offset correction of pure tungsten is the smallest among the others due to its shortest straggling range of carbon ion beam in MLC. The positions of 50% dose of all MLC materials are always located in between X tang.p and X mlc.p under the largest field of 12 cm by 12 cm. MLC offset should be adjusted carefully at different field sizes in the treatment planning systems especially of its small penumbra characteristic in the carbon ion beam. It is necessary to find out the dose 50% position for adjusting MLC leaf edge on-axis location in the treatment planning system to reduce dose calculation error.


DEDICATE: proposal for a conceptual framework to develop dementia-friendly integrated eCare support.
Evidence shows that the implementation of information and communication technologies (ICT) enabled services supporting integrated dementia care represents an opportunity that faces multi-pronged challenges. First, the provision of dementia support is fragmented and often inappropriate. Second, available ICT solutions in this field do not address the full spectrum of support needs arising across an individual's whole dementia journey. Current solutions fail to harness the potential of available validated e-health services, such as telehealth and telecare, for the purposes of dementia care. Third, there is a lack of understanding of how viable business models in this field can operate. The field comprises both professional and non-professional players that interact and have roles to play in ensuring that useful technologies are developed, implemented and used. Starting from a literature review, including relevant pilot projects for ICT-based dementia care, we define the major requirements of a system able to overcome the limitations evidenced in the literature, and how this system should be integrated in the socio-technical ecosystem characterizing this disease. From here, we define the DEDICATE architecture of such a system, and the conceptual framework mapping the architecture over the requirements. We identified three macro-requirements, namely the need to overcome: deficient technology innovation, deficient service process innovation, and deficient business models innovation. The proposed architecture is a three level architecture in which the center (data layer) includes patients' and informal caregivers' preferences, memories, and other personal data relevant to sustain the dementia journey, is connected through a middleware (service layer), which guarantees core IT services and integration, to dedicated applications (application layer) to sustain dementia care (formal support services, FSS), and to existing formal care infrastructures, in order to guarantee care coordination (care coordination services, CCS). The proposed DEDICATE architecture and framework envisages a feasible means to overcome the present barriers by: (1) developing and integrating technologies that can follow the patient and the caregivers throughout the development of the condition, since the early stages in which the patient is able to build up preferences and memories will be used in the later stages to maximise personalization and thereby improve efficacy and usability (technology innovation); (2) guaranteeing the care coordination between formal and informal caregivers, and giving an active yet supported role to the latter (service innovation); and (3) integrating existing infrastructures and care models to decrease the cost of the overall care pathway, by improving system interoperability (business model innovation).


Effects of the dissolved organic matter on Cs transport in the weathered granite soil.
It is important to understand the migration of Cesium (Cs) in soils, particularly after the nuclear power plant accident at Fukushima Dai-ichi, Japan. Dissolved organic matter (DOM) is one of factors affecting the migration of Cs in soils under flowing water conditions. We investigated the effect of DOM on the migration of Cs adsorbed to the clay planar site via laboratory column experiments. The sequence of DOM application had a significant influence on Cs transport in the soil. When DOM was applied concurrently with or prior to Cs application, the DOM adsorbed on to the clay planar site adsorbed onto the soil solid surface and enhanced Cs adsorption; consequently, it slowed Cs migration in the soil. In particular, in the case of DOM loaded prior to the application of Cs solution, a noticeable delay in Cs migration was observed. On the other hand, when DOM was applied to the soil where the Cs solution had been previously applied, the DOM desorbed Cs from the soil. DOM in liquid phase enhanced the migration of Cs through the formation of binding to organic matter. Majority of Cs affected by DOM was the exchangeable fraction that adsorbed to the clay planar site. In other words, DOM attached to the soil would adsorb Cs as a easily exchangeable form and depress migration of Cs. On the other hand, DOM in the soil solution may up take adsorbed Cs from the soil and enhanced the transport in the form of Cs bound to DOM.


Relationships between human serum resistin, inflammatory markers and insulin resistance.
Data on the association of resistin levels with markers of insulin resistance are highly contrasting in humans and very few studies about its role in inflammation are available. This study investigates associations between serum resistin levels and markers of insulin resistance, inflammation (C-reactive protein (CRP)) and of oxidative stress (nytrotirosine (NT)). A randomly collected sample of 300 men from a population-based cohort was analysed, separated into two groups according to body mass index (BMI) and waist values. Correlations between resistin and BMI, waist, triglyceride, uric acid, fasting glucose, insulin and Homeostasis Model Assessment (HOMA) values were significant in subjects with normal BMI, but not in overweight/obese subjects. In a multiple regression model, after multiple adjustments and exclusion of diabetic patients, only fasting glucose remained significantly associated with resistin levels. Otherwise, resistin is associated to CRP levels in all individuals, after multiple adjustments and exclusion of diabetic patients (in normal BMI beta=0.82; 95% CI 0.21, 1.42; in overweight/obese beta=0.43; 95% CI 0.10, 0.76). In the same model, resistin values are negatively related to NT levels in normal weight individuals (beta=-1.61; 95% CI -0.77-2.45). Serum resistin is weakly associated with metabolic abnormalities in subjects with normal BMI, while in overweight/obese patients this correlation is not significant, perhaps due to the higher fat content in these subjects. Serum resistin is directly correlated with CRP and inversely to NT. An intriguing hypothesis, which needs to be tested, is that resistin is secreted in response to a chronic low-grade inflammation, and has antioxidant properties.


Psychosocial risk, symptom burden, and concerns in families affected by childhood cancer.
The revised Psychosocial Assessment Tool (PATrev) is a common family-level risk-based screening tool for pediatric oncology that has gained support for its ability to predict, at diagnosis, the degree of psychosocial support a family may require throughout the treatment trajectory. However, ongoing screening for symptoms and concerns (e.g., feeling alone, understanding treatment) remains underutilized. Resource limitations necessitate triaging and intervention based on need and risk. Given the widespread use of the PATrev, we sought to explore the association between family psychosocial risk, symptom burden (as measured by the revised Edmonton Symptom Assessment System (ESAS-r)), and concerns (as measured by the Canadian Problem Checklist (CPC)). Families (n = 87) with children ≤ 18 years of age (M = 11.72, male: 62.1%) on or off treatment for cancer were recruited from the Alberta Children's Hospital. One parent from each family completed the PATrev and the CPC. Participants 8-18 years of age completed the ESAS-r. Risk category (universal/low risk = 67.8%, targeted/intermediate risk = 26.4%, clinical/high risk = 5.7%) predicted symptom burden (F[2, 63.07] = 4.57, p = .014) and concerns (F[2, 82.06] = 16.79, p < .001), such that universal risk was associated with significantly lower symptom burden and fewer concerns. Family psychosocial risk is associated with cross-sectionally identified concerns and symptom burden, suggesting that resources might be prioritized for families with the greatest predicted need. Future research should evaluate the predictive validity of the PATrev to identify longitudinal concerns and symptom burden throughout the cancer trajectory.


Factor VIII heavy chain polypeptides in plasma and concentrates.
Factor VIII polypeptides in plasma and FVIII concentrates have been analysed by an electrophoretic technique based on that of Weinstein et al (1981). Samples were complexed with radiolabelled anti-FVIII Fab', and the immunocomplexes visualized by SDS-polyacrylamide electrophoresis. The technique visualized FVIII heavy chain polypeptides in all types of samples, including plasma, without further purification. Fresh or frozen normal plasma (collected into protease inhibitors) contained a range of polypeptides with the largest dominant band at an apparent Mr of 250-300 kDa, and the smallest at 80-90 kDa: no bands were produced from samples of severe haemophilic plasma. Cryoprecipitate had a similar polypeptide distribution to normal plasma, but intermediate purity FVIII concentrates showed more degraded patterns which varied between products: the 250-300 kDa bands were reduced or absent, the 80-90 kDa bands were more pronounced than in plasma, and in one product a polypeptide was seen at approximately 40-50 kDa. In some products heat treatment for viral inactivation increased the proportion of smaller FVIII polypeptides. Highly-purified FVIII concentrate derived from plasma was also degraded relative to plasma FVIII, and two products obtained by recombinant DNA technology both showed degraded, though slightly different, profiles. The native structure of FVIII in fresh plasma appears heterogeneous with a predominance of higher Mr forms: these are degraded to a greater or lesser extent during concentrate production, dependent on the manufacturing processes used.


Isolation and characterization of an atypical Mycoplasma gallisepticum strain showing a new mgc2 variant.
Mycoplasma gallisepticum (MG) is an important pathogen of the poultry industry able to cause chronic respiratory disease in chickens and infectious sinusitis in turkeys. Despite the application of biosecurity measures and the availability of vaccines for chickens, monitoring systems routinely applied for MG detection are still essential for infection control. Pathogen isolation is time-consuming and not suitable for rapid detection, albeit it is a compulsory step for genetic typing and antimicrobial susceptibility evaluation of single strains. The mgc2 gene is a species-specific molecular target adopted by most of the PCR protocols available for MG diagnosis, which are also included in the WOAH Terrestrial Manual. We describe the case of an atypical MG strain, isolated in 2019 from Italian turkeys, characterized by an mgc2 sequence not detectable by common endpoint PCR primers. Considering the potential risk of false negative results during diagnostic screenings with the endpoint protocol, the authors propose an alternative mgc2 PCR endpoint protocol, named MG600, which should be considered as a further diagnostic tool.


Relationship between Hand Eczema Severity and Occupational Stress: A Cross-Sectional Study.
Stress has been recently implicated as a contributing factor of hand eczema (HE) severity. However, published data are both rare and contradictory justifying the need of further research. The purpose of this study was to evaluate the relation between stress and HE severity. This is a cross-sectional study enrolling all patients who have been attending the Dermato-allergology unit of Farhat Hached University Hospital of Sousse over a period of one year. The HE severity was assessed by the Osnabrück Hand Eczema Severity Index (OHSI). The stress level was assessed by the Perceived Stress Scale-10 (PSS-10) in its validated Arabic version. During the study period, 109 participants meeting the inclusion criteria were identified. The mean age was 40 ± 9.9 years with a sex-ratio of 0.8. Severe eczema was found in 76 participants (69.7%). A high level of perceived stress was found in 18.3% of cases. A statistically significant association was noted between HE severity and the high level of perceived stress (p=0.039, OR = 4.46, 95% CI [0.96-20.59]) and the number of dependent children ≥3 (p=0.0039, OR = 1.92, 95% CI [0.51-7.22]). Leisure activity was found to be a protective factor against HE severity (p=0.031, OR = 0.27, 95% CI [0.09-0.80]). Although the link between the severity of eczema and atopy, wet work, and contact with irritants and allergens is well known, the relation remains questionable for other factors including stress.


Fermented Dessert with Whey, Ingredients from the Peel of Jabuticaba (Myrciaria cauliflora) and an Indigenous Culture of Lactobacillus plantarum: Composition, Microbial Viability, Antioxidant Capacity and Sensory Features.
The use of agro-industrial wastes in combination with indigenous lactic acid bacteria is an interesting option to confer functional potential to food products. The microbial viability, chemical composition, antioxidant capacity, texture and sensory acceptability of a fermented dairy dessert containing the indigenous culture Lactobacillus plantarum CNPC003, whey and ingredients obtained from the jabuticaba (Myrciaria cauliflora) peel were compared with formulations without lactobacilli (control) or containing a commercial probiotic culture (Lactobacillus rhamnosus LR32). L. plantarum presented viability higher than 7 log CFU g-1 in the dessert, as did the commercial probiotic, for 21 days at 4 ± 1 °C. Total phenolic contents (45⁻60 mg gallic acid equivalents, GAE, 100 g-1) were comparable to those of other studies evaluating dairy products containing plant sources. The formulations were low in fat, presenting as acceptable for overall consumption, with attractive color and appreciable texture. Considering the total antioxidant capacity, 200⁻250 g of dessert would be necessary to capture 1 g of 1,1-diphenyl-2-picrylhydrazyl (DPPH) radicals. The dessert with Lactobacillus plantarum CNPC003 is seen as a viable alternative for the use of whey and jabuticaba peel, as well as a potential functional food due to the concentration of lactobacilli reached, besides the presence of antioxidant phenolic compounds.


Antenatal and perinatal strategies to prevent mother-to-child transmission of HIV infection.
Mother-to-child transmission (MTCT) is the dominant mode of acquisition of HIV infection for children. Each day an estimated 1600 children born to HIV-infected mothers become infected, 1500 of whom are in sub-Saharan Africa. Mother-to-child transmission can occur before, during and after delivery; overall rates of MTCT range from 15 to 35%. Risk factors for MTCT include maternal viral load levels, vaginal delivery, prematurity and breastfeeding. Approaches to reduce the risk of MTCT include reduction of maternal viral load through antiretroviral prophylaxis, avoidance of exposure through birth canal cleansing or elective caesarean section delivery and refraining from breastfeeding, and boosting the host immune system through nutritional supplementation or immunization. Substantial reductions in the risk of MTCT can be achieved with antiretroviral prophylaxis during pregnancy, delivery and in the neonatal period, both in settings with and without breastfeeding. Elective caesarean section independently decreases the risk, but is not a safe and feasible option in most high prevalence areas. Birth canal cleansing with chlorhexidine does not reduce the rate overall, but may be beneficial in a subgroup of women with prolonged duration of ruptured membranes. Micronutrient supplementation, including vitamin A, does not reduce MTCT of HIV, but may improve pregnancy outcome generally.


Principles of nonexperimental assessment of excess risk, with special reference to adverse drug reactions.
The risk of a particular kind of adverse reaction to a particular agent must be thought of with reference to the contemplated type of exposure and the type of person potentially exposed, and critically important in the contemplated exposure is its duration. In the general case, a distinction has to be made between risk during exposure and that after its discontinuation. For both of these risks, modifications of their magnitudes especially by previous exposure to the same agent must be considered. These risks are studied by focusing on incidence densities specific to subintervals of the total periods of risk. Assessment of these densities is generally best accomplished by following a (very large) dynamic (open) population, not specified on the basis of exposure. Cases of the adverse event, without regard for their etiology, that occur in this source population over the period of follow-up need to be identified and classified, first as to whether they arose from the study population proper or from the extraneous segment of the source population. Those arising from the study population and characterized by "recent" exposure--implying potential causation by it--need to be classified according to the attained duration of exposure and, where applicable, time since its discontinuation at the time of the inception of the adverse event. An appropriate sample of the source population over its follow-up needs to be obtained and classified in like manner.(ABSTRACT TRUNCATED AT 250 WORDS)


Large extracellular vesicles in bovine follicular fluid inhibit the apoptosis of granulosa cell and stimulate the production of steroid hormones.
The cargo carried by extracellular vesicles (EVs) plays an important physiological role in their corresponding target organs or target tissue cells. Extracellular vesicles are classified into large extracellular vesicles (LEVs) and small extracellular vesicles (SEVs) according to their diameters. Since different subtypes contain different contents, their roles are also different. In this study, the morphology and size of LEVs were analyzed by transmission electron microscopy and nanoparticle size, and the marker proteins of LEVs (CD63, GP96, TSG101, ALB) were identified by western blot, and high-purity LEVs were obtained. Through the uptake of extracellular vesicles by purified ovarian granulosa cells and the determination of granulosa cell viability, cell apoptosis, and steroid hormone production, the result indicated that LEVs significantly enhanced cell viability (P < 0.05), reduced the rate of granulosa cell apoptosis (P < 0.05). Meanwhile, LEVs promoted the secretion of estradiol in granulosa cells (P < 0.05). This study provides a reference for the in-depth study of the function of follicular fluid extracellular vesicle subtypes and the research on the regulation of extracellular vesicles on follicle and oocyte development.


Quercetin-induced growth inhibition and cell death in prostatic carcinoma cells (PC-3) are associated with increase in p21 and hypophosphorylated retinoblastoma proteins expression.
Prostate cancer is the major health problem and the leading cause of male cancer death. Quercetin is a novel antitumor and antioxidant, whose molecular mechanism involved in cell cycle arrest in androgen independent prostate cancer cells remains unclear. In this study, we investigated the effects of quercetin on proliferation and cell cycle arrest by modulation of Cdc2/Cdk-1 protein in prostate cancer cells (PC-3). PC- 3 cells are human androgen independent cancer cells and were cultured with quercetin at concentrations of 50 and 100 microM for 24 h. Cell proliferation, apoptosis and cell cycle distribution were analyzed. Expression of Cdc2/Cdk-1, cyclin B1, cyclin A, p21/Cip1, pRb, pRb2/p130, Bcl-2, Bcl-X(L), Bax and caspase-3 proteins were studied with western blot analysis. Addition of quercetin led to substantial decrease in the expression of Cdc2/Cdk-1, cyclin B1 and phosphorylated pRb and increase in p21. Flowcytometric analysis showed that quercetin blocks G2-M transition, with significant induction of apoptosis. Apoptosis markers like Bcl-2 and Bcl-X(L) were significantly decreased and Bax and caspase-3 were increased. From this study, it was concluded that quercetin inhibits prostate cancer cell proliferation by altering the expression of cell cycle regulators and apoptotic proteins.


Neutrophil and natural killer cell imbalances prevent muscle stem cell-mediated regeneration following murine volumetric muscle loss.
Volumetric muscle loss (VML) overwhelms the innate regenerative capacity of mammalian skeletal muscle (SkM), leading to numerous disabilities and reduced quality of life. Immune cells are critical responders to muscle injury and guide tissue resident stem cell– and progenitor-mediated myogenic repair. However, how immune cell infiltration and intercellular communication networks with muscle stem cells are altered following VML and drive pathological outcomes remains underexplored. Herein, we contrast the cellular and molecular mechanisms of VML injuries that result in the fibrotic degeneration or regeneration of SkM. Following degenerative VML injuries, we observed the heightened infiltration of natural killer (NK) cells as well as the persistence of neutrophils beyond 2 wk postinjury. Functional validation of NK cells revealed an antagonistic role in neutrophil accumulation in part via inducing apoptosis and CCR1-mediated chemotaxis. The persistent infiltration of neutrophils in degenerative VML injuries was found to contribute to impairments in muscle stem cell regenerative function, which was also attenuated by transforming growth factor beta 1 (TGFβ1). Blocking TGFβ signaling reduced neutrophil accumulation and fibrosis and improved muscle-specific force. Collectively, these results enhance our understanding of immune cell–stem cell cross talk that drives regenerative dysfunction and provide further insight into possible avenues for fibrotic therapy exploration.


TRP channels and mice deficient in TRP channels.
Transient receptor potential (TRP) channels are a superfamily of functionally versatile cation-permeant ion channels present in almost all mammalian cell types. Although they were initially proposed as store-operated calcium channels, recent progress shows that they exhibit a variety of regulatory and functional themes. Here, we summarize the most salient features of TRP channels, the approaches that are providing meaningful discoveries, and the challenges ahead. We primarily emphasize the understanding gleaned from mouse models engineered to be deficient in various members of TRP superfamily and from the human patients that suffer clinically due to defects in TRP channels.


Bronchial carcinoid tumors in children and adolescents - A report and management considerations from the German MET studies.
Bronchial carcinoid tumors (BC) are exceptionally rare in childhood, with an incidence of <0.2/1,000,000 per year. Typical low-grade BCs are distinguished from atypical, intermediate-grade BCs. Little is known about BCs in pediatric patients and management guidelines are missing. In this study, we explored characteristics and outcome of pediatric patients with BC prospectively registered with the Malignant Endocrine Tumor studies. We performed a retrospective multicenter study in children, adolescents, and young adults (aged 0-20 years) with BC reported to the German MET registry between January 1997 and December 2022. Data were last updated on 28 of February 2023. Thirty-two patients were diagnosed at a median age of 15.0 years (range, 9.8-19.2). Atypical BCs (23.3%) were less frequent than typical, but more common than in adulthood. Lymph node metastases were present in 14.3% of cases (atypical BC: 28.6%, typical BC: 10.5%), distant metastases in one (3.1%) patient with atypical BC. 92.6% of patients were in complete remission after surgical resection (median follow-up: 2.7 years). The patient with metastatic spread and one patient with atypical BC and multiple recurrences were on treatment at last follow-up. 5-year event-free survival of typical BC was 100% and 83.3% in atypical BC. Completely resected localized BCs in pediatric patients have a favorable outcome also with lung tissue sparing surgery. Atypical BC with risk of metastatic spread and recurrence occurred more frequently compared to adults. Interdisciplinary management and collaborative efforts are needed to improve our understanding and the management of pediatric BC.


Prevalence of Fusarium Wilt Disease of Cucumber (Cucumis sativus Linn) in Peninsular Malaysia Caused by Fusarium oxysporum and F. solani.
Fusarium wilt disease is one of the most problematic and destructive disease in cucumber production. The causative agents are Fusarium oxysporum and F. solani. These pathogens are soil borne and transmitted through infested soil and water. A field survey was conducted to study the disease prevalence in the major growing areas of cucumber in Peninsular Malaysia. Field study revealed that the disease was highly prevalence in the field with the disease incidence was in the range of 10%-60%. The morphological properties of F. oxysporum are microconidia (3.8-15.7 μm × 2.9-4.9 μm), macroconidia (14.8-38.5 μm × 2.4-5.7 μm) and number of septate was 1-4. While for F. solani are microconidia (3.39-14.63 μm × 2.36-4.44 μm), macroconidia (7.22-50.46 μm × 2.43-6.14 μm) and number of septate was 1-5. Based on molecular identification had confirmed that the disease is caused by F. oxysporum and F. solani with similarity index of 99%-100% based on internal transcribed spacer (ITS) gene sequences. The pathogenicity test showed that the symptoms of Fusarium wilt disease was firstly appeared as yellowing of old leaves. Progressively, the infected plant will be wilted and finally died. The outputs of this study are highly important to establish an effective disease management programme to reduce disease prevalence and yield loss in the field.


Application of the 3D digital ostectomy template (DOT) in mandibular angle ostectomy (MAO).
Mandibular angle ostectomy (MAO) is a standard approach in reconstruction of facial contour that is commonly used in East Asian patients with prominent mandibular angles (PMA). MAO is commonly performed via an intraoral approach to reduce scar visibility and risk of facial nerve injury. Since this intraoral approach for MAO has limited visual guidance during the procedure, plastic surgeons often perform the operation based on personal clinical experience. Therefore, we designed a 3D digital ostectomy template (DOT) for guidance during surgery to improve the accuracy and safety of MAO. 10 female patients (average age 25.3 years) with PMA were enrolled in this study from August 2014 to October 2015. The DOTs were designed and printed preoperatively and utilized in the operation to guide the osteotomy. The excised mandibular angle bone and the DOTs were measured respective to each other. The data were analyzed to verify the feasibility and safety of the DOT. All of the patients were satisfied with the surgical results, and no complications such as fracture, hemorrhage and infection occurred. The distance from gonion (Go) along inferior margin of mandible forward to the distal end of the excised bone is "a". The distance from Go along posterior margin of ramus upward to the distal end of the excised bone is "b". The widest distance from Go to the ostectomy line is denoted by "c". Similarly, the corresponding distance in the DOT is denoted by "a'", "b'", "c'". The statistical results showed that left a vs a', b vs b', c vs c' was 63.27 ± 6.39 mm vs 62.97 ± 6.30 mm (p > 0.05), 23.98 ± 2.25 mm vs 21.83 ± 2.27 mm (p < 0.05), 13.58 ± 2.24 mm vs 13.37 ± 2.14 mm (p > 0.05), respectively. The right a vs a', b vs b', c vs c' was 62.92 ± 5.00 mm vs 62.72 ± 4.99 mm (p > 0.05), 24.03 ± 1.88 mm vs 21.80 ± 1.91 mm (p < 0.05), 13.36 ± 1.70 mm vs 13.22 ± 1.72 mm (p > 0.05), respectively. The results indicate a significant difference between b and b' both on the right and left sides. Through the application of DOT in MAO, the accuracy and safety of the operation were improved significantly. Unfortunately, the osteotomy could not be guided well in the posterior rim of the ramus. Further improvements in the surgical template are needed for application in PMA associated with oversized chin deformity or in PMA associated with large mandibular angle and severe involution.


Protective roles of the skin against infection: implication of naturally occurring human antimicrobial agents beta-defensins, cathelicidin LL-37 and lysozyme.
Beside its physical barrier against invading microorganisms, the skin has the ability to produce a number of antimicrobial peptides and proteins, including human beta-defensins, cathelicidin LL-37 and lysozyme that participate in the innate host defense. These antimicrobial agents are strongly active against a wide spectrum of various pathogens such as bacteria, viruses and fungi. Thus, antimicrobial agents are proposed to be promising candidates for innovative anti-infective drugs, and some antimicrobial peptides are currently used in clinical trials for treatment of various skin infections. In addition to their direct antimicrobial functions against invading pathogenic microorganisms, antimicrobial agents have also multiple roles as mediators of inflammation with the effects on epithelial and inflammatory cells, influencing cell proliferation, wound healing, cytokine/chemokine production and chemotaxis. This review describes the biology of these antimicrobial molecules and discusses their structure, expression and functions. Understanding the actions of antimicrobial agents in skin will provide further insight into the mechanism of innate cutaneous disease control, and yield novel therapeutic approaches to the treatment of skin disorders.


Uptake and genotoxic effects of ochratoxin A in cultured porcine urinary bladder epithelial cells.
Uptake of radiolabelled ochratoxin A (OTA) into porcine urinary bladder epithelial cells (PUBEC) was measured at neutral (pH 7.5) or acidic (pH 5.0) conditions. Genotoxicity of OTA was evaluated with the Comet assay and cytotoxicity with the neutral red uptake assay.At acidic pH-conditions, the bladder cells were able to take up more OTA than at neutral conditions. Cytotoxic effects were not increased at pH 5.0 compared to pH 7.5, but higher OTA uptake correlated with stronger genotoxic effects in the Comet assay at pH 5.0 compared to pH 7.5.These results demonstrate that uptake of OTA has to be regarded as an important factor for the toxicity of OTA as adverse effects depend on the amount of OTA taken up by the cells.


Carbon dioxide laser excision and vaporization of nonplunging ranulas: a comparison of two treatment protocols.
A carbon dioxide laser in a defocused beam was used to vaporize four ranulas and four were treated by a combination of focused beam excision of the dome and vaporization of the wall and base. There was no recurrence in any patient at 6 months and no complications were noted.


A New Family of Multilevel Grid Connected Inverters Based on Packed U Cell Topology.
In this paper a novel packed U cell (PUC) based multilevel grid connected inverter is proposed. Unlike the U cell arrangement which consists of two power switches and one capacitor, in the proposed converter topology a lower DC power supply from renewable energy resources such as photovoltaic arrays (PV) is used as a base power source. The proposed topology offers higher efficiency and lower cost using a small number of power switches and a lower DC power source which is supplied from renewable energy resources. Other capacitor voltages are extracted from the base lower DC power source using isolated DC-DC power converters. The operation principle of proposed transformerless multilevel grid connected inverter is analyzed theoretically. Operation of the proposed multilevel grid connected inverter is verified through simulation studies. An experimental prototype using STM32F407 discovery controller board is performed to verify the simulation results.


Effects of retinoic acid on the growth of cultured rabbit articular chondrocytes: Relation with alkaline phosphatase activity and beta receptor.
The effects of retinoic acid (RA) on rabbit articular cartilage cells were studied for concentrations ranging from 5.10(-5) M to 10(-7) M; the treatment with RA over three days resulted in dose dependent inhibition of chondrocyte proliferation between 5.10(-5) and 10(-5) M with persistence of the inhibitory effect until 10(-6) M. RA until 10(-7) M induced a slight, but significant, enhancement of cell proliferation. This growth stimulating effect seems to be related to the Beta receptor system because Beta blockers, such as sotalol and DL propranolol, were able to suppress the stimulating action of agonist type isoprenaline. The activity of alkaline phosphatase (AP) was also determined. The highest dose of RA (5.10(-5) M) induced an increase (x 3) of AP activity, and 10(-7) M RA decreased it (x 0.4).


Flux control coefficients determined by inhibitor titration: the design and analysis of experiments to minimize errors.
This paper is a study into the effects of experimental error on the estimated values of flux control coefficients obtained using specific inhibitors. Two possible techniques for analysing the experimental data are compared: a simple extrapolation method (the so-called graph method) and a non-linear function fitting method. For these techniques, the sources of systematic errors are identified and the effects of systematic and random errors are quantified, using both statistical analysis and numerical computation. It is shown that the graph method is very sensitive to random errors and, under all conditions studied, that the fitting method, even under conditions where the assumptions underlying the fitted function do not hold, outperformed the graph method. Possible ways of designing experiments to minimize the effects of experimental errors are analysed and discussed.


Effects of a Pre-surgery Supervised Exercise Training 1 Year After Bariatric Surgery: a Randomized Controlled Study.
We have previously reported on the benefits of Pre-Surgical Exercise Training (PreSET) on physical fitness and social interactions in subjects awaiting bariatric surgery (BS). However, data are needed to know whether these benefits are maintained post-BS. The purpose of this paper was to evaluate the effect of PreSET on physical activity (PA) level, physical fitness, PA barriers, and quality of life (QoL) 1 year (1-Y) after BS. Of the 30 participants randomized into two groups (PreSET and usual care), 25 were included in the final analysis. One year after BS, time spent in different PA intensities and number of steps were assessed with an accelerometer. Before BS and until 1-Y after BS, physical fitness was assessed with symptom-limited cardiac exercise test, 6-min walk test (6MWT), and sit-to-stand, half-squat, and arm curl tests. QoL, PA barriers, and PA level were evaluated with questionnaires. The number of steps (7460 vs 4287) and time spent in light (3.2 vs 2.2 h/day) and moderate (0.6 vs 0.3 h/day) PA were higher in the PreSET group 1-Y after BS. The changes in 6MWT heart cost (1.3 vs 0.6 m/beats/min), half-squat test (38.8 vs 10.3 s), and BMI (- 16.8 vs - 13.5 kg/m2) were significantly greater in the PreSET group compared to those in the usual care group. No other significant difference between groups was observed. The addition of the PreSET to individual lifestyle counseling seems effective to improve PA level and submaximal physical fitness 1-Y after BS. Studies with larger cohorts are now required to confirm these results. The trial was registered at clinicaltrials.gov (NCT01452230).


Citrobacter telavivum sp. nov. with chromosomal mcr-9 from hospitalized patients.
Strains 6105T and 6106, recovered from colonized patients in a hospital in Tel-Aviv, Israel, were compared with currently known species of the genus Citrobacter by a polyphasic taxonomic approach. Strains were characterized by whole-genome sequencing, 16S rRNA and recN gene sequencing, multilocus sequence analysis (MLSA), average nucleotide identity (ANI), Genome-to-Genome Distance Calculator (GGDC), and biochemical tests. The location and genetic surrounding of antibiotic resistance genes were investigated, and antibiotic susceptibility profiles were determined by broth microdilution or agar dilution methods. Phylogenetic analysis based on recN and MLSA revealed that both strains formed a distinct cluster from all currently recognized species. The ANI and GGDC were 90.7% and 54.3% with Citrobacter farmeri, respectively. The ability to metabolize various compounds also differentiated both strains from closely related Citrobacter species. Chromosomes of the isolates contained locus encoding a novel class A β-lactamase (TEL-1; 90.5% amino acid identity with CdiA of Citrobacter koseri) plus a LysR-like transcriptional regulator (TEL-R) and an ~ 25.5-kb mcr-9 mosaic region. The direct mcr-9 context matched with those previously identified in several plasmids and chromosomes of diverse Enterobacteriaceae, yet similarity with the plasmidic loci extended further. Untypeable plasmids, pCTEL-2 (~ 235 kb) and pCTEL-1 (~ 114 kb), devoid of resistance genes, were identified in the strains. The isolates were non-susceptible to β-lactams. The name Citrobacter telavivum sp. nov. is proposed, with 6105T (CECT 9989T or DSM 110286T) as the type strain. C. telavivum may represent a bacterial species adapting to hospital settings, able to disseminate and acquire antimicrobial resistance genes.


Hibernating patterns of free-ranging Columbian ground squirrels.
The patterns of torpor and euthermy during hibernation was documented for 28 free-ranging Columbian ground squirrels (Spermophilus columbianus) fitted with temperature-sensitive radio transmitter collars. Adult males began hibernation earlier, were euthermic for a greater proportion of the hibernating season and emerged earlier than other age and sex classes. The patterns of hibernation of adult females did not differ significantly from those of juveniles. Emergence from the hibernaculum was preceded by a long (3-12 d) euthermic interval in adult males but not in adult females or juveniles. Changes in soil temperature did not appear to initiate emergence. The greater time spent euthermic by adult males is interpreted as a significantly greater energy cost of hibernation for adult males than for other age and sex classes. The benefits offsetting these costs may be increased reproductive potential in spring and avoidance of predation in late summer.


Acute disseminated encephalomyelitis after dengue.
Dengue fever, transmitted by Aedes aegypti mosquitoes, is one of the most common vector-borne disease. Its incidence is increasing steadily worldwide, becoming a major public health problem in the tropical and subtropical zone. Neurological manifestations after dengue are not very common and acute disseminated encephalomyelitis (ADEM) following dengue infections is rare with a few cases documented in literature. Clinical characteristics and typical lesions of ADEM on magnetic resonance imaging (MRI) of brain along with serologic positivity for dengue usually confirm the diagnosis. We report a case of ADEM which developed as a neurological complication of dengue during an epidemic in a 39-year-old woman.


Effects of glucocorticosteroids on the skin and eye.
The dermatologic anachronistic adage, "If wet--dry it, if dry--wet it!" has bee perhaps justifiably replaced by "Call the dermatologist to prescribe a steroid!" To say this without knowledge of the contents of this article and more importantly, to accept such cliches, is a disservice to the patient and a litigious liability to the prescriber. Recognizing the risk/benefit ratio of the most commonly used anti-inflammatory agents is essential. All therapies are most effective when used for their specific diagnosis. This article attempts to provide an update on the geometrically progressing knowledge regarding the uses and misuses of GCSs for the eye and skin.


New data on the genus Derops Sharp (Coleoptera, Staphylinidae, Tachyporinae) from China with description of two new species.
Two new Chinese species of Derops are described: Derops hainanus sp. n. from Hainan and Derops yunnanus sp. n. from Yunnan. Females of Derops punctipennis Schülke and Derops schillhammeri Schülke are described for the first time and new provinces records of Derops smetanai Schülke and Derops dingshanus Watanabe are reported. The key to Chinese species of Derops published by Schülke 2003 is modified to include the new species.


Cumulative improvements of thermostability and pH-activity profile of Aspergillus niger PhyA phytase by site-directed mutagenesis.
Aspergillus niger phytase (PhyA) has been used as a feed supplement to reduce manure phosphorus excretion of swine and poultry but lacks sufficient thermostability for feed pelleting and appropriate pH-activity profile for phytate hydrolysis in the stomach of animals. Previously, a thermostable mutant PhyA18 and two pH-activity profile-improved mutants E228K and K300E were developed. In this study, the mutations were combined to determine if both improvements were cumulative. Four substitutions (S149P, F131L, K112R, and K195R) identified from random mutagenesis were added sequentially to the combined mutants to further improve their thermostability. Mutant E228K shifted the optimum pH of the parent one from 5.5 to 4.0 and increased (P < 0.05) its specific activity at pH 3.5, whereas mutant K300E eliminated the activity dip at pH 3.5 shown in the wild type. Mutant S149P further improved thermostability over PhyA18. Our results illustrate the feasibility and structural basis to improve thermostability and pH-activity profile of PhyA phytase by assembling mutations derived from rational design and random mutagenesis.


A non-invasive micronucleus assay in the rat liver.
The potent rat-liver mitogen 4-acetylaminofluorene (4AAF) is shown here to provide an effective replacement for the surgical procedure of 2/3 partial hepatectomy (2/3PH) in the in vivo rat-liver micronucleus assay described by Tates and his colleagues. This protocol modification enables the assay to be conducted on a routine basis. Control observations for both 2/3PH and 4AAF-treated rats are presented, together with evidence indicating 4AAF itself to be without activity in the assay, irrespective of the mitogenic stimulus. The activities of the rat carcinogens DMN, 2AAF, DMH and 6BT, and of the non-carcinogens 4AAF and 4N are demonstrated. Recommendations for the conduct of the modified assay are made.


Primary sooty mangabey simian immunodeficiency virus and human immunodeficiency virus type 2 nef alleles modulate cell surface expression of various human receptors and enhance viral infectivity and replication.
The nef gene of the pathogenic simian immunodeficiency virus (SIV) mac239 clone has been well characterized. Little is known, however, about the function of nef alleles derived from naturally SIVsm-infected sooty mangabeys (Cercocebus atys) and from human immunodeficiency virus type 2 (HIV-2)-infected individuals. Addressing this, we demonstrate that, similarly to the SIVmac239 nef, primary SIVsm and HIV-2 nef alleles down-modulate cell surface expression of human CD4, CD28, CD3, and class I or II major histocompatibility complex (MHC-I or MHC-II, respectively) molecules, up-regulate surface expression of the invariant chain (Ii) associated with immature MHC-II, inhibit early T-cell activation events, and enhance virion infectivity. Both also stimulate viral replication, although HIV-2 nef alleles were less active in this assay than SIVsm nef alleles. Mutational analysis showed that a dileucine-based sorting motif in the C-proximal loop of SIV or HIV-2 Nef is critical for its effects on CD4, CD28, and Ii but dispensable for down-regulation of CD3, MHC-I, and MHC-II. The C terminus of SIV and HIV-2 Nef was exclusively required for down-modulation of MHC-I, further demonstrating that analogous functions are mediated by different domains in Nef proteins derived from different groups of primate lentiviruses. Our results demonstrate that none of the eight Nef functions investigated had been newly acquired after cross-species transmission of SIVsm from naturally infected mangabeys to humans or macaques. Notably, HIV-2 and SIVsm nef alleles efficiently down-modulate CD3 and C28 surface expression and inhibit T-cell activation more efficiently than HIV-1 nef alleles. These differences in Nef function might contribute to the relatively low levels of immune activation observed in HIV-2-infected human individuals.


Sulpiride: a weak antagonist of norepinephrine and 5-hydroxytryptamine.
Antagonism of norepinephrine (NE) and 5-hydroxytryptamine (5-HT) by sulpiride was studied in vitro on rabbit aortic strips. Concentrations of sulpiride ranging from 3 X 10(-5) to 3 X 10(-3) M caused a progressive shift of the dose response curves of both NE and 5-HT to the right without inhibiting the responses to KCl. pA2 values of sulpiride calculated from Schild plots against NE and 5-HT were 4.6 and 4.4, respectively. Thus, sulpiride, which has been previously shown to be the most potent antagonist of the dopamine vascular receptors, is a very weak alpha-adrenergic or 5-HT antagonist.


[Effect of titanium substructure on color of porcelain-fused-to-titanium restoration].
To study the effect of titanium substructure on color of porcelain-fused-to-metal restoration. Standard samples of Dentsply DETREY-Carat and Tibond porcelain fused-to-metal restorations were made. Color Parameters were tested by cs-5 spectrophotometer. Statistic analysis was done and the color differences were calculated. Most of color parameters were found to be statistically significant at the P < or = 0.05 level at substructure layer. But no statistical significance existed after putting opaque and dentin porcelain. The values of color difference between two groups at opaque and dentin porcelain layers were all smaller than 1.5. Titanium substructure had no visually apparent effect on final color of porcelain-fused-to-metal restoration. There was no perceived color difference between corresponding shade of two Dentsply porcelain systems (DETREY-Carat and Tibond).


A fast and specific method to screen for intracellular amyloid inhibitors using bacterial model systems.
The aggregation of a large variety of amyloidogenic proteins is linked to the onset of devastating human disorders. Therefore, there is an urgent need for effective molecules able to modulate the aggregative properties of these polypeptides in their natural environment, in order to prevent, delay or halt the progression of such diseases. On the one hand, the complexity and cost of animal models make them inefficient at early stages of drug discovery, where large chemical libraries are usually screened. On the other hand, in vitro aggregation assays in aqueous solutions hardly reproduce (patho)physiological conditions. In this context, because the formation of insoluble aggregates in bacteria shares mechanistic and functional properties with amyloid self-assembly in higher organisms, they have emerged as a promising system to model aggregation in the cell. Here we show that bacteria provide a powerful and cost-effective system to screen for amyloid inhibitors using fluorescence spectroscopy and flow cytometry, thanks to the ability of the novel red fluorescent ProteoStat dye to detect specifically intracellular amyloid-like aggregates. We validated the approach using the Alzheimer's linked Aβ40 and Aβ42 peptides and tacrine- and huprine-based aggregation inhibitors. Overall, the present method bears the potential to replace classical in vitro anti-aggregation assays.


A synaptic learning rule for exploiting nonlinear dendritic computation.
Information processing in the brain depends on the integration of synaptic input distributed throughout neuronal dendrites. Dendritic integration is a hierarchical process, proposed to be equivalent to integration by a multilayer network, potentially endowing single neurons with substantial computational power. However, whether neurons can learn to harness dendritic properties to realize this potential is unknown. Here, we develop a learning rule from dendritic cable theory and use it to investigate the processing capacity of a detailed pyramidal neuron model. We show that computations using spatial or temporal features of synaptic input patterns can be learned, and even synergistically combined, to solve a canonical nonlinear feature-binding problem. The voltage dependence of the learning rule drives coactive synapses to engage dendritic nonlinearities, whereas spike-timing dependence shapes the time course of subthreshold potentials. Dendritic input-output relationships can therefore be flexibly tuned through synaptic plasticity, allowing optimal implementation of nonlinear functions by single neurons.


The use of feeding noises to determine the algal foods being consumed by individual intertidal molluscs.
To study the diets of individual animals in the context of intraspecific resource partitioning, it is desirable to detect what individuals are eating without disturbing them. Animals such as slow-moving molluscs on two-dimensional algal foods would be convenient to study, but the mouth is usually difficult to see, especially with limpets. However, one can often hear how an herbivorous mollusc is feeding. Even when the mouth region can be checked for feeding movement, feeding noises can indicate to what degree a mollusc is "licking" microscopic material off the surface of a plant versus biting into the plant, though licking microscopic material off the plants seems to be rare. Noises also indicate the food's texture, identifying the food species when several different algae are near the mollusc's mouth. Comparing various molluscan taxa, differences in radular structure and movement are associated with different feeding noises, even while different molluscs are eating the same alga. Sound thus aids in specifying which species are feeding where molluscs are close together.Feeding is most common on wet surfaces at night. While the molluscs are above water or less than 5 cm deep in calm water, several listening methods are useful after some practice. Even the unaided ear can hear emerged molluscs rasping resonant kelps. One can detect rasping by molluscs greater than 1 cm in length by gently contacting the alga closest to the mouth with a stethoscope or with a gum rubber tube sealed against one's ear. A cassette tape recorder with a contact microphone and headphones is useful for both emerged and submerged animals. Representative feeding noises have been documented using oscillograms from tape recordings. Analogous sounds in both terrestrial and marine environments can be useful in numerous behavioral studies.


Serum homocysteine, folate and risk of stroke: Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study.
Homocysteine and folate have been suggested to have opposite effects on the risk of stroke, although the results are controversial. The purpose of this study was to assess the effects of serum total homocysteine (tHcy) and serum folate levels on the risk of stroke in a prospective cohort study. The subjects were 1015 men aged 46-64 years and free of prior stroke, examined in 1991-1993 in the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) Study. At baseline the mean serum tHcy concentration was 10.9 micromol/l (SD 3.4). During an average follow-up time of 9.6 years, 49 men experienced a stroke, of which 34 were ischaemic. In Cox proportional hazards models, men in the highest tHcy third had a risk factor-adjusted hazard rate ratio (RR) of 2.77 [95% confidence interval (CI): 1.23-6.24] for any stroke and 2.61 (95% CI: 1.02-6.71) for ischaemic stroke, compared with men in the lowest third. The mean baseline serum folate concentration was 10.4 nmol/l (SD 4.1). Men in the highest third of serum folate (>11.2 nmol/l) had an adjusted RR for any stroke of 0.35 (95% CI: 0.14-0.87) and for ischaemic stroke of 0.40 (95% CI: 0.15-1.09), compared with men in the lowest third. Elevated serum tHcy is associated with increased risk of all strokes and ischaemic strokes in middle-aged eastern Finnish men free of prior stroke. On the other hand, high serum folate concentration may protect against stroke.


The acid phosphatase test two minute cut-off: an insufficient time to detect some semen stains.
The ability to detect semen in sexual offence cases is a crucial first step to locating stains which may be suitable for DNA profiling. Since the development of the acid phosphatase test in the late 1950s by Stuart S. Kind, the process undertaken to perform the test has gone largely unchanged. The method currently accepted by operational forensic science laboratories allows 2 min for a reaction to be obtained, and until relatively recently, this has not been challenged. In this research, samples of semen were obtained from three donors and a range of dilutions for each sample were prepared. Each dilution was subjected to acid phosphatase testing using both direct testing and the 'press test' method. The results showed that semen could be detected in excess of 15 min in dilutions up to 1 in 400 using the press test method and in dilutions up to 1 in 1000 using the direct method. Of further significance was the observation that using the press test method, the two minute cut-off was insufficient to detect the majority of stains and in some cases, semen stains as strong as 1 in 20 dilutions. This research provides compelling evidence for protocols currently utilised in forensic practice to be reviewed in order that forensic scientists do not overlook potential evidential material that may prove suitable for body fluid identification such as DNA STR profiling.


Plate-on-plate structured MoS2/Cd0.6Zn0.4S Z-scheme heterostructure with enhanced photocatalytic hydrogen production activity via hole sacrificial agent synchronously strengthen half-reactions.
The practicable technology for producing hydrogen energy was mainly photocatalytic water splitting. Recently, heterostructural photocatalysts have attracted much attention due to its unique band structures and interfacial interactions. Herein, plate-on-plate MoS2/Cd0.6Zn0.4S heterostructure was rationally designed and fabricated by a simple strategy. It was revealed that Zn-doping content in the Cd0.6Zn0.4S solid solution as well as the mass ratio of MoS2 in the MoS2/Cd0.6Zn0.4S heterostructure can significantly affect the photocatalytic hydrogen evolution reaction (HER) activity. Especially, when Zn doping content is 40 % and the mass ratio of MoS2 is approximately 0.8 % (0.8 % MoS2/Cd0.6Zn0.4S), it exhibits the highest hydrogen production (47.68 µmol·g-1 at 2.5 h) without sacrificial agents. When Na2S/Na2SO3 is employed as sacrificial agent, its HER activity reaches 13466.50 µmol·g-1·h-1, 1.3 folds higher than Cd0.6Zn0.4S. The boosted HER activity of the Z-scheme MoS2/Cd0.6Zn0.4S heterostructure was ascribed to the greatly improved separation efficiency of photogenerated carriers. Most importantly, studies have revealed that the existence of sacrificial agents (Na2S/Na2SO3) can not only accelerate the kinetics of oxidation half reaction, but also synchronously strengthen HER half-reactions. The present work reveals a facile strategy for construction of Z-scheme heterostructures for efficient hydrogen evolution via hole sacrificial agent synchronously strengthen half-reactions.


Investigation on the mechanism of H(2)S removal by biological activated carbon in a horizontal biotrickling filter.
The use of supporting media for the immobilization of microorganisms is widely known to provide a surface for microbial growth and a shelter that protects the microorganisms from inhibitory compounds. In our previous studies, activated carbon (AC) alone used as a support medium for H(2)S biological removal was proved prompt and efficient in a bench-scale biofilter and biotrickling filter. In this study, the mechanisms of H(2)S elimination using microbial immobilized activated carbon, i.e., biological activated carbon (BAC), are investigated. A series of BAC as supporting medium were taken from the inlet to outlet of a bench-scale horizontal biotrickling filter to examine the different effects of physical/chemical adsorption and microbial degradation on the overall removal of H(2)S. The surface properties of BAC together with virgin and exhausted carbon (after H(2)S breakthrough test, non-microbial immobilization) were characterized using the sorption of nitrogen (Braunner-Emmett-Teller test), scanning electron microscopy (SEM), surface pH, thermal, carbon-hydrogen-nitrogen-sulfur (CHNS) elemental and Fourier transform infrared (FTIR) analyses. Tests of porosity and surface area provide detailed information about the pore structure of BAC along the bed facilitating the understanding of potential pore blockages due to biofilm coating. A correlation between the available surface area and pore volume with the extent of microbial immobilization and H(2)S uptake is evidenced. SEM photographs show the direct carbon structure and biofilm coated on carbon surface. FTIR spectra, differential thermogravimetric curves and CHNS results indicate less diversity of H(2)S oxidation products on BAC than those previously observed on exhausted carbon from H(2)S adsorption only. The predominant oxidation product on BAC is sulfuric acid, and biofilm is believed to enhance the oxidation of H(2)S on carbon surface. The combination of biodegradation and physical adsorption of using BAC in removal of H(2)S could lead to a long-term (i.e., years) good performance of biotrickling filters and biofilters based on BAC compared to carbon adsorption only.


COVID-19 Presenting as Lupus Erythematosus-Like Syndrome.
The 2019 coronavirus disease (COVID-19) infection had newly emerged with predominant respiratory complications. Other extrapulmonary features had been recently described. Here, we describe a COVID-19 patient presenting with multiorgan involvement mimicking systemic lupus erythematosus. He was successfully treated with glucocorticoids and tocilizumab.


Regulation of the biosynthesis of acyl analogs of platelet-activating factor by purinergic agonist in endothlial cells.
We have previously shown that platelet-activating factor (PAF)-dependent transacetylase (TA) contains three catalytic activities, namely PAF: lysophospholipid TA (TAL), PAF: sphingosine TA (TAs) and PAF acetylhydrolase. It serves as a modifier of PAF actions by producing different lipid signal molecules. The TAL activity is involved in the biosynthesis of acyl analogs of PAF (acyl-PAF, 1-acyl-2-acetyl-sn-glycero-3-phosphocholine, acylacetyl-GPC) in agonist-stimulated endothelial cells. In the present investigation, we have studied the mechanism(s) by which the TA activity is regulated in ATP-treated endothelial cells. We have demonstrated that ATP, and thiol-modifying agents with ATP, specifically regulate only the TAL part of the TA activities.


Responsiveness of a neural pacemaker near the bifurcation point.
We compared the responsiveness of a neural firing pacemaker in different dynamic states during the process of period-adding bifurcation to excitatory and inhibitory electrical field stimulus. In the region far from the bifurcation point, with the increase of the intensity of excitatory stimulus, the firing rate increased in an approximately linear manner and no firing pattern transition was observed. While in the region near the bifurcation point, the firing rate increased markedly higher accompanied with the transition of firing pattern when the intensity of excitatory stimulus remained the same. The stimulus-response of the region near the bifurcation point shifted upward significantly compared to that of the region far from the bifurcation point. Inhibitory stimulus with the same intensity, however, decreased the firing rate slightly without the transition of firing pattern in the region near the bifurcation point. These results suggest that the responsiveness in the region near the bifurcation point is more sensitive than that in the region far from the bifurcation point, which we named "critical sensitivity", and this has directional selectivity.


Rasch Properties of the Cognitive and Linguistic Scale and Optimization for Outcome Trajectory Modeling in Pediatric Acquired Brain Injury.
To (1) determine if items on the Cognitive and Linguistic Scale (CALS) follow a Rasch distribution and (2) explore the relationship between Rasch-derived Cognitive Ability Estimates and outcome trajectory parameters using a nonlinear mixed-effects modeling approach. Retrospective study. Pediatric inpatient rehabilitation hospital. A total of 252 children (N=252) aged of 2-21 years (median, 11.8 [IQR, 6.4-15.9] years) consecutively admitted to an inpatient rehabilitation brain injury unit (2008-2014) for a first inpatient admission after acquired brain injury. Not applicable. Rasch-derived Cognitive Ability Estimates from the CALS and associated outcome trajectory parameters. The CALS demonstrates adequate interval-scale properties with removal of scores from the arousal and responsivity items. Rasch-derived Cognitive Ability Estimates were associated with age (β=0.025, P<.001) such that older age was associated with a faster rate of recovery and more complete ultimate recovery. Slower recovery initiation was associated with a less complete overall cognitive recovery (Spearman ρ=-0.31; P<.001). The Cognitive Ability Estimates derived from the CALS and associated outcome parameters (eg, rate of recovery) may serve as an ideal outcome measure for clinical trials evaluating interventions for acquired brain injury in a pediatric rehabilitation setting.


Pharmacokinetic interaction of brivaracetam on other antiepileptic drugs in adults with focal seizures: Pooled analysis of data from randomized clinical trials.
To assess the effect of brivaracetam (BRV) on steady-state plasma concentrations of commonly prescribed antiepileptic drugs (AEDs). Data were pooled from five randomized, double-blind, placebo-controlled efficacy studies (NCT00175929, NCT00175825, NCT00490035, NCT00464269, and NCT01261325) in which adults with refractory epilepsy, and receiving stable doses of 1-2 AEDs, initiated adjunctive treatment with BRV (or placebo) for up to 12 weeks, following a 4-8 week baseline period. Concentrations of carbamazepine, carbamazepine epoxide, clobazam, clonazepam, lacosamide, lamotrigine, levetiracetam, oxcarbazepine (MHD), phenobarbital, phenytoin, pregabalin, topiramate, valproic acid and zonisamide, were measured during baseline and during BRV or placebo evaluation periods. Log-transformed data for patients receiving BRV dosages of 50-200 mg/day (or placebo) were evaluated using repeated measures analysis of covariance. Geometric least-squares means ratios of respective AED concentrations (treatment vs baseline) and their 90% confidence intervals (CIs) were calculated. Relevant interaction of BRV on the respective AED was inferred if CIs were entirely outside of 0.80-1.25 limits. Within the population for analysis (n = 1402), relevant interaction was observed for carbamazepine epoxide alone which increased up to 2-fold from baseline due to inhibition of epoxide hydrolase by BRV, and the effect size was not influenced by concomitant valproic acid. Relevant interaction was not observed for other AEDs. In adults with focal seizures, adjunctive BRV treatment does not affect plasma concentrations of the evaluated AEDs but increases carbamazepine epoxide metabolite. Carbamazepine dose reduction should be considered if tolerability issues arise.


Determination of mifepristone levels in wild canid serum using liquid chromatography.
An HPLC method was developed to determine levels of mifepristone, in coyote (Canis latrans) serum where mifepristone will be used as an oral contragestive agent for nonlethal predator control. Serum samples were extracted using C(18) solid-phase extraction cartridges. A synthetic analog of mifepristone, RTI-3021-003, was used as the internal standard. Separation of the compounds was achieved by using a C(18) (150 x 4.6 mm) column. The mobile phase was 55% acetonitrile in water running at 1.0 ml/min with UV detection at 305 nm. The assay was linear in the range of 10 to 1000 ng/ml. Inter-day accuracies for 10, 200 and 1000 ng/ml were 95.9, 99.4 and 104.7%, respectively. Inter-day precisions measured by RSD were 19.8, 9.7 and 4.5%. Intra-day accuracies were 117, 106.9 and 99.4% for 10, 200 and 1000 ng/ml, respectively. Intra-day RSDs were 19.7, 3.7 and 9.3%, respectively. A simple, sensitive and validated HPLC analytical method was developed to quantitate mifepristone in canine serum.


Mycobacterium avium subsp. paratuberculosis, genetic susceptibility to Crohn's disease, and Sardinians: the way ahead.
The present study was performed to determine what proportion of people in Sardinia with or without Crohn's disease were infected with Mycobacterium avium subspecies paratuberculosis and had a preponderance of allelic variants of Nod 2, an intracellular protein involved in Crohn's disease susceptibility. Genetic analysis of the alleles of the NOD 2/CARD 15 gene (ins C 3020, G 908 R, and R 702 W alleles), linked to susceptibility or genetic predisposition to Crohn's disease in humans, was carried out on specimens from 37 Crohn's disease patients and 34 patients without Crohn's disease. Our results show that more than 70 percent of people in Sardinia with Crohn's disease carry at least one of the susceptibility-associated NOD 2/CARD 15 alleles and were infected with Mycobacterium avium subspecies paratuberculosis.


Modulation of adenovirus infection in vitro by antisense oligodeoxynucleotides.
Antisense oligodeoxynucleotides (ODNs) may represent a novel, airway directed approach to the treatment of adenovirus infection of the lung, for which no specific therapy exists. This study assessed the efficacy of antisense ODNs in modulating adenovirus infection in vitro. A biological assay, which quantified viral plaque formation by wild type adenovirus 5 in a lung epithelial cell line (A549), was used to evaluate the inhibitory effect of a number of antisense ODNs targeted to the early (E) 1 A and protein IX genes of adenovirus 5. Antisense ODNs (20-21mers, phosphorothioate end-protected) were designed to straddle the initiation of translation (AUG) codon of the mRNA of the targeted gene. There was a consistent and significant (P < 0.005) reduction in viral plaque formation in those cells treated with an E1A antisense ODN, compared with the nonsense control ODN. Neither the addition of a cationic lipid (Lipofectamine), nor increasing the concentration of ODN from 1 micro mol to 15 micro mol enhanced the original inhibitory effect observed with the E1A antisense ODN. An antisense ODN targeted to the E1A gene can specifically inhibit adenovirus 5 infection in vitro, suggesting a potential therapeutic role for antisense ODNs in adenovirus infection of the lung.


White matter abnormalities are related to microstructural changes in preterm neonates at term-equivalent age: a diffusion tensor imaging and probabilistic tractography study.
Preterm infants have a high risk of brain injury and neurodevelopmental impairment, often associated with WMA on conventional MR imaging. DTI can provide insight into white matter microstructure. The aim of this study was to investigate the association between WMA on conventional MR imaging and DTI parameters in specific fibers in preterm neonates at term-equivalent age. Seventy preterm neonates (39 boys and 31 girls) were included in the study. WMA were classified as no, mild, moderate, or severe. Probabilistic tractography provided tract volumes, FA, MD, λ(//), and λ(⊥) in the CST, SLF, TRs, and corpus callosum. Data were compared by using MANOVA, and adjustment for multiple comparisons was performed. Important associations were found between WMA and microstructural changes. Compared with neonates with no WMA (n = 41), those with mild WMA (n = 27) had significantly increased λ(⊥) and MD in the left ATR, the left sensory STR, the bilateral motor STR, and for λ(⊥) also in the right CST; FA decreased significantly in the left sensory STR. Diminished tract volumes and altered diffusion indices were also observed in the 2 neonates with moderate WMA. Altered DTI indices in specific tracts, with λ(⊥) as most prominent, are associated with mild WMA in preterm neonates at term-equivalent age.


Comparative in vivo forefoot kinematics of Homo sapiens and Pan paniscus.
The human metatarsophalangeal joints play a key role in weight transmission and propulsion during bipedal gait, but at present, the identification of when a habitual, human-like metatarsi-fulcrimating mechanism first appeared in the fossil record is debated. Part of this debate can be attributed to the absence of certain detailed quantitative data distinguishing human and great ape forefoot form and function. The aim of this study is to quantitatively test previous observations that human metatarsophalangeal joints exhibit greater amounts of dorsal excursion (i.e., dorsiflexion) than those of Pan at the terminal stance phase of terrestrial locomotion. Video recordings were made in order to measure sagittal excursions of the medial metatarsophalangeal joints in habitually shod/unshod adult humans and adult bonobos (Pan paniscus). Results indicate that the human first and second metatarsophalangeal joints usually dorsiflex more than those of bonobos. When timing of maximum excursion of the first metatarsophalangeal joint is coupled with existing plantar pressure data, the unique role of the human forefoot as a key site of leverage and weight transmission is highlighted. These results support hypotheses that significant joint functional differences between great apes and humans during gait underlie taxonomic distinctions in trabecular bone architecture of the forefoot.


The motor system estimates uncertainty and higher order statistics for the control of grip forces.
Successful manipulation of an object requires exerting grip forces (GF) sufficient to prevent slippage. To prevent slip in more uncertain environments, GF would need to increase. Here we investigate the brain's ability to efficiently control grasp by producing GFs that correspond to confidence estimates of uncertain environments that are characterized by probability density functions of different variances and higher order moments. We found that GFs increased dramatically with the level of environmental uncertainty, and even when environmental uncertainty was held constant while higher order moments were varied, GFs changes in a way that was appropriate for kurtosis.


Human leucocyte urokinase inhibitor--purification, characterization and comparative studies against different plasminogen activators.
A plasminogen activator inhibitor (PA-I) which inhibits primarily plasminogen activator of the urokinase type (u-PA) was isolated from the cytosol of human peripheral leukocytes. The inhibitor was isolated using ion exchange chromatography, gel filtration and FPLC. This inhibitor has an apparent molecular weight of 45 kDa, determined by SDS-PAGE, and a pI of 5.5-5.7. The inhibitor is a fast reacting inhibitor, is thermally unstable and is inactivated outside the pH range 7-9. Treatment of cytosol to pH 9 for 30 min at 37 degrees C resulted in a large increase in inhibitory activity. Antibodies against human placental UK-I completely quenched the inhibitory activity of human leucocyte UK-I.


Artificial Intelligence Bias in Health Care: Web-Based Survey.
Resources are increasingly spent on artificial intelligence (AI) solutions for medical applications aiming to improve diagnosis, treatment, and prevention of diseases. While the need for transparency and reduction of bias in data and algorithm development has been addressed in past studies, little is known about the knowledge and perception of bias among AI developers. This study's objective was to survey AI specialists in health care to investigate developers' perceptions of bias in AI algorithms for health care applications and their awareness and use of preventative measures. A web-based survey was provided in both German and English language, comprising a maximum of 41 questions using branching logic within the REDCap web application. Only the results of participants with experience in the field of medical AI applications and complete questionnaires were included for analysis. Demographic data, technical expertise, and perceptions of fairness, as well as knowledge of biases in AI, were analyzed, and variations among gender, age, and work environment were assessed. A total of 151 AI specialists completed the web-based survey. The median age was 30 (IQR 26-39) years, and 67% (101/151) of respondents were male. One-third rated their AI development projects as fair (47/151, 31%) or moderately fair (51/151, 34%), 12% (18/151) reported their AI to be barely fair, and 1% (2/151) not fair at all. One participant identifying as diverse rated AI developments as barely fair, and among the 2 undefined gender participants, AI developments were rated as barely fair or moderately fair, respectively. Reasons for biases selected by respondents were lack of fair data (90/132, 68%), guidelines or recommendations (65/132, 49%), or knowledge (60/132, 45%). Half of the respondents worked with image data (83/151, 55%) from 1 center only (76/151, 50%), and 35% (53/151) worked with national data exclusively. This study shows that the perception of biases in AI overall is moderately fair. Gender minorities did not once rate their AI development as fair or very fair. Therefore, further studies need to focus on minorities and women and their perceptions of AI. The results highlight the need to strengthen knowledge about bias in AI and provide guidelines on preventing biases in AI health care applications.


[Repair of defects in the Achilles tendon with the peroneus brevis muscle (author's transl)].
The authors report a dynamic plastic repair of the Achilles tendon in cases of neglected rupture: The peroneus brevis muscle is used to bridge the gap. The muscle remains intact at the proximal end, its tendon is dissected immediately above its insertion, then pulled through the calcaneus by a bore-hole and fastened to itself and to the ends of the Achilles tendon. If a plantaris tendon exists, it may be used to strengthen the defect by resecting it as far as possible proximally and then fanning it out to cover the gap. The distal end of the peroneus brevis tendon is sutured side-by-side to the peroneus longus tendon. This technique was first applied in 1968. During the last 5 years 8 patients underwent repair of the Achilles tendon by this method at the Department of Orthopaedic Surgery at the University of Kiel. In all cases the results obtained were good or excellent. The patients were very content and returned to a comparable level of preoperative activity. They were able to go as well on tip-toes as on the heels, though dorsal extension in several cases was slightly restricted. Calf atrophy up to 3 cm was found in several cases, which, however, was due partly to preoperational influences. In two cases wound healing complications occured without disturbing the functional results. The authors can recommend their technique, which seems to be superior to other methods especially in difficult cases with large gaps and unfavourably anatomic conditions.


Effect of gentamicin lavage of the axillary surgical bed after lymph node dissection on drainage discharge volume.
The purpose of this study was to evaluate the effect of axillary lavage with a gentamicin solution before wound closure on drainage volume. A prospective, randomized study was performed. Inclusion criteria were a diagnosis of breast neoplasms and plans to undergo an elective axillary lymph node dissection due to axillary metastasis. The patients were randomized into 2 groups: patients undergoing 2 lavages with 500 ml normal saline (Group 1) and patients first undergoing lavage with 500 ml normal saline followed by a second lavage with a 500 ml of a gentamicin (240 mg) solution (Group 2). Microbiological samples were obtained before any lavage, after each lavage and at the time of drain removal. 40 patients were included. Mean number of days maintaining the drain in place was 7.7 ± 3.2 days in Group 1 and 4.3 ± 1.4 days in Group 2 (p = 0.001). Total drainage volume before removal was 465 ± 250.9 ml in Group 1 and 169 ± 102.2 ml in Group 2 (p = 0.003). After a second lavage with normal saline in Group 1 and after a lavage with gentamicin solution in Group 2, microbiological culture was positive in 10 patients (50%) in Group 1 and 1 case (5%) in Group 2 (p = 0.016). Positive cultures were associated with higher drainage volumes. The postoperative drainage volume of the axillary drain is significantly lower in the patients undergoing a lavage of the surgical bed with a gentamicin solution than in the control group undergoing a lavage with normal saline. A significant reduction in the contamination is only obtained after a lavage with gentamicin solution. NCT01700504.


An improved assay for the detection of interleukin 1.
A 24 h, highly sensitive assay for detection of interleukin 1 (IL-1) is described. A thioguanine-resistant mutant of the murine lymphoma cell line LBRM 33 was selected (LBRM TG6). When this cell line was incubated with low concentrations of PHA and IL-1 it produced interleukin 2 (IL-2). IL-2-dependent HT2 cells were co-cultured with the LBRM cells to measure the released IL-2. Prior to addition of tritiated thymidine to the co-culture, hypoxanthine and azaserine were added to metabolically block DNA synthesis by LBRM TG6 cells. This resulted in a sensitive, short term assay requiring minimal technical manipulations and characterized by a high signal to noise ratio.


Effects of premature depolarization on refractoriness of ischemic canine myocardium.
In 25 pentobarbital anesthetized dogs we measured refractory periods (RPs) of regularly driven complexes and premature ventricular depolarizations (PVDs) with a range of coupling intervals or of regularly driven complexes and the complex following the PVD, i.e. the postextrasystolic depolarization (PED). Measurements were made during control periods and during occlusion of a branch of the left anterior descending coronary artery. The difference in control and occlusion RPs was less following some PVDs with short coupling intervals than following other PVDs with longer coupling intervals. Variations in the coupling interval of PVDs had less effect on RPs of the PVDs in ischemic than in nonischemic tissue. RPs of PEDs were prolonged with respect to RPs of regularly driven complexes in both ischemic and nonischemic tissue, but the prolongation in ischemic tissue was significantly greater than that in nonischemic tissue, 8 +/- 4 msec and 2 +/- 2 msec respectively, p less than .001. The difference in effect of PVDs on RPs of ischemic and nonischemic tissue results in greater disparity of refractoriness between ischemic and nonischemic tissue following some long coupling interval PVDs than following some PVDs with shorter coupling intervals. In addition the greater prolongation of RPs of PEDs in ischemic than in nonischemic tissue can result in increased disparity in RPs than the disparity between ischemic and nonischemic tissue present during regular drive.


Insights into the behavior of unsaturated diacylglycerols in mixed lipid bilayers in relation to protein kinase C activation-A molecular dynamics simulation study.
The lipid second messenger diacylglycerol (DAG) is known for its involvement in many types of cellular signaling, especially as an endogenous agonist for protein kinase C (PKC). Evidence has emerged that the degree of saturation of the DAG molecules can affect PKC activation. DAG molecules with different acyl chain saturation have not only been observed to induce varying extents of PKC activation, but also to express selectivity towards different PKC isozymes. Both qualities are important for precise therapeutic activation of PKC; understanding DAG behavior at the molecular level in different environments has much potential in the development of drugs to target PKC. We used molecular dynamics simulations to study the behavior of two different unsaturated DAG species in lipid environments with varying degrees of unsaturation. We focus on phosphatidylethanolamine (PE) instead of phosphatidylcholine (PC) to more accurately model the relevant biomembranes. The effect of cholesterol (CHOL) on these systems was also explored. We found that both high level of unsaturation in the acyl chains of the DAG species and presence of CHOL in the surrounding membrane increase DAG molecule availability at the lipid-water interface. This can partially explain the previously observed differences in PKC activation strength and specificity, the complete mechanism is, however, likely to be more complex. Our simulations coupled with the current understanding of lipids highlight the need for more simulations of biologically accurate lipid environments in order to determine the correct correlations between molecular mechanisms and biological behavior when studying PKC activation.


Role of Drugs Used for Chronic Disease Management on Susceptibility and Severity of COVID-19: A Large Case-Control Study.
This study aimed to investigate whether specific medications used in the treatment chronic diseases affected either the development and/ or severity of coronavirus disease 2019 (COVID-19) in a cohort of 610 COVID-19 cases and 48,667 population-based controls from Zhejiang, China. Using a cohort of 578 COVID-19 cases and 48,667 population-based controls from Zhejiang, China, we tested the role of usage of cardiovascular, antidiabetic, and other medications on risk and severity of COVID-19. Analyses were adjusted for age, sex, and body mass index and for presence of relevant comorbidities. Individuals with hypertension taking calcium channel blockers had significantly increased risk (odds ratio (OR) = 1.73, 95% confidence interval (CI) 1.2-2.3) of manifesting symptoms of COVID-19, whereas those taking angiotensin receptor blockers and diuretics had significantly lower disease risk (OR = 0.22, 95% CI 0.15-0.30 and OR = 0.30, 95% CI 0.19-0.58, respectively). Among those with type 2 diabetes, dipeptidyl peptidase-4 inhibitors (OR = 6.02, 95% CI 2.3-15.5) and insulin (OR = 2.71, 95% CI 1.6-5.5) were more and glucosidase inhibitors were less prevalent (OR = 0.11, 95% CI 0.1-0.3) among with patients with COVID-19. Drugs used in the treatment of hypertension and diabetes influence the risk of development of COVID-19, but, not its severity.