Modulation of GABAergic synaptic currents and current responses by α-thujone and dihydroumbellulone.
α-Thujone (1a), a constituent of wormwood, has been suspected to cause adverse psychoactive reactions in addicted drinkers of absinthe. While the content of 1a in absinthe is too low for such effects, at higher doses it can indeed induce seizures and inhibit GABA(A) receptors (GABA(A)Rs). The effect of 1a on GABAergic synaptic currents and the mechanisms by which it modulates GABA(A)Rs remain unknown. To address these issues, cultured hippocampal neurons were used to investigate the action of 1a on GABAergic miniature inhibitory postsynaptic currents (mIPSCs) and on responses to exogenous GABA applications. Since lipophilic compounds often show nonspecific actions related to their hydrophobicity, the action of 1a was compared to that of dihydroumbellulone (2), a configurationally pseudoenantiomeric constitutional isomer. α-Thujone (1a) reduced mIPSC frequency and amplitude and also moderately affected their kinetics, indicating both pre- and postsynaptic mechanisms. Analysis of current responses to exogenous GABA revealed that 1a reduced their amplitude, affecting their onset, desensitization, and deactivation, suggesting an effect on receptor gating. In contrast, 2 caused only a weak or negligible effect on GABAergic currents, supporting the effects of 1a on GABAergic inhibition as being due to specific interactions with GABA(A)Rs.


Differences between acute and chronic wounds and the role of wound bed preparation.
There are major differences in the way acute and chronic wounds heal. An understanding of these differences enables practitioners to plan more appropriate care and management for patients. A simple framework such as wound bed preparation can be used to identify problems and plan realistic and appropriate outcomes of care.


Localization of YAP activity in developing skeletal rudiments is responsive to mechanical stimulation.
Normal skeletal development, in particular ossification, joint formation and shape features of condyles, depends on appropriate mechanical input from embryonic movement but it is unknown how such physical stimuli are transduced to alter gene regulation. Hippo/Yes-Associated Protein (YAP) signalling has been shown to respond to the physical environment of the cell and here we specifically investigate the YAP effector of the pathway as a potential mechanoresponsive mediator in the developing limb skeleton. We show spatial localization of YAP protein and of pathway target gene expression within developing skeletal rudiments where predicted biophysical stimuli patterns and shape are affected in immobilization models, coincident with the period of sensitivity to movement, but not coincident with the expression of the Hippo receptor Fat4. Furthermore, we show that under reduced mechanical stimulation, in immobile, muscle-less mouse embryos, this spatial localization is lost. In culture blocking YAP reduces chondrogenesis but the effect differs depending on the timing and/or level of YAP reduction. These findings implicate YAP signalling, independent of Fat4, in the transduction of mechanical signals during key stages of skeletal patterning in the developing limb, in particular endochondral ossification and shape emergence, as well as patterning of tissues at the developing synovial joint.


Challenges and physiological implications of wood feeding in termites.
Termites are fascinating insects for a number of reasons, one of which being their specialization on diets of wood lignocellulose. The goal of this review is to consider stress-inducing characteristics of wood and apparent molecular-physiological adaptations in termite guts to overcome these stressors. Defensive factors present in wood include extractive secondary plant metabolites, lignin and related phenolics, crystalline cellulose, and low nitrogen content. Molecular-physiological adaptations of the termite gut to deal with these factors include robust detoxification and antioxidant machinery, the production of a peritrophic matrix and a wide range of cellulases from host and symbiotic sources, and creation of niches available to nitrogen-fixing bacterial symbionts. Considering termite gut physiology and symbioses in the context of stress-response has applied implications. These outcomes can include development of efficient biomass breakdown strategies, protection of microbes during industrial processing applications, and safeguarding wooden structures from termite damage.


A genetic predisposition score for muscular endophenotypes predicts the increase in aerobic power after training: the CAREGENE study.
It is widely accepted that genetic variability might explain a large part of the observed heterogeneity in aerobic capacity and its response to training. Significant associations between polymorphisms of different genes with muscular strength, anaerobic phenotypes and body composition have been reported. Muscular endophenotypes are positively correlated with aerobic capacity, therefore, we tested the association of polymorphisms in twelve muscular related genes on aerobic capacity and its response to endurance training. 935 Coronary artery disease patients (CAD) who performed an incremental exercise test until exhaustion at baseline and after three months of training were included. Polymorphisms of the genes were detected using the invader assay. Genotype-phenotype association analyses were performed using ANCOVA. Different models for a genetic predisposition score (GPS) were constructed based on literature and own data and were related to baseline and response VO(2) scores. Carriers of the minor allele in the R23K polymorphism of the glucocorticoid receptor gene (GR) and the ciliary neurotrophic factor gene (CNTF) had a significantly higher increase in peakVO(2) after training (p < 0.05). Carriers of the minor allele (C34T) in the adenosine monophosphate deaminase (AMPD1) gene had a significantly lower relative increase (p < 0.05) in peakVO(2). GPS of data driven models were significantly associated with the increase in peakVO(2) after training. In CAD patients, suggestive associations were found in the GR, CNTF and the AMPD1 gene with an improved change in aerobic capacity after three months of training. Additionally data driven models with a genetic predisposition score (GPS) showed a significant predictive value for the increase in peakVO(2).


The driving factors of mercury storage in the Tibetan grassland soils underlain by permafrost.
Soils, especially permafrost in the Arctic and the Tibetan Plateau, are one of the largest reservoirs of mercury (Hg) in the global environment. The Hg concentration in the grassland soils over the Tibetan Plateau and its driving factors have been less studied. This study analyzes soil total mercury (STHg) concentrations and its vertical distribution in grassland soil samples collected from the Tibetan Plateau. We adopt a nested-grid high-resolution GEOS-Chem model to simulate atmospheric Hg deposition. The relationship between STHg and soil organic carbon (SOC), as well as atmospheric deposition, are explored. Our results show that the STHg concentrations in the Tibetan Plateau are 19.8 ± 12.2 ng/g. The concentrations are higher in the south and lower in the north in the Tibetan Plateau, consistent with the previous results. Our model shows that the average deposition flux of Hg is 3.3 μg m-2 yr-1, with 57% contributed by dry deposition of elemental mercury (Hg0), followed by dry (19%) and wet (24%) deposition of divalent mercury. We calculate the Hg to carbon ratio (RHg:C) as 5.6 ± 6.5 μg Hg/g C, and the estimated STHg is 86.6 ± 101.2 Gg in alpine grasslands in the Tibetan Plateau. We find a positive relationship between STHg and SOC in the Tibetan Plateau (r2 = 0.36) and a similar positive relationship between STHg and atmospheric total Hg deposition (r2 = 0.24). A multiple linear regression involving both variables better model the observed STHg (r2 = 0.42). We conclude that SOC and atmospheric deposition influence STHg simultaneously in this region. The data provides information to quantify the size of the soil Hg pool in the Tibetan Plateau further, which has important implications for the Hg cycles in the permafrost regions as well as on the global scale.


Sex differences in learning and performing the Go/NoGo tasks.
The quality of learning and post-learning performances is critical for daily life. The behavioral flexibility is equally important for adapting the changing circumstances. The learning process requires repeated practices, which enhances prompt and proper behavioral responses, in turn, which promotes habits formation as well. Despite the well-documented sex differences in learning and performances, contradictory results were reported. A possible cause might be a systematic analysis due to specific research interests, regardless of the continuity of natural acquisition process. Here, we investigate the potential sex differences in learning, performances and adjustments of habited behaviors with regular and reversal Go/NoGo tasks. Both male and female Sprague-Dawley rats were used in this study. All rats were trained for a regular rodent Go/NoGo task and a subset of rats were trained for a reversal rodent Go/NoGo task, both with strict elimination criteria. The behavioral performance data were stored in PC for off-line analysis. Multiple behavioral indices were analyzed for both passed and retired rats. The ability of learning the regular the reversal Go/NoGo tasks was similar for both male and female rats, however, the female rats took longer time to master the task principles in later stages for both tasks. In the regular Go/NoGo task, the female rats spent more time on completing the trial in performance optimization phases, which implied female rats were more cautious than male rats. Along with the progression of training, both male and female rats developed Go-preference strategies to perform the regular Go/NoGo task, which induced failure to meet the setting success criteria. The retired male rats exhibited shorter RTs and MTs than the retired female rats after developing Go-preference. Moreover, the time needed to complete the Go trials was significantly prolonged for male rats in the reversal Go/NoGo task. Overall, we conclude that distinctive strategies were employed in performing Go/NoGo tasks for both male and female rats. Male rats required less time to stabilize the performance in behavioral optimization phase. In addition, male rats were more accurate in estimating time elapsing. In contrast, female rats took more cautious considerations in performing the task, through which minimal influences were manifested in the reversal version of task.


Two-Dimensional Hetero- to Homochiral Phase Transition from Dynamic Adsorption of Barbituric Acid Derivatives.
Barbituric acid derivative (TDPT) is an achiral molecule, and its adsorption on a surface results in two opposite enantiomerically oriented motifs, namely TDPT-Sp and Rp. Two types of building blocks can be formed; block I is enantiomer-pure and is built up of the same motifs (format SpSp or RpRp) whereas block II is enantiomer-mixed and composes both motifs (format SpRp), respectively. The organization of the building blocks determines the formation of different nanoarchitectures which are investigated using scanning tunneling microscopy at a liquid/HOPG interface. Sophisticated, highly symmetric "nanowaves" are first formed from both building blocks I and II and are heterochiral. The "nanowaves" are metastable and evolve stepwisely into more close-packed "nanowires" which are formed from enantiomer-pure building block I and are homochiral. A dynamic hetero- to homochiral transformation and simultaneous multi-scale phase transitions are demonstrated at the single-molecule level. Our work provides novel insights into the control and the origin of chiral assemblies and chiral transitions, revealing the various roles of enantiomeric selection and chiral competition, driving forces, stability and molecular coverage.


Cost analysis of bluetongue virus serotype 8 surveillance and vaccination programmes in Austria from 2005 to 2013.
This study was designed to evaluate the costs between 2005 and 2013 of the national bluetongue virus (BTV) surveillance and vaccination programmes before, during and after the BTV serotype 8 (BTV-8) outbreak in Austria commencing in 2008. In addition to an assessment of the temporal development of costs, a spatial cost analysis was performed. Within the context of this study, the term 'costs' refers to actual financial expenditure and imputed monetary costs for contributions in-kind. Costs were financed directly by the private-public sectors, by the European Commission (EC), and (in-kind) by responsible national institutions and individuals (e.g. blood sampling by veterinarians). The total net cost of the BTV-8 surveillance and vaccination programmes arising from the outbreak amounted to €22.8 million (0.86% of the national agricultural Gross Value Added), of which 32% was allocated to surveillance and 68% to the vaccination programme. Of the total programme costs, the EC supplied €4.9 million, while the remaining costs (€18 million) were directly financed from national resources. Of the latter, €14.5 million was classed as public costs, including €2 million contributions in-kind, and €3.4 million as private costs. The assessment of the costs revealed heterogeneous temporal and spatial distributions. The methodology of this analysis might assist decision makers in calculating costs for other surveillance and intervention programmes. The assessment of contributions in-kind is of importance to public authorities as it increases visibility of the available resources and shows how they have been employed. This study also demonstrates the importance of tracking changing costs per payer over time.


Hypoxia in tumors: pathogenesis-related classification, characterization of hypoxia subtypes, and associated biological and clinical implications.
Hypoxia is a hallmark of tumors leading to (mal-)adaptive processes, development of aggressive phenotypes and treatment resistance. Based on underlying mechanisms and their duration, two main types of hypoxia have been identified, coexisting with complex spatial and temporal heterogeneities. Chronic hypoxia is mainly caused by diffusion limitations due to enlarged diffusion distances and adverse diffusion geometries (e.g., concurrent vs. countercurrent microvessels, Krogh- vs. Hill-type diffusion geometry) and, to a lesser extent, by hypoxemia (e.g., in anemic patients, HbCO formation in heavy smokers), and a compromised perfusion or flow stop (e.g., due to disturbed Starling forces or intratumor solid stress). Acute hypoxia mainly results from transient disruptions in perfusion (e.g., vascular occlusion by cell aggregates), fluctuating red blood cell fluxes or short-term contractions of the interstitial matrix. In each of these hypoxia subtypes oxygen supply is critically reduced, but perfusion-dependent nutrient supply, waste removal, delivery of anticancer or diagnostic agents, and repair competence can be impaired or may not be affected. This detailed differentiation of tumor hypoxia may impact on our understanding of tumor biology and may aid in the development of novel treatment strategies, tumor detection by imaging and tumor targeting, and is thus of great clinical relevance.


Immunohistochemical localization of glial fibrillary acidic protein (GFAP) and vimentin in the subcommissural organ of the Mongolian gerbil (Meriones unguiculatus).
The chemical composition of intermediate filaments (IF's) in the ependyma of the subcommissural organ (SCO) of the Mongolian gerbil (Meriones unguiculatus) was investigated immunohistochemically in paraffin-embedded tissue. Antibodies against glial fibrillary acidic protein (GFAP), vimentin, neurofilament proteins and cytokeratins were used. Only GFAP and vimentin were detected in the non-specialized diencephalic ependyma and in the ependymocytes of the SCO. Staining could be observed in apical and basal processes of the SCO-cells. The latter processes extended into the posterior commissure up to the subpial surface, thus establishing a well-developed leptomeningeal route of ependymal projections. In contrast to the homogeneous vimentin-labeling, the SCO was particularly immunoreactive for GFAP in its lateral aspects and in the supra- and precommissural parts. The coexpression of GFAP and vimentin in a subclass of SCO-ependymocytes was demonstrated on differentially immunostained semithin sections. The present study confirms the glial nature of the SCO-ependyma, which has been a matter of debate recently. It appears from this investigation that the high degree of secretory activity in the SCO does not necessarily lead to the disappearance of glial IF proteins. Moreover, the SCO-cells belong to the expanding group of mature astroglia, which is characterized by coexpression of GFAP and vimentin. The morphological similarity between SCO-ependymocytes and tanycytes is underscored by their common immunoreactivity against these two IF proteins. In view of the absence of GFAP from the rat SCO, interspecific differences must be considered in the evaluation of the IF protein composition.


On the assessment of self- and object representations from the Rorschach: a review of the research and commentary.
While the research on the use of the Rorschach to assess object relations has been comprehensively reviewed in 1990 by Fishler, Sperling, and Carr and by Stricker and Healey, the research on the use of the Rorschach to assess object representations has not. This was the purpose of this paper. Research on the structure and content of Rorschach-derived object representations were examined. This research indicates that severity of clinical manifestation of psychopathology is accompanied by severity of distortion in the structure of Rorschach percepts and their perceived malevolence. Issues raised by this research and the kinds of research still needed were discussed.


Use of multi-velocity encoding 4D flow MRI to improve quantification of flow patterns in the aorta.
To show that the use of a multi-velocity encoding (VENC) 4D-flow approach offers significant improvements in the characterization of complex flow in the aorta. Four-dimensional flow magnetic resonance imaging (MRI) (4D-flow) can be used to measure complex flow patterns and dynamics in the heart and major vessels. The quality of the information derived from these measures is dependent on the accuracy of the vector field, which is limited by the vector-to-noise ratio. A 4D-flow protocol involving three different VENC values of 150, 60, and 20 cm/s was performed on six control subjects and nine patients with type-B chronic aortic dissection at 3T MRI. Data were processed using a single VENC value (150 cm/s) or using a fused dataset that selected the lowest appropriate VENC for each voxel. Performance was analyzed by measuring spatial vector angular correlation, magnitude correlation, temporal vector conservation, and "real-world" streamline tracing performance. The multi-VENC approach provided a 31% improvement in spatial and 53% improvement in temporal precision of velocity vector measurements during the mid-late diastolic period, where 99% of the flow vectors in the normal aorta are below 20 cm/s. In low-flow conditions this resulted in practical improvements of greater than 50% in pathline tracking and streamline tracing quantified by streamline curvature measurements. A multi-VENC 4D-flow approach provides accurate vector data across normal physiological velocities observed in the aorta, dramatically improving outputs such as pathline tracking, streamline estimation, and further advanced analyses.


Anthropological implication of the SDF1-3'A allele distribution in Southeast Asia and Melanesia.
The distribution of the SDF1-3'A allele among 1848 individuals in Southeast Asia and Melanesia was studied with the polymerase chain reaction-restriction fragment length polymorphism assay. The SDF1-3'A allele frequency in the populations of mainland Southeast Asia ranged from 0.0 to 0.355, whereas in the populations of insular Southeast Asia and Melanesia, it ranged from 0.233 to 0.733, with an increasing cline from west to east. Correlation between SDF1-3'A frequency and longitude values was highly significant for the populations in the Pacific region (r = 0.867, P < 0.001). The geographic distribution of the SDF1-3'A frequencies in the Pacific region was interpreted by an admixture of Austronesians with the aboriginal people in situ. In addition, this study found high proportions of SDF1-3'A/3'A homozygous individuals in several populations, which will enable us to evaluate roles of the SDF1 genotypes in SDF-1 expression.


Catalase-Loaded TaOx Nanoshells as Bio-Nanoreactors Combining High-Z Element and Enzyme Delivery for Enhancing Radiotherapy.
A novel type of bio-nanoreactor with catalase loaded inside TaOx hollow nanoshells is fabricated via a mild one-step method. Such bio-nanoreactors could efficiently improve the tumor oxygenation by supplying oxygen via decomposition of endogenic H2 O2 in a tumor microenvironment, and thus synergistically enhance the efficacy of cancer radiotherapy by both depositing radiation energy within the tumor and overcoming hypoxia-induced radiotherapy resistance.


Phase 2 trial of maintenance bevacizumab alone after bevacizumab plus pemetrexed and carboplatin in advanced, nonsquamous nonsmall cell lung cancer.
The authors performed a phase 2 study of bevacizumab plus pemetrexed and carboplatin followed by maintenance bevacizumab in patients with advanced, nonsquamous nonsmall cell lung cancer. Previously untreated patients with advanced, nonsquamous nonsmall cell lung cancer and an Eastern Cooperative Oncology Group performance status of 0 or 1 received bevacizumab 15 mg/kg, pemetrexed 500 mg/m(2) and carboplatin at an area under the concentration-time curve of 6 intravenously on day 1 every 21 days. Responding or stable patients who completed 6 cycles then received bevacizumab maintenance every 21 days until disease progression. In total, 43 patients (40 who were evaluable for response) were entered on the study. Treatment-related grade 3/4 toxicities were low and included febrile neutropenia (2%), neutropenia (28%), anemia (18%), thrombocytopenia (11%), hypertension (7%), epistaxis (5%), venous thrombosis (8%), dyspnea (7%), rectovaginal fistula (2.3%), infusion reaction (2%), and cerebrovascular event (2%). One patient died from complications of venous thromboembolism and cerebrovascular accident after Cycle 2. Minimal clinically significant toxicity occurred during maintenance bevacizumab. Two complete responses (5%) were observed, and 17 patients (42%) had a partial response. Fifteen patients (38%) displayed disease stability. The overall disease control rate was 85%. At a median follow-up of 15.8 months, the median progression-free survival was 7.1 months (95% confidence interval, 5.9-8.3 months), and the median overall survival was 17.1 months (95% confidence interval, 8.8-25.5 months). Combined bevacizumab, pemetrexed, and carboplatin followed by maintenance bevacizumab was well tolerated and displayed remarkable activity in patients with previously untreated, advanced, nonsquamous nonsmall cell lung cancer.


A comparison of cost-effectiveness of three protocols for diagnosis and treatment of gonococcal and chlamydial infections in women in Africa.
The cost-effectiveness of different STD diagnosis and treatment approaches has not been evaluated previously. The goals of the study were to compare the cost-effectiveness of "gold standard" care (GS), syndromic management (SM), and mass treatment (MT) protocols for the treatment of cervical gonococcal and chlamydial infections in a hypothetical model of 1 million women in Africa. A decision tree model was constructed for each of the protocols. Sensitivity analyses were conducted and 10,000 Monte Carlo simulations were run to test the robustness of the cost-effectiveness estimates to changes in underlying assumptions. MT with doxycycline for chlamydia was the most cost-effective protocol in terms of cost per cure. SM protocol had the lowest total programmatic costs. For the GS protocol, using azithromycin for chlamydial infections was found to be more cost-effective than using doxycycline. For both the GS and SM protocols, the total cost of the program was most sensitive to the percentage of women seeking STD treatment and the prevalence of non-STD vaginal discharge, whereas the cost of MT was almost exclusively determined by coverage rates. No single protocol carries with it all the desired conditions of an optimal cost-effective program. The treatment-seeking behavior, STD prevalence, and coverage of each locale must be evaluated to determine the most cost-effective and highest impact program. MT was found to be the most cost-effective protocol in terms of cost per woman treated when compared with the SM and GS protocols for STDs in women.


Syntheses in the group of aminoguanidine derivatives with immunosuppressive and cytostatic properties.
A number of new derivatives of amino-, nitroamino- and diaminoguanidine (I, II, III) were synthetized. The course of the reactions was studied and the structure of new compounds obtained was confirmed. Some of them exhibited strong immunosuppressive and cytostatic activities, especially compounds: IV, VI, VII, VIII and IX.


Direct-to-implant versus autologous tissue transfer: A meta-analysis of patient-reported outcomes after immediate breast reconstruction.
The effect of immediate implant and autologous breast reconstruction on complication rates has been studied extensively; however, the patient-reported outcomes for these procedures during immediate, one-stage reconstruction has yet to be comprehensively investigated. This study compared the patient-reported outcomes for immediate implant reconstruction with those associated with immediate autologous reconstruction to determine the advantages and disadvantages for each modality from the patient's perspective. A literature search of PubMed between 2010 and 2021 was performed, and 21 studies containing patient-reported outcomes were selected for the analysis. A meta-analysis of patient-reported outcome scores was performed separately for immediate breast reconstruction using autologous tissue transfer and synthetic implants. Nineteen manuscripts were included, representing data on a total of 1342 patients across all studies. The pooled mean of patients' satisfaction with their breasts was 70.7 (95% CI, 69.4-72.0) after immediate autologous reconstruction and 68.5 (95% CI, 67.1-69.9) after immediate implant reconstruction, showing a statistically significant difference in outcomes (p < 0.05). The pooled mean of patients' sexual well-being was 59.3 (95% CI, 57.8-60.8) after immediate autologous reconstruction and 62.8 (95% CI, 60.7-64.8) after immediate implant reconstruction (p < 0.01). The pooled mean of patients' satisfaction with their outcome was 78.8 (95% CI, 76.2-81.3) after immediate autologous reconstruction and 82.3 (95% CI, 80.4-84.1) after immediate implant reconstruction (p < 0.05). The results of each meta-analysis were summarized on forest plots depicting the distribution of patient-reported outcome scores from each study. Immediate reconstruction with implants may have a similar or greater capacity to achieve patient satisfaction and improve patients' QoL compared to those associated with immediate reconstruction with autologous tissue transfer when both procedures are available.


Current Status and Time Trends of Oral Anticoagulation Use Among Chinese Patients With Nonvalvular Atrial Fibrillation: The Chinese Atrial Fibrillation Registry Study.
Reported rates of oral anticoagulation (OAC) use have been low among Chinese patients with atrial fibrillation (AF). With improved awareness, changing guidelines, this situation may be changing over time. We aimed to explore the current status and time trends of OAC use in Beijing. We used the data set from the Chinese Atrial Fibrillation Registry (CAFR), a prospective, multicenter, hospital-based registry study involving 20 tertiary and 12 nontertiary hospitals in Beijing. A total of 11 496 patients with AF were enrolled from 2011 to 2014. Seven thousand nine hundred seventy-seven eligible patients were included in this ancillary study. The proportions of OAC use were 36.5% (2268/6210), 28.5% (333/1168), and 21.4% (128/599) for patients with CHA2DS2-VASc scores ≥2, 1, and 0, respectively. Persistent AF, history of stroke/transient ischemic attack/peripheral embolism, diabetes mellitus, higher body mass index, and tertiary hospital management were factors positively associated with OAC use, whereas older age, previous bleeding, hypercholesterolemia, and established coronary artery disease were factors negatively associated with OAC use. Among patients with CHADS2 scores ≥2 and CHA2DS2-VASc scores ≥2, the proportion of OAC use increased from 31.3% to 64.5% and 30.2% to 57.7%, respectively, from 2011 to 2014. Variation in OAC use was substantial among different hospitals. An improvement of OAC use among Chinese patients with AF in Beijing is observed in recent years although only 36.5% of patients with CHA2DS2-VASc score ≥2 received OAC. However, variations between different hospitals were large, suggesting that better education and awareness are needed to improve efforts for stroke prevention among AF patients. URL: http://www.chictr.org.cn/showproj.aspx?proj=5831. Unique identifier: ChiCTR-OCH-13003729.


Intramuscular pressure in the erector spinae and intra-abdominal pressure related to posture and load.
Intramuscular pressures in both Erectors Spinae and intra-abdominal pressures were measured during different holding tasks. To investigate the potential for using intramuscular pressure measurements in both Erectors Spinae to better quantitate the role of muscles during different lifting tasks in vivo. Intramuscular pressure and intra-abdominal pressure were measured previously under isometric and dynamic conditions. However, no previous study systematically has addressed the relation between intramuscular and intra-abdominal pressures and different loads, tasks, and postures. Intramuscular and intra-abdominal were measured simultaneously with microtip pressure transducers in 10 healthy volunteers performing 24 different static holding tasks. Tasks included different weights (10 kg and 20 kg), postures (squat or back lift), and positions of the weight. Intramuscular pressures were dependent on posture. Kyphotic back posture produced intramuscular pressures of 120-130 mm Hg, compared with the 10-25 mm Hg produced when volunteers were in the erect position (P < 0.001). Holding a 10-kg weight at the thighs close to the body produced significantly (P < 0.001) lower intramuscular pressures (25-32 mm Hg) than that produced by holding it 25 cm in front of the body (47-56 mm Hg). In all tasks, intramuscular pressures were significantly higher with the 20-kg weight than with the 10-kg weight (P < 0.001). Highest values (> 300 mm Hg) were measured when the 20-kg weight was held in the kyphotic posture above the floor and 25 cm away from the body. Intramuscular pressure measurements in the erector spinae seem to be a valuable tool for quantitating the role of back muscles during different lifting tasks.


Effect of Crocus sativus (Saffron) Intake on Top of Standard Treatment, on Disease Outcomes and Comorbidities in Patients with Rheumatic Diseases: Synthesis without Meta-Analysis (SWiM) and Level of Adherence to the CONSORT Statement for Randomized Controlled Trials Delivering Herbal Medicine Interventions.
Rheumatic diseases (RDs) are often complicated by chronic symptoms and frequent side-effects associated with their treatment. Saffron, a spice derived from the Crocus sativus L. flower, is a popular complementary and alternative medicine among patients with RDs. The present systematic review aimed to summarize the available evidence regarding the efficacy of supplementation with saffron on disease outcomes and comorbidities in patients with RD diagnoses. PubMed, CENTRAL, clinicaltrials.gov and the grey literature were searched until October 2021, and relevant randomized controlled trials (RCTs) were screened for eligibility using Rayyan. Risk of bias was assessed using the Cochrane's Risk of Bias-2.0 (RoB) tool. A synthesis without meta-analysis (SWiM) was performed by vote counting and an effect direction plot was created. Out of 125 reports, seven fulfilled the eligibility criteria belonging to five RCTs and were included in the SWiM. The RCTs involved patients with rheumatoid arthritis, osteoarthritis and fibromyalgia, and evaluated outcomes related to pain, disease activity, depression, immune response, inflammation, oxidative stress, health, fatigue and functional ability. The majority of trials demonstrated some concerns regarding overall bias. Moreover, the majority of trialists failed to adhere to the formula elaborations suggested by the CONSORT statement for RCTs incorporating herbal medicine interventions. Standardization of herbal medicine confirms its identity, purity and quality; however, the majority of trials failed to adhere to these guidelines. Due to the great heterogeneity and the lack of important information regarding the standardization and content of herbal interventions, it appears that the evidence is not enough to secure a direction of effect for any of the examined outcomes.


Infections related to Granulicatella adiacens: Report of two cases and review of literature.
Infections due to nutritionally variant streptococci are diagnosed rarely due to difficulties encountered during identification and isolation. Mortality rate in these infections is high therefore appropriate supplemented media and reliable detection systems should be implemented to isolate these fastidious organisms. Here, we describe two cases of Granulicatella adiacens infections. All microbiologic identifications were made with MALDI-TOF Vitek MS (BioMerieux, France), and the results confirmed by 16S ribotyping.


Effect of vaccine dosing intervals on Omicron surrogate neutralization after three doses of BNT162b2.
Increasing the interval between the first and second SARS-CoV-2 vaccine doses enhances vaccine immunogenicity, however the optimal timing of the third vaccine is unknown. In this study, we investigated how the time interval between the first and second (V1-V2), or second and third (V2-V3) doses affects immunogenicity after three doses of the BNT162b2 (Comirnaty, Pfizer-BioNTech) vaccine. This is an observational cohort consisting of 360 participants enrolled in the COVID-19 Occupational Risks, Seroprevalence, and Immunity among Paramedics in Canada (CORSIP) study. Immune responses to BA.1 and other variants were measured from serum using an ACE2 competitive binding assay for surrogate SARS-CoV-2 neutralization. We fit a multiple linear regression model to estimate the independent association between both the V1-V2 and V2-V3 intervals and serum SARS-CoV-2 neutralization, while adjusting for age, sex, and the V3-to-blood collection interval. We examined vaccine dosing intervals as continuous variables and categorized them into quartiles. The mean age was 40 years, 45% were female sex (at birth), and the median BA.1 surrogate neutralization was 61% (IQR 38-77%). The multivariate analysis indicated that longer V1-V2 (β = 0.1292, 95% CI: 0.04807-0.2104) and V2-V3 (β = 0.2653, 95% CI: 0.2291-0.3015) intervals were associated with increased surrogate neutralization of BA.1. These results were consistent when examining responses against Spike from other SARS-CoV-2 strains. When categorized into V2-V3 quartiles, the first (56-231 days), and second (231-266 days) quartiles demonstrated decreased BA.1 surrogate neutralization compared to the longest V2-V3 quartile (282-329 days). There was no significant difference in surrogate neutralization between the long (266-282 days) and longest (282-329 days) V2-V3 intervals. Longer intervals between first, second and third doses are independently associated with increased immunogenicity for all tested SARS-CoV-2 strains. Increasing the intervals between the second and third vaccine doses up to 8.9 months provided additive benefits increasing the immunogenicity of BNT162b2 vaccine schedules.


L-type calcium channel: Clarifying the "oxygen sensing hypothesis".
The heart is able to respond acutely to changes in oxygen tension. Since ion channels can respond rapidly to stimuli, the "ion channel oxygen sensing hypothesis" has been proposed to explain acute adaptation of cells to changes in oxygen demand. However the exact mechanism for oxygen sensing continues to be debated. Mitochondria consume the lion's share of oxygen in the heart, fuelling the production of ATP that drives excitation and contraction. Mitochondria also produce reactive oxygen species that are capable of altering the redox state of proteins. The cardiac L-type calcium channel is responsible for maintaining excitation and contraction. Recently, the reactive cysteine on the cardiac L-type calcium channel was identified. These data clarified that the channel does not respond directly to changes in oxygen tension, but rather responds to cellular redox state. This leads to acute alterations in cell signalling responsible for the development of arrhythmias and pathology.


PHMB modified photothermally triggered nitric oxide release nanoplatform for precise synergistic therapy of wound bacterial infections.
Bacterial infection has been considered as a significant obstacle for wound healing. Nitric oxide (NO), as a novel alternative for antibiotics, has emerged as a promising antibacterial agent. However, the precise spatiotemporal controlled release of NO still remains a major challenge. Herein, a near-infrared (NIR) light triggered NO release nanoplatform (designated as PB-NO@PDA-PHMB) with enhanced broad-spectrum antibacterial and anti-biofilm properties was constructed. Given that PB-NO@PDA-PHMB has strong absorption in the NIR region and exhibits excellent photothermal effect, it can rapidly trigger NO release by NIR irradiation. PB-NO@PDA-PHMB can effectively contact and capture bacteria, and then exhibit synergistic effect of photothermal and gas therapy. In vitro and in vivo experiments indicated that PB-NO@PDA-PHMB exhibited excellent biocompatibility, satisfactory synergistic antibacterial efficacy and the capability of accelerating wound healing. Under NIR irradiation (808 nm, 1 W cm-2, 7 min), PB-NO@PDA-PHMB (80 μg mL-1) achieved 100% bactericidal activity against both Gram-negative bacteria Escherichia coli (E. coli) and Gram-positive bacteria Staphyloccocus aureus (S. aureus), removed 58.94% of S. aureus biofilm. Therefore, this all-in-one antibacterial nanoplatform with high NIR responsiveness provides a promising antibiotic-free strategy for bacterial infection treatment.


CryoEM of bacterial secretion systems.
The need for bacteria to interact with their environment has driven the evolution of elaborate secretion systems. By virtue of their function, secretion systems are macromolecular complexes associated with the cell envelope and therefore inherently difficult to study by conventional structural biology techniques. Cryo-electron microscopy (cryoEM) has become an invaluable technique to study large membrane-embedded complexes and led to major advances in the mechanistic understanding of secretion systems. CryoEM comprises of two main modalities, namely single particle analysis and tomography. Here, we review how detailed structures retrieved by single particle analysis combine elegantly with tomography experiments in which the secretion systems are observed in their native cellular context.


Cytokines and anticytokines in psoriasis.
Psoriasis is a chronic autoimmune hyperproliferative skin disease of varying severity affecting approximately 2-3% of the general population in the USA and Europe. Although the pathogenesis of psoriasis has not been fully elucidated, an immunologic-genetic relationship is likely. Cutaneous and systemic overexpression of various proinflammatory cytokines (TNF, interleukins, interferon-gamma) has been demonstrated in psoriatic patients. We reviewed the current database literature and summarized the involvement of cytokines and their receptors in the pathogenesis and treatment of psoriasis. Although many cytokine/anti-cytokine therapies have been conducted, TNF antagonists in the treatment of both psoriasis arthropatica and vulgaris appear to be the most widely used clinically. Interestingly, the efficacy and tolerability of some cytokines (rhIL-11 or ABX-IL-8,) were found to be much lower than expected. Preliminary results obtained with cytokine and anti-cytokine therapies appear promising and as such continued research is clearly indicated.


Cellobiose dehydrogenase modified electrodes: advances by materials science and biochemical engineering.
The flavocytochrome cellobiose dehydrogenase (CDH) is a versatile biorecognition element capable of detecting carbohydrates as well as quinones and catecholamines. In addition, it can be used as an anode biocatalyst for enzymatic biofuel cells to power miniaturised sensor-transmitter systems. Various electrode materials and designs have been tested in the past decade to utilize and enhance the direct electron transfer (DET) from the enzyme to the electrode. Additionally, mediated electron transfer (MET) approaches via soluble redox mediators and redox polymers have been pursued. Biosensors for cellobiose, lactose and glucose determination are based on CDH from different fungal producers, which show differences with respect to substrate specificity, pH optima, DET efficiency and surface binding affinity. Biosensors for the detection of quinones and catecholamines can use carbohydrates for analyte regeneration and signal amplification. This review discusses different approaches to enhance the sensitivity and selectivity of CDH-based biosensors, which focus on (1) more efficient DET on chemically modified or nanostructured electrodes, (2) the synthesis of custom-made redox polymers for higher MET currents and (3) the engineering of enzymes and reaction pathways. Combination of these strategies will enable the design of sensitive and selective CDH-based biosensors with reduced electrode size for the detection of analytes in continuous on-site and point-of-care applications.


Regulation of urea synthesis by glucose and glucagon in normal man.
The separate effects of glucose and glucagon on alanine stimulated hepatic amino-N to urea-N conversion, quantified by the Functional Hepatic Nitrogen Clearance (FHNC) (i.e. the linear slope of the relation between urea synthesis rate and blood alpha-amino-N concentration), were studied in 7 healthy subjects. FHNC was measured four times in each: during constant infusion of alanine alone; alanine superimposed on constant glucose infusion; alanine superimposed on glucose and low stepwise glucagon infusions; and alanine super-imposed on glucose and high constant glucagon infusions. Glucose halved the glucagon response to alanine. This reduction was abolished by the low stepwise glucagon infusion, aimed at re-establishing portal glucagon levels. The high glucagon infusion resulted in 3-fold elevated glucagon levels. During alanine infusion alone FHNC was (mean +/- SEM) 32.5 +/- 1.9 l/h. Glucose reduced FHNC by 43% to 18.4 +/- 0.9 l/h (p < 0.01). The low stepwise glucagon infusion only partially normalized FHNC as reduced by glucose (to 24.6 +/- 1.5 l/h, (p < 0.01 vs alanine alone)). The high glucagon infusion increased FHNC by 35% despite hyperglycaemia (to 44.1 +/- 1.5 l/h, (p < 0.01 vs alanine alone)). The results show that both glucose and glucagon are independent but opposite regulators of hepatic amino-N conversion. The physiological glucose effect is accomplished by a combination of both the effect of glucose itself and the inhibition by glucose of the glucagon response to alanine. Hyperglucagonaemia increases FHNC and overrules the inhibition by glucose. This may explain the defect nitrogen sparing by glucose and to some extent the catabolism in hyperglucagonaemic stress conditions, despite prevailing hyperglycaemia.


Different effects of low muscle mass on the risk of non-alcoholic fatty liver disease and hepatic fibrosis in a prospective cohort.
Non-alcoholic fatty liver disease (NAFLD) and sarcopenia share insulin resistance as a common pathophysiology and have overlapping clinical manifestation of metabolic derangement; hence, it is difficult to differentiate the independent effect of sarcopenia on the development of NAFLD from concomitant metabolic disorders. Using a community-based prospective cohort study, the contributions of low muscle mass and genetic risk factors to the development of NAFLD and NAFLD-related hepatic fibrosis were investigated in the Korean population. This prospective community-based cohort study included 40-70-year-old adults, followed up biennially from 2001-2002 to 2017-2018. NAFLD was defined as a hepatic steatosis index of ≥36, and hepatic fibrosis was defined based on the fibrosis-4 index. Sex-specific quartiles of body mass index (BMI)-adjusted muscle mass were calculated (muscle mass/BMI), and low muscle mass was defined as the lowest quartile (Q1). Cox proportional hazard models for incident NAFLD or hepatic fibrosis incorporating age, sex, BMI of ≥25 kg/m2 , metabolic syndrome and PNPLA3 and TM6SF2 risk alleles were used to assess the independent determinants for incident NAFLD and hepatic fibrosis among individuals with NAFLD at baseline. Among the 4038 participants without NAFLD at baseline (mean age, 51.5 ± 8.8 years), 920 (22.8%) developed NAFLD during the 12-year follow-up period. As muscle mass decreased, the risk of NAFLD increased even after adjustment for age, sex, obesity, metabolic syndrome and PNPLA3 and TM6SF2 risk alleles [hazard ratio (HR) per quartile, 1.18, 95% confidence interval (CI), 1.11-1.27, P < 0.001]. TM6SF2 also affected the risk of NAFLD development [HR 1.19, (95% CI, 1.00-1.40), P = 0.044]. Of the 1176 patients with NAFLD but without hepatic fibrosis at baseline, the incident of hepatic fibrosis was found in 51.8%, 44.7%, 42.6% and 41.0% in Q1, Q2, Q3 and Q4 of BMI-adjusted muscle mass, respectively, during the follow-up period (P for trend = 0.006). However, this trend lost its statistical significance when adjusted for confounders. The PNPLA3 risk variant, but not the TM6SF2 genotype, was an independent risk factor for developing hepatic fibrosis among patients with NAFLD (HR 1.17, 95% CI 1.04-1.32, P = 0.010). Both lower muscle mass index and genetic risk variants are important contributors to the development of NAFLD. In patients already diagnosed with NAFLD, however, PNPLA3 confers a greater risk for hepatic fibrosis progression than lower muscle mass.


Temporary epicardial pacing wires post-cardiac surgery: a literature review.
Although epicardial pacing wires are routinely inserted after cardiac surgical procedures, there is little in the medical literature to help standardise their use and identify associated risks and benefits. Much of the decision-making surrounding pacing wires are based on the surgeon's preference and vary highly between centers. A literature review was conducted exploring the evidence, indications, and current practice for temporary pacing wires. Risk factors for developing post-operative arrhythmias necessitating use of temporary pacing wires and complications were also reviewed. Although temporary epicardial pacing wires have a crucial role to play in the post-operative recovery period, the current literature suggests that they should be considered on an individual basis in all high-risk patients including increased age, low ejection fraction, diabetes mellitus, elevated pulmonary artery pressures, prolonged cross clamp time, pacing required to wean from bypass, pre-operative arrhythmia, and multiple valvular and transplant operations. Although complications from pacing wires are low, this figure is likely underreported and further studies are required to focus on the risks and benefits of insertion.


Genital tract actinomycosis caused by Actimyces israëlii.
We report a case of actinomycosis caused by actinomyces israelii, related to the removal of intrauterine device (IUD). Diagnosing actinomycosis is difficult but should be considered in the event of any acute abdominal problems in a woman carrying an IUD. All abdominal organs may be affected. Even with a disseminated infection, the combination of appropriate antibiotic therapy (penicillin G) and surgery ensures a full recovery in most cases.


Ultrasound cavitation enhanced chemotherapy: In vivo research and clinical application.
The novelty of this research is that we used ultrasound cavitation to enhance the effects of chemotherapy in the subcutaneous and orthotopic hepatic carcinomas in nude mice. Case reports of the effects of the targeting ultrasound cavitation and chemotherapy on malignant tumors in clinical patients were also examined. We found that low-frequency ultrasound cavitation combined with chemotherapy is effective in the inhibition of tumor growth to some extent.


Nonrandom orientation of transposon Tn5supF insertions in phage lambda.
Transposition of mini-transposon Tn5supF to phage lambda can be selected in two ways: (i) by plaque formation on a dnaB amber strain of Escherichia coli, which requires expression of the transposon-borne suppressor tRNA gene (supF) during lytic phage growth, or (ii) by lysogenization of a strain with amber mutations in tet and amp resistance genes, and selection of TcR ApR (Sup+) transductant colonies. Tn5supF insertions in several lambda clones were isolated and mapped using a polymerase chain reaction (PCR) amplification method. Among insertions selected during lytic growth, more than 90% were oriented such that supF could be transcribed from an upstream lambda promoter. In contrast, half of those selected by transduction were in each orientation. These results indicate that Tn5supF insertion occurs with equal frequency in each orientation. However, Tn5supF insertion phages in which transcription from the lambda and supF promoters would collide tend to be lost when supF is selected during lytic growth. The tendency to recover Tn5supF insertions in only one orientation is useful in a transposon- and crossover-PCR-based method for preparing templates for DNA sequencing.


alpha-Tocopherol protects against pentylenetetrazol- and methylmalonate-induced convulsions.
Increased excitatory amino acid transmission and decreased GABAergic inhibitory responses seem to be important mechanisms in the genesis of convulsions, where reactive oxygen species (ROS) have recently been suggested to play a critical role. Therefore, administration of antioxidants may be potentially beneficial for the treatment of convulsive states. In the current study we investigated the effect of the systemic Vitamin E administration, an antioxidant, on the convulsions and oxidative damage induced by two convulsant agents with different mechanisms of action: methylmalonic acid (MMA), which induces convulsions through energy depletion and secondary activation of glutamatergic mechanisms and ROS production and pentylenetetrazol (PTZ), which is a chemical convulsant that causes convulsions by blocking the GABAA receptor-coupled chloride ionophore. Adult male Wistar rats (270-300 g) were injected with vehicle (5% Tween 80 in 0.9% NaCl; 1 ml/kg, i.p.) or alpha-tocopherol (25, 75 or 225 mg/kg, i.p.), once a day for 7 days. On the seventh day of antioxidant treatment, the animals were injected with the antioxidant (or vehicle) and, 30 min later, they were intrastriatally injected with NaCl (9 micromol/2 microl) or with MMA (6 micromol/2 microl) or PTZ (3.26 mmicromol/2 microl). The animals were observed for the appearance of convulsive behavior and the striatal content of thiobarbituric acid-reactive substances (TBARS) and total protein carbonylation were determined. Intrastriatal injection of increasing amounts of PTZ and of MMA caused the appearance of convulsive behavior. PTZ- and MMA-induced convulsions, TBARS production and total protein carbonylation were attenuated by alpha-tocopherol in a dose-dependent manner.


Corrigendum: Global Lysine Crotonylation Alterations of Host Cell Proteins Caused by Brucella Effector BspF.
[This corrects the article DOI: 10.3389/fcimb.2020.603457.].


Causal associations between obstructive sleep apnea and COVID-19: A bidirectional Mendelian randomization study.
The COVID-19 pandemic has caused significant impact on human health. Whether obstructive sleep apnea (OSA) increases the risk of COVID-19 remains unclear. We sought to clarify this issue using two-sample Mendelian randomization (TSMR) analysis in large cohorts. Bidirectional two-sample Mendelian randomization (MR) was used to evaluate the potential causality between OSA and COVID-19 by selecting single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) from genome-wide association studies (GWAS). The inverse-variance weighted (IVW) method was selected as the main approach for data analysis to estimate the possible causal effects. Alternative methods such as MR-Egger, the MR pleiotropy residual sum and outlier (MR-PRESSO), and leave-one-out analysis methods were implemented as sensitivity analysis approaches to ensure the robustness of the results. All forward MR analyses consistently indicated the absence of a causal relationship between OSA and any COVID-19 phenotype. In the reverse MR analysis, the IVW mode demonstrated that severe respiratory confirmed COVID-19 was correlated with a 4.9% higher risk of OSA (OR, 1.049; 95%CI, 1.018-1.081; P = 0.002), consistent in MR-PRESSO (OR = 1.049, 95%CI 1.018-1.081, P = 0.004), weighted median (OR = 1.048, 95%CI 1.003-1.095, P = 0.035), and MR-Egger (OR = 1.083, 95%CI 1.012-1.190, P = 0.041) methods. There is no significant evidence supporting a causal association between OSA and any COVID phenotype, while we identified potential evidence for a causal effect of severe COVID-19 on an increased risk of OSA.


Minireview: the diverse roles of nuclear receptors in the regulation of embryonic stem cell pluripotency.
Extensive research has been devoted to the goal of understanding how a single cell of embryonic origin can give rise to every somatic cell type and the germ cell lineage, a hallmark defined as "pluripotency." The aggregate of this work supports fundamentally important roles for the gene transcription networks inherent to the pluripotent cell. Transcription networks have been identified that are both required for pluripotency, as well as sufficient to reprogram somatic cells to a naive pluripotent state. Several members of the nuclear receptor (NR) superfamily of transcription factors have been identified to play diverse roles in the regulation of pluripotency. The ligand-responsive nature of NRs coupled with the abundance of genetic models available has led to a significant advance in the understanding of NR roles in embryonic stem cell pluripotency. Furthermore, the presence of a ligand-binding domain may lead to development of small molecules for a wide range of therapeutic and research applications, even in cases of NRs that are not known to respond to physiologic ligands. Presented here is an overview of NR regulation of pluripotency with a focus on the transcriptional, proteomic, and epigenetic mechanisms by which they promote or suppress the pluripotent state.


Dysregulation of MiR-199a/IL8 pathway in chronic Cr (VI)-induced tumor growth and angiogenesis.
Hexavalent chromium [Cr(VI)] is a well-known environmental carcinogen. Recent studies revealed that chronic exposure of human bronchial epithelial cells (BEAS-2B, B2B) to Cr(VI) activated several signaling pathways and induced cell malignant transformation and tumor growth. However, new mechanisms of Cr(VI) in inducing carcinogenesis remains to be elucidated. This study showed that miR-199a expression levels were significantly lower in Cr(VI)-transformed Cr-T cells. By using the mouse model, the expression levels of miR-199a were significantly decreased in blood samples and lung tissues of mice intranasally exposed to Cr(VI) for 12 weeks compared to the solvent exposure control. Overexpression of miR-199a inhibited tube formation and angiogenesis. C-X-C motif chemokine ligand 8 (CXCL8, IL8) levels were significantly higher in blood samples of Cr (VI)-exposed workers compared to normal workers, and forced expression of miR-199a in the cells suppressed IL8 levels. miR-199a suppression induced expression of hypoxia-inducible factor 1α (HIF-1α) and nuclear factor kappa B (NF-κB) p65 to increase IL8 expression. With animal experiment, the results showed that miR-199a overexpression inhibited tumor growth and angiogenesis through inhibiting IL8, HIF-1α and NF-κB p65 expression in vivo. These results show that miR-199a/IL8 pathway is important in Cr(VI)-induced carcinogenesis and angiogenesis.


Tat protein expression in MDBK cells does not confer susceptibility to bovine immunodeficiency virus.
The ability of BIV strain R29 to infect bovine cell lines in the presence or absence of a functional lentiviral Tat protein is described. Jembrana disease virus (JDV) Tat protein was stably expressed in MDBK cells. No viral replication could be detected in this cell line after infection with BIV R29. Transfection of MDBK cells and MDBK Tat expressing cells with BIV R29 proviral DNA established that BIV R29 could not replicate in MDBK cells. Whether viral entry into MDBK cells is also a block to BIV R29 infection of MDBK cells has yet to be established.


An integrated metabonomic and proteomic study on Kidney-Yin Deficiency Syndrome patients with diabetes mellitus in China.
To investigate specific changes in metabolites and proteins of Kidney-Yin Deficiency Syndrome (KYDS) patients with diabetes mellitus (DM) in China. KYDS (n=29) and non-KYDS (n=23) patients with DM were recruited for this study. The KYDS was diagnosed by two senior TCM clinicians separately. The metabonomic and proteomic profiles of the patients were assessed using a metabonomic strategy based on NMR with multivariate analysis and a proteomic strategy based on MALDI-TOF-MS, respectively. Eighteen upregulated peptides and thirty downregulated peptides were observed in the plasma of the KYDS patients. Comparing the proteomic profiles of the KYDS and non-KYDS groups, however, no significantly differentially expressed peptides were found. At the same time, major metabolic alterations were found to distinguish the two groups, including eight significantly changed metabolites (creatinine, citrate, TMAO, phenylalanine, tyrosine, alanine, glycine and taurine). The levels of creatinine, citrate, TMAO, phenylalanine and tyrosine were decreased, whereas the levels of alanine, glycine and taurine were increased in the KYDS patients. These biochemical changes were found to be associated with alterations in amino acid metabolism, energy metabolism and gut microflora. The identification of distinct expression profiles of metabolites and signaling pathways in KYDS patients with DM suggests that there are indeed molecular signatures underlying the principles of 'Syndrome Differentiation' in traditional Chinese medicine.


The utilization of transcutaneous electric nerve stimulation in postoperative ileus.
Pain stimuli with resulting sympathetic hyperactivity are responsible for the inhibition of intestinal motility. In this clinical study on 30 adult patients after laparotomy, the effect of intermittent transcutaneous stimulation with a diadynamic current on intestinal motility was determined. It was established that bowel sounds return soon after transcutaneous nerve stimulation, and more than 50% of the patients passed flatus within 24 hours after the commencement of stimulation.


[Complementary nuclear DNA in embryo sac cells of Haemanthus albiflos and Ornithogalum caudatum].
Cytophotometric measurements of Feulgen-DNA were carried out in the nuclei of embryo sac cells of Haemanthus albiflos and Ornithogalum caudatum. It was found that the nuclei of the egg system, haploid in the number of chromosomes, became polyploid in DNA amount at the final stages of gametophyte development.


Trehalase from the bean-shaped accessory glands and the spermatophore of the male mealworm beetle, Tenebrio molitor.
In Tenebrio molitor, male adults transfer sperm to the female via a spermatophore or sperm sac. The spermatophore is formed from secretions of the bean-shaped accessory glands (BAGs) and the tubular accessory glands (TAGs) of the male beetle. Trehalase is found in the adult BAGs. During the pupal stage, the activity in the BAGs was very low. After adult ecdysis, the total activity increased 100-fold from 0 days to 6 days and reached maximum levels at 9 days. The specific activity increased 20-fold from the time of ecdysis to 6 days thereafter. In the 10 day adult, trehalase levels in testes, seminal vesicles, vas deferens, TAGs, or ejaculatory ducts, were lower by two orders of magnitude than in the BAGs. However, the specific activity in the spermatophore was similar to that in the BAGs. Trehalases in the BAGs and the spermatophores showed very similar properties (soluble, optimum pH of 5.75 and Km value of 5.4 mM for trehalose). Thus trehalase appears to be secreted from the BAGs and becomes incorporated into the spermatophores.


Recovery of Valuable Materials and Methods for Their Management When Recycling Thin-Film CdTe Photovoltaic Modules.
Due to the development of new photovoltaic technologies, there is a need to research new recycling methods for these new materials. The recovery of metals from photovoltaic (PV) modules would reduce the consumption of raw materials. Therefore, the development of recycling technologies for used and damaged modules of newer generations is important for environmental reasons. The aim of the research is to shed light on the nature of the chemical reactions that occur in recycling technology for second-generation photovoltaic modules. This work is focused mainly on cells made of Cadmium Telluride (CdTe). It was proven that prior thermal delamination was necessary. Moreover, an improvement in understanding of the recovery process depending on used leaching solution was achieved.


Endotoxin-induced ocular inflammation increases prostaglandin E2 synthesis by rabbit lens.
Twenty-four hours after the intravitreal injection of 0.1-100 ng of Escherichia coli endotoxin into one eye of the New Zealand white rabbit, lenses from the inflamed eyes synthesized significantly more prostaglandin E2 (PGE2) than their contralateral, control lenses at all doses of endotoxin greater than 0.1 ng. PGE2 elevations were also seen in the aqueous and vitreous humors from inflamed eyes. Lenses did not synthesize 6-keto-PGF1alpha (a stable metabolite of PGI2). Incubation of untreated lenses with 1 microgram ml-1 of endotoxin for 24 h did not increase PGE2 production. These results indicate that rabbit lens can synthesize PGE2, that this synthesis is significantly increased 24 hr after the intravitreal infusion of E. coli endotoxin, and that this increased PGE2 synthesis is most likely not due to a direct action of endotoxin on the lens.


Risk factors and preventative measures of early and persistent dysphagia after anterior cervical spine surgery: a systematic review.
To conduct a systematic review of literature to determine risk factors and preventative measures of early and persistent dysphagia after anterior cervical spine surgery (ACSS). On March 2017, we searched the database PubMed, Medline, EMBASE, the Cochrane library, Clinical key, Springer link and Wiley Online Library without time restriction using the term 'dysphagia', 'swallowing disorders', and 'anterior cervical spine surgery'. Selected papers were examined for the level of evidence by published guidelines as level I, level II, level III, level IV studies. We investigated risk factors and preventative measures of early or persistent dysphagia after ACSS from these papers. The initial search yielded 515 citations. Fifty-nine of these studies met the inclusion and exclusion criteria. Three of them were level I evidence studies, 29 were level II evidence studies, 22 were level III evidence studies, and 3 were level IV evidence studies. Preventable risk factors included prolonged operative time, use of rhBMP, endotracheal tube cuff pressure, cervical plate type and position, dC2-C7 angle, psychiatric factors, tobacco usage, prevertebral soft tissue swelling, SLN or RLN palsy or injury of branches. Preventative measures included preoperative tracheal traction exercise, maintaining endotracheal tube cuff pressure at 20 mm Hg, avoiding routine use of rhBMP-2, use of zero-profile implant, use of Zephir plate, use of new cervical retractor, steroid application, avoiding prolonged operating time, avoiding overenlargement of cervical lordosis, decreasing surgical levels, ensuring knowledge of anatomy of superior laryngeal nerve and recurrent laryngeal nerve, to comfort always, patients quitting smoking and doctors ensuring improved skills. Unpreventable risk factors included age, gender, multilevel surgery, revision surgery, duration of preexisting pain, BMI, blood loss, upper levels, preoperative comorbidities and surgical type. Adequate preoperative preparation of the patients including preoperative tracheal traction exercise and quitting smoking, proper preventative measures during surgery including maintaining endotracheal tube cuff pressure at 20 mm Hg, avoiding routine use of rhBMP-2, use of zero-profile implant, use of Zephir plate, use of new cervical retractor, steroid application, avoiding prolonged operating time, avoiding overenlargement of cervical lordosis and decreasing surgical levels, doctors ensuring knowledge of anatomy, improved surgical techniques and to comfort always are essential for preventing early and persistent dysphagia after ACSS.


Salivary gland emergencies.
Salivary gland disorders are uncommon in the emergency department setting. Given the vast differential that spans infectious, autoimmune, neoplastic, and metabolic processes, they can pose a diagnostic challenge even to skilled clinicians. There is a paucity of evidence-based data regarding the management of these disorders with frequent incongruence between specific sources. Although by no means exhaustive or absolute, this article reconciles existing literature and serves as a concise and informative guide to salivary gland disorders encountered by the emergency care practitioner.


Assessing the Impact of COVID-19 on Retention in HIV Primary Care: A Longitudinal Multisite Analysis.
We compared retention in care outcomes between a pre-COVID-19 (Apr19-Mar20) and an early-COVID-19 (Apr20-Mar21) period to determine whether the pandemic had a significant impact on these outcomes and assessed the role of patient sociodemographics in both periods in individuals enrolled in the Data for Care Alabama project (n = 6461). Using scheduled HIV primary care provider visits, we calculated a kept-visit measure and a missed-visit measure and compared them among the pre-COVID-19 and early-COVID-19 periods. We used logistic regression models to calculated odds ratios (OR) and accompanying 95% confidence intervals (CI). Overall, individuals had lowers odds of high visit constancy [OR (95% CI): 0.85 (0.79, 0.92)] and higher odds of no-shows [OR (95% CI): 1.27 (1.19, 1.35)] during the early-COVID-19 period. Compared to white patients, Black patients were more likely to miss an appointment and transgender people versus cisgender women had lower visit constancy in the early-COVID-19 period.


High-pressure stopped-flow fluorometry at subzero temperatures: application to kinetics of the binding of NADH to liver alcohol dehydrogenase.
A stopped-flow apparatus operating in fluorescence mode over temperature and pressure ranges of +30 to -30 degrees C and 10(-3) to 2 kbar, respectively, is described. The system was interfaced on a special spectrofluorometer. Its general design is an improvement of the previous instrument (C. Balny, J. L. Saldana, and N. Dahan, (1984) Anal. Biochem. 139, 178-189) in that the observation chamber and the driving mechanism have been modified. The application of the method to kinetics of the binding of NADH to horse liver alcohol dehydrogenase at subzero temperatures and as a function of hydrostatic pressure is described.


Yellow fever virus strains Asibi and 17D-204 infect human umbilical cord endothelial cells and induce novel changes in gene expression.
Yellow fever (YF) is a zoonotic infection with more than 200,000 cases reported annually. Relatively little is known about YF pathogenesis in humans. In this study, we demonstrate that human vascular endothelial cells are susceptible to infection with wild-type and vaccine strains of the YFV and that these infections lead to a differential cellular response to infection. The infection of endothelial cells with either virus resulted in a significant induction of interferon-inducible genes p 78 and Cig 5 while wild-type virus induced a much more pronounced IL 6 and Bc l2 response than did the vaccine strain. Both viruses induced RANTES gene expression, but only the wild-type virus had corresponding increases in RANTES protein expression. The results demonstrate that the wild-type and vaccine strains of YFV elicit significantly different responses to infection in endothelial cells, despite being nearly identical genetically. These differences may account for the attenuated phenotype of the YFV vaccine strain, though the mechanism remains unclear. These data also point to a role for vascular endothelial cells in YF hemorrhagic fever and also suggest that IL 6 may play a role in increased viral pathogenesis, perhaps by influencing coagulation via release of coagulation co-factors such as fibrin or fibrinogen.


Bronchial compression: an unusual manifestation of sarcoidosis.
A patient with sarcoidosis is presented, in whom computed tomography demonstrated significant compression of the bronchi by surrounding lymphadenopathy.


Pegylated liposomal doxorubicin (PLD) in daily practice-A single center experience of treatment with PLD in patients with comorbidities and older patients with metastatic breast cancer.
Real-world data about pegylated liposomal doxorubicin (PLD) in patients with metastatic breast cancer (MBC) are limited. We have aimed to highlight the role of PLD in daily practice focusing on older patients and patients with comorbidities with MBC. We analyzed electronic records of all patients with advanced/metastatic breast cancer treated with single-agent PLD at the University Hospital Basel between 2003 and 2021. Primary endpoint was time to next chemotherapy or death (TTNC). Secondary endpoints were overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). We performed univariate and multivariate analysis for clinical variables. 112 patients with MBC having received single-agent PLD in any treatment line were analyzed, including 34 patient who were older than 70 years and 61 patients with relevant comorbidities. Median TTNC, OS, and PFS for treatment with PLD were 4.6, 11.9, and 4.4 months, respectively. ORR was 13.6%. Age >70 years predicted shorter OS (median 11.2 months) in multivariate analysis (hazard ratio [HR] 1.83, 95% CI 1.07-3.11, p = 0.026). Age and comorbidities did not significantly affect other endpoints. Unexpectedly, hypertension predicted longer TTNC (8.3 months, p = 0.04) in univariate analysis, maintained in multivariate analysis as a trend for both TTNC (HR 0.62, p = 0.07) and OS (HR 0.63, p = 0.1). Age predicted shorter OS significantly but median OS was not relevantly shorter in older patients. PLD remains a treatment option in patients with comorbidities and older patients with MBC. However, our real-world results of PLD appear underwhelming compared to relevant phase II trials through all age groups, pointing to an efficacy-effectiveness gap, possibly due to sampling bias.


Seasonal variation in trachoma prevalence among children, District Dera Ghazi Khan of Punjab, Pakistan.
The study objective was to estimate trachoma prevalence in relation to seasonal variation among children. Study Design was cross sectional and data was collected during all seasons of the year. After randomization of population units, 10% of them were identified by lottery and 5% of them were selected and examined for active trachoma case detection by simple random sampling technique. Total number of study participants were nine thousand seven hundred and ten (n=9710) from both urban and rural population units. The study was conducted during January -December 2018 during all three seasons of the year. After clinical examination, data was entered into a questionnaire Performa, which was used as tool for data collection. A Chi-square test was applied to compare trachoma cases among different seasons and among both boys and girls. Maximum burden of disease (62.4%) was reported during spring and winter season. Both spring and winter seasons have six months duration. During summer season, 70(37.6%) cases were reported. A highly significant (<0.01) relationship was reported between summer and spring seasons and trachoma prevalence (p < 0.01). A high prevalence was noted among female children. Higher prevalence of active trachoma was noted during summer season.


Microfiberoptic fluorescence photobleaching reveals size-dependent macromolecule diffusion in extracellular space deep in brain.
Diffusion in brain extracellular space (ECS) is important for nonsynaptic intercellular communication, extracellular ionic buffering, and delivery of drugs and metabolites. We measured macromolecular diffusion in normally light-inaccessible regions of mouse brain by microfiberoptic epifluorescence photobleaching, in which a fiberoptic with a micron-size tip is introduced deep in brain tissue. In brain cortex, the diffusion of a noninteracting molecule [fluorescein isothiocyanate (FITC)-dextran, 70 kDa] was slowed 4.5 +/- 0.5-fold compared with its diffusion in water (D(o)/D), and was depth-independent down to 800 microm from the brain surface. Diffusion was significantly accelerated (D(o)/D of 2.9+/-0.3) in mice lacking the glial water channel aquaporin-4. FITC-dextran diffusion varied greatly in different regions of brain, with D(o)/D of 3.5 +/- 0.3 in hippocampus and 7.4 +/- 0.3 in thalamus. Remarkably, D(o)/D in deep brain was strongly dependent on solute size, whereas diffusion in cortex changed little with solute size. Mathematical modeling of ECS diffusion required nonuniform ECS dimensions in deep brain, which we call "heterometricity," to account for the size-dependent diffusion. Our results provide the first data on molecular diffusion in ECS deep in brain in vivo and demonstrate previously unrecognized hindrance and heterometricity for diffusion of large macromolecules in deep brain.


Cytogenetic studies of 19 meningiomas and their clinical significance. I.
Cytogenetic analysis of 19 meningiomas from 10 female and 9 male patients are reported. Chromosomal abnormalities were found in all cases with a stemline karyotype 45, XY, -22 or 45, XX, -22. Three of these had additional sidelines: (a) 44, XX, -1, -4, -6, -8, -22, +19, +del(1) (:p33----q43), +dup(1) (p24----q31) t(1;1) (pter----p33::ter): (b) 44, X, -9, -14, -22, -X, +4, +del(X) (pter----q26), and (c) 44, XY, -19, -22, respectively.


Bioethanol production from deacetylated yellow poplar pretreated with oxalic acid recovered through electrodialysis.
Electrodialysis (ED) was used to develop a multistage oxalic acid recovery and pretreatment system to produce ethanol from deacetylated yellow poplar. Pretreatment of the biomass was performed at 150°C for 42 min using 0.16 M oxalic acid. The efficiency of oxalic acid recovery from the hydrolysate reached up to 92.32% in all the stages. Ethanol production and ethanol yield of ED-treated hydrolysate in each stage showed a uniform pattern ranging from 6.81 g/L to 7.21 g/L and 0.40 g/g to 0.43 g/g, respectively. The results showed that efficiency of ethanol production increased when deacetylated biomass and ED process was used. Ethanol yield from the pretreated biomass using simultaneous saccharification and fermentation (SSF) was in the range of 80.59-83.36% in all the stages. The structural characterization of the pretreated biomass at each stage was investigated and structural changes were not significantly different among the various pretreated biomass.


Topographical mapping of GnRH receptors on dispersed mouse pituitary cells by backscattered electron imaging.
Mouse anterior pituitary cells cultured for 2 days were stimulated with one of three biotinylated-GnRH probes ([biotinyl-Lys6]-[D-Lys6]GnRH, [biotinyl-Ser4]-[D-Lys6]GnRH, [biotinyl-Ser4]-[D-Trp6, des-Gly10]GnRH) in the cold (4 degrees C) for 1 hr. These cells were subsequently fixed and an avidin-gold complex was conjugated to the bound GnRH. After a second fixation, the gold label was silver-enhanced for viewing with a scanning electron microscope. Gonadotropes were identified as a result of the labeling procedure, measured for size, and the number of GnRH receptor sites counted. Gonadotropes ranged from 3 to 13 microns in diameter and contained from 23.2 +/- 3.3 to 338.4 +/- 25.2 sites per cell depending upon the size of the cell and the ligand employed. The methods described should be applicable for studying the topographical distribution of a variety of cellular receptors.


Mitoxantrone as a prospective photosensitizer for photodynamic therapy of breast cancer.
Photodynamic therapy has the potential to become an effective alternate to surgery for the treatment of cancer. In recent years, there has been a focus on identifying more effective and less toxic photosentisizers for use in photodynamic therapy. The purpose of this study was to assess the effectiveness of mitoxantrone, a chemotherapeutic agent, as a photosensitizer for photodynamic therapy in the MCF-7 human breast cancer cell line. Cytotoxicity was evaluated for different concentrations of mitoxantrone, and photosensitivity was assessed using a non-coherent light source. The percentage of the cell survival after 24 h was investigated using the MTT assay. Overall, the results showed that mitoxantrone is a remarkably efficient photosensitizer that could mediate MCF-7 cell death at a low concentration (5 μM) with modest exposure to light. It is surprising to find that a chemotherapeutic agent can be an effective photosensitizer for PDT in vitro.


Study of antioxidant activity of fodder grasses using microbial test systems.
To measure the biological activities of extracts of fodder grasses Onobrýchis arenária, Galéga orientális and Rhaponticum carthamoides that are commonly planted in Europe, Middle East and eastern Africa. Microbial test-systems based on Escherichia coli BW25113 that allow measurement of gene expression, growth and survival, biofilm formation (BF) in combination with the standard chemical procedures were used. The extracts studied had radical scavenging and metal-chelating activities and induced expression of antioxidant genes via generation of hydrogen peroxide. However, the extracts did not affect bacterial growth in planktonic cultures but dose-dependently inhibited BF. The most remarkable effects were observed in G. orientalis, a high-yielding crop, rich in crude protein and fibres. Taking into account the antibiofilm activities of the extracts, a perspective for decreasing colonization of ruminants' gut with pathogenic bacteria might be suggested in case of feeding with all the grasses studied.


Oral versus intramuscular administration of vitamin B12 for vitamin B12 deficiency in primary care: a pragmatic, randomised, non-inferiority clinical trial (OB12).
To compare the effectiveness of oral versus intramuscular (IM) vitamin B12 (VB12) in patients aged ≥65 years with VB12 deficiency. Pragmatic, randomised, non-inferiority, multicentre trial in 22 primary healthcare centres in Madrid (Spain). 283 patients ≥65 years with VB12 deficiency were randomly assigned to oral (n=140) or IM (n=143) treatment arm. The IM arm received 1 mg VB12 on alternate days in weeks 1-2, 1 mg/week in weeks 3-8 and 1 mg/month in weeks 9-52. The oral arm received 1 mg/day in weeks 1-8 and 1 mg/week in weeks 9-52. Serum VB12 concentration normalisation (≥211 pg/mL) at 8, 26 and 52 weeks. Non-inferiority would be declared if the difference between arms is 10% or less. Secondary outcomes included symptoms, adverse events, adherence to treatment, quality of life, patient preferences and satisfaction. The follow-up period (52 weeks) was completed by 229 patients (80.9%). At week 8, the percentage of patients in each arm who achieved normal B12 levels was well above 90%; the differences in this percentage between the oral and IM arm were -0.7% (133 out of 135 vs 129 out of 130; 95% CI: -3.2 to 1.8; p>0.999) by per-protocol (PPT) analysis and 4.8% (133 out of 140 vs 129 out of 143; 95% CI: -1.3 to 10.9; p=0.124) by intention-to-treat (ITT) analysis. At week 52, the percentage of patients who achieved normal B12 levels was 73.6% in the oral arm and 80.4% in the IM arm; these differences were -6.3% (103 out of 112 vs 115 out of 117; 95% CI: -11.9 to -0.1; p=0.025) and -6.8% (103 out of 140 vs 115 out of 143; 95% CI: -16.6 to 2.9; p=0.171), respectively. Factors affecting the success rate at week 52 were age, OR=0.95 (95% CI: 0.91 to 0.99) and having reached VB12 levels ≥281 pg/mL at week 8, OR=8.1 (95% CI: 2.4 to 27.3). Under a Bayesian framework, non-inferiority probabilities (Δ>-10%) at week 52 were 0.036 (PPT) and 0.060 (ITT). Quality of life and adverse effects were comparable across groups. 83.4% of patients preferred the oral route. Oral administration was no less effective than IM administration at 8 weeks. Although differences were found between administration routes at week 52, the probability that the differences were below the non-inferiority threshold was very low. NCT01476007; EUDRACT (2010-024129-20).


Atrial natriuretic factor inhibits the CRH-stimulated secretion of ACTH and cortisol in man.
Corticotrophic secretion of ACTH is stimulated by corticotropin-releasing hormone (CRH) and arginine vasopressin (AVP), and suppressed by glucocorticoids. In vitro and preclinical studies suggest that atrial natriuretic factor (ANF) may be a peptidergic inhibitor of pituitary-adrenocortical activity. The aim of this study was to elucidate a possible role of ANF as a modulator of ACTH release in humans. A bolus injection of 100 micrograms human CRH (hCRH) during a 30 min intravenous infusion of 5 micrograms/min human alpha atrial natriuretic factor (h alpha ANF) was administered at 19:00 to six healthy male volunteers. In comparison to saline, a blunted CRH-stimulated secretion of ACTH (mean maximum plasma level +/- SD 45 min after hCRH: saline 46.2 +/- 14.2 pg/ml, h alpha ANF 34.6 +/- 13.8 pg/ml, p-value = 0.007) and a delayed rise (10 min) in cortisol were detected. The maximum plasma cortisol levels remained nearly unchanged between saline and h alpha ANF administration (mean maximum plasma level +/- SD 60 min after hCRH: saline 182 +/- 26 ng/ml, h alpha ANF 166 +/- 54 ng/ml). No effects of h alpha ANF on basal cortisol levels were observed; in contrast, basal ACTH plasma levels were slightly reduced. Basal blood pressure and heart rate remained unaffected. In the control experiment, infusion of 3 IU AVP in the same experimental paradigm increased basal and stimulated ACTH and cortisol levels significantly in comparison to saline. These observations suggest that intravenously administered haANF inhibits the CRH-stimulated release of ACTH in man.


Testosterone enhances cardiomyogenesis in stem cells and recruits the androgen receptor to the MEF2C and HCN4 genes.
Since a previous study (Goldman-Johnson et al., 2008 [4]) has shown that androgens can stimulate increased differentiation of mouse embryonic stem (mES) cells into cardiomyocytes using a genomic pathway, the aim of our study is to elucidate the molecular mechanisms regulating testosterone-enhanced cardiomyogenesis. Testosterone upregulated cardiomyogenic transcription factors, including GATA4, MEF2C, and Nkx2.5, muscle structural proteins, and the pacemaker ion channel HCN4 in a dose-dependent manner, in mES cells and P19 embryonal carcinoma cells. Knock-down of the androgen receptor (AR) or treatment with anti-androgenic compounds inhibited cardiomyogenesis, supporting the requirement of the genomic pathway. Chromatin immunoprecipitation (ChIP) studies showed that testosterone enhanced recruitment of AR to the regulatory regions of MEF2C and HCN4 genes, which was associated with increased histone acetylation. In summary, testosterone upregulated cardiomyogenic transcription factor and HCN4 expression in stem cells. Further, testosterone induced cardiomyogenesis, at least in part, by recruiting the AR receptor to the regulatory regions of the MEF2C and HCN4 genes. These results provide a detailed molecular analysis of the function of testosterone in stem cells and may offer molecular insight into the role of steroids in the heart.


Pelvic vein thrombosis as a cause of acute pelvic pain.
Pelvic vein thrombosis may occur in nonpuerperal patients with hypercoagulable conditions and have significant sequelae. The purpose of this report is to describe a nonpuerperal woman with factor V Leiden mutation who developed acute pelvic pain secondary to pelvic varix thrombosis. A multiparous woman, status post-bilateral tubal interruption, presented with acute onset of severe left-sided pelvic pain 5-6 weeks from the onset of her last menstrual period. A pelvic computed tomography scan showed left pelvic varix thrombosis. Hematologic studies were consistent with heterozygous factor V Leiden mutation. The patient was treated with heparin and warfarin, and had complete resolution of her pain. Pelvic vein thrombosis may cause acute pelvic pain in nonpuerperal women, especially those with primary hypercoagulopathies. This should be included in the differential diagnosis of acute pelvic pain in reproductive-age women.


The importance of intercalation in the covalent binding of benzo(a)pyrene diol epoxide to DNA.
The primary mode of non-covalent interaction of the strong carcinogen, benzo(a)pyrene diol epoxide, with DNA is through intercalation. It has variously been suggested that intercalative complexes may be prerequisite for either covalent binding or DNA-catalysed hydrolysis of the epoxide or both. Geacintov [Geacintov, N. E. (1986). Carcinogenesis 7, 589.] has recently argued that intercalation is important in covalent binding and presented theoretical constructs consistent with this proposal. A more general theoretical model is presented here which includes the possibilities that either catalysis of hydrolysis or covalent binding of benzo(a)pyrene diol epoxide DNA can occur (a) in an intercalation complex, or (b) without formation of a detectable, physically bound complex. It is shown that a variety of possible mechanisms formulated under this general theory lead to equations for overall reaction rates and covalent binding fractions which are all of the same form with respect to DNA concentration dependence. A consequence of this is that experimental studies of the dependence of hydrolysis rates and covalent binding fractions on DNA concentration do not distinguish between the various possible mechanisms. These findings are discussed in relation to the interactions of benzo(a)pyrene diol epoxide with chromatin in cells.


Intramolecular OH···FC hydrogen bonding in fluorinated carbohydrates: CHF is a better hydrogen bond acceptor than CF2.
An intramolecular bifurcated H-bond from the axial HO-2 group to the axial F-4 atom and to the O5 atom of α-D-hexopyranosides in apolar solvents is evidenced in (1)H NMR spectra. The H-accepting properties of the F atom are modulated by the orientation of the O-substituent at the C3 atom and by an additional F atom at the C4 atom.


Endocrine disruption caused by two common pollutants at "acceptable" concentrations.
This report focuses on the impact of low concentrations of two purported endocrine-disrupting xenobiotic compounds, nonylphenol and methoxychlor, on two freshwater teleosts of the genus Xiphophorus, X. maculatus, commonly known as the platyfish, and X. helleri, commonly known as the swordtail. Nonylphenol exposure increased mortality rates, elicited stress behaviors, decreased body weight and significantly hampered gonadal development and reproductive function. Methoxychlor exposure elicited stress behaviors, decreased body weight and significantly retarded sexual development. This report demonstrates that, even at "acceptable" concentrations, these compounds pose a serious threat to our aquatic ecosystems.


Aortic valve calcification and increased stiffness of the proximal thoracic ascending aorta: association with left ventricular diastolic dysfunction and early chronic kidney disease.
The aim of this study was to clarify the relationship between the severity of aortic valve calcification (AVC) and stiffness of the proximal thoracic ascending aorta (TAA), and to examine their influence on left ventricular (LV) function and renal function. A total of 138 hypertensive patients including 32 with diabetes mellitus and 60 with dyslipidemia were divided into four groups based on the severity of AVC. We analyzed the elastic properties of the proximal TAA from the following strain-rate indices based on tissue Doppler imaging: maximum strain rate [SR(+)], minimum SR [SR(-)], and the time between the QRS peak and the peak SR(-) of the proximal TAA (SRT). SR(+) and SRT were significantly greater in patients with moderate AVC than in patients with mild AVC. SRT and SR(-) were well correlated with age, peak velocity across AV, TAA wall thickness (IMC), LV diastolic function, and renal function. SRT was independently related to IMC, dyslipidemia, and LV diastolic function. The severity of AVC was correlated with the elastic properties of the proximal TAA. The SR indices are useful for assessing the relation of TAA stiffness to LV function and renal function in patients with AVC.


Mitochondrial UQCC3 controls embryonic and tumor angiogenesis by regulating VEGF expression.
Mitochondria play important roles in angiogenesis. However, the mechanisms remain elusive. In this study, we found that mitochondrial ubiquinol-cytochrome c reductase complex assembly factor 3 (UQCC3) is a key regulator of angiogenesis. TALEN-mediated knockout of Uqcc3 in mice caused embryonic lethality at 9.5-10.5 days postcoitum, and vessel density was dramatically reduced. Similarly, knockout of uqcc3 in zebrafish induced lethality post-fertilization and impaired vascular development. Knockout of UQCC3 resulted in slower tumor growth and angiogenesis. Mechanistically, UQCC3 was upregulated under hypoxia, promoted reactive oxygen species (ROS) generation, enhanced HIF-1α stability and increased VEGF expression. Finally, higher expression of UQCC3 was associated with poor prognosis in multiple types tumors, implying a role for UQCC3 in tumor progression. In conclusion, our findings highlight the important contribution of UQCC3 to angiogenesis under both physiological and pathological conditions, indicating the potential of UQCC3 as a therapeutic target for cancer.


Emotional distress in mothers of preterm hospitalized infants: a feasibility trial of nurse-delivered treatment.
Mothers of preterm infants in a hospital neonatal intensive care unit (NICU) are at risk for clinically significant depression and anxiety, but for these women their own treatment is likely a secondary priority. This study evaluated the feasibility, acceptability and effectiveness of an evidence-based, nurse-delivered, on-site depression treatment: listening visits (LVs). Therapeutic LVs were delivered on site to 23 distressed mothers of NICU infants. The intervention was conducted by a neonatal nurse practitioner and the outcome was examined in an open-trial, pre-post evaluation. A part-time nurse practitioner delivered six LVs to each participant within a 1-month time frame. LVs were associated with significantly improved mood and well-being in mothers. The majority of eligible women took advantage of LVs and felt satisfied with their care. This open trial provides 'proof-of-concept', with results that warrant further evaluation in a multisite randomized controlled trial.


A diflunisal related fatality: a case report.
A case is reported where the death of an individual resulted from the ingestion of diflunisal. Diflunisal was identified by a combination of liquid chromatography, UV spectrophotometry and colorimetry. Diflunisal was quantified in blood (260 mg/l), bile (71 mg/l), kidney (350 mg/kg), liver (400 mg/kg), stomach contents (34 mg) and urine (78 mg/l). No previous literature references discussing diflunisal related fatalities were available.


[Non-traumatic anterior knee dislocation in a patient with osteoarthritis of the knee].
Complete knee dislocation is a rare and severe injury and usually follows high-energy trauma. Non-traumatic knee dislocations are exceedingly rare, while severe overweight appears to be the main cause of the knee dislocation. We here report on a spontaneous knee dislocation in a patient with severe osteoarthritis of the left knee. A 68-year-old woman was admitted to our hospital for an elective total knee replacement. One year prior to admission, a planned joint replacement was not performed due to an existing ulcus cruris. After healing of the ulcus cruris, the patient presented with progressive pain and instability of the left knee without any trauma. The clinical examination showed a multidirectional instability of the left knee with a restricted range of motion (ROM) with 0-0-40 degrees for extension and flexion. The performed radiological examination revealed an anterior knee dislocation of the left knee. Intraoperative findings suggest a non-traumatic aetiology. We suspect that osteoarthritis of the left knee has caused the dislocation. Therefore, we recommend, even in usually "harmless" osteoarthritis, close clinical and radiological follow-up examinations to detect and treat possible complications.


Search for DNA alterations in Alzheimer's disease.
The DNA of brain cortex obtained from autopsy specimens of eight patients with Alzheimer's disease and eight controls was examined for content of normal and abnormal bases. DNA, purified by hydroxyapatite chromatography, was hydrolyzed under mild conditions and the deoxynucleosides were measured by high performance liquid chromatography (HPLC). No differences in the mole percentages of deoxynucleosides in DNA were detected in patients with Alzheimer's disease compared to controls, nor were abnormal deoxynucleosides found. Restriction-nuclease digests examined by agarose gel electrophoresis also showed no changes. Thus, diffuse and persistent damage to the DNA in brain in Alzheimer's disease was not detected by these methods.


The general approach to the difficult patient.
Difficult patients are familiar to emergency physicians. This article explores characteristics of the difficult patient, recognized emergency department processes, and physician characteristics that can contribute to difficulties. These difficulties can be minimized by caregivers who are skilled in managing the therapeutic relationship. This relationship is characterized by firm boundaries, good communication, patient trust, wisdom, and an effective system that supports both patients and caregivers.


Mucin-producing hepatocellular carcinoma without morphological features of biliary differentiation: A case report.
Hepatocellular carcinoma has been believed not to produce mucin unless it has biliary differentiation. However, some cases of hepatocellular carcinoma with extracellular myxoid change have been reported recently, raising the possibility that, in rare cases, hepatocellular carcinoma cells produce mucin. Here we report a case of hepatocellular carcinoma that contained intracellular and extracellular myxoid matrix without morphological evidence of biliary differentiation, although cells in a portion of the tumor were positive for the epithelial markers cytokeratin 7 and 19. She was brought to our hospital due to abnormal liver tests and a large liver tumor found by ultrasound examination. The liver tumor showed typical imaging findings of hepatocellular carcinoma. The tumor was resected with negative margins, and pathologically diagnosed as hepatocellular carcinoma with mucin production. The patient has been free from recurrence of cancer during two-years' follow-up. Our case suggests that hepatocellular carcinoma cells can produce mucin without or before morphological differentiation to biliary phenotypes, an observation that may help elucidate the mechanism for the development of combined hepatocellular and cholangiocarcinoma.


[Pathophysiology, diagnostics and treatment of the respiratory pump].
Diseases of the lung result in oxygen deficiency, hypoxemia, with the indications for oxygen supplementation, whereas hypercapnia and dyspnea are consequences of disorders and failure of the ventilatory pump, which need to be treated by mechanical ventilation. Early diagnostics enable a timely noninvasive ventilation treatment and can prevent overt ventilatory failure and avoid acute invasive ventilation. Diagnostic measures are available, so that the risk of developing overt respiratory failure can be ascertained in time. Treatment of respiratory pump insufficiency, i.e. ventilatory insufficiency, is also established. Many patients with ventilatory insufficiency use intermittent or continuous ventilation every day in order to relieve the respiratory musculature. Many studies have confirmed an extension of life expectancy and a better quality of life, when this relief together with a lowering of the pCO2 is achieved under ventilation and more importantly while breathing spontaneously. If the target of lowering the pCO2 is not achieved, an effect of intermittent ventilation cannot be detected. The more severe the disease, the more difficult it is to achieve relief, because the substantial effort needed for breathing by the patient can hardly be relieved by assisted ventilation alone. The relief is always guaranteed by a total passive mechanical ventilation below the apnea threshold so that the patient does not need to independently breathe. A high tidal volume, an adequately high respiratory rate and a prolonged inspiration time are necessary in order to reduce the pCO2 to below the normal range and to induce passive ventilation. No lung damage has been observed with this treatment strategy in a large number of patients.