'Pawing' uncertainty! how dogs attenuate the impact of daily hassles at work on uncertainty.
This study relied on the integrative model of uncertainty tolerance to delineate an argument proposing that daily hassles trigger uncertainty, and this influences adaptive performance. Furthermore, relying on the "furr-recovery method" -where interactions with dogs allow dog owners to recover from negative situations or job demands - this study tested whether having a dog would moderate the relationship between daily hassles and uncertainty. To test this proposed model, daily data during ten working days was gathered with a sample of white-collar workers who were teleworking (N = 233 × 10 = 2,330). Multilevel results showed that daily hassles influenced adaptive performance via perceived uncertainty. However, the relationship between daily hassles and uncertainty was conditional on the ownership of a dog, in such a way that the relationship became weaker for those who had dogs. That is, those who did not have dogs had increased levels of uncertainty after daily hassles when compared to those who had dogs. Managers may consider the adoption of pet-friendly work practices (for instance, telework - working from home allow employees to work nearby and interact with their dogs during worktime) as dogs appear to have a beneficial effect to help employees effectively cope with daily hassles and reduce their uncertain reactions. This study advances knowledge regarding the pawing-effect (the reduced uncertainty to daily hassles on dog owners) on employees' uncertainty to daily hassles and opens new venues for research regarding their role in work-related outcomes. Further, future research could examine how human-dog interactions or the quality of their relationship may benefit owners and explore the benefits of bringing dogs to work periodically.


Towards health-based nano reference values (HNRVs) for occupational exposure: Recommendations from an expert panel.
Unique physicochemical characteristics of engineered nanomaterials (ENMs) suggest the need for nanomaterial-specific occupational exposure limits (OELs). Setting these limits remains a challenge. Therefore, the aim of this study was to set out a framework to evaluate the feasibility of deriving advisory health-based occupational limit values for groups of ENMs, based on scientific knowledge. We have used an expert panel approach to address three questions: 1) What ENM-categories should be distinguished to derive advisory health-based occupational limit values (or health-based Nano Reference Values, HNRVs) for groups of ENMs? 2) What evidence would be needed to define values for these categories? And 3) How much effort would it take to achieve this? The panel experts distinguished six possible categories of HNRVs: A) WHO-fiber-like high aspect ratio ENMs (HARNs), B) Non-WHO-fiber-like HARNs and other non-spheroidal ENMs, C) readily soluble spheroidal ENMs, D) biopersistent spheroidal ENMs with unknown toxicity, E) biopersistent spheroidal ENMs with substance-specific toxicity and F) biopersistent spheroidal ENMs with relatively low substance-specific toxicity. For category A, the WHO-fiber-like HARNs, agreement was reached on criteria defining this category and the approach of using health-based risk estimates for asbestos to derive the HNRV. For category B, a quite heterogeneous category, more toxicity data are needed to set an HNRV. For category C, readily soluble spheroidal ENMs, using the OEL of their molecular or ionic counterpart would be a good starting point. For the biopersistent ENMs with unknown toxicity, HNRVs cannot be applied as case-by-case testing is required. For the other biopersistent ENMs in category E and F, we make several recommendations that can facilitate the derivation of these HNRVs. The proposed categories and recommendations as outlined by this expert panel can serve as a reference point for derivation of HNRVs when health-based OELs for ENMs are not yet available.


Positive node-ratio in curative-intent treatment for gastric cancer is a strong independent prognostic factor for 5-year overall survival.
This study addressed whether the positive node-ratio (N-ratio) for patients who underwent curative-intent treatment was an independent prognostic factor of overall survival (OS) for gastric adenocarcinoma (GA). Consecutive patients who underwent gastrectomy for GA with at least 15 harvested nodes were evaluated for 5-year OS. The best threshold was determined using the area under an receiver operating characteristic (ROC) curve. Univariate and multivariate models were assessed looking for independent prognostic factors for OS. From 1994 to 2015, 398 consecutive patients were evaluated. The N-ratio ≥11% had an accuracy of 0.764, the sensitivity of 71.1%, the specificity of 81.7%, positive predictive value (PPV) of 91.7%, and odds ratio (OR) of 11. After multivariate analysis for OS, age ≥70 years (HR 1.44), need for total gastrectomy (HR 1.45), need for extended resection (HR 1.7), and N-ratio ≥11% (HR 3.7) were unfavorable prognostic factors. D2 lymphadenectomy (HR 0.53) was a protective factor. The median OS according to N-ratio was 14 months for N-ratio >11 vs 58 months for N-ratio <11%. The N-ratio ≥11% was an independent negative prognostic factor for patients who underwent treatment for GA with curative intent. The N-ratio ≥11% presented high specificity, high PPV and high OR for risk of death for 5 years after surgery.


Outcome of hepatitis C-related liver transplantation in direct-acting antiviral era.
Hepatitis C virus (HCV) has become an easily treatable disease after the introduction of sofosbuvir-based direct-acting antiviral (DAA) regimens. This is a large single center experience of changing severity and outcome profile of HCV-related liver disease after availability of DAAs. A retrospective analysis of prospectively collected liver transplantation (LT) database of adults (age > 18 years at the time of LT) was performed from June 2010 to July 2018. A total of 410 patients (including 26 co-infection with hepatitis B) underwent LT for hepatitis C-related decompensated cirrhosis and/or hepatocellular carcinoma (HCC) out of 1754 adult transplantation in the defined period. The study group comprised of 296 males and 114 females aged 52.1 ± 7.9 years. HCV-related decompensated cirrhosis and/or HCC as indication of LT was present in 289/1016 (28.4%) during 2010-2014, which was reduced to 121/738 (16.3%) during 2015-2018 (p = 0.000). The LT recipients for HCV-related cirrhosis had significantly lower Child's and model for end-stage liver disease (MELD) score during 2015-2018 as compared to that during 2010-2014; Child's score was 7.9 ± 2.2 vs. 8.6 ± 2.1, p = 0.003; MELD score was 13.9 ± 5.3 vs. 17.1 ± 5.8, p = 0.000, respectively. There was a trend towards better survival in HCV patients during 2015-2018 as compared to that during 2010-2014. Significantly more patients had HCV RNA negative status before LT during 2015-2018 (38.8% vs. 13%, p = 0.000); moreover, the proportion of LT for decompensated cirrhosis (without HCC) decreased significantly in the latter period, 64.0% vs. 42.1% (p = 0.000). In the DAA era, HCV as an indication for LT has decreased and patients have less severe disease at transplantation. There is a trend towards better patient survival.


Chemical composition and sensory properties of Albariño wine: Fertigation effects.
Interannual climate variability and management practices, including fertigation, can alter volatile compound concentrations in wines from a given grapevine cultivar. These compounds are highly relevant for wine aroma. The current study aimed to assess the effect of two levels of fertigation on the volatile composition and sensory properties of wines from Albariño grown in two vineyards in NW Spain over three years. Treatments were fertigation to 60% (F-60) and 100% (F-100) of crop needs since budbreak, and a rain-fed control (F-0). Volatile compounds were determined through gas chromatography and mass spectrometry (GC-MS) and wine sensory evaluation was performed by nine experts using quantitative descriptive analysis. General chemical parameters of wines were similar among treatments; however, F-60 and F-0 slightly reduced volatile total concentrations in both vineyards. Wines from the fertigation treatments had greater concentrations of volatile fatty acids, ethyl esters, acetates and C6 compounds. However, terpene concentrations slightly decreased when fertigation was applied. Higher alcohols showed a different behavior between vineyards, mainly related with grapevine water status during the growing season. Seven sensory descriptors differed significantly between vineyards. This study indicates that fertigation could be a tool for modulating wine chemical and sensory characteristics.


Neuroanatomical tracing by use of Phaseolus vulgaris-leucoagglutinin (PHA-L): electron microscopy of PHA-L-filled neuronal somata, dendrites, axons and axon terminals.
Following iontophoretic application of the plant lectin Phaseolus vulgaris-leucoagglutinin (PHA-L) to brain areas of rats, and subsequent immunohistochemistry, reaction product can be observed with the light microscope to fill neurons completely, including their somata, dendrites, dendritic appendages and axons. Moreover, axons often show profuse collateralization and indications of termination, including numerous en passant and terminal varicosities. The present report describes a protocol for combining light microscopic examination of PHA-L-stained neurons and electron microscopy of details of their processes, including the axonal varicosities. The results support the hypothesis that axonal varicosities are the light microscopic representations of synaptic axon terminals seen in electron microscopic preparations.


Professor Raj Suryanarayanan: Scientist, Educator, Mentor, Family Man and Giant in Pharmaceutical Research.
This special edition of the Journal of Pharmaceutical Sciences is dedicated to Professor Raj Suryanarayanan (Professor and William & Mildred Peters Endowed Chair, University of Minnesota, School of Pharmacy) and honors his extensive and distinguished career as a scientist, educator and mentor. The goal of this commentary is to provide an overview of Professor Suryanarayanan's noteworthy career path and summarize his key research contributions. The commentary concludes with the personal summaries by guest editors.


Impact of Initial Emotional States and Self-Efficacy Changes on Nursing Students' Practical Skills Performance in Simulation-Based Education.
Training through simulation has shown to increase relevant and specific skills sets across a wide range of areas in nursing and related professions. Increasing skills has a reciprocal relation to the development of self-efficacy. A study was conducted to assess changes in the development of self-efficacy in simulation training for 2nd year nursing students. Initial emotional states, pre and post self-efficacy, and expert ratings of simulation performance were assessed. Results show that students who displayed an increase in self-efficacy as a result of simulation training were also judged to perform better by expert ratings. The effect of simulation on self-efficacy could be influenced by initial states of physiological activation and over control. Results also showed that initial emotional states did not moderate self-efficacy development on outcome measures. These findings improve our understanding on the relationship between students' self-efficacy and performance of practical skills and inform pedagogical designs and targeted interventions in relation to feedback and supervision in nursing education.


Budd-Chiari syndrome associated with oral contraceptive steroids. Review of treatment of 47 cases.
Oral contraceptive steroids (OCS) have been implicated as the cause of a number of instances of hepatic vein thrombosis (Budd-Chiari syndrome). Survival appears to be related to early diagnosis and treatment, but there does not appear to be a consensus as to the most appropriate management of these patients. Portosystemic shunting has frequently been advocated, although the results have been quite variable. Some patients appear to do well with conservative measures only. In the effort to obtain a clearer understanding of the effects of different medical and surgical therapies in this disorder, we analyzed the treatment of 47 cases associated with OCS, 29 of which were found in the literature and 18 additional cases identified through a questionnaire survey mailed to members of the AASLD. Surgery had been performed in 27 of these 47 patients (57%); 17 patients had been treated medically (36%); two individuals had received unspecified treatment, and one patient died before any treatment could be initiated. In the surgical group 13 patients underwent portosystemic shunt surgery with six surviving up to 5 years. Two patients survived more than 15 months following orthotopic liver transplant and one patient is well after partial hepatectomy. Of 10 patients who underwent exploratory laparotomy (three with the intent to perform a shunt), seven died postoperatively. Mean survival for the surgically treated group was 19.4 months (range 10 days to 7 years). Of those patients treated medically with combinations of diuretics, anticoagulants, antiplatelet agents, fibrinolytic agents, and peritoneovenous shunts to control ascites, 11 (65%) have survived from 3 months to 6 years (mean survival 29.0 months). We conclude that a satisfactory response may accompany either medical or surgical management of patients with Budd-Chiari syndrome associated with OCS. Patients with severe occlusive disease may benefit most from surgical decompression of the hepatic veins. However, for those with mild to moderate disease, the proper role for operative intervention remains to be defined.


Wave I of early auditory evoked potentials in multiple sclerosis.
Early auditory evoked potentials (EAEPs) were recorded in a series of 71 consecutively examined patients suffering from clinically definite or probable multiple sclerosis (MS). Wave I abnormalities, i.e., delayed latency, with or without reduced amplitude, were observed in 15 such patients and were interpreted as due to MS in 8 of them. As EAEP wave I is identical with the potential N1 in electrocochleography and corresponds to activity of the most distal part of the acoustic nerve or the spiral ganglion, it is concluded that the peripheral part of the acoustic nerve is involved in about 10% of MS patients. In two cases normalization of initially delayed wave I latencies were demonstrated during follow-up recording. The pattern of a late wave I but normal hearing in 3 patients is interpreted in terms of a desynchronized compound nerve activity with fully preserved conductivity, segmental demyelination of a considerable number of acoustic nerve fibres being the most likely cause.


Salivary gland involvement in rheumatoid arthritis and its relationship to induced oxidative stress.
The objective of the present study was to analyse salivary gland and free radical involvement in rheumatoid arthritis (RA). Thirty-four consenting RA patients (rheumatoid factor-positive) and 18 healthy controls, matched in age and gender, participated in the study. Plasma and saliva samples were harvested and subjected to compositional analysis and various free radical-related tests. The mean salivary flow rate was lower in the RA patients than in the control group, whereas all plasma and salivary antioxidants were increased. Mean values of plasma malondialdehyde and ceruloplasmin were higher in the RA patients. The effects of RA on salivary gland flow rates and antioxidant compositional parameters may be of great importance for the further elucidation of the role of free radicals in RA pathogenesis and for its general diagnosis and evaluation. The demonstrated correlation between the altered salivary parameters and the severity of the disease may indicate that evaluation of the salivary status of RA patients is warranted.


CaMKK2 facilitates Golgi-associated vesicle trafficking to sustain cancer cell proliferation.
Calcium/calmodulin-dependent protein kinase kinase 2 (CaMKK2) regulates cell and whole-body metabolism and supports tumorigenesis. The cellular impacts of perturbing CAMKK2 expression are, however, not yet fully characterised. By knocking down CAMKK2 levels, we have identified a number of significant subcellular changes indicative of perturbations in vesicle trafficking within the endomembrane compartment. To determine how they might contribute to effects on cell proliferation, we have used proteomics to identify Gemin4 as a direct interactor, capable of binding CAMKK2 and COPI subunits. Prompted by this, we confirmed that CAMKK2 knockdown leads to concomitant and significant reductions in δ-COP protein. Using imaging, we show that CAMKK2 knockdown leads to Golgi expansion, the induction of ER stress, abortive autophagy and impaired lysosomal acidification. All are phenotypes of COPI depletion. Based on our findings, we hypothesise that CAMKK2 sustains cell proliferation in large part through effects on organelle integrity and membrane trafficking.


Cellular O-Glycome Reporter/Amplification to explore O-glycans of living cells.
Protein O-glycosylation has key roles in many biological processes, but the repertoire of O-glycans synthesized by cells is difficult to determine. Here we describe an approach termed Cellular O-Glycome Reporter/Amplification (CORA), a sensitive method used to amplify and profile mucin-type O-glycans synthesized by living cells. Cells convert added peracetylated benzyl-α-N-acetylgalactosamine to a large variety of modified O-glycan derivatives that are secreted from cells, allowing for easy purification for analysis by HPLC and mass spectrometry (MS). Relative to conventional O-glycan analyses, CORA resulted in an ∼100-1,000-fold increase in sensitivity and identified a more complex repertoire of O-glycans in more than a dozen cell types from Homo sapiens and Mus musculus. Furthermore, when coupled with computational modeling, CORA can be used for predictions about the diversity of the human O-glycome and offers new opportunities to identify novel glycan biomarkers for human diseases.


Mitotic and meiotic instability of the CAG trinucleotide repeat in spinocerebellar ataxia type 1.
Spinocerebellar ataxia type 1 (SCA1) is an autosomal, dominantly inherited neurodegenerative disease caused by an unstable CAG trinucleotide repeat expansion in the ataxin-1 gene located on chromosome 6p22-p23. The expanded CAG repeat is unstable during transmission, and a variation in the CAG repeat length has been found in different tissues, including sperm samples from affected males. In order further to examine the mitotic and meiotic instability of the (CAG)n stretch we have performed single sperm and low-copy genome analysis in SCA1 patients and asymptomatic carriers. A pronounced variation in the size of the expanded allele was found in sperm cells and peripheral blood leucocytes, with a higher degree of instability seen in the sperm cells, where an allele with 50 repeat units was contracted in 11.8%, further expanded in 63.5% and unchanged in 24.6% of the single sperm analysed. We found a low instability of the normal alleles; the normal alleles from the individuals carrying a CAG repeat expansion were significantly more unstable than the normal alleles from the control individuals (P<0.001), indicating an interallelic interaction between the expanded and the normal alleles.


Inflammatory consequences of lung ischemia-reperfusion injury and low-pressure ventilation.
Lung ischemia-reperfusion injury (LIRI) is a clinical problem observed during thoracic surgery, and adversely affects patient recovery. A better understanding of the mechanisms of LIRI could be helpful to develop new therapeutic strategies. The objective was to assess the inflammatory and apoptotic consequences of LIRI using an in vivo rat model. The left lung of Sprague-Dawley rats was subjected to ischemia for 120 min and reperfusion for up to 4 h. Ventilated controls underwent sham surgery and low-pressure mechanical ventilation for the above mentioned time points. Lung tissue was analyzed for histopathology and for the expression of inflammatory and apoptotic mediators. Low-pressure ventilated controls showed a clear increase in myeloperoxidase activity, macrophage inflammatory protein-2, interleukin-6, and caspase-3 expression compared with naïve animals. However, LIRI animals showed faster kinetics of pulmonal myeloperoxidase activity and caspase-3 expression. Moreover, only LIRI animals showed increased inducible nitric oxide synthase and interleukin-6 expression and had a decreased interleukin-10 expression in the lung compared to ventilated controls. Furthermore, lungs of LIRI animals contained much more cellular infiltrates compared with ventilated controls. Low-pressure mechanical ventilation induces an inflammatory response in the lung, but LIRI accelerates the kinetics of granulocyte infiltration and apoptosis. Moreover, LIRI skews the cytokine balance to a pro-inflammatory profile. Finally, LIRI deteriorates lung histology much more than ventilation only.


Effect of ultrasonic waves on the stability of all-trans lutein and its degradation kinetics.
Ultrasound treatment has been widely applied in the extraction of biologically active compounds including carotenoids. However, there are few reports on their effects on the stability of these compounds. In the present study, the stability of all-trans lutein, one of the carotenoids, was investigated under the action of ultrasound. Results showed that ultrasound induced the isomerization of all-trans lutein to its isomers, namely to 13-cis lutein, 13'-cis lutein, 9-cis lutein and 9'-cis lutein as analyzed by HPLC coupled with DAD and LC-MS; and the percentage of the isomerization increased with increasing both ultrasonic frequency and power. The stability of all-trans lutein in dichloromethane was worst among multiple kinds of solvents. Interestingly, the retention rate of all-trans lutein improved as the temperature increased, which runs counter to the Arrhenius law. Under ultrasound irradiation, the degradation mechanism might be different with various temperatures, the degradation of all-trans lutein followed first-order kinetics at 20°C, while second-order kinetics was followed at 30-50°C. As the ultrasonic reaction time prolonged, lutein epoxidation nearly occurred. Those results presented here emphasized that UAE techniques should be carefully used in the extraction of all-trans lutein.


Intravascular large B-cell lymphoma presenting with fulminant pseudomembranous colitis.
Intravascular large B-cell lymphoma is a rare entity that usually presents in late stages with non-specific symptoms. We present a case of an incidentally discovered intravascular large B-cell lymphoma in a 78-year-old man who underwent colectomy for medically refractory pseudomembranous colitis. The malignant lymphocytes were preferentially localized to small colonic submucosal vasculature, without any evidence of an extravascular tumor mass. The gastrointestinal system is an exceeding rare initial diagnostic site for intravascular lymphoma, and presentation with pseudomembranous colitis has not been previously reported. We discuss the current definition of intravascular lymphoma, clinicopathological variants, differential diagnoses, as well as current therapy.


Thresholds for postprandial hyperglycemia and hypertriglyceridemia associated with increased mortality risk in type 2 diabetes patients: A real-world longitudinal study.
To identify thresholds for postprandial hyperglycemia and hypertriglyceridemia predictive of all-cause mortality in patients with type 2 diabetes. A total of 1,928 patients with type 2 diabetes visited our clinic for the first time from 1995 to 1999 and were followed up for ≥1 year. During the first year, 2-h post-breakfast blood glucose (2h-BG) levels were measured in 1,122 patients (BG cohort) and postprandial serum triglyceride (ppTG) levels were measured in 1,826 patients (TG cohort). Patients were retrospectively followed until 2017 and administered questionnaires. Associations between 2h-BG and ppTG levels and mortality risk were assessed by the multivariate Cox regression analysis. Over of 17,429 person-years, 162 deaths occurred in the BG cohort, and over 28,026 person-years, 253 deaths occurred in the TG cohort. Hazard ratios (HRs) with 95% confidence intervals for all-cause mortality per 1-standard deviation increases in 2h-BG and ppTG were 1.34 (1.08-1.67) and 1.24 (1.06-1.45), respectively. HRs showed increasing trends across quintiles of 2h-BG (P = 0.034) and ppTG (P = 0.007). The HR was significantly elevated (2.37, 1.26-4.47) in the fifth quintile of 2h-BG (≥13.8 mmol/L) compared with the first quintile (<7.0 mmol/L; P = 0.008). The HR was also significantly elevated (1.63, 1.03-2.60) in the fifth quintile of ppTG (≥2.30 mmol/L) compared with the first quintile (<0.91 mmol/L; P = 0.038). Postprandial hyperglycemia and hypertriglyceridemia were associated with all-cause mortality in patients with type 2 diabetes. We propose thresholds of 13.8 mmol/L 2h-BG and 2.30 mmol/L ppTG to identify patients at increased risk of mortality.


Heartburn treated with tapwater.
A very simple and effective method against heartburn (Hb) is described; it consists in drinking 1-2 glasses of tapwater. A larger scale trial of the method is also recommended against heartburn during the first trimester of pregnancy and possibly against peptic ulcer.


Cellular, molecular, and genetic substrates underlying the impact of nicotine on learning.
Addiction is a chronic disorder marked by long-lasting maladaptive changes in behavior and in reward system function. However, the factors that contribute to the behavioral and biological changes that occur with addiction are complex and go beyond reward. Addiction involves changes in cognitive control and the development of disruptive drug-stimuli associations that can drive behavior. A reason for the strong influence drugs of abuse can exert on cognition may be the striking overlap between the neurobiological substrates of addiction and of learning and memory, especially areas involved in declarative memory. Declarative memories are critically involved in the formation of autobiographical memories, and the ability of drugs of abuse to alter these memories could be particularly detrimental. A key structure in this memory system is the hippocampus, which is critically involved in binding multimodal stimuli together to form complex long-term memories. While all drugs of abuse can alter hippocampal function, this review focuses on nicotine. Addiction to tobacco products is insidious, with the majority of smokers wanting to quit; yet the majority of those that attempt to quit fail. Nicotine addiction is associated with the presence of drug-context and drug-cue associations that trigger drug seeking behavior and altered cognition during periods of abstinence, which contributes to relapse. This suggests that understanding the effects of nicotine on learning and memory will advance understanding and potentially facilitate treating nicotine addiction. The following sections examine: (1) how the effects of nicotine on hippocampus-dependent learning change as nicotine administration transitions from acute to chronic and then to withdrawal from chronic treatment and the potential impact of these changes on addiction, (2) how nicotine usurps the cellular mechanisms of synaptic plasticity, (3) the physiological changes in the hippocampus that may contribute to nicotine withdrawal deficits in learning, and (4) the role of genetics and developmental stage (i.e., adolescence) in these effects.


Implicit mechanisms of intention.
High-level cortical regions encode motor decisions before or even absent awareness, suggesting that neural processes predetermine behavior before conscious choice. Such early neural encoding challenges popular conceptions of human agency. It also raises fundamental questions for brain-machine interfaces (BMIs) that traditionally assume that neural activity reflects the user's conscious intentions. Here, we study the timing of human posterior parietal cortex single-neuron activity recorded from implanted microelectrode arrays relative to the explicit urge to initiate movement. Participants were free to choose when to move, whether to move, and what to move, and they retrospectively reported the time they felt the urge to move. We replicate prior studies by showing that posterior parietal cortex (PPC) neural activity sharply rises hundreds of milliseconds before the reported urge. However, we find that this "preconscious" activity is part of a dynamic neural population response that initiates much earlier, when the participant first chooses to perform the task. Together with details of neural timing, our results suggest that PPC encodes an internal model of the motor planning network that transforms high-level task objectives into appropriate motor behavior. These new data challenge traditional interpretations of early neural activity and offer a more holistic perspective on the interplay between choice, behavior, and their neural underpinnings. Our results have important implications for translating BMIs into more complex real-world environments. We find that early neural dynamics are sufficient to drive BMI movements before the participant intends to initiate movement. Appropriate algorithms ensure that BMI movements align with the subject's awareness of choice.


Multiple organ toxicity of Datura stramonium seed extracts.
Datura stramonium seed ranks top among major plants commonly abused as drug in Nigeria. The present study therefore sought to unravel the target organs of toxicity as well as underscore the role of extraction solvent in the toxicity of Datura stramonium seed. Twenty male Wistar rats were randomly placed into four groups (I-IV) of five animals per group. Group I served as the control and was administered with distilled water only, while groups II, III and IV animals received 50 mg/kg body weight of aqueous, methanolic and diethylether extracts of Datura stramonium seeds by oral gavage for 14 days. Specific biomarkers of toxicity such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and lipid peroxidation (MDA) were estimated in the liver, brain, kidney and heart homogenates as well as serum of experimental animals. Lipid profile and activity of antioxidant enzymes such as superoxide (SOD) and catalase were determined in selected tissues while creatinine and urea were estimated in the kidney and serum. Results indicated that Datura stramonium seed extract generally caused a significant decrease in ALT, AST, ALP and MDA in selected tissue homogenates while these parameters increased significantly in the serum relative to the control group. Lipid profile was significantly deranged across selected tissues while SOD and catalase activity were significantly decreased relative to control. Put together, toxicity of Datura stramonium seed extract is diverse depending on the organ involved and solvent used for its extraction. Therefore, illicit use of Datura stramonium seeds as drugs among young people should be discouraged.


Solitary bone cyst of the jaws: a review of the etiopathogenic hypotheses.
Solitary bone cysts (SBCs) of the jaws are often polymorphic, show scalloped borders when located between the teeth roots, are devoid of an epithelial lining, and are usually empty or contain blood or a straw-colored fluid. The numerous synonyms referring to these lesions reflect their uncertain nature (eg, traumatic bone cyst, simple bone cyst). SBC, also found in other skeletal locations, is often suspected after epidemiologic and radiologic test results and confirmed at surgery. Histology usually shows fibrous connective tissue or only bone. The various etiologic elements responsible for SBC include tumor degeneration, trauma, or abnormalities during bone growth. The pathogenesis of the SBC is unknown, but it is widely accepted that it could be the result of a vascular dysfunction leading to a local posthemorrhagic ischemia, inducing an osseous aseptic necrosis. This article reviews likely but still-debated etiopathogenic hypotheses of lesions of the jaws and other, more frequent bony locations, such as the humeral and femoral metaphysis.


Expression of human erythropoietin transgenes and of the endogenous WAP gene in the mammary gland of transgenic rabbits during gestation and lactation.
An understanding of the expression of transgenes in the mammary gland during gestation and lactation is crucial for the use of transgenic mammals as bioreactors. Here we describe the temporal pattern of expression of the endogenous rabbit WAP gene and human erythropoietin (hEPO) transgenes under the control of rabbit WAP promoter and 3' flanking sequences. The endogenous rabbit WAP gene was expressed throughout gestation including the day of mating, as well as during lactation in transgenic rabbits bearing a minigene construct. In non-pregnant cycling females, WAP expression was found independent of transgenic status; however, WAP expression was not detected in non-cycling females. The significance of this new finding is not clear at present. hEPO mRNA was detected in mammary gland biopsies from pregnant transgenic rabbits only on day 28 of gestation. During lactation, transcripts were present in mammary gland biopsy samples taken on days 0, 7, 14 and 21. A sharp decline in the levels of transcripts was found for an hEPOcDNA gene construct at the end of lactation (day 28). Although the levels of hEPO were too low to allow a conclusion to be drawn regarding temporal or position-dependent expression, this finding may reflect an integration position effect.


The Impact of Exercise On Depression and Anxiety Symptoms Among Abstinent Methamphetamine-Dependent Individuals in A Residential Treatment Setting.
This paper reports data from a study designed to determine the impact of an 8-week exercise program on depression and anxiety symptoms among newly abstinent methamphetamine (MA)-dependent individuals in residential treatment. One hundred thirty-five MA-dependent individuals, newly enrolled in residential treatment, were randomly assigned to receive either a 3-times-per-week, 60-minute structured exercise program for 8 weeks (24 sessions) or an equivalent number of health education sessions. Using mixed-modeling repeated-measures regression, we examined changes in weekly total depression and anxiety scores as measured by the Beck Depression Inventory and Beck Anxiety Inventory over the 8-week study period. Mean age of participants was 31.7 (SD = 6.9); 70.4% were male and 48% Latino. Analyses indicate a significant effect of exercise on reducing depression (β = -0.63, P = 0.001) and anxiety (β = -0.95, P=0.001) symptoms (total scores) over the 8-week period compared to a health education control group. A significant dose interaction effect between session attendance and exercise was found as well on reducing depression (β = -0.61, P < 0.001) and anxiety symptoms (β = -0.22, P=0.009) over time compared to the control group. Results support the role of a structured exercise program as an effective intervention for improving symptoms of depression and anxiety associated with MA abstinence.


Quantification of the drawing of an Archimedes spiral through the analysis of its digitized picture.
We have developed a new quantitative analysis of spiral drawing that is able to evaluate any spiral execution and it has not temporal or spatial limitations in the obtaining of specimens. Thirty-one patients with action tremor and 24 control subjects were asked to draw an Archimedes spiral over a print template. Specimens were scanned and then treated through a semiautomatic computer program that reconstructs the temporal sequence of the spiral drawing by the subject. The spirals were first analysed by means of the cross-correlation coefficient with the spiral template. Secondly, the mean and the standard deviation of the distance between each point of the spiral drawing and the corresponding point of the spiral model were determined. Finally, the reconstructed spiral was analysed using the Fourier Transform. Its results were interpreted with the aid of a computer model of a tremulous spiral. The experimental variables were greater in the patients group respect to age-matched controls. There was also a high linear correlation between them and the clinical score given by three neurologists. Finally, Receiver Operating Characteristic (ROC) curves analysis shown that the method classified the spirals better than human ratters.


T serotyping of group a streptococcus isolated from patients with pharyngitis or streptococcal toxic shock syndrome in Japan between 2005 and 2017.
Streptococcus pyogenes (group A streptococcus; GAS) is an important gram-positive human pathogen capable of causing diseases ranging from mild superficial skin and pharyngeal infections to more severe invasive diseases, including streptococcal toxic shock syndrome (STSS). GAS produces a T protein, and T serotyping has considerable discriminatory power for epidemiological characterization of GAS. To clarify the relationship between STSS and pharyngitis in Japan, we examined the T serotypes of GAS strains isolated from clinical specimens of streptococcal infections (STSS, 951 isolates; pharyngitis, 16268 isolates) from 2005 to 2017. The most prevalent T serotype from pharyngitis isolates was T12, followed by T1, T4, and TB3264. The most prevalent T serotype from STSS isolates was T1, followed by TB3264. Trend of increase and decrease in the frequency of T1 or TB3264 isolation from pharyngitis was correlated with that of STSS patients. The increase of T1 or TB3264 strain-infection in pharyngitis patients may increase the probability of causing STSS, indicating that careful monitoring of GAS serotypes is essential for the prediction of rapid increase of STSS in time to develop effective management strategies.


Mieap-induced accumulation of lysosomes within mitochondria (MALM) regulates gastric cancer cell invasion under hypoxia by suppressing reactive oxygen species accumulation.
Mitochondrial quality control (MQC) protects against potentially damaging events, such as excessive generation of mitochondrial reactive oxygen species (mtROS). We investigated the contribution of the two major MQC processes, namely, mitophagy and Mieap-induced accumulation of lysosomes within mitochondria (MALM), to the response to hypoxia of two human gastric cancer (GC) cell lines. We found that hypoxia increased mtROS generation and cell invasion in 58As9, but not in MKN45, although the transcription factor hypoxia-inducible factor 1α was induced in both cell lines. Colocalisation of lysosomes with mitochondria was found only in hypoxic MKN45 cells, suggesting that hypoxia-induced MQC functions normally in MKN45 but may be impaired in 58As9. Hypoxia did not lead to decreased mitochondrial mass or DNA or altered appearance of autophagosomes, as judged by electron microscopy, suggesting that mitophagy was not induced in either cell line. However, western blot analysis revealed the presence of the MALM-associated proteins Mieap, BNIP3 and BNIP3L, and the lysosomal protein cathepsin D in the mitochondrial fraction of MKN45 cells under hypoxia. Finally, Mieap knockdown in MKN45 cells resulted in increased mtROS accumulation and cell invasion under hypoxia. Our results suggest that hypoxia-induced MALM suppresses GC cell invasion by preventing mtROS generation.


[A study of factors affecting the efficiency of electrofusion of enucleated eggs and cell-donors of nuclei].
We studied the capacity of rabbit oocytes for electrofusion with morula blastomeres and fetal fibroblasts. The morula blastomeres fused with aging ooplasts more readily than the fetal fibroblasts: 92.9 versus 63.0%, p < 0.001. The fetal fibroblasts fused with young enucleated oocytes more efficiently than with the aging ones: 98.4 versus 63.0%, p < 0.001. Serum starvation of the fetal fibroblasts in DMEM medium for 7-14 days reduced their capacity for fusion with young ooplasts, as compared to that after starvation for 0-4 days: 67.2 versus 98.9%, p < 0.01). The increased time of "starvation" in an "impoverished" medium reduced the capacity of fetal fibroblasts with aging ooplasts as compared to the fibroblasts cultivated in the full medium and in the "impoverished" medium for one or two days: 64.5 versus 37.4%, p < 0.01. Hence, the efficiency of the fusion of the oocytes with nuclear donor cells depends on the age of the recipient oocyte, the origin of nuclear donor cells, and the conditions of cultivation.


A non-adrenergic nerve ending containing small granular vesicles in the guinea-pig gut.
Two distinct types of small granular vesicle(SGV)-containing nerve ending are described in the gastrointestinal tract of the guinea-pig. One of these types of ending accumulates 5- and 6-hydroxydopamine (OHDA) and is therefore adrenergic. The other type remains unchanged after in vivo exposure to these drugs. The widespread distribution of this nerve in the smooth muscle layers of the large and small bowel suggests that it may play a role in gut motility.


A Six-Year Longitudinal Study of Consumption of Pornographic Materials in Chinese Adolescents in Hong Kong.
Using longitudinal data collected over 6 years, consumption of pornographic materials in adolescents in Hong Kong and the related demographic and psychosocial correlates were examined in this study. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: A longitudinal research design with 6 waves of data was used to examine consumption of pornographic materials in high school students. A total of 3291 high school students from 28 schools responded to the questionnaire at wave 1. Consumption of online pornography was higher than traditional pornography. There was an increase in consumption of pornographic materials in the high school years. Gender, family functioning, and positive youth development were related to the initial status of pornography consumption. Besides, gender, family intactness and positive youth development predicted rates of change in consumption of pornographic material over time. The present findings showed that gender, family functioning, and positive youth development are significant predictors for pornography consumption in Chinese adolescents.


Surgical management of necrotising enterocolitis in Sweden: A national cohort study.
Necrotising enterocolitis (NEC) is the dominating surgical emergency in preterm neonates. The aims were to investigate indications, surgical management and mortality for surgically treated neonates with NEC. Data were retrieved from the Swedish Neonatal Quality Register for Swedish neonates with surgically treated NEC from 1 January 2017 to 31 December 2021. Diagnosis was validated by surgical records and histopathology. Neonates with isolated spontaneous intestinal perforation were excluded. In total, 109 neonates were included. Median gestational age was 25 weeks (22-38), and median birth weight was 771 g (269-3920). Preoperative pneumoperitoneum was found in 32%, portal venous gas in 25% and clinical deterioration on conservative treatment in 26% of the neonates. Among the 97 neonates presenting with small bowel necrosis, single-focal NEC occurred in 38 (39%), multifocal NEC in 35 (36%) and panintestinal NEC in 24 (25%). A primary anastomosis was performed in 10/87 (11%) of the neonates with bowel resection at primary surgery. Clip-and-drop technique was applied in 24/87 (28%).Mortality rate was 37%. Mortality was well comparable with earlier reports considering exclusion of spontaneous intestinal perforation (SIP) and the low gestational age of the study population. Resection of necrotic bowel with stoma formation was the dominating surgical method.


Cumulative impact of high job demands, low job control and high job insecurity on midlife depression and anxiety: a prospective cohort study of Australian employees.
There is a lack of evidence concerning the prospective effect of cumulative exposure to psychosocial job stressors over time on mental ill-health. This study aimed to assess whether cumulative exposure to poor quality jobs places employees at risk of future common mental disorder. Data were from the Personality and Total Health Through Life project (n=1279, age 40-46 at baseline). Data reported on the cumulative exposure to multiple indicators of poor psychosocial job quality over time (ie, a combination of low control, high demands and high insecurity) and future common mental disorder (ie, depressive and/or anxiety symptom scores above a validated threshold) 12 years later. Data were analysed using logistic regression models and controlled for potential confounders across the lifespan. Cumulative exposure to poor-quality work (particularly more secure work) on multiple occasions elevated the risk of subsequent common mental disorder, independent of social, health, verbal intelligence and personality trait confounders (OR=1.30, 95% CI 1.06 to 1.59). Our findings show that cumulative exposure to poor psychosocial job quality over time independently predicts future common mental disorder-supporting the need for workplace interventions to prevent repeated exposure of poor quality work.


[Fresh bipolar osteochondral allograft of the ankle. Review of the literature and case report of a young patient with bilateral post-traumatic osteoarthritis].
The treatment of severe post-traumatic ankle arthritis remains a challenge nowadays. Since patients suffering from this pathology are mainly young and active people, a correct reconstruction, if possible, of the articular cartilage defects of the tibiotalar joint is very important to achieve a good result. Fresh bipolar osteochondral allograft (FBOA) is a promising operative technique, as an alternative to arthrodesis and total ankle replacement, in pain relief, restoration of function and indefinite delay of arthritic disease progression. The authors made a review of the literature and present a case report of a young 30 years-old man, with bilateral post-traumatic osteoarthritis of the ankle, treated with (FBOA). The patient was evaluated clinically and radiographically monthly. Pain relief and postoperative function was significantly improved reaching 94 points in the left ankle (preoperative of 40 points), and 92 points in the right ankle (preoperative 42 points) AOFAS score. Fresh tibiotalar allografting seems to be a good alternative to arthrodesis and prosthetic replacement, in the treatment of ankle arthropathy and big articular cartilage defects mainly in young and active patients. This procedure achieves a good pain relief, maintaining functional joint motion and decreasing the risk of adjacent joint arthritis.


Association between iron-folic acid supplementation and pregnancy-induced hypertension among pregnant women in public hospitals, Wolaita Sodo, Ethiopia 2021: a case- control study.
Pregnancy-induced hypertension is the new onset of high blood pressure after 20 weeks of gestation in women with previously normal blood pressure. To the best of our knowledge, no study has been conducted in our country to investigate the association between this pregnancy problem and iron-folic acid supplementation. The aim of this study was to determine the association between iron-folic acid supplementation and pregnancy-induced hypertension (PIH) in pregnant women at public hospitals in the Wolaita Sodo zone. An institution-based case-control study was conducted among pregnant women who visited public hospitals in the Wolaita Sodo zone from March 3, 2022, to August 30, 2022. A consecutive sampling method was used to select the study participants. The total sample size was 492, of which 164 were cases and 328 were controls. The data were collected by conducting face-to-face interviews and measurements. The data were entered into EpiData version 4.6 and exported to STATA 14 for analysis. Those variables with a p-value less than 0.05 were considered statistically significant. Descriptive statistics and odds ratios were presented using texts, tables, and figures. A total of 471 women participated in this study, yielding a response rate of 96%. The cases had a mean age of 25 ± 4.43, while the controls had a mean age of 25 ± 3.99. The mean age at first pregnancy among cases was 20 ± 2.82 and among controls was 20 ± 2.97. The average number of deliveries for cases and controls was 1.97 ± 1.41 and 1.95 ± 1.38, respectively. There is no significant association between iron-folic acid supplementation and PIH. Pregnant women with high hemoglobin levels had higher odds of PIH as compared to those without it (AOR = 3.65; 95% CI: 1.0-12.9). Eating kocho (AOR = 14.4; 95% CI: 1.2-16.7) was positively associated with PIH. There is no association between iron-folic acid supplementation during pregnancy and pregnancy-induced hypertension. Pregnant women with high hemoglobin levels had higher odds of PIH as compared to those without it. There is an association between kocho consumption and PIH. More research should be done using stronger designs.


The determination of smoking types: evidence for a sociological-pharmacological continuum.
The Horn-Waingrow smoking typology was partially replicated in a sample of college women. Findings from regression analyses, using the types as dependent variables and the smoking behavior of parents and peers, age, the age smoking begun regularly, frequency and amount of smoking as independent variables, supported the notion of a sociological-pharmacological continuum underlying the types. Zero-order correlation of quitting influence factors with the types suggested different strategies for cessation based on the types and indicated the usefulness of the type concept.


WITHDRAWN: Ethno-botanical survey and ecological study of anti-pathogenic organisms medicinal plants species used in the Congolese folk medicine.
This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.


Immune response induced in vitro by CD16- and CD16+ monocyte-derived dendritic cells in patients with metastatic renal cell carcinoma treated with dendritic cell vaccines.
Monocyte-derived dendritic cells (mDC) are increasingly used as cancer vaccines. However, human monocytes are a heterogeneous cell population. We showed previously that DC derived from a monocyte subset expressing CD16 (16+mDC) stimulated allogeneic naïve T lymphocytes to secrete higher levels of IL-4 than DC derived from regular CD14(high)CD16(-) monocytes (16-mDC). Th1-type responses have been associated with effective antitumor responses, thus the use of mDC containing 16+mDC as cancer vaccines might be disadvantageous. Here, we evaluate the primary and memory immune response elicited in vitro by 16+mDC and 16-mDC in five patients with metastatic renal cell carcinoma vaccinated with autologous mDC pulsed with tumor lysates (TuLy) and keyhole limpet hemocyanin (KLH). After therapy, three of the five patients had stable disease. Surprisingly, patients with longer survival showed the highest amount of peripheral blood CD16+ monocytes. Analysis of KLH-specific antibodies revealed high titers of IgG2 in patients with longer survival. CD4+ T lymphocyte proliferation against KLH and TuLy increased after treatment, and some patients showed an augmented rate of CD4+ T lymphocyte proliferation against KLH (3/5) and TuLy (2/3) when 16+mDC were used as antigen presenting cells (APC). Before treatment, the IFN-gamma/IL-4 ratio against TuLy and KLH was higher when using 16-mDC as APC, but after vaccination four of five patients had an increased ratio for TuLy with 16+mDC. These results suggest that the immune response elicited by 16-mDC and 16+mDC is modified when memory or naïve T cells are stimulated, and 16+mDC could favor a stronger and more beneficial antitumoral Th1 memory response in vivo.


Magnitude of rate of change in kidney function and future risk of cardiovascular events.
Using a community-based cohort we sought to investigate the association between change in estimated glomerular filtration rate (eGFR) and risk of incident cardiovascular disease including congestive heart failure (CHF), acute myocardial infarction (AMI), and stroke. We identified 479,126 adults without a history of cardiovascular disease who had at least 3 outpatient eGFR measurements over a 4 year period in Alberta, Canada. Change in eGFR was estimated as the absolute annual rate of change (categorized as ≤-5, -4, -3, -2, -1, 0, 1, 2, 3, 4, and ≥5 mL/min/1.73 m2/year). In a sensitivity analysis we also estimated change as the annual percentage change (categorized as ≤-7, -6 to -5, -4 to -3, -2 to -1, 0, 1 to 2, 3 to 4, 5 to 6, and ≥7%/year). The adjusted risk of incident CHF, AMI, and stroke associated with each category of change in eGFR was estimated, using no change in eGFR as the reference, There were 2622 (0.6%) CHF, 3463 (0.7%) AMI, and 2768 (0.6%) stroke events over a median follow-up of 2.5 years. Compared to participants with stable eGFR, those with the greatest decline (≤-5 mL/min/1.73 m2/year) had more than a two-fold increased risk of CHF (HR 2.57; 95% CI: 2.28 to 2.89). Risk for AMI and stroke was increased by 31% and 29%, respectively. After adjusting for the last eGFR at the end of the accrual period, the observed association remained significantly higher for CHF but diminished for AMI and stroke. A similar pattern was observed when change in eGFR was quantified as annual percentage change. In this large community-based cohort, we observed that a declining eGFR was associated with an increased risk of CHF, AMI, and stroke. However, when the risk of CVD events was adjusted for the last eGFR measurement, decline in eGFR per se was no longer associated with increased risk of AMI or stroke, and the association with CHF remained significant but was attenuated. These results demonstrate the importance of monitoring change in eGFR over time to improve cardiovascular risk prognostication.


[A direct current amplifier for measuring eye saccades].
For testing saccadic eye movements three methods are used today: the coil-, the infrared- and the electrode-method. All of these techniques are endowed with advantages and disadvantages. The electrode-method that uses the dipole-character of the eye needs a DC-amplifier with small noise and drift error. The amplifier described here complies with these requirements. It has been used for a long time and disapproves the general opinion that the coil- and the infrared-method are the more expensive but in all cases the better methods.


FDG-PET/CT Brain Findings in a Patient With Macrophagic Myofasciitis.
Brain Positron Emission Tomography/Computed Tomography with (18)F-fluorodeoxyglucose (FDG PET/CT) was performed in a 44-year-old woman with marked cognitive impairment, diffuse myalgias, sensory, memory and visual disorders, and chronic fatigue, presenting with histopathological features of macrophagic myofasciitis (MMF) at deltoid muscle biopsy. Cerebromedullary Magnetic Resonance Imaging (MRI), electromyography, ophthalmic examination, and cerebrospinal fluid analysis were normal. Visual analysis of FDG PET/CT images showed an atypical pattern of hypometabolism, involving symmetrically the occipital cortex, temporal lobes, and limbic system (including in particular amygdalo-hippocampal complexes), and the cerebellum. Posterior cingulate cortex and parietal areas were preserved. This pattern was confirmed by a voxel-based procedure using Statistical Parametric Mapping (SPM12) that compared a patient's images to normal reference samples from six healthy subjects with adjustment to age obtained using the same PET/CT camera. These results provide a glucose metabolism substrate for cognitive complaints in patients with long-lasting aluminium hydroxide-induced MMF.


Developmental change in the second half of life--strategies for modification of selected compartments of aging.
Age-related changes of different individuals multicentric and polymorphic. We have approached this problem of age-related changes by examining (1) membrane densities of receptors of various ligands in different organs, and (2) changes in different classes of T cells and of antibody response. Three strategies have been developed to modify progression of age-related changes to different extents in different compartments in which age-related changes occur. The first is based on administration of hormones, the second on administration of purine analogues and the third on administration of diets which differ in fatty acid content. Details of this last approach are reviewed in this paper. Lifespan of different species is a component of the evolution of each species. The variables which are decisive in the evolutionary processes which affect lifespans of different species are not necessarily variables which play a decisive role in the different health span of different individuals of the same species. For each individual of a given species, relative health span represents variations within the limits of the evolved lifespan of the species and depends on alleles of many different genes.


Primary structure of human alpha 2-macroglobulin. V. The complete structure.
The primary structure of the tetrameric plasma glycoprotein human alpha 2-macroglobulin has been determined. The identical subunits contain 1451 amino acid residues. Glucosamine-based oligosaccharide groups are attached to asparagine residues 32, 47, 224, 373, 387, 846, 968, and 1401. Eleven intrachain disulfide bridges have been placed (Cys25-Cys63, Cys228-Cys276, Cys246-Cys264, Cys255-Cys408, Cys572-Cys748, Cys619-Cys666, Cys798-Cys826, Cys824-Cys860, Cys898-Cys1298, Cys1056-Cys1104, and Cys1329-Cys1444). Cys-447 probably forms an interchain bridge with Cys-447 from another subunit. The beta-SH group of Cys-949 is thiol esterified to the gamma-carbonyl group of Glx-952, thus forming an activatable reactive site which can mediate covalent binding of nucleophiles. A putative transglutaminase cross-linking site is constituted by Gln-670 and Gln-671. The primary sites of proteolytic cleavage in the activation cleavage area (the "bait" region) are located in the sequence: -Arg681-Val-Gly-Phe-Tyr-Glu-. The molecular weight of the unmodified alpha 2-macroglobulin subunit is 160,837 and approximately 179,000, including the carbohydrate groups. The presence of possible internal homologies within the alpha 2-macroglobulin subunit is discussed. A comparison of stretches of sequences from alpha 2-macroglobulin with partial sequence data for complement components C3 and C4 indicates that these proteins are evolutionary related. The properties of alpha 2-macroglobulin are discussed within the context of proteolytically regulated systems with particular reference to the complement components C3 and C4.


NBAS disease: 14 new patients, a recurrent mutation, and genotype-phenotype correlation among 24 Chinese patients.
Neuroblastoma amplified sequence (NBAS)-associated disease has a wide phenotypic spectrum, including infantile liver failure syndrome type 2 (ILFS2, OMIM #616483), short stature with optic nerve atrophy and Pelger-Huët anomaly (SOPH) syndrome (OMIM #614800), and a combined phenotype overlapping ILFS2 and SOPH syndrome. The mutation spectra of NBAS and its genotype-phenotype correlation among Chinese were not clear. Clinical and genetic data were retrospectively collected from the medical charts of patients with biallelic NBAS mutations, as well as from Chinese patients in previously published reports. Fourteen new patients were identified, including 10 novel mutations: c.648-1G>A, c.2563_c.2577+5del/p.His855_Gln859del, c.3115C>T/p.Gln1039Ter, c.3284G>A/p.Trp1095Ter, c.2570C>T/p.Ala857Val, c.6859G>T/p.Asp2287Tyr, c.1028G>A/p.Ser343Asn, c.1177_1182delinsAGATAGA/p.Val393ArgfsTer2, c.3432_3435dupCAGT/p.Ala1146GlnfsTer14, and c.680_690dupACTGTTTCAGC/p.Phe231ThrfsTer35. All 14 patients presented as fever-triggered liver injury, including nine patients that satisfied the criteria of acute liver failure (ALF) in whom c.3596G>A/p.Cys1199Tyr occurred five times. Nine patients had extrahepatic manifestations including short stature, skeletal abnormalities, intellectual disability, ophthalmic abnormalities, low levels of serum immunoglobulins, facial dysmorphism, and cardiac abnormalities. Ten other Chinese patients were collected through a review of published works. Genotype-phenotype analysis in 24 Chinese patients revealed that the percentage of ALF patients with variants in the Sec39 domain was significantly higher than that in the C-terminal (100% vs. 12.5%, P = 0.000), and the percentage of multi-organ/system involvement in patients with variants in the Sec39 domain was significantly lower than that in the C-terminal (40% vs. 100%, P = 0.0128). We reported 14 new patients, 10 novel mutations, and a unique recurrent mutation. Correlation analysis indicated that the domain of missense and non-frameshift insertion/deletion mutations in NBAS protein is related to phenotype among Chinese patients.


Stopped-in-loop flow analysis system for successive determination of trace vanadium and iron in drinking water using their catalytic reactions.
An automated stopped-in-loop flow analysis (SILFA) system is proposed for the successive catalytic determination of vanadium and iron. The determination of vanadium was based on the p-anisidine oxidation by potassium bromate in the presence of Tiron as an activator to form a reddish dye, which has an absorption maximum at 510 nm. The selectivity of the vanadium determination was greatly improved by adding diphosphate as a masking agent of iron. For the iron determination, an iron-catalyzed oxidative reaction of p-anisidine by hydrogen peroxide with 1,10-phenanthroline as an activator to produce a reddish dye (510 nm) was employed. The SILFA system consisted of two peristaltic pumps, two six-port injection valves, a four-port selection valve, a heater device, a spectrophotometric detector and a data acquisition device. One six-port injection valve was used for the isolation of a mixed solution of standard/sample and reagent to promote each catalytic reaction, and another six-port injection valve was used for switching the reagent for vanadium or iron to achieve selective determination of each analyte. The above mentioned four-port selection valve was used to select standard solutions or sample. These three valves and the two peristaltic pumps were controlled by a built-in programmable logic controller in a touchscreen controller. The obtained results showed that the proposed SILFA monitoring system constituted an effective approach for the selective determination of vanadium and iron. The limits of detection, 0.052 and 0.55 µg L(-1), were obtained for vanadium and iron, respectively. The proposed system was successfully applied to drinking water samples without any preconcentration procedures.


Physical activity trajectory in the first 10 months of the COVID-19 pandemic in Southern Brazil: a follow-up study.
A continuous tracking of the PA level during the COVID-19 pandemic is important to understand how people's behaviour has varied along time. The aim of this study was to evaluate the physical activity (PA) trajectory over the first 10 months of the COVID-19 pandemic in the south of Brazil. Data from three timepoints of the PAMPA Cohort were used, as follows: (1) pre-COVID-19 (retrospective); (2) Jun/Jul 2020; (3) Dec 2020/Jan 2021. Self-reported PA practice, frequency, duration, as well as place where activities were performed (at or out of home) were assessed. A reduction in any (from 68.7 to 47.7%), sufficient (from 41.5 to 22.1%) and out of home PA (from 59.4 to 30.1%) was observed from the first (pre-COVID-19) to the second (Jun/Jul 2020) timepoint, followed by an increase in the third timepoint (Dec 2020/Jan 2021) (60.1%, 37.9%, and 54.3% for any, sufficient, and out of home PA, respectively). The PA trajectory was similar, regardless of sex, educational level or income. Only any (p = 0.0007) and sufficient (p = 0.0012) PA showed significant interaction with time by sex. Female participants were less likely to engage in any (OR 0.45 95% CI 0.26; 0.77) and sufficient PA (OR 0.40 95% CI 0.24; 0.66). During the first 10 months of COVID-19 pandemic there was a marked fluctuation on PA pattern in adults from southern Brazil. An ongoing tracking of PA behaviour during COVID-19 pandemic is important to understand how this behaviour varies. Public policies should focus on increasing PA in a higher standard than pre-COVID levels.


Immunosuppressive activity in human embryo growth media is associated with successful pregnancy: effect of gonadotropin releasing hormone agonist (GnRHa) treatment of patients undergoing in vitro fertilization and embryo transfer (IVF-ET).
The aim of the present study was to determine whether the secretion of embryo-associated immunosuppressor factor (EASF) by preimplantation embryo correlates with pregnancy outcome and whether this relationship is influenced by pretreatment of gonadotropin releasing hormone agonist (GnRHa) in patients undergoing in vitro fertilization and embryo transfer (IVF-ET). EASF activity was measured using concanavalin A-induced human lymphocyte proliferation assay in 256 embryo growth media obtained from 61 patients undergoing IVF-ET. EASF activity was then correlated with GnRHa treatment and pregnancy outcome in these IVF patients. Results indicate that (i) the presence of immunosuppressive activity in human embryo growth media is associated with success of pregnancy in GnRHa nontreated patients and (ii) serum factors present in GnRHa-treated patients may affect the EASF secretion by preembryos in vitro.


Evidence supports adjuvant radiotherapy in selected patients with rectal cancer.
Much recent data have been published on the risk of local recurrence (LR) following curative surgery for rectal cancer and the impact of adjuvant radiation therapy (RT). With improvements in surgical technique apparently reducing the risk of LR, the relevance of older data upon which the current recommendations for adjuvant RT are based has been questioned. A focused review was undertaken of the published literature on the risk of LR following surgery for rectal cancer and the impact of adjuvant radiation. In particular the authors attempt to define how accurately the risk for an individual patient can be predicted, trends in reported LR rates over the time period of randomized trials, and the relevance of changing surgical and RT techniques. Many of the perceived differences in published results can be explained by variations in study entry criteria, length of follow up and data recording. Comparisons between studies are most accurate when defined subsets of patients, such as those with stage III disease, followed for the same period of time, are considered. In parallel with improvements in surgical technique, which may have reduced the risk of LR, modifications to RT delivery have resulted in recent series not reporting an increased mortality in those patients treated with modern RT techniques. All of the available evidence supports the use of adjuvant RT in selected patients with rectal cancer. Ongoing studies will better define individual patient risk and the risk-benefit ratio of adjuvant RT.


Imperforate anus: avoiding a colostomy.
Early assessement of imperforate anus, combining clinical and radiographic data, determines the course of treatment. "High" lesions most often require combined abdominal and sacroperineal repair, usually preceded by a decompression colostomy. "Low" lesions are repaired through a perineal or sacroperineal approach not requiring a previous colostomy. Patients who do not have an apparent fistulous tract through which accurate radiographic assessment can be made frequently undergo preliminary colostomy to avoid colonic perforation. This occurs in patients who have "low" lesions and in whom colostomy may be avoided. Combining a new procedure and an old procedure may avoid unnecessary colostomy. A 14 Medicut intravenous cannula is inserted in the perineum and under fluoroscopic control is advanced into the radiolucent area identified in the pelvis as the probable lower rectal pouch. The position is confirmed by aspiration of gas or meconium and injection of contrast material. A limited contrast enema will clearly identify the level of the lesion and identify a fistula if one is present. If a low lesion is identified and no fistula is present to allow temporary colonic decompression, a fistulous tract may be created mechanically. A No. 4 Fogarty catheter is inserted through the previously placed cannula, the catheter balloon is inflated, and the entire apparatus is extracted under tension. This creates a small fistulous tract to the perineal surface. Subsequent dilation of this tract allows colonic decompression, and definitive operative repair may be planned at the most appropriate time. By employing this technique, we have avoided colostomy in 4 of 6 patients.


Current status in the discovery of dual BET/HDAC inhibitors.
The development of desired multitarget agents may provide an attractive and cost-effective complement or alternative to drug combinations. BET and HDAC, as important epigenetic modulators, are both attractive targets in drug discovery and development. Considering the fact that BET and HDAC inhibitors exert a synergistic effect on cellular processes in cancer cells, the design of dual BET/HDAC inhibitors may be a rational strategy to improve the efficacy of their single-target drugs for tumor treatment. In current review, we depict the development of dual BET/HDAC inhibitors and particularly highlight their SARs, binding modes and biological functions with the aim to facilitate rational design and develop more dual BET/HDAC inhibitors.


Relationship between effects of added albumin, initial free thyroxine value and endogenous serum-binding protein concentrations on Amerlex free thyroxine estimations.
We studied the effect of adding purified human albumin to sera on free thyroxine (FT4) values obtained with Amerlex radioimmunoassays. Apparent FT4 values increased with progressive addition of albumin in vitro. The effect was smallest with low and greatest with high initial FT4 concentrations, which were also linearly correlated with the incremental increase in FT4 values per g/l albumin added. Wide variations in either endogenous thyroxine binding globulin (TBG) or albumin concentrations in patient serum had little effect on the rate of increase in FT4 values when albumin was added in vitro. From Mass Action theory, calculations of the binding affinity of the endogenous albumin for the analog (2.1 X 10(5) l/mol) gave values nearly half that of the added albumin (3.94 X 10(5) l/mol). Distortions in Amerlex FT4 values caused by adding albumin in vitro may exaggerate its importance as a tracer binder and such results may be unrepresentative of patient samples.


Empowering environmental change: role of green bonds in shaping green e-commerce and sustainable business.
This research aims to investigate the impact of green bonds on the development of sustainable and environmentally friendly e-commerce businesses, with a focus on promoting environmental empowerment. Recognizing the necessity of preparing for economic changes and strengthening institutional frameworks, this study addresses the shortcomings identified in previous research, including statistical limitations, insufficient inclusion of variables, and a lack of diversity. By bridging these gaps, the research explores the interconnections between economic expansion, sustainability, profitability, and effective governance. To account for country-specific variations, a robust reduced-form modeling strategy is employed, supplemented by generalized method of moments estimates to address potential variability. The study analyzes survey data spanning the years 1990 to 2019. The research findings confirm the significant role of organizational excellence and economic growth in fostering sustainability, lending support to the presence of the environmental Kuznets curve hypothesis. Additionally, the study underscores the potential adverse consequences for the natural environment if economic liberalization proceeds without robust governance structures. By providing original empirical evidence on the effectiveness of green bonds in driving the growth of sustainable e-commerce businesses, this research contributes to the field of environmental empowerment and emphasizes the importance of well-designed frameworks to guide economic transitions. The insights derived from this study have implications for policymakers, businesses, and organizations aiming to align economic growth with sustainability goals, ultimately facilitating a more environmentally conscious and resilient future.


Arbuscular mycorrhizal symbiosis alleviates ozone injury in ozone-tolerant poplar clone but not in ozone-sensitive poplar clone.
Tropospheric ozone (O3) is a typical air pollutant with harmful effects on plants, whereas arbuscular mycorrhizal (AM) fungi are ubiquitous plant symbionts that enhance plant resistance to various abiotic stresses. However, whether AM symbiosis decreases plant O3 sensitivity and what the underlying mechanisms are remain unclear. In this study, O3-tolerant poplar clone 107 and O3-sensitive poplar clone 546 were used as test plants. An open-top chamber experiment was conducted to investigate the effects of AM inoculation on plant growth and physiological parameters under O3 enrichment. The results showed that O3 enrichment significantly decreased plant biomass and net photosynthetic rate and increased the leaf shedding rate and malondialdehyde concentration of clone 546. Generally, clone 107 was less responsive to O3 enrichment than clone 546 was. Differences in antioxidant enzyme activity, rather than in specific leaf weight or stomatal conductance, were responsible for the differences in O3 sensitivity between the two clones. AM inoculation significantly increased the biomass and decreased the leaf shedding rate and malondialdehyde concentration of clone 107 but had no significant effect on almost all the indexes of clone 546, suggesting a species-specific mycorrhizal effect on plant O3 sensitivity. Mechanistically, AM symbiosis did not significantly affect nutrient uptake, stomatal conductance, or specific leaf weight of poplar but did significantly increase antioxidant enzyme activity. Linear regression analysis of antioxidant enzyme activities and the effect of O3 on growth and physiological parameters showed that AM symbiosis mediated antioxidant enzyme activities to mitigate O3 injury to the two poplar clones. This study improved the understanding of the protective effects of AM fungi on plants against O3 pollution.


Determination of the 32P activity in angioplastic balloons by LSC.
The determination of the 32P activity in angioplastic balloons involves two problems: the extraction of 32P, which is covered with plastic foils, and the determination of the 33P impurity. At PTB the active balloons are destroyed by combustion in an oxygen stream. The active phosphorus is extracted quantitatively from the tube. The activities of 32P and 33P are determined by measurements performed over a period of one month or more by a subsequent data fit.


Managing cancer in the EU: the Organisation of European Cancer Institutes (OECI).
Organization of European Cancer Institutes (OECI) has the mission to facilitate the development of European comprehensive cancer centres by integrating care and prevention with research and education. Core issues are to deliver a complete multidisciplinary care of high quality and stimulate translational cancer research. The goal is to innovate the cancer care. The increasing problem of critical mass will be solved by networking comprehensive cancer centres containing quality assured harmonized infrastructures. This will give Europe a new potential to extend the cancer research to areas not possible to cover by single centres.


A micro solid-phase radioimmunoassay for detection of herpesvirus type-specific antibody: specificity and sensitivity.
The specificity and sensitivity of a micro solid-phase radioimmunoassay (micro-SPRIA) that detects type-specific IgG antibody to herpes simplex virus types 1 and 2 (HSV1 and HSV2) were evaluated. Glycoproteins VP123 (molecular weight, 123,000) of HSV1 and VP119 (molecular weight, 119,000) of HSV2 were found to display the greatest degree of antigenic type-specificity of several HSV antigens tested with the micro-SPRIA technique. When testing a group of sera, negative for anti-HSV antibodies by microneutralization, in the micro-SPRIA, a range of negative reactivities was noted, suggesting that cut-points should be determined for each antigen preparation. The micro-SPRIA detected appropriate antibody activity in patients with recurrent infection and a marked agreement was noted in comparison to detection of anti-HSV antibodies measured with the microneutralization test. The type-specificity of the micro-SPRIA was substantiated by the independence of test results using VP119 and VP123 antigens for a random group of positive sera. The assay is rapid, specific, and sensitive and allows the testing of multiple serum samples with a standardized set of reagents.


Chronological changes in the ultrasonic findings of gallbladder metastasis from renal cell carcinoma: a case report and review.
The present case involves a gallbladder metastasis from renal cell carcinoma (GBMRCC). During 11 months of ultrasound follow-up examinations, the mass, covered with a highly echoic surface layer, exhibited the following changes: the wide base became constricted, the tumor surface became irregular, and the mass increased in diameter. A histopathological examination confirmed that the tumor cells were mainly present in the subepithelial layer, the gallbladder epithelium had ruptured, and necrotic debris covered the tumor surface. The highly echoic surface layer observed on the latest ultrasound images corresponded to the necrotic debris. These findings suggested that GBMRCCs initially develop in the subepithelial layer and then undergo expansive intraluminal growth. They subsequently cause the epithelium to rupture, resulting in necrotic debris appearing on the tumor surface.


Anion-exchange high-performance liquid chromatography of water-soluble chromium (VI) and chromium (III) complexes in biological materials.
A high-performance anion-exchange liquid chromatograph coupled to visible-range (370 nm) and UV (280 nm) detectors and an atomic-absorption spectrometer allowed the rapid determination of CrVI and/or complexes of CrIII in rat plasma, erythrocyte lysate and liver supernatant treated with CrVI or CrIII in vitro. CrVI in the eluates was determined using both the visible-range detector and atomic-absorption spectrometer (AAS). The detection limits of CrVI in standard solutions using these methods were 2 and 5 ng (signal-to-noise ratio = 2), respectively. Separations of the biological components and of CrIII complexes were monitored by UV and AAS analyses, respectively. Time-related decreases of CrVI accompanied by increases in CrIII complexes were observed, indicating the reduction of CrVI by some of the biological components. The reduction rates were considerably higher in the liver supernatant and erythrocyte lysate than in the plasma. These results indicate that the anion-exchange high-performance liquid chromatographic system is useful for simultaneous determination of CrVI and CrIII complexes in biological materials.


Nitroproteins in Human Astrocytomas Discovered by Gel Electrophoresis and Tandem Mass Spectrometry.
Protein tyrosine nitration is involved in the pathogenesis of highly fatal astrocytomas, a type of brain cancer. To understand the molecular mechanisms of astrocytomas and to discover new biomarkers/therapeutic targets, we sought to identify nitroproteins in human astrocytoma tissue. Anti-nitrotyrosine immunoreaction-positive proteins from a high-grade astrocytoma tissue were detected with two-dimensional gel electrophoresis (2DGE)-based nitrotyrosine immunoblots, and identified with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Fifty-seven nitrotyrosine immunopositive protein spots were detected. A total of 870 proteins (nitrated and non-nitrated) in nitrotyrosine-immunopositive 2D gel spots were identified, and 18 nitroproteins and their 20 nitrotyrosine sites were identified with MS/MS analysis. These nitroproteins participate in multiple processes, including drug-resistance, signal transduction, cytoskeleton, transcription and translation, cell proliferation and apoptosis, immune response, phenotypic dedifferentiation, cell migration, and metastasis. Among those nitroproteins that might play a role in astrocytomas was nitro-sorcin, which is involved in drug resistance and metastasis and might play a role in the spread and treatment of an astrocytoma. Semiquantitative immune-based measurements of different sorcin expressions were found among different grades of astrocytomas relative to controls, and a semiquantitative increased nitration level in high-grade astrocytoma relative to control. Nitro-β-tubulin functions in cytoskeleton and cell migration. Semiquantitative immunoreactivity of β-tubulin showed increased expression among different grades of astrocytomas relative to controls and semiquantitatively increased nitration level in high-grade astrocytoma relative to control. Each nitroprotein was rationalized and related to the corresponding functional system to provide new insights into tyrosine nitration and its potential role in the pathogenesis of astrocytoma formation. Graphical Abstract .


Dock1 promotes the mesenchymal transition of glioma and is modulated by MiR-31.
This research aimed to examine the relationship between Dock1 and miR-31 and to determine the effect of miR-31 on the mesenchymal transition and invasiveness of glioma. Real-time PCR was used to measure the expression of miR-31 and other RNAs. The transfection was used to manipulate the expression levels of Dock1 and miR-31 in cancer cells. Western blot was used to detect the expression of Dock1 and other related proteins. Wound healing, Matrigel invasion and chemotaxis assays were performed to detect the invasion and migration of glioma cell lines. The actual binding site of miR-31 to the 3'-untranslated region of Dock1 was confirmed through luciferase assay and RNA immunoprecipitation. Methylation-specific PCR was performed to detect the methylation level of miR-31 in both glioma cell lines and tissues. Dock1 can promote the IL8-induced chemotaxis and mesenchymal transition of glioma cells through the NF-κB/Snail signalling pathway. The protein levels of Dock1 in glioma cell lines and clinical specimens were negatively correlated with miR-31 expression, and Dock1 was directly targeted by miR-31. Animal experiments showed that Dock1 downregulation and miR-31 overexpression reduced glioma cell invasion. Investigation of the underlying molecular mechanism revealed that miR-31 downregulation was attributable to the hypermethylation of the promoter region of miR-31 in glioma cells. Dock1 modulation by miR-31 plays an important function in glioma invasion both in vitro and in vivo. This study provides new insights into the invasion of glioma cells and might therefore contribute to the development of new antiglioma strategies.


Binocular switch suppression: a new method for persistently rendering the visible 'invisible'.
Rendering the usually visible 'invisible' has long been a popular experimental manipulation. With one notable exception, 'continuous flash suppression' [Tsuchiya, N., & Koch, C. (2005). Continuous flash suppression reduces negative afterimages. Nature Neuroscience, 8, 1096-1101], existing methods of achieving this goal suffer from being either unable to suppress stimuli from awareness for prolonged periods, from being unable to reliably suppress stimuli at specific epochs, or from a combination of both of these limitations. Here we report a new method, binocular switch suppression (BSS), which overcomes these restrictions. We establish that BSS is novel as it taps a different causal mechanism to the only similar pre-existing method. We also establish that BSS is superior to pre-existing methods both in terms of the depth and duration of perceptual suppression achieved. BSS should therefore prove to be a useful tool for the large number of researchers interested in exploring the neural correlates and functional consequences of conscious visual awareness.


Atypical absences and recurrent absence status in an adult with Angelman syndrome due to the UBE3A mutation.
Angelman syndrome is a neurogenetic disorder resulting in refractory epilepsy and profound psychomotor retardation in its most prevalent form, caused by deletion of maternal chromosome 15q11-13. We report the case of a 29-year-old, mentally retarded man with unusual electroencephalographic changes during periods of atypical absence status epilepticus, a previously unreported manifestation of the usually milder, drug-responsive epilepsy associated with Angelman syndrome due to the UBE3A mutation.[Published with video sequences].


Molecular characterization of a poxvirus isolated from an American flamingo (Phoeniconais ruber rubber).
An avian poxvirus from the beak scab of an American flamingo (Phoeniconais ruber rubber) was isolated by inoculation on the chorioallantoic membrane (CAM) of specific-pathogen-free (SPF) chicken embryos. The virus produced multifocal areas of epithelial hyperplasia along with foci of inflammation in the CAM, and rare cells contained small eosinophilic intracytoplasmic bodies. Chickens inoculated with the isolated virus in the feather follicle of the leg did not develop significant lesions. Nucleotide sequence comparison of a PCR-amplified 4.5 kb HindIII fragment of the genome of flamingo poxvirus (FlPV) revealed very high homology (99.7%) with condor poxvirus (CPV), followed by approximately 92% similarity with canary poxvirus (CNPV) and Hawaiian goose poxvirus (HGPV), but less similarity (approximately 69%) to fowl poxvirus (FPV), the type species of the genus Avipoxvirus of family Poxviridae. As in the cases with CPV, CNPV, and HGPV, genetic analysis of FlPV revealed an absence of three corresponding FPV open reading frames (ORF199, 200, and 202) and an absence of any reticuloendotheliosis virus (REV) sequences in this region. There are only nine nucleotide substitutions observed between FlPV and CPV in the 4.5 kb fragment; those were clustered in the ORF201 region, which in FPV genome is a site for integration of REV sequences. Phylogenetic analysis of the predicted amino acid sequences of the ORF201-coded hypothetical protein demonstrated FlPV to be more closely related to CPV, as well as to CNPV and HGPV, than to FPV.


Global nickel anomaly links Siberian Traps eruptions and the latest Permian mass extinction.
Anomalous peaks of nickel abundance have been reported in Permian-Triassic boundary sections in China, Israel, Eastern Europe, Spitzbergen, and the Austrian Carnic Alps. New solution ICP-MS results of enhanced nickel from P-T boundary sections in Hungary, Japan, and Spiti, India suggest that the nickel anomalies at the end of the Permian were a worldwide phenomenon. We propose that the source of the nickel anomalies at the P-T boundary were Ni-rich volatiles released by the Siberian volcanism, and by coeval Ni-rich magma intrusions. The peaks in nickel abundance correlate with negative δ13C and δ18O anomalies, suggesting that explosive reactions between magma and coal during the Siberian flood-basalt eruptions released large amounts of CO2 and CH4 into the atmosphere, causing severe global warming and subsequent mass extinction. The nickel anomalies may provide a timeline in P-T boundary sections, and the timing of the peaks supports the Siberian Traps as a contributor to the latest Permian mass extinction.


Transformation of LMTK- cells with purified HLA class I gene. VI. Serological characterization of HLA-B7 and AW24 molecules.
Serological characterization of HLA-B7 and HLA-AW24 class I molecules following transfection of murine LMTK- cells with purified HLA class I genes was performed using human alloantisera. Induction by murine alpha interferon of the expression of class I molecules was required to obtain unambiguous identification of these molecules which appear serologically identical to the HLA-B7 and HLA-AW24 molecules expressed at the surface of human peripheral blood lymphocytes of 20 unrelated individuals. Analysis of the transformed cells with 8 different anti-HLA class I monoclonal antibodies results in the definition of 3 separate clusters of antigenic determinants shared by all HLA class I molecules. These studies further suggest the existence of locus-specific serological reactivities associated either with the HLA-A or with the HLA-B and C gene products.


Carbon monoxide production in ventilated premature infants weighing less than 1500 g.
Mean pulmonary excretion rate of carbon monoxide in 13 premature babies on ventilators was significantly higher (p less than 0.001) than that of 19 healthy infants born at full term. This correlated with carboxyhaemoglobin concentrations in blood, indicating that the premature infants on ventilators produced abnormally large amounts of bilirubin.


APExpose_DE, an air quality exposure dataset for Germany 2010-2019.
Exposure to poor air quality is considered a major influence on the occurrence of cardiovascular and respiratory diseases. Air pollution has also been linked to the severity of the effects of epidemics such as COVID-19 caused by the SARS-CoV-2 virus. Epidemiological studies require datasets of the long-term exposure to air pollution. We present the APExpose_DE dataset, a long-term (2010-2019) dataset providing ambient air pollution metrics at yearly time resolution for NO2, NO, O3, PM10 and PM2.5 at the NUTS-3 spatial resolution level for Germany (corresponding to the Landkreis or Kreisfreie Stadt in Germany, 402 in total).


CSF-induced and HIV-1-mediated distinct regulation of Hck and C/EBPbeta represent a heterogeneous susceptibility of monocyte-derived macrophages to M-tropic HIV-1 infection.
Granulocyte/macrophage colony-stimulating factor (GM-CSF)-induced monocyte-derived macrophages (GM-MPhi) are permissive to M-tropic HIV-1 entry, but inhibit viral replication at posttranscriptional and translational levels, whereas M-CSF-induced macrophages (M-MPhi) produce a large amount of HIV-1. M-MPhi express a high level of Hck and a large isoform of C/EBPbeta, and HIV-1 infection increases the expression of Hck but not of C/EBPbeta. GM-MPhi express a high level of C/EBPbeta and a low level of Hck, and HIV-1 infection drastically increases the expression of a short isoform of C/EBPbeta but decreases that of Hck. Treatment of M-MPhi with antisense oligonucleotide for Hck (AS-Hck) not only suppresses the expression of Hck, but also stimulates the induction of the short isoform of C/EBPbeta and inhibits the viral replication. Treatment of GM-MPhi with a moderate amount of AS-C/EBPbeta not only inhibits the expression of the small isoform of C/EBPbeta preferentially, but also stimulates the induction of Hck and stimulates the virus production at a high rate. These results suggest that CSF-induced and HIV-1-mediated distinct regulation of Hck and small isoform of C/EBPbeta represent the heterogeneous susceptibility of tissue MPhi to HIV-1 infection, and the regulation of Hck and C/EBPbeta are closely related and these two molecules affect one another.


Dhh signaling pathway regulates reconstruction of seminiferous tubule-like structure.
The reconstruction of a tubule-like structure in vitro has provided a promising system to analyze factors that drive morphogenesis and the underlying mechanisms. In this study, we took advantage of the inhibitor cyclopamine and a smoothened agonist to detect the role of the Dhh signaling pathway in the reconstructed tubule-like structure. Sertoli cells did not show polarity, rounded peritubular myoid cells and scattered Leydig cells were observed, combined with less laminin and lower proliferation of Leydig, peritubular myoid, germ, and Sertoli cells. However, in the presence of SAG, elongated peritubular myoid cells gathered at the bottom of polarized Sertoli cells, and most of the Leydig cells gathered at the outer part of the elongated peritubular myoid cells. Moreover, SAG promoted the secretion of laminin, assisting in the formation of the basal membrane and promoting the proliferation of Leydig, peritubular myoid, and germ cells. The level of Gli1 was significantly downregulated when treated with cyclopamine, whereas it was significantly upregulated when treated with SAG. These results indicate that the Dhh signaling pathway regulates the reconstruction of tubule-like structures by regulating the expression of Gli1.


Evaluation of a scoring system for assessing prognosis in pediatric acute liver failure.
Pediatric acute liver failure (PALF) results in death or need for liver transplantation (LT) in up to 50% of patients. A scoring system for predicting death or LT (Liver Injury Units [LIU] score) in PALF was previously derived by our group, and used peak values during hospital admission of total bilirubin, prothrombin time/international normalized ratio, and ammonia as significant predictors of outcome. The aims of this study were to test the predictive value of the LIU score in a subsequent validation set of patients and to derive a hospital admission LIU (aLIU) score predictive of outcome. Data were obtained from 53 children admitted with PALF from 2002 to 2006. Outcome was defined at 16 weeks as alive without LT, death, or LT. Survival without LT at 16 weeks for each LIU score quartile was 92%, 44%, 60%, and 12%, respectively (P < .001). The receiver operating characteristic C index for predicting death or LT by 4 weeks was 86.3. An admission LIU score was derived using admission total bilirubin and prothrombin time/international normalized ratio. Survival without LT at 16 weeks for each quartile using the aLIU score was 85%, 77%, 69%, and 31% (P = .001). The receiver operating characteristic C index for predicting death or LT by 4 weeks was 83.7. The original LIU score is a valid predictor of outcome in PALF. The aLIU score is promising and needs to be validated in subsequent patients.


Direct spectorphotometric assay of quaternary ammonium compounds using bromthymol blue.
Benzalkonium chloride, benzethonium chloride, and chlorhexidine gluconate were assayed quantitatively by a direct spectrophotometric method with bromthymol blue buffered at pH 7.5. The method shows good results at concentrations of 0--300 microgram/ml and in the presence of epinephrine bitartrate, phenylephrine hydrochloride, pilocarpine hydrochloride, and polyvinyl alcohol.


Quantitative assessment of beam perturbations caused by silicon diodes used for in vivo dosimetry.
To measure the effect of silicon diode detectors used for in vivo dosimetry on beam characteristics and determine whether this effect is clinically significant. Commercially available photon and electron diodes were placed on the central axis of photon and electron beams. The beam characteristics were measured for 6- and 10-MV photon and 6-20-MeV electron energies from a Varian Clinac 1800 medical linear accelerator. Water was used for the medium, and measurements were made for various clinically common field sizes and depths. Beam attenuations along the central axis were 10 and 7.5% for 6- and 10-MV photons, respectively. Electron beam dose reductions were between 13 and 25% for 20-6-MeV electrons. Photon beam flatness varied up to 7% at different depths, but the symmetry was not affected much. Electron beam flatness and symmetry were significantly changed to as much as 18 and 6%, respectively. Use of diode detectors on central axis of photon and electron beams for in vivo dosimetry causes significant attenuation and alteration of the beam characteristics. The percentage of the volume affected is significant (e.g., 23% of the volume in a 4 x 4 field gets 10% less dose for a 6-MV photon beam), especially if these diodes are used for in vivo dosimetry on the central axis every day for every treatment, as is done in some clinics. Other beam parameters such as penumbra and skin dose are also affected. It is therefore recommended that the diodes be used only as needed.


Catecholamine mechanisms in the stimulation of mouse locomotor activity by nitrous oxide and morphine.
Nitrous oxide, like morphine, produces a significant increase in mouse locomotor activity. This stimulation of locomotor activity is antagonized by the narcotic antagonist naloxone (10 mg/kg). The catecholamine synthesis inhibitor alpha-methyl-p-tyrosine (300 mg/kg) also significantly reduced the nitrous oxide stimulation of mouse locomotor activity. Administration of naloxone (10 mg/kg) to mice previously treated with alpha-methyl-p-tyrosine resulted in a further decrease in nitrous oxide stimulated activity levels. Haloperidol (0.08-0.64 mg/kg), a potent dopamine receptor antagonist, dose dependently reduced the activity stimulation resulting from exposure to nitrous oxide. Administration of haloperidol (0.08 mg/kg) in conjunction with naloxone (10 mg/kg) further reduced the nitrous oxide effect. In view of the fact that morphine's activity stimulating effects are reduced by alpha-methyl-p-tyrosine and haloperidol, the results reported here suggest additional similarities in the pharmacology of morphine and nitrous oxide. The stimulation of mouse locomotor activity produced by nitrous oxide appears to be mediated by both endogenous opioid and catecholamines.