The Effects of Elgucare on Degenerated Intervertebral Disc-Induced Low Back Pain and Disc Regeneration: A Clinical Trial.
Chronic low back pain (LBP) has a wide range of causes. However, most cases are induced by degeneration of the lumbar intervertebral discs (IVDs), and the aching caused by local compression of the affected region has considerable impacts on quality of life. This clinical trial investigated the use of Elgucare, a Chinese herbal formula, as a food supplement to reduce the pain of patients with LBP induced by degeneration of the lumbar IVDs. The study assessed patient subjective quality of life, functional limitations caused by LBP, and variations in pain. The assessment was done through the visual analogue scale (VAS) and effects on lumbar IVD thickness, water content, and bone mineral density (BMD). These parameters were evaluated before and after the administration of Elgucare or a placebo, one of which was taken by each participant for a 12-month period. Elgucare reduced the patients' mean VAS pain score by 2.25 points and improved their mean LBP-hampered mobility as assessed by the Roland-Morris Questionnaire by 5.17 points. The results of another questionnaire indicated that Elgucare slowed the LBP-induced deterioration of patients' quality of life, while objective assessment indices obtained through X-ray and magnetic resonance imaging showed that the height and water retention of their IVDs were increased. However, the BMD results showed no improvements. Elgucare can increase the water retention and height of IVDs and reduce LBP, thereby enhancing quality of life. Therefore, Elgucare can potentially be used as a clinical supplement.


Preliminary Flow Modeling by Hybrid Automata Alternating Continuous Reaction and Discrete Transit for Pharmacokinetics.
In traditional pharmacokinetic models, blood flow or liquid transit is often expressed as first-order kinetics. When the flow expression by first-order kinetics is used for dynamic simulation, the flow velocity illogically depends on the step size of a solver of ordinary differential equations. In this study, we propose flow modeling using hybrid automata that combine ordinary differential equations and recursive equations, and we have preliminarily applied the constructed models to several examples. The blood concentration-time profiles of p-aminohippurate and propranolol after intravenous administration were successfully reproduced by simple hybrid automata. The simulation results of one-dimensional tube flow have demonstrated that the fluid velocity in the hybrid automata was independent of the step size of the ordinary differential equation solver. A body fluid model coordinated various flows in a human body with scheduled daily activities and could be used as a drug container to describe formulation-dependent disposition of 5-aminosalicylic acid and enterohepatic circulation of a virtual drug. These findings suggested that flow modeling using hybrid automata could avoid the logical inconsistency in the traditional pharmacokinetic modeling and that the hybrid automata have high versatility and a wide range of applicability to pharmacokinetic analysis. Because our method can define various intervals for multiple recursive equations, the resolution of a specific part of a model can be adjusted relatively freely while the whole body is being roughly modeled, which would be beneficial to refine a coarse model into a fine model in future. SIGNIFICANCE STATEMENT: There is a logical inconsistency in flow expression by first-order kinetics in ordinary differential equations used in traditional pharmacokinetic modeling. It is difficult to model a whole human body using flow models in partial differential equations because of the excessive calculation costs. Our simulations on tube flow and body fluids have demonstrated that the flow modeling using hybrid automata could avoid the problems. The preliminary applications of hybrid automata to several examples highlighted its high versatility in pharmacokinetic analysis.


Pathogenesis of cerebral vasospasm following aneurysmal subarachnoid hemorrhage: putative mechanisms and novel approaches.
Cerebral vasospasm is a potentially incapacitating or lethal complication in patients with aneurysmal subarachnoid hemorrhage (SAH). The development of effective preventative and therapeutic interventions has been largely hindered by the fact that the underlying pathogenic mechanisms of cerebral vasospasm remain poorly understood. However, intensive research during the last 3 decades has identified certain mechanisms that possibly play a role in its development. Experimental data suggest that calcium-dependent and -independent vasoconstriction is taking place during vasospasm. It appears that the breakdown products of blood in the subarachnoid space are involved, through direct and/or indirect pathways, in the development of vasospasm after SAH. Free radicals reactions, an imbalance between vasoconstrictor and vasodilator substances (endothelium derived substances, e.g., nitric oxide, endothelin; arachidonic acid metabolites, e.g., prostaglandins, prostacyclin), inflammatory processes, an upheaval of neuronal mechanisms that regulate vascular tone, endothelial proliferation, and apoptosis have all been put forward as causative and/or pathogenic factors. Translational research in the field of vasospasm has traditionally aimed to identify agents/interventions in order to block the cascades initiated after SAH. The combination of novel approaches such as cerebral microdialysis, magnetic resonance spectroscopy, proteomics, and lipidomics could serve a dual purpose: elucidating the complex pathobiochemistry of vasospasm and providing clinicians with tools for early detection of this feared complication. The purpose of this Mini-Review is to provide an overview of the pathogenesis of cerebral vasospasm and of novel approaches used in basic and translational research.


Assessing the post-treatment therapeutic effect of tongxie in irritable bowel syndrome: A randomized controlled trial.
Diarrhea predominant irritable bowel syndrome (IBS) is a highly relapsing gastrointestinal disorder decreasing the quality of life. Existing studies indicated that the therapeutic effects maintained for a period of time after the treatments were discontinued (post-treatment therapeutic effects or PTTE). In this study, we aim to assess the PTTE of tongxie. We performed a multiple center, controlled, double blind study of patients with IBS randomized to tongxie (n = 120) or placebo (n = 120) for 4 weeks and followed up for 57 weeks. The primary outcomes were abdominal pains and stool consistency. The secondary outcomes were pain frequency and stool frequency. Tertiary outcomes were adverse effects and global overall symptom. The outcome data were collected at days 1, 2, 3, weeks 1 and 4 during the treatment and at days 1, 2, 3, until week 57 during the post-treatment. Significantly more patients receiving tongxie were clinical responders to the primary and secondary endpoints from day 1 until the end of the treatment. The positive effects of tongxie were maintained until 17-25 weeks after tongxie was discontinued. The relapse-free probabilities in the tongxie group were significantly higher than those in the placebo group (P < .001). Twenty-five weeks after the therapies were discontinued could be considered as IBS natural history. During this period, an average of 53.8-56.3% of patients (pool tongxie and placebo data together) had IBS symptoms (pain scale ≥ 3, stool consistency ≥ 5). In particular, at the end of this study (week 61), 145 (54.2%) patients had IBS symptoms. Our results provide clinical insights into efficient and cost-effective management of refractory IBS, and lend support to the IBS management that the selection of a therapy should consider both its effectiveness during treatment and its PTTE after the treatment.


Brusatol enhances MEF2A expression to inhibit RCC progression through the Wnt signalling pathway in renal cell carcinoma.
Renal cell carcinoma (RCC) is the most aggressive subtype of kidney tumour with a poor prognosis and an increasing incidence rate worldwide. Brusatol, an essential active ingredient derived from Brucea javanica, exhibits potent antitumour properties. Our study aims to explore a novel treatment strategy for RCC patients. We predicted 37 molecular targets of brusatol based on the structure of brusatol, and MEF2A (Myocyte Enhancer Factor 2A) was selected as our object through bioinformatic analyses. We employed various experimental techniques, including RT-PCR, western blot, CCK8, colony formation, immunofluorescence, wound healing, flow cytometry, Transwell assays and xenograft mouse models, to investigate the impact of MEF2A on RCC. MEF2A expression was found to be reduced in patients with RCC, indicating a close correlation with MEF2A deubiquitylation. Additionally, the protective effects of brusatol on MEF2A were observed. The overexpression of MEF2A inhibits RCC cell proliferation, invasion and migration. In xenograft mice, MEF2A overexpression in RCC cells led to reduced tumour size compared to the control group. The underlying mechanism involves the inhibition of RCC cell proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) through the modulation of Wnt/β-catenin signalling. Altogether, we found that MEF2A overexpression inhibits RCC progression by Wnt/β-catenin signalling, providing novel insight into diagnosis, treatment and prognosis for RCC patients.


Craniocervical junction abnormalities with atlantoaxial subluxation caused by ventral subluxation of C2 in a dog.
Craniocervical junction abnormalities with atlantoaxial subluxation caused by ventral subluxation of C2 were diagnosed in a 6-month-old female Pomeranian with tetraplegia as a clinical sign. Lateral survey radiography of the neck with flexion revealed atlantoaxial subluxation with ventral subluxation of C2. Computed tomography revealed absence of dens and atlanto-occipital overlapping. Magnetic resonance imaging showed compression of the spinal cord and indentation of caudal cerebellum. The diagnosis was Chiari-like malformation, atlantoaxial subluxation with ventral displacement of C2, atlanto-occipital overlapping, and syringomyelia. The dog underwent foramen magnum decompression, dorsal laminectomy of C1, and ventral fixation of the atlantoaxial joint. Soon after the operation, voluntary movements of the legs were recovered. Finally, the dog could stand and walk without assistance. The dog had complicated malformations at the craniocervical junction but foramen magnum decompression and dorsal laminectomy for Chiari-like malformation, and ventral fixation for atlantoaxial subluxation resulted in an excellent clinical outcome.


Efficacy, safety, and cost-effectiveness of therapeutic drug monitoring (TDM) for TNF inhibitor therapy in rheumatic disease: A systematic review and meta-analysis.
The benefits of TDM-guided TNFi therapy in patients with rheumatic disease was still controversial. This systematic review and meta-analysis was conducted to explore if the TDM-guided TNFi therapy is superior to empirical-guided therapy. We systematically searched PubMed, Web of Science, Cochrane Library, and EMBASE databases for articles published between database inception and October 05, 2023. Studies reporting endpoints in TDM-guided TNFi therapy and empirical therapy were included. Results would be presented in risk ratio (RR) and mean difference, with 95 % confidence interval (CI) reported. This study is registered with PROSPERO (CRD42022353956). A total of 14 studies (eight RCTs and six cohort studies) involving 2427 patients were included in this meta-analysis. In the scenario of response prediction, compared with empirical-guided therapy, TDM-guided TNFi therapy had association with higher treat-to-target rates (RR 1.30, 95 % CI 1.02-1.65, P=0.03, I2=79 %), more specifically, higher low disease activity rates (RR 2.11, 95 % CI 1.22-3.66, P=0.007, I2=61 %), but no difference in clinical remission rates (RR 0.98,95 % CI 0.87-1.11, P=0.75, I2=0 %). In the scenario of dose reduction prediction, lower relapse rates (RR 0.73, 95 % CI 0.65-0.82, P <0.00001, I2=0 %) were observed compared with empirical-guided dose reduction strategy, but no difference (RR 1.24, 95 % CI 0.85-1.80, P=0.27, I2=57 %) between TDM-guided dose reduction and standard-dosing therapy. No significant difference was observed in change of disease activity score, mean disease activity score, radiographic progression, and safety. And TDM-guided therapy was associated with reduced cost per patient per year calculated as the total accumulated sum of therapy cost. TDM-guided TNFi therapy was associated with increased rates of low disease activity and decreased risks of relapse, and may save cost compared with empirical-guided therapy in patients with rheumatic disease. But this does not mean that the use of TDM-guided TNFi therapy can be advocated, because there is no difference in clinical remission rates and many other outcomes. More researches, especially randomized clinical trials are needed to verify this conclusion in the future.


Effects of cortical anodal transcranial direct current stimulation on swallowing biomechanics.
Anodal transcranial direct current stimulation (tDCS) has demonstrated effects on corticobulbar excitability and swallowing function as assessed via clinical rating scales in stroke cohorts. Biomechanical effects of anodal tDCS on swallowing remain largely unexplored. We investigated how anodal tDCS applied over the floor of mouth (FOM) representation on the primary motor cortex affects swallowing biomechanics in healthy participants. Anodal and sham tDCS were applied for 20 minutes at 1.5 mA. Corticobulbar excitability was assessed using motor evoked potentials at baseline and 0, 15, 30 and 45 minutes post-tDCS, as assessed by transcranial magnetic stimulation. Swallowing function was assessed pre- and post-tDCS using routine clinical assessments (Study 1) and pharyngeal high resolution impedance manometry (Study 2). Study 1 (n = 17) showed increased corticobulbar excitability and performance on a skilled swallowing task following anodal wetDCS, but not sham tDCS. In Study 2 (n = 10) anodal tDCS resulted in increased bolus admittance across the upper esophageal sphincter, but decreased pharyngeal and upper esophageal contractile vigor. Clinical improvements of dietary intake are likely driven by swallowing neuroplastic reorganization which improves bolus admittance across the upper esophageal sphincter (UES). The documented changes make motor cortical application of anodal tDCS a promising adjunct to swallowing rehabilitation practice.


Hippocampal tandem mass tag (TMT) proteomics analysis during kindling epileptogenesis in rat.
Epilepsy is a neurological disorder that remains difficult to treat due to the lack of a clear molecular mechanism and incomplete understanding of involved proteins. To identify potential therapeutic targets, it is important to gain insight into changes in protein expression patterns related to epileptogenesis. One promising approach is to analyze proteomic data, which can provide valuable information about these changes. In this study, to evaluate the changes in gene expression during epileptogenesis, LC-MC2 analysis was carried out on hippocampus during stages of electrical kindling in rat models. Subsequently, progressive changes in the expression of proteins were detected as a result of epileptogenesis development. In line with behavioral kindled seizure stages and according to the proteomics data, we described epileptogenesis phases by comparing Stage3 versus Control (S3/C0), Stage5 versus Stage3 (S5/S3), and Stage5 versus Control group (S5/C0). Gene ontology analysis on differentially expressed proteins (DEPs) showed significant changes of proteins involved in immune responses like Csf1R, Aif1 and Stat1 during S3/C0, regulation of synaptic plasticity like Bdnf, Rac1, CaMK, Cdc42 and P38 during S5/S3, and nervous system development throughout S5/C0 like Bdnd, Kcc2 and Slc1a3.There were also proteins like Cox2, which were altered commonly among all three phases. The pathway enrichment analysis of DEPs was also done to discover molecular connections between phases and we have found that the targets like Csf1R, Bdnf and Cox2 were analyzed throughout all three phases were highly involved in the PPI network analysis as hub nodes. Additionally, these same targets underwent changes which were confirmed through Western blotting. Our results have identified proteomic patterns that could shed light on the molecular mechanisms underlying epileptogenesis which may allow for novel targeted therapeutic strategies.


Levels of risk: maternal-, middle childhood-, and neighborhood-level predictors of adolescent disinhibitory behaviors from a longitudinal birth cohort in the United States.
OBJECTIVE: Disruptive behavior in adolescence may indicate a broad vulnerability to disinhibition, which begins in childhood and culminates in adult externalizing psychopathology. We utilized prospective birth cohort data to assess childhood predictors of adolescent disinhibition. We also examined the effect of pre-adolescent fluctuation in cognitive ability. METHODS: Data were drawn from the Child Health and Development Study cohort, born 1961-1963; we used the subsample who participated in follow-up through adolescence (n=1752). Six indicators of behavioral disinhibition (BD), reported in adolescence, were analyzed as a count outcome. Predictor variables were drawn from several waves of data collection and included individual-, maternal-, and neighborhood-level measures. Cognitive ability was assessed with the Peabody Picture Vocabulary Test at two time points. Neighborhood characteristics were assessed using census data from 1970. RESULTS: Number of BD indicators was predicted by maternal characteristics at prenatal assessment (maternal age and alcohol consumption) and age-10 assessment (maternal smoking, education, and separation from father). Characteristics of the child that predicted BD included birth order and conduct problems in middle childhood. Neighborhood poverty did not predict BD. Regardless of initial cognitive ability score, movement to a higher quartile by adolescence was associated with lower BD, while movement to a lower quartile was associated with higher BD. CONCLUSION: Risk for adolescent BD exists prenatally and extends through middle childhood. Change in cognitive ability during pre-adolescence emerged as a potentially important factor that merits further investigation. A greater focus on the life course can aid in comprehensively understanding disruptive behavior emergence in adolescence.


Circulating tetrahydrobiopterin as a novel biomarker for abdominal aortic aneurysm.
Rupture of abdominal aortic aneurysm (AAA) is unpredictable and lethal. A clinically valid biomarker to monitor the disease has not been available. Based on our recent discoveries that uncoupled endothelial nitric oxide synthase (eNOS)/tetrahydrobiopterin deficiency plays a causal role in various models of AAA, the present study examined the relationship between circulating and tissue levels of tetrahydrobiopterin (H4B) in angiotensin II-infused hyperphenylalaninemia (hph-1) and apoE null mice. For apoE null mice, tissue and plasma H4B levels decreased time dependently, to 2.69 ± 0.15 and 1.99 ± 0.06 pmol/mg, respectively (from 4.86 ± 0.32 and 3.31 ± 0.13 pmol/mg at baseline) by week 3, when aneurysms developed. For hph-1 mice, tissue and plasma H4B levels decreased significantly to 1.02 ± 0.10 and 0.98 ± 0.09 pmol/mg, respectively (from 1.84 ± 0.18 and 1.48 ± 0.12 pmol/mg at baseline), by week 1, when aneurysms developed. Oral folic acid administration, which has been shown to improve aortic H4B levels to completely prevent or markedly decrease the incidence of AAA, significantly increased tissue and plasma H4B levels in both animal models starting at week 1. The two H4B measurements at all conditions showed significant linear correlation, suggesting that plasma H4B accurately predicts its tissue levels when H4B is either reduced or enhanced. Together, these data demonstrate that H4B levels decrease with AAA development and increase with folic acid treatment in two different murine models of AAA and that plasma H4B levels accurately reflect H4B levels in the tissue, suggesting that circulating H4B levels may be used clinically as a novel and powerful biomarker for the development and response to treatment of AAA.


ERS statement on exercise training and rehabilitation in patients with severe chronic pulmonary hypertension.
Objectives of this European Respiratory Society task force were to summarise current studies, to develop strategies for future research and to increase availability and awareness of exercise training for pulmonary hypertension (PH) patients.An evidence-based approach with clinical expertise of the task force members, based on both literature search and face-to-face meetings was conducted. The statement summarises current knowledge and open questions regarding clinical effects of exercise training in PH, training modalities, implementation strategies and pathophysiological mechanisms.In studies (784 PH patients in total, including six randomised controlled trials, three controlled trials, 10 prospective cohort studies and four meta-analyses), exercise training has been shown to improve exercise capacity, muscular function, quality of life and possibly right ventricular function and pulmonary haemodynamics. Nevertheless, further studies are needed to confirm these data, to investigate the impact on risk profiles and to identify the most advantageous training methodology and underlying pathophysiological mechanisms.As exercise training appears to be effective, cost-efficient and safe, but is scarcely reimbursed, support from healthcare institutions, commissioners of healthcare and research funding institutions is greatly needed. There is a strong need to establish specialised rehabilitation programmes for PH patients to enhance patient access to this treatment intervention.


Oil shales and carbon dioxide.
During retorting of oil shales in the western United States, carbonate minerals are calcined, releasing significant amounts of carbon dioxide. Residual organic matter in the shales may also be burned, adding more carbon dioxide to the atmosphere. The amount of carbon dioxide produced depends on the retort process and the grade and mineralogy of the shale. Preliminary calculations suggest that retorting of oil shales from the Green River Formation and burning of the product oil could release one and one-half to five times more carbon dioxide than burning of conventional oil to obtain the same amount of usable energy. The largest carbon dioxide releases are associated with retorting processes that operate at temperatures greater than about 600 degrees C.


The Family Caregiving Crisis Meets an Actual Pandemic.
The coronavirus disease 2019 (COVID-19) pandemic presents unique challenges to those who work with the seriously ill population, including both health care providers and the family caregivers providing unpaid care. We rely on this lay workforce as health care routinely transitions care to the home, and now more than ever, we are depending on them in the current pandemic. As palliative care and other health care providers become overwhelmed with patients critically ill with COVID-19, and routine care becomes delayed, we have a charge to recognize and work with family caregivers. Our commentary provides rationale for the need to focus on family caregivers and key considerations for how to include them in pandemic clinical decision making.


Rural considerations in establishing network adequacy standards for qualified health plans in state and regional health insurance exchanges.
The Affordable Care Act (ACA) requires Health Insurance Exchanges (HIEs) to specify network adequacy standards for the Qualified Health Plans (QHPs) they offer to consumers. This article examines rural issues surrounding network adequacy standards, and offers recommendations for crafting standards that optimize rural access. This policy analysis reviews ACA requirements for QHP network adequacy standards, considering Medicaid managed care and Medicare Advantage (MA) standards as models. We analyze the implications of stringent vs flexible access standards in terms of how choices might affect health plans' participation in rural markets and rural enrollees' access to care. Finally, we propose strategies for designing standards with the degree of flexibility most likely to benefit rural consumers. A traditional approach to safeguarding rural access is to impose strict network adequacy standards on plans in rural areas. However, if strict standards prove difficult to meet due to rural provider scarcity, they might diminish QHPs' willingness to serve rural areas. Thus, they could exacerbate rather than alleviate rural access problems. To benefit rural communities, network adequacy standards must be strong enough to provide real protections for beneficiaries, yet flexible enough to accommodate rural delivery system constraints and remain attainable for QHPs. Useful strategies to achieve this balance might include: adjusting standards according to degrees of rurality and rural utilization norms; counting midlevel clinicians toward fulfillment of patient-provider ratios; and allowing plans to ensure rural access through delivery system innovations such as telehealth.


Impact of Contaminating DNA in Whole-Genome Amplification Kits Used for Metagenomic Shotgun Sequencing for Infection Diagnosis.
Whole-genome amplification (WGA) is a useful tool for amplification of very small quantities of DNA for many uses, including metagenomic shotgun sequencing for infection diagnosis. Depending on the application, background DNA from WGA kits can be problematic. Three WGA kits were tested for their utility in a metagenomics approach to identify the pathogens in sonicate fluid comprised of biofilms and other materials dislodged from the surfaces of explanted prosthetic joints using sonication. The Illustra V2 Genomiphi, Illustra single cell Genomiphi, and Qiagen REPLI-g single cell kits were used to test identical sonicate fluid samples. Variations in the number of background reads, the genera identified in the background, and the number of reads from known pathogens known to be present in the samples were observed between kits. These results were then compared to those obtained with a library preparation without prior WGA using an NEBNext Ultra II paired-end kit, which requires a very small amount of input DNA. This approach also resulted in the presence of contaminant bacterial DNA and yielded fewer reads from the known pathogens. These findings highlight the impact that WGA kit selection can have on metagenomic analysis of low-biomass samples and the importance of the careful selection and consideration of the implications of using these tools.


Rapid Increase in Genome Size as a Consequence of Transposable Element Hyperactivity in Wood-White (Leptidea) Butterflies.
Characterizing and quantifying genome size variation among organisms and understanding if genome size evolves as a consequence of adaptive or stochastic processes have been long-standing goals in evolutionary biology. Here, we investigate genome size variation and association with transposable elements (TEs) across lepidopteran lineages using a novel genome assembly of the common wood-white (Leptidea sinapis) and population re-sequencing data from both L. sinapis and the closely related L. reali and L. juvernica together with 12 previously available lepidopteran genome assemblies. A phylogenetic analysis confirms established relationships among species, but identifies previously unknown intraspecific structure within Leptidea lineages. The genome assembly of L. sinapis is one of the largest of any lepidopteran taxon so far (643 Mb) and genome size is correlated with abundance of TEs, both in Lepidoptera in general and within Leptidea where L. juvernica from Kazakhstan has considerably larger genome size than any other Leptidea population. Specific TE subclasses have been active in different Lepidoptera lineages with a pronounced expansion of predominantly LINEs, DNA elements, and unclassified TEs in the Leptidea lineage after the split from other Pieridae. The rate of genome expansion in Leptidea in general has been in the range of four Mb/Million year (My), with an increase in a particular L. juvernica population to 72 Mb/My. The considerable differences in accumulation rates of specific TE classes in different lineages indicate that TE activity plays a major role in genome size evolution in butterflies and moths.


Continuous spinal anesthesia versus continuous femoral nerve block for elective total knee replacement.
Continuous spinal analgesia (CSA) and continuous femoral nerve blockade (CFNB) are well-established procedures for postoperative pain relief. This study compares the efficacy, adverse effects and complications associated with these two analgesic methods in patients undergoing total knee arthroplasty (TKA). Data were analyzed from consecutive patients undergoing TKA under either CSA or spinal anesthesia plus CFNB. Quality of analgesia was assessed based on opioid consumption and pain intensity (visual analogue scale [VAS] where 0=no pain and 10=utmost imaginable pain) until postoperative day 4. In addition, joint mobility was assessed, and any adverse reactions or side effects were noted. Sixty-two patients had satisfactory postoperative pain relief, and maximum pain scores were reported between 12 and 24 hrs. Median pain scores in the CSA group were significantly lower than those in the CFNB group (1.0 [0.9-1.9] vs. 2.0 [1.5-3.6] for resting pain and 2.0 [1.7-3.1] vs. 5.0 [3.0-5.5] for dynamic pain, respectively; P<0.001 for days 0 and 1; P<0.05 for all other days). Piritramide consumption was significantly higher in the CFNB group (P<0.01). There were no significant differences between the groups for postoperative mobility of the joint or patient satisfaction. Both methods demonstrated analgesic efficacy after total knee arthroplasty, although there was less pain severity and opioid consumption use reported with continuous spinal analgesia. However, the use of continuous spinal analgesia is limited by concerns about the risk profile and absence of approved devices for continuous intrathecal infusion.


[The Dutch foundation "Voet en Schoeisel" (foot and shoe)].
The author gives information about the foundation "Voet en Schoeisel" (foot and shoe). He describes in brief the origin, the compostion, the aims and also the works. He hopes to give publicicty to the foundation what possible leads to more international contacts.


Application of solid phase-microextraction (SPME) and electronic nose techniques to differentiate volatiles of sesame oils prepared with diverse roasting conditions.
Headspace volatiles of sesame oil (SO) from sesame seeds roasted at 9 different conditions were analyzed by a combination of solid phase microextraction (SPME)-gas chromatography/mass spectrometry (GC/MS), electronic nose/metal oxide sensors (MOS), and electronic nose/MS. As roasting temperature increased from 213 to 247 °C, total headspace volatiles and pyrazines increased significantly (P < 0.05). Pyrazines were major volatiles in SO and furans, thiazoles, aldehydes, and alcohols were also detected. Roasting temperature was more discrimination factor than roasting time for the volatiles in SO through the principal component analysis (PCA) of SPME-GC/MS, electronic nose/MOS, and electronic nose/MS. Electronic nose/MS showed that ion fragment 52, 76, 53, and 51 amu played important roles in discriminating volatiles in SO from roasted sesame seeds, which are the major ion fragments from pyrazines, furans, and furfurals. SO roasted at 213, 230, and 247 °C were clearly differentiated from each other on the base of volatile distribution by SPME-GC/MS, electronic nose/MOS, and electronic nose/MS analyses. Practical Application: The results of this study are ready to apply for the discriminating samples using a combinational analysis of volatiles. Not only vegetable oils prepared from roasting process but also any food sample possessing volatiles could be targets for the SPME-GC/MS and electronic nose assays. Contents and types of pyrazines in sesame seed oil could be used as markers to track down the degree of roasting and oxidation during oil preparation.


Optogenetic Inhibition of Nav1.8 Expressing Corneal Afferents Reduces Persistent Dry Eye Pain.
The aim of the present study was to investigate the contribution of Nav1.8 expressing corneal afferent neurons to the presence of ongoing pain in lacrimal gland excision (LGE)-induced dry eye. The proton pump archaerhodopsin-3/eGFP (ArchT/eGFP) was conditionally expressed in corneal afferents using Nav1.8-cre mice. Dry eye was produced by unilateral LGE. Real time place preference was assessed using a three-chamber apparatus. A neutral, unlit center chamber was flanked by one illuminated with a control light and one illuminated with an ArchT activating light. For real-time preference, animals were placed in the neutral chamber and tracked over five 10-minute sessions, with the lights turned on during the second and fourth sessions. In other studies, movement was tracked over three 10-minute sessions (the lights turned on only during the second session), with animals tested once per day over the course of 4 days. A local anesthetic was used to examine the role of ongoing corneal afferent activity in producing place preference. The corneal afferent nerves and trigeminal ganglion cell bodies showed a robust eGFP signal in Nav1.8-cre;ArchT/eGFP mice. After LGE, Nav1.8-cre;ArchT/eGFP mice demonstrated a preference for the ArchT activating light paired chamber. Preference was prevented with pre-application to the cornea of a local anesthetic. Nav1.8-cre;ArchT/eGFP mice with sham surgery and LGE wild-type control mice did not develop preference. Results indicate LGE-induced persistent, ongoing pain, driven by Nav1.8 expressing corneal afferents. Inhibition of these neurons represents a potential strategy for treating ongoing dry eye-induced pain.


A brief history of the study of nerve dependent regeneration.
Nerve dependence is a phenomenon observed across a stunning array of species and tissues. From zebrafish to fetal mice to humans, research across various animal models has shown that nerves are critical for the support of tissue repair and regeneration. Although the study of this phenomenon has persisted for centuries, largely through research conducted in salamanders, the cellular and molecular mechanisms of nerve dependence remain poorly-understood. Here we highlight the near-ubiquity and clinical relevance of vertebrate nerve dependence while providing a timeline of its study and an overview of recent advancements toward understanding the mechanisms behind this process. In presenting a brief history of the research of nerve dependence, we provide both historical and modern context to our recent work on nerve dependent limb regeneration in the Mexican axolotl.


Patient experiences with treatment in private practice compared with public mental health services.
The study compared patient experiences with psychiatric treatment provided by private practitioners and public outpatient clinics. Questionnaires were completed by 642 outpatients in private practice and 6,677 outpatients in public clinics. The questionnaire included a measure of patient experiences comprising six items: treatment outcome, enough time for contact and dialogue with clinician, clinicians' understanding of patient's situation, suitability of therapy and treatment, clinician follow-up of planned actions, and influence on treatment. Patients in private practice had generally better experiences than patients in public outpatient treatment. The difference between private and public patients was largest for patients with poor self-evaluated mental health or those who had just one consultation in the previous three months. Private practitioners appear to have an important role in mental health services delivery, and patients have relatively good experiences with services. Further studies that assess the patient - clinician interaction in different mental health services may give further insights into potential service improvements.


The impact of rainfall events on dissolved oxygen concentrations in a subtropical urban reservoir.
Understanding controls of dissolved oxygen (DO) concentrations in reservoirs is important as they are important for fisheries and a significant driver of greenhouse gas emissions. The latter is of global significance as IPCC inventories now require greenhouse gas emissions from artificial reservoirs to be included. Declines in dissolved oxygen (DO) concentrations in lakes and reservoirs have been linked to climate change and human activity. However, these effects can vary widely in any given region under various meteorological conditions. There is a clear need to know how changes in weather patterns affect DO in reservoirs by changing internal processes. Based on a six-year (2016-2021) high-frequency (twice a week) dataset from a shallow urban reservoir (Xinglinwan Reservoir) in subtropical China, the long-term (six years) and short-term (8-72-h) drivers of DO concentrations in surface waters were evaluated. Over the past six years, the concentration of DO has gradually decreased in the reservoir from 2016 to 2021. Multivariate adaptive regression spline (MARS) models were developed to identify the key factors explaining variability in DO and partial least squares path models (PLS-PM) were used to explore the short-term relationships between DO and environmental variables in rainy and non-rain periods, separately. We identified three key drivers operating on different time scales. First, the long-term decline of DO in Xinglinwan Reservoir from 2016 to 2021 was best explained by anthropogenic nutrient inputs. Second, rainy periods prior to sampling reduced DO concentrations indirectly by affecting the algal biomass and nutrient concentrations. This effect varied in complexity with the duration of the rainfall period. Third, temperature best explained DO concentrations after dry periods, while wind reduced DO by reducing algal biomass. We conclude that anthropogenic nutrient and organic matter inputs drive long-term oxygen declines in urban subtropical reservoirs, while meteorological factors determine short-term variability in DO concentrations.


Contribution of Src tyrosine kinase to cerebral vasospasm after subarachnoid hemorrhage.
Mitogen-activated protein kinase (MAPK) has been implicated in cerebral vasospasm after subarachnoid hemorrhage (SAH). This study was conducted to investigate whether Src tyrosine kinase, an upstream regulator of MAPK, is involved in cerebral vasospasm. An established canine double-hemorrhage model was used. Twenty-four dogs were divided into four groups: control, vehicle-treated, Src inhibitor PP2-treated, and Src inhibitor damnacanthal-treated groups. Vehicle (dimethyl sulfoxide), PP2, or damnacanthal was injected daily into the cisterna magna of 18 dogs at 3 to 6 days after induction of SAH. Angiography was performed on Day 0 (the day on which the first blood injection was administered to induce SAH) and on Day 7. Western blot analysis of Src and MAPK activation in basilar arteries (BAs) collected on Day 7 post-SAH was performed. Severe vasospasm was observed in the BAs of vehicle-treated dogs. Mild vasospasm was observed in all dogs treated with Src inhibitors. Phosphorylated Src and MAPK were increased after SAH and activation of these kinases in the BAs was abolished by PP2 and damnacanthal. The tyrosine kinase Src is an important upstream regulator of MAPK, and inhibition of Src might offer a new therapy in the management of cerebral vasospasm.


Blood-brain barrier dysfunction in canine epileptic seizures detected by dynamic contrast-enhanced magnetic resonance imaging.
Dogs with spontaneous or acquired epilepsy exhibit resemblance in etiology and disease course to humans, potentially offering a translational model of the human disease. Blood-brain barrier dysfunction (BBBD) has been shown to partake in epileptogenesis in experimental models of epilepsy. To test the hypothesis that BBBD can be detected in dogs with naturally occurring seizures, we developed a linear dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) analysis algorithm that was validated in clinical cases of seizing dogs and experimental epileptic rats. Forty-six dogs with naturally occurring seizures of different etiologies and 12 induced epilepsy rats were imaged using DCE-MRI. Six healthy dogs and 12 naive rats served as control. DCE-MRI was analyzed by linear-dynamic method. BBBD scores were calculated in whole brain and in specific brain regions. Immunofluorescence analysis for transforming growth factor beta (TGF-β) pathway proteins was performed on the piriform cortex of epileptic dogs. We found BBBD in 37% of dogs with seizures. A significantly higher cerebrospinal fluid to serum albumin ratio was found in dogs with BBBD relative to dogs with intact blood-brain barrier (BBB). A significant difference was found between epileptic and control rats when BBBD scores were calculated for the piriform cortex at 48 hours and 1 month after status epilepticus. Mean BBBD score of the piriform lobe in idiopathic epilepsy (IE) dogs was significantly higher compared to control. Immunohistochemistry results suggested active TGF-β signaling and neuroinflammation in the piriform cortex of dogs with IE, showing increased levels of serum albumin colocalized with glial acidic fibrillary protein and pSMAD2 in an area where BBBD had been detected by linear DCE-MRI. Detection of BBBD in dogs with naturally occurring epilepsy provides the ground for future studies for evaluation of novel treatment targeting the disrupted BBB. The involvement of the piriform lobe seen using our linear DCE-MRI protocol and algorithm emphasizes the possibility of using dogs as a translational model for the human disease.


Natural history of merkel cell carcinoma following locoregional recurrence.
Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine malignancy with an ill-defined natural history following locoregional recurrence. This is a retrospective review of patients with MCC diagnosed at the Mayo Clinic from 1981 to 2008. For each outcome (subsequent locoregional recurrence, distant recurrence, and death) the survival-free of the outcome was estimated using the Kaplan-Meier method. Associations of patient and clinical characteristics with the outcomes were assessed by fitting Cox proportional hazards regression models. Among the 240 patients diagnosed with MCC, 70 (29%) patients were identified who developed locoregional recurrence as the first site of recurrence. The median time from diagnosis to locoregional recurrence was 6 months. The pattern of first locoregional failure in this group includes 25 (10.4%) local, 18 (7.5%) in-transit, and 27 (11.3%) nodal recurrences. Recurrences were most commonly treated by surgery and radiation. At 3 years after the initial recurrence, locoregional recurrence-free survival was 75% and the distant recurrence-free survival was 56%. Locoregional recurrence is a poor prognostic sign associated with a 3-year overall survival of 39%. Nodal status at time of original surgery and time to first recurrence were important predictors of distant recurrence (P < 0.006) and overall survival following locoregional recurrence (P < 0.001). Locoregional recurrence is a substantial problem in patients with MCC and is a poor prognostic sign. In those patients who experience a locoregional recurrence, aggressive efforts to regain locoregional control appear warranted and may result in long-term survival.


Increased survivin expression confers chemoresistance to tumor-associated endothelial cells.
Growing evidence suggests that survivin, a member of the inhibitor of apoptosis gene family, is responsible for drug resistance in cancer cells, yet little is known about its role in the endothelial cells of the tumor vasculature. We have previously reported that tumor-associated endothelial cells derived from gliomas (TuBECs) are resistant to anticancer chemotherapy whereas normal brain endothelial cells (BECs) are sensitive. The focus of this study is to investigate the mechanism behind this chemoresistance. Here we show that survivin is constitutively overexpressed in the glioma vasculature but not in the blood vessels of normal brain. To determine whether survivin contributes to TuBEC chemoresistance, we used a lentiviral siRNA system or the drug roscovitine to down-regulate survivin expression. Reduced levels of survivin sensitized TuBECs to the chemotherapeutic agents VP-16, paclitaxel, thapsigargin, and temozolomide. This cell death was mediated through caspases 7 and 4. Conversely, forced expression of survivin in BECs was protective against drug cytotoxicity. These data suggest that overexpression of survivin in endothelial cells serves as a protective mechanism that defends the vasculature from drug cytotoxicity. Our studies demonstrate that targeting survivin may be an effective approach to chemosensitization and anti-vascular therapy for brain tumors.


Comparison of basis functions and q-space sampling schemes for robust compressed sensing reconstruction accelerating diffusion spectrum imaging.
Time constraints placed on magnetic resonance imaging often restrict the application of advanced diffusion MRI (dMRI) protocols in clinical practice and in high throughput research studies. Therefore, acquisition strategies for accelerated dMRI have been investigated to allow for the collection of versatile and high quality imaging data, even if stringent scan time limits are imposed. Diffusion spectrum imaging (DSI), an advanced acquisition strategy that allows for a high resolution of intra-voxel microstructure, can be sufficiently accelerated by means of compressed sensing (CS) theory. CS theory describes a framework for the efficient collection of fewer samples of a data set than conventionally required followed by robust reconstruction to recover the full data set from sparse measurements. For an accurate recovery of DSI data, a suitable acquisition scheme for sparse q-space sampling and the sensing and sparsifying bases for CS reconstruction need to be selected. In this work we explore three different types of q-space undersampling schemes and two frameworks for CS reconstruction based on either Fourier or SHORE basis functions. After CS recovery, diffusion and microstructural parameters and orientational information are estimated from the reconstructed data by means of state-of-the-art processing techniques for dMRI analysis. By means of simulation, diffusion phantom and in vivo DSI data, an isotropic distribution of q-space samples was found to be optimal for sparse DSI. The CS reconstruction results indicate superior performance of Fourier-based CS-DSI compared to the SHORE-based approach. Based on these findings we outline an experimental design for accelerated DSI and robust CS reconstruction of the sparse measurements that is suitable for the application within time-limited studies.


Formyl-methionyl-leucyl-phenylalanine induces prostaglandin E2 release from human amnion-derived WISH cells by phospholipase C-mediated [Ca+]i rise.
The presence of binding sites for formyl-methionyl-leucyl-phenylalanine (fMLP), its effect on prostaglandin E (PGE) release, and the signal transduction pathway activated by the peptide were investigated in human amnion-derived WISH cells. Our results demonstrate that specific binding sites for fMLP are present on WISH cells and that the peptide induces a significant increase of prostaglandin (PG)E2 release. The kinetic properties of binding are similar to those previously found in amnion tissue prior to the onset of labor, i.e., only one population of binding sites with low affinity for the peptide is present. Binding of 3H-fMLP in WISH cells is inhibited by N-t-butoxycarbonyl-methionyl-leucyl-phenylalanine, an fMLP receptor antagonist, with an IC50 value very close to that shown by nonlaboring amnion. The fMLP-induced PGE2 output is inhibited by indomethacin, quinacrine, and U-73122, inhibitors of cyclooxygenase, phospholipase A2, and phospholipase C, respectively. As regards the transduction pathway activated by fMLP, we demonstrate that phospholipase C activation, followed by an increase of intracellular calcium concentration ([Ca2+]i), is involved in response to the peptide. Our results add further evidence to the role of proinflammatory agents in the determination of labor. Furthermore, because WISH cells appear to behave like nonlaboring amnion tissue, they represent the ideal candidate for in vitro investigation of the events triggering the mechanism of delivery.


Effect of Atorvastatin on Serum Para-Oxonase-1 and C-Reactive Protein in Wistar Rats.
Statins have been widely used in the treatment of hypercholesterolemia and atherosclerotic disease. Atherosclerosis is an ongoing inflammatory response which is involved in mediating all stages of this multifactorial disease. The present study focuses on the long term effect of atorvastatin on the anti-atherogenic and anti-inflammatory properties with reference to para-oxonase and C-reactive protein levels in rats. Thirty six Wistar albino rats obtained from the central animal house were divided into 6 groups with 6 rats in each group. Group I and IV served as the control for male and female rats respectively. Group II and V comprised of male and female rats that received low dose of atorvastatin (10 mg/kg body weight). Group III and VI comprised of male and female rats that received high dose of atorvastatin (40 mg/kg body weight) for period of 45 days. Blood was collected by cardiac puncture. The plasma was analysed for total cholesterol, HDL cholesterol, C-reactive protein (CRP) and Paraoxonase-1, both basal Paraoxonase (BPON) & Salt stimulated Paraoxonase (SPON) by standard procedures. Results of the present study showed a reduction in TC and increase in HDL-C in both groups of rats receiving low and high dose of Atorvastatin. Both male and female rats responded similarly. The levels of CRP decreased in the male rats receiving either low or high dose of atorvastatin. Activity of SPON and BPON was increased only in the group receiving high dose of atorvastatin in both male and female rats.


Megavoltage computed tomography imaging: a potential tool to guide and improve the delivery of thoracic radiation therapy.
Helical tomotherapy is an innovative means of delivering intensity-modulated radiation therapy (IMRT) using a device that merges features of a linear accelerator and a helical computed tomography (CT) scanner. The tomotherapy unit can generate CT images from the megavoltage radiation it uses for treatment as often as needed during a course of radiation therapy. These megavoltage CT (MVCT) images offer verification of patient position prior to and potentially during radiation therapy, and provide considerably more anatomical detail than the conventional radiation therapy port films used for patient set-up verification. Also, MVCT imaging may enable reconstruction of the radiation dose delivered, thereby providing unprecedented verification of the actual treatment. These key features of helical tomotherapy distinguish it from other IMRT approaches. We report results from a pilot feasibility trial of 10 patients with non-small-cell lung cancer (NSCLC) on whom we obtained MVCT images using a prototype helical tomotherapy system. All patients underwent conventional CT imaging for radiation therapy treatment planning. Specific aims were to subjectively compare MVCT and conventional CT images and then to objectively compare the 2 modalities by contouring tumors and performing a volumetric comparison. Seven patients had disease located primarily in the lung parenchyma, 2 primarily in the mediastinum, and 1 in both. When evaluated by location, all 7 patients with lesions primarily in the lung parenchyma had subjectively high-quality MVCT images. Objectively, the volumetric agreement between conventional and MVCT for parenchymal lesions was excellent in 5 of the 7 patients. Megavoltage CT imaging via the helical tomotherapy prototype provided adequate information for use in verification of patient position and dose reconstruction for lesions within the pulmonary parenchyma, but presently appears suboptimal for primarily mediastinal disease. Further studies are ongoing to optimize MVCT imaging and better define its utility in patients with NSCLC.


Effects of Self-Rated Health and Self-Rated Economic Situation on Depressed Mood Via Life Satisfaction Among Older Adults in Costa Rica.
The study examined the relationship of self-rated health and self-rated economic situation with depressed mood, and life satisfaction as mediator of this relationship among older adults in Costa Rica. A longitudinal study was conducted with a subsample (N = 1,618) from the Costa Rican Longevity and Healthy Aging Study (CRELES). Self-rated health, self-rated economic situation, depressed mood, and life satisfaction were measured at baseline, and depressed mood was reassessed 18 months later. Putative mechanisms for changes in depressed mood were examined by means of conditional process analysis. Self-rated health was negatively associated to depressed mood. This effect took place via life satisfaction. An interaction showed that better economic situation compensated the effect of a low self-rated health on life satisfaction. This study suggests that subjective variables such as self-rated health, economic situation, and life satisfaction should be considered when addressing the onset of depressed mood.


The Peer Education Approach in Adolescents- Narrative Review Article.
Adolescence is an important stage of human life span, which crucial developmental processes occur. Since peers play a critical role in the psychosocial development of most adolescents, peer education is currently considered as a health promotion strategy in adolescents. Peer education is defined as a system of delivering knowledge that improves social learning and provides psychosocial support. As identifying the outcomes of different educational approaches will be beneficial in choosing the most effective programs for training adolescents, the present article reviewed the impact of the peer education approach on adolescents. In this review, databases such as PubMed, EMBASE, ISI, and Iranian databases, from 1999 to 2013, were searched using a number of keywords. Peer education is an effective tool for promoting healthy behaviors among adolescents. The development of this social process depends on the settings, context, and the values and expectations of the participants. Therefore, designing such programs requires proper preparation, training, supervision, and evaluation.


Thrombophilia in cancer.
Malignancy is an acquired thrombophilic condition associated with a significant risk of thrombosis. Venous and arterial thromboembolism is a common complication for patients with cancer, who also present with a hypercoagulable state, even in the absence of manifest thrombosis. Furthermore, clotting activation may play a role in tumor progression. The pathogenesis of thrombosis in cancer is multifactorial; however, a relevant role is attributed to the tumor cell capacity to interact with and activate the host hemostatic system. Among other factors, the prothrombotic action of antitumor therapies is also important. Thrombotic events can influence the morbidity and mortality of the underlying disease. Therefore, preventing these complications in cancer patients is a clinically relevant issue. Recently, new approaches to the prevention and cure of thrombosis in cancer have been investigated, and the hypothesis that strategies to inhibit clotting mechanism may favorably affect malignant disease is gaining increasing interest. In this article, the various aspects of the complex relationship between thrombosis and cancer, from pathophysiology to therapy, are reviewed.


[Myocardial Infarction Registry conducted forty years ago in Hungary].
Authors summarize the most important findings of the Myocardial Infarction Community Registry conducted in Hungary 40 years ago. The report is important because data are not available on the internet through literature search and since 40 years such study has not been performed. The incidence of acute myocardial infarction in subjects older than 20 years of age in the population of South Pest with 400 000 inhabitants in 1971 was 50.9/10 000 in men and 23.7/10 000 in women. The mortality rate of myocardial infarction during the first year was 56.2% in men and 60.7% in women. Two-third of the first-year death occurred in the first 24 hours and 85% of it in the prehospital period. Only 6% of the patients with acute myocardial infarction were admitted and treated in Coronary Care Units. Based on the data of the Myocardial Infarction Community Registry, measures were introduced which decreased the 28-days mortality rate at the population level. Authors emphasize that in the last decades the diagnosis and treatment of myocardial infarction has substantially changed which makes it necessary to re-evaluate by epidemiologic methods the natural history, incidence and mortality of acute myocardial infarction in Hungary.


The clinical features, course, prognosis and treatment of juvenile arthritis.
The author's classification of juvenile arthritis (JA) differs from most by utilizing both the type of onset and the disease course separated into individual subgroups. The clinical aspects of each are described in detail, along with the special tests and studies to be done to differentiate them. Particular attention is given to the differences between the four subgroups of the pauciarticular onset group. There are different genetic factors for each subgroup and new data on HLA typing utilizing DNA techniques may be helpful in the prognosis of the disease course. The therapy of JA begins with non-steroidal anti-inflammatory drugs, continues with second-line drugs such as gold and penicillamine, and finally leads to the use of immunosuppressive agents. The range of doses, the maximal dose, and the frequency of administration is given for each medication. The long-term prognosis is generally good, with a low death rate, primarily seen in the systemic onset patients. The causes of death vary around the world. Prognosis for continued joint activity and joint function is determined significantly by the type of onset and is worse in the rheumatoid factor positive polyarticular onset group.


Dating Violence Against HIV-Infected Youth in South Africa: Associations With Sexual Risk Behavior, Medication Adherence, and Mental Health.
As perinatal HIV-infected youth become sexually active, the potential for onward transmission becomes an increasing concern. In other populations, intimate partner violence (IPV) is a risk factor for HIV acquisition. We build on this critical work by studying the role of IPV in facilitating onward transmission among HIV-infected youth-an important step toward effective intervention. Soweto, South Africa. Self-report surveys were completed by 129 perinatal HIV-infected female youth (aged 13-24 years). We calculated the IPV prevalence and used logistic models to capture the association between IPV and health outcomes known to facilitate onward HIV transmission (eg, risky sex, poor medication adherence, depression, and substance abuse). A fifth of perinatal HIV-infected participants reported physical and/or sexual IPV in the past year; one-third reported lifetime IPV. Childhood adversity was common and positively associated with IPV. Past-year physical and/or sexual IPV was positively correlated with high-risk sex [odds ratio (OR) = 8.96; 95% confidence interval (CI): 2.78 to 28.90], pregnancy (OR = 6.56; 95% CI: 1.91 to 22.54), poor medication adherence to antiretroviral therapy (OR = 5.37; 95% CI: 1.37 to 21.08), depression (OR = 4.25; 95% CI: 1.64 to 11.00), and substance abuse (OR = 4.11; 95% CI: 1.42 to 11.86). Neither past-year nor lifetime IPV was associated with viral load or HIV status disclosure to a partner. We find that IPV may increase risk for onward HIV transmission in perinatal HIV-infected youth by both increasing engagement in risky sexual behaviors and lowering medication adherence. HIV clinics should consider integrating primary IPV prevention interventions, instituting routine IPV screening, and collocating services for victims of violence.


ldne: a program for estimating effective population size from data on linkage disequilibrium.
ldne is a program with a Visual Basic interface that implements a recently developed bias correction for estimates of effective population size (N(e) ) based on linkage disequilibrium data. The program reads genotypic data in standard formats and can accommodate an arbitrary number of samples, individuals, loci, and alleles, as well as two mating systems: random and lifetime monogamy. ldne calculates separate estimates using different criteria for excluding rare alleles, which facilitates evaluation of data for highly polymorphic markers such as microsatellites. The program also introduces a jackknife method for obtaining confidence intervals that appears to perform better than parametric methods currently in use.


Thermal imaging of receptor-activated heat production in single cells.
Changes in enthalpy (i.e., heat content) occur during the diverse intracellular chemical and biophysical interactions that take place in the life cycle of biological cells. Such changes have previously been measured for cell suspensions or cell-free biochemical extracts by using microcalorimetry, thermocouples, or pyroelectric films, all of which afford minimal spatial or temporal resolution. Here we present a novel thermal imaging method that combines both diffraction-limited spatial (approximately 300 nm) and sampling-rate-limited time resolution, using the temperature-dependent phosphorescence intensity of the rare earth chelate Eu-TTA (europium (III) thenoyltrifluoro-acetonate). With this thermosensitive dye, we imaged intracellular heat waves evoked in Chinese hamster ovary cells after activation of the metabotropic m1-muscarinic receptor. Fast application of acetylcholine onto the cells evoked a biphasic heat wave that was blocked by atropine, and after a brief delay was followed by a calcium wave. Atropine applied by itself produced a monophasic heat wave in the cells, suggesting that its interactions with the receptor activate some intracellular metabolic pathways. The thermal imaging technique introduced here should provide new insights into cellular functions by resolving the location, kinetics, and quantity of intracellular heat production.


Antioxidative, antibrowning and antibacterial activities of sixteen floral honeys.
Commonly consumed honeys from sixteen different single floral sources were analyzed for their in vitro antioxidant capacities by several methods including DPPH, ABTS, FRAP, SASR and MDA assays. The total polyphenol contents varied among the tested honeys and were highly correlated to their antioxidant capacity values. The antioxidant capacity of Chinese milk vetch flower honeys was significantly higher than those of other flower honeys. All honeys tested were active in inhibiting the browning of apple homogenate and linden honey displayed the highest inhibition rate as 85%. When the antimicrobial activity of the investigated honeys was screened using Gram-positive bacteria (Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli), clover honey exhibited the strongest antibacterial activity as 2.2 mg mL(-1) kanamycin equivalent inhibition.


Performance rating scale for peer and self assessment.
A performance rating scale was developed and tested on a class of junior medical students who rated themselves and four to ten of their peers. When 928 ratings were factor analysed, two strong factors, knowledge and relationship, emerged. Test-retest reliabilities were good. Validity was measured by correlation of ratings with grades, and though both sources of ratings correlated significantly with grades given by faculty, peer ratings were more highly related to grades than were self ratings. Students tended to rate themselves lower than they were rated by their peers. Grades are probably not the best estimate of performance, but are currently one of the most reliable. Use of the scale to judge performance of physicians in practice has not been tested. The question of how such evaluation of peer and self would relate to other measures of quality of care is raised.


Fungaemia caused by Candida glabrata with reduced susceptibility to fluconazole due to altered gene expression: risk factors, antifungal treatment and outcome.
The role of Candida glabrata in fungaemia is attributed in part to its reduced susceptibility to azoles, usually due to altered expression of genes encoding drug efflux pumps. The aims of this study were to identify risk factors for fungaemia due to C. glabrata isolates with decreased susceptibility to fluconazole and to analyse the response to antifungal treatment and the clinical outcome of C. glabrata infections in hospitalized patients. A retrospective case-case-control study was conducted at a university hospital from 2000 to 2006. Three patient groups were studied: 14 patients infected by a fluconazole-less-susceptible isolate [susceptible-dose-dependent (SDD) or resistant]; 21 patients infected by a fluconazole-susceptible (FS) isolate; and 70 uninfected controls. We measured expression of the drug efflux pump-encoding CgCDR1 and CgCDR2 genes in isolates of the two infected groups using quantitative real-time PCR. Multivariable analysis found that patients with prior fluconazole use [odds ratio (OR) 12.24, 95% confidence intervals (CIs) 1.77-84.39, P = 0.01], diabetes (OR 10.47, 95% CI 1.96-55.96, P = 0.006) and a central venous catheter (CVC) (OR 8.48, 95% CI 1.82-39.36, P = 0.006) were more likely to develop fungaemia due to a less-susceptible isolate. Previous surgery (OR 7.73, 95% CI 2.18-27.41, P = 0.002) was an independent risk factor for fungaemia due to a susceptible isolate, in addition to the presence of a CVC (OR 5.48, 95% CI 1.69-17.72, P = 0.004). The crude 30 day mortality rate was high for both case groups. Seven patients received inadequate antifungal treatment, including five infected by a fluconazole-resistant isolate but empirically treated with fluconazole; six of these seven patients died. Expression of the CgCDR genes was up-regulated in all fluconazole-resistant and, to a lesser extent, SDD isolates, but not in the FS isolates. Our data suggest that when candidaemia is suspected or detected, a more broad-spectrum antifungal drug (i.e. echinocandins or amphotericin B) should be considered as initial treatment for patients with prior azole exposure.


[Optimal patient position for catheterisation of the subclavian vein: in the Trendelenburg position without a rolled towel between the shoulder blades].
To determine the optimal patient position for subclavian-vein catheterisation. Descriptive. The anteroposterior diameter of the right and left subclavian vein was measured using B-mode ultrasound in 26 healthy volunteers lying in 4 different positions: horizontally with or without a rolled towel between the should blades, or in the Trendelenburg position with or without a rolled towel. The mean diameter of the subclavian vein was 10.7 mm. There was a statistically significant association between the diameter of the vein and the position of the volunteer, the use of the rolled towel, and the side of the body. The least favourable results were obtained on the left side when the patient was lying horizontally with a rolled towel (8.65 mm). The most favourable results were obtained on the right side when the patient was in the Trendelenburg position without a rolled towel (12.05 mm). For successful catheterisation of the subclavian vein, the patient should be placed in the Trendelenburg position without a rolled towel between the shoulder blades, and the puncture should be preferably on the right side.


HL-A 27 and acute anterior uveitis.
51 (30 men and 21 women) of 90 consecutive patients with acute non-granulomatous anterior uveitis were HL-A 27 positive. This frequency of 55-7 per cent compares with 8-2 per cent in controls. Twenty-three patients (18 men and 5 women) had in addition evidence of systemic disease, including ankylosing spondylitis, sacroiliitis and Reiter's syndrome, sometimes associated with psoriasis. Twenty-eight of 63 patients without evidence of systemic disease were HL-A 27 positive, suggesting that the uveitis in many of these cases has a similar aetiology to those with rheumatic disease. The uveitis associated with HL-A 27 is typically unilateral, associated with mechanical ptosis, and a painful diffusely red, photophobic, and lacrimating eye, generally lasting 3 weeks or more. Protein extravasation into the aqueous is considerable, cells are usually present in the aqueous and anterior vitreous, and keratic precipitates are never mutton fat in appearance. Recurrent episodes are characteristic. The association with HL-A 27 suggests that many if not most cases of non-granulomatous anterior uveitis have a close aetiological relationship to ankylosing spondylitis and Reiter's syndrome and it is likely that infective agents, leading to an unusual immunologically mediated inflammatory response in predisposed individuals, are involved. Ten patients with granulomatous anterior uveitis were HL-A 27 negative.


Radiation protection in digestive endoscopy: European Society of Digestive Endoscopy (ESGE) guideline.
This article expresses the current view of the European Society of Gastrointestinal Endoscopy (ESGE) about radiation protection for endoscopic procedures, in particular endoscopic retrograde cholangiopancreatography (ERCP). Particular cases, including pregnant women and pediatric patients, are also discussed. This Guideline was developed by a group of endoscopists and medical physicists to ensure that all aspects of radiation protection are adequately dealt with. A two-page executive summary of evidence statements and recommendations is provided. The target readership for this Guideline mostly includes endoscopists, anesthesiologists, and endoscopy assistants who may be exposed to X-rays during endoscopic procedures.


COVID-19 vaccine rumors and conspiracy theories: The need for cognitive inoculation against misinformation to improve vaccine adherence.
Rumors and conspiracy theories, can contribute to vaccine hesitancy. Monitoring online data related to COVID-19 vaccine candidates can track vaccine misinformation in real-time and assist in negating its impact. This study aimed to examine COVID-19 vaccine rumors and conspiracy theories circulating on online platforms, understand their context, and then review interventions to manage this misinformation and increase vaccine acceptance. In June 2020, a multi-disciplinary team was formed to review and collect online rumors and conspiracy theories between 31 December 2019-30 November 2020. Sources included Google, Google Fact Check, Facebook, YouTube, Twitter, fact-checking agency websites, and television and newspaper websites. Quantitative data were extracted, entered in an Excel spreadsheet, and analyzed descriptively using the statistical package R version 4.0.3. We conducted a content analysis of the qualitative information from news articles, online reports and blogs and compared with findings from quantitative data. Based on the fact-checking agency ratings, information was categorized as true, false, misleading, or exaggerated. We identified 637 COVID-19 vaccine-related items: 91% were rumors and 9% were conspiracy theories from 52 countries. Of the 578 rumors, 36% were related to vaccine development, availability, and access, 20% related to morbidity and mortality, 8% to safety, efficacy, and acceptance, and the rest were other categories. Of the 637 items, 5% (30/) were true, 83% (528/637) were false, 10% (66/637) were misleading, and 2% (13/637) were exaggerated. Rumors and conspiracy theories may lead to mistrust contributing to vaccine hesitancy. Tracking COVID-19 vaccine misinformation in real-time and engaging with social media to disseminate correct information could help safeguard the public against misinformation.


The herbal medicine Dai-Kenchu-Tou stimulates upper gut motility through cholinergic and 5-hydroxytryptamine 3 receptors in conscious dogs.
The herbal medicine Dai-Kenchu-To, composed of zanthoxylum fruit, ginseng root, and dried ginger rhizome, is clinically effective for uncomplicated postoperative adhesive intestinal obstruction. We investigated the effect of Dai-Kenchu-To and each ingredient on upper gastrointestinal motility and its mechanism of action. Five mongrel dogs were equipped with 4-strain gauge-force transducers on the gastric body, antrum, duodenum, and jejunum to measure contractile activity of the circular muscle. Dai-Kenchu-To (1.5 g) or the separate ingredients zanthoxylum fruit, ginseng root, or dried ginger rhizome (1.0 g each) were administered by bolus into the gastric lumen. The effect of atropine, hexamethonium, phentolamine, propranolol, and ondansetron on intragastric Dai-Kenchu-To-induced contractions was studied. Intragastric Dai-Kenchu-To induced phasic contractions in the antrum, duodenum, and jejunum. Zanthoxylum fruit elicited phasic contractions mainly in the duodenum and jejunum, whereas dried ginger rhizome induced phasic contractions in the antrum. Ginseng root had no effect. Phasic contractions induced by intragastric Dai-Kenchu-To were inhibited by atropine and hexamethonium at all sites, although ondansetron inhibited these contractions in the antrum and duodenum. Intragastric Dai-Kenchu-To stimulates upper gastrointestinal motility through cholinergic and 5-hydroxytryptamine 3 receptors.


Facial paralysis due to benign parotid tumors.
On rare occasions, facial paralysis associated with a parotid tumor need not denote malignancy. We present two cases in which, contrary to appropriate conventional wisdom, facial paralysis resulted from benign mixed tumors. Each patient presented over 8 years following primary surgical excision. In neither patient was a mass palpable, and facial paralysis was the sole sign of recurrent disease. Each patient had been followed up for several months with a presumptive diagnosis of Bell's palsy prior to discovery of recurrent tumor by radiologic imaging. In each case, at operation the tumor was found to infiltrate the temporal bone via the stylomastoid foramen. Facial paralysis presumably resulted from extrinsic compression of the facial nerve. These two cases add to the few previous reports of facial paralysis due to benign parotid gland tumors.


Phase transition in spin systems with various types of fluctuations.
Various types ordering processes in systems with large fluctuation are overviewed. Generally, the so-called order-disorder phase transition takes place in competition between the interaction causing the system be ordered and the entropy causing a random disturbance. Nature of the phase transition strongly depends on the type of fluctuation which is determined by the structure of the order parameter of the system. As to the critical property of phase transitions, the concept "universality of the critical phenomena" is well established. However, we still find variety of features of ordering processes. In this article, we study effects of various mechanisms which bring large fluctuation in the system, e.g., continuous symmetry of the spin in low dimensions, contradictions among interactions (frustration), randomness of the lattice, quantum fluctuations, and a long range interaction in off-lattice systems.


A comparative study of antimony accumulation in plants growing in two mining areas in Iran, Moghanlo, and Patyar.
Antimony occurs locally at high concentrations in some mineralized soils. Very little is known about behavior of antimony in plants. In this study, we analyzed the soil and vegetation of two mining areas in Iran, Patyar, and Moghanlo. Total Sb concentrations in soil were 358-3482 mg/kg in Moghanlo and 284-886 mg/kg in Patyar. Corresponding Sb concentrations in plant shoots were 0.8-287 and 1.3-49 mg/kg, respectively. In both areas, foliar Sb concentrations increased with acid-extractable soil Sb, although the slope was about 2-fold steeper for Patyar than for Moghanlo. Regressing the foliar concentrations on water-soluble Sb yielded identical slopes for both areas, suggesting that the soluble fraction of Sb rather than total Sb is the direct determinant of foliar Sb accumulation. Both in Patyar and Moghanlo, only a minor part of the total variance of shoot Sb was explained by soluble Sb. The major part was explained by plant species, demonstrating that plant taxonomic identity is the most important determinant of foliar Sb accumulation capacity in both areas. The translocation factor (TF) was highly variable too, with species as the only significant variance component. Only four species were able to accumulate more than 100 mg/kg Sb in their leaves. Among these species, Achillea wilhelmsii and Matthiola farinosa were by far the best Sb accumulators, with, on average, 141 and 132 mg/kg Sb in their leaves. Of these two, only Matthiola farinosa consistently maintained TF values far above unity across the whole range of soluble Sb in Moghanlo.


Chemical Composition of Defatted Cottonseed and Soy Meal Products.
Chemical composition is critical information for product quality and exploration of new use. Hence defatted cottonseed meals from both glanded (with gossypol) and glandless (without gossypol) cotton seeds were separated into water soluble and insoluble fractions, or water soluble, alkali soluble as well as total protein isolates. The contents of gossypol, total protein and amino acids, fiber and carbohydrates, and selected macro and trace elements in these products were determined and compared with each other and with those of soy meal products. Data reported in this work improved our understanding on the chemical composition of different cottonseed meal products that is helpful for more economical utilization of these products. These data would also provide a basic reference for product standards and quality control when the production of the cottonseed meal products comes to pilot and industrial scales.


Anorectal malformation as a cause of recurring perineal abscesses - value of anorectal endosonography and magnetic resonance imaging: a case report.
Malformations of the rectum and urinary tract frequently coexist, and the prevalence of urogenital defects in patients with a rectal defect ranges from 20 to 54%. In most patients, anorectal malformations are diagnosed and treated surgically in early childhood. In this report, we present a case of a 52-year-old male with a history of urological operations in infancy due to a congenital urethral malformation and multiple recurrent episodes of perineal abscesses with urinary retention. Anorectal endosonography and magnetic resonance imaging revealed the presence of a large cystic lesion adjacent to the rectal wall which became smaller at the level of the puborectalis. The walls of the lesion had a layered structure identical to the wall of the rectum. In addition, the examinations showed hypotrophy of the left lobe of the prostate and lack of left semnal vesicles. Thus, the lesion was diagnosed as duplication of the rectum or rectal diverticulum. Surgery was performed by an interdisciplinary team of colorectal surgeons and urologist. The lesion was removed laparoscopically. The pathological report revealed that the cystic wall was typical of the intestinal wall, consistent with a diagnosis of rectal duplication.


[Secretory activity of the small intestine after resection of the pancreas].
The experiments on dogs have shown that during 3-5 weeks after resection of 1/3 and 2/3 of the pancreas the total amount of the excreted intestinal juice and the content of proper enteric enzymes in it (enterokinase, alkaline phosphatase and saccharase) are decreased. According to the author's data the activity of intestinal juice amylase and lipase being enzymes mostly of the pancreatic origin, transferred in the small intestine from blood, is enhanced due to impairment of the histo-hematic barrier in the region of the resected pancreatic stump. 2-3 months following resection of 2/3 of the pancreatic gland the amount of excreted intestinal juice was nearly unchanged, but the content of proper enteric enzymes was somewhat increased, as compared with background indices.


Hepatoprotective and antioxidant potential of Pycnogenol® in acetaminophen-induced hepatotoxicity in rats.
Pycnogenol® (PYC) has already being used as a food supplement and herbal medicine due to its potent antioxidant properties. The aim of the present study was to examine the protective effect of PYC on acetaminophen-induced acute liver injury in rats. The effect of PYC on acetaminophen-induced hepatotoxicity in rats was examined by determining biochemical parameters, in vitro antioxidant activity, histological assessment, and oxidative status in liver homogenates. The best antioxidant properties were demonstrated in methanolic extracts. Seven-day pretreatment with PYC suppressed elevation of CYP2E1 protein expression induced by administration of toxic dose of acetaminophen. PYC at 50 mg/kg showed the ability to significantly decrease malondialdehyde (MDA) level compared with the group received acetaminophen. Xanthine oxidase (XOD) enzyme activity was significantly elevated in acetaminophen-treated group compared with control, whereas concomitant administration of PYC in a dose of 50 mg/kg significantly reduced activity of this enzyme. Significant decrease of glutathione (GSH) hepatic content in acetaminophen-intoxicated rats compared with the control rats was improved by concomitant administration of PYC at 50 mg/kg. Protective effect of PYC on acetaminophen-induced acute liver injury in rats has showed the best in vitro antioxidant potential expressed in methanolic extract and consequent histological assessment and oxidative status in liver homogenates.


Role of CYP2E1 in the epoxidation of acrylamide to glycidamide and formation of DNA and hemoglobin adducts.
Acrylamide (AA) is an animal carcinogen, neurotoxin, and reproductive toxin. AA is formed in baked and fried carbohydrate-rich foods. Metabolism of AA occurs via epoxidation to glycidamide (GA) or direct conjugation with glutathione. Using CYP2E1-null mice, recent studies in this laboratory demonstrated that induction of somatic and germ cell mutagenicity in AA-treated mice is dependent on CYP2E1. We hypothesized that AA metabolism to GA is a prerequisite for the induction of AA-induced mutagenicity. Current studies were undertaken to assess the role of CYP2E1 in the epoxidation of AA to GA and the formation of DNA and hemoglobin (HGB) adducts. AA was administered to CYP2E1-null or wild-type mice at 50 mg/kg ip. Mice were euthanized 6 h later and blood and tissues were collected. Using LC-ES/MS/MS, AA, GA, and DNA- and HGB-adducts were measured. While the plasma levels of AA and GA were 115 +/- 14.0 and 1.7 +/- 0.31 microM in CYP2E1-null mice, they were 0.84 +/- 0.80 and 33.0 +/- 6.3 microM in the plasma of AA-treated wild-type mice. Administration of AA to wild-type mice caused a large increase in N7-GA-Gua and N3-GA-Ade adducts in the liver, lung, and testes. While traces of N7-GA-Gua adducts were measured in the tissues of AA-treated CYP2E1-null mice, these levels were 52- to 66-fold lower than in wild-type mice. Significant elevation of both AA- and GA-HGB adducts was detected in AA-treated wild-type mice. In AA-treated CYP2E1-null mice, levels of AA-HGB adducts were roughly twice as high as those in wild-type mice. In conclusion, current work demonstrated that CYP2E1 is the primary enzyme responsible for the epoxidation of AA to GA, which leads to the formation of GA-DNA and HGB adducts.


Reduction in coagulation factor VII plasma levels by R353Q but not the -323P0/10 promoter polymorphism in healthy Tunisians.
The association between the R353Q and -323P0/10 (10-bp insertion in the promoter region at position -323) factor VII mutations and plasma factor VII levels was investigated in a group of 214 healthy Tunisians. The frequency for the Q allele was 0.253 and that for the 10-bp allele was 0.206, and their distribution was variable, with a high prevalence of the 10-bp allele (0.306) seen in North Tunisia and a high prevalence of the Q allele (0.288) see in the Sahel region. No significant linkage disequilibrium was observed between the two mutations, and the most prevalent haplotype was -323P0/353R (0.589 +/- 0.054). Carriers of the R353Q (P < 0.001), but not -323P0/10 (P = 0.088), factor VII mutations had lower mean factor VII serum concentrations. This reduction in mean serum factor VII was more pronounced among homozygous (Q/Q) carriers and among males (49.9%) compared to females (32.7%). Adjusting for all other variables in the linear regression analysis (sex, age, region, smoking, and R353Q and -323P0/10 mutations), heterozygous carriers of the -323P0/10 and R353Q mutation had on average reductions of 10 units (P = 0.005) and 30 units (P < 0.001) in plasma factor VII, respectively, compared to noncarriers, while homozygote carriers of the R353Q (-43.3, P < 0.001), but not carriers of the -323P0/10 (-6.30, P = 0.356), had significantly lower levels of mean plasma factor VII. These data suggest that part of the previously described effects on FVIIc levels associated with the R/Q polymorphism may be explained by genetic variation in the promoter region of the FVII gene.


A 5-year clinical evaluation of ceramic inlays (Cerec) cemented with a dual-cured or chemically cured resin composite luting agent.
Sixty-six class-II CAD/CAM-manufactured ceramic inlays (Cerec) were placed in 27 patients. Each patient received at least one inlay luted with a dual-cured resin composite and one inlay luted with a chemically cured resin composite. The inlays were examined 5 years after luting using the California Dental Association (CDA) criteria. Eighty-nine percent of the 66 inlays were rated 'satisfactory'. During the follow-up period replacement was required for 3 inlays because of inlay fractures (4.5%) and 1 inlay because of fracture of the tooth substance (1.5%). All those inlays were luted with the dual-cured resin composite luting agent. Of the remaining 62 inlays the CDA rating 'excellent' was given to 84% for color, 97% for surface, and 81% for anatomic form. 'Excellent' margin integrity was seen in 52% of the dual-cured resin composite luted inlays and in 61% of the chemically cured resin composite luted inlays. No statistically significant (P> 0.05) difference was observed between the two luting agents.


Effects of estradiol on ischemic factor-induced astrocyte swelling and AQP4 protein abundance.
In the early hours of ischemic stroke, cerebral edema forms as Na, Cl, and water are secreted across the blood-brain barrier (BBB) and astrocytes swell. We have shown previously that ischemic factors, including hypoxia, aglycemia, and arginine vasopressin (AVP), stimulate BBB Na-K-Cl cotransporter (NKCC) and Na/H exchanger (NHE) activities and that inhibiting NKCC and/or NHE by intravenous bumetanide and/or HOE-642 reduces edema and infarct in a rat model of ischemic stroke. Estradiol also reduces edema and infarct in this model and abolishes ischemic factor stimulation of BBB NKCC and NHE. There is evidence that NKCC and NHE also participate in ischemia-induced swelling of astrocytes. However, little is known about estradiol effects on astrocyte cell volume. In this study, we evaluated the effects of AVP (100 nM), hypoxia (7.5% O(2)), aglycemia, hypoxia (2%)/aglycemia [oxygen glucose deprivation (OGD)], and estradiol (1-100 nM) on astrocyte cell volume using 3-O-methyl-d-[(3)H]glucose equilibration methods. We found that AVP, hypoxia, aglycemia, and OGD (30 min to 5 h) each significantly increased astrocyte cell volume, and that estradiol (30-180 min) abolished swelling induced by AVP or hypoxia, but not by aglycemia or OGD. Bumetanide and/or HOE-642 also abolished swelling induced by AVP but not aglycemia. Abundance of aquaporin-4, known to participate in ischemia-induced astrocyte swelling, was significantly reduced following 7-day but not 2- or 3-h estradiol exposures. Our findings suggest that hypoxia, aglycemia, and AVP each contribute to ischemia-induced astrocyte swelling, and that the edema-attenuating effects of estradiol include reduction of hypoxia- and AVP-induced astrocyte swelling and also reduction of aquaporin-4 abundance.


Spinal cord infarction during use of zolmitriptan: a case report.
A 50-year-old woman with a history of migraine without aura, predominantly occurring around her menstrual periods, developed a spinal cord lesion following the use of zolmitriptan. The partial lesion of the cord at T7 predominantly involved the spinothalamic pathways on the left side. Clinical features suggested that the lesion was an ischemic infarct, and this was confirmed by an MRI scan. There were no other known risk factors for vascular disease. There has been mild improvement of her symptoms, but most of the symptoms did not resolve. There are isolated case reports of stroke secondary to the use of triptans, however, this is the first case of spinal cord infarction reported following the use of this group of drugs. The temporal relationship suggests that the spinal cord infarction may be related to the use of zolmitriptan.


Computer-generated display for three-dimensional static perimetry.
A display method has been developed for imaging the results of static perimetric examinations performed over contiguous areas of the central visual field. Points are examined using a rectangular coordinate pattern. A three-dimensional display surface is interpolated between the recorded points. A two-dimensional representation of the interpolated surface is then drawn, using superposition of foreground elements to produce an illusion of depth. Refinements of surface fit to the data points and truncation and rotation of the images allow immediate appreciation of visual field topography. The use of rectangular coordinate patterns increases the probability of detection of small defects and improves the resolution of structural detail.


Changes in mouse whole saliva soluble proteome induced by tannin-enriched diet.
Previous studies suggested that dietary tannin ingestion may induce changes in mouse salivary proteins in addition to the primarily studied proline-rich proteins (PRPs). The aim of the present study was to determine the protein expression changes induced by condensed tannin intake on the fraction of mouse whole salivary proteins that are unable to form insoluble tannin-protein complexes. Two-dimensional polyacrylamide gel electrophoresis protein separation was used, followed by protein identification by mass spectrometry. Fifty-seven protein spots were excised from control group gels, and 21 different proteins were identified. With tannin consumption, the expression levels of one α-amylase isoform and one unidentified protein increased, whereas acidic mammalian chitinase and Muc10 decreased. Additionally, two basic spots that stained pink with Coomassie Brilliant Blue R-250 were newly observed, suggesting that some induced PRPs may remain uncomplexed or form soluble complexes with tannins. This proteomic analysis provides evidence that other salivary proteins, in addition to tannin-precipitating proteins, are affected by tannin ingestion. Changes in the expression levels of the acidic mammalian chitinase precursor and in one of the 14 salivary α-amylase isoforms underscores the need to further investigate their role in tannin ingestion.


Identifying 2 prenylflavanones as potential hepatotoxic compounds in the ethanol extract of Sophora flavescens.
Zhixue capsule is a prescription for hemorrhoid commonly used in traditional Chinese medicine. This drug was recalled by the State Food and Drug Administration in 2008 because of severe adverse hepatic reactions. Zhixue capsule is composed of ethanol extracts of Cortex Dictamni (ECD) and Sophora flavescens (ESF). In our preliminary study, we observed the hepatotoxic effects of ESF on rat primary hepatocytes. However, ECD did not exhibit hepatotoxicity at the same concentration range. In this study, ESF was evaluated for its potential hepatotoxic effects on rats. Bioassay-guided isolation was used to identify the material basis for hepatotoxicity. Treatment with 1.25 g/kg and 2.5 g/kg ESF significantly elevated the alanine aminotransferase and aspartate aminotransferase levels in the serum. The changes in the levels of transaminases were supported by the remarkable fatty degeneration of liver histopathology. Further investigations using bioassay-guided isolation and analysis indicated that prenylated flavanones accounted for the positive hepatotoxic results. Two isolated compounds were identified, kurarinone and sophoraflavanone G, using nuclear magnetic resonance and mass spectrometry techniques. These compounds have potent toxic effects on primary rat hepatocytes (with IC50 values of 29.9 μM and 16.5 μM) and human HL-7702 liver cells (with IC50 values of 48.2 μM and 40.3 μM), respectively. Consequently, the hepatotoxic constituents of S. flavescens were determined to be prenylated flavanones, kurarinone, and sophoraflavanone G.


The early years: child development in undergraduate medical school training.
There are substantial gaps in knowledge about early child development among graduating family physicians. The main objective of this program was to develop, implement, and evaluate an early child development curriculum for undergraduate medical clerks doing their family medicine rotations. The Early Years Program at McMaster University in Hamilton, Ont, consists of 2 small group sessions during the family medicine rotation and a site visit to a community agency that provides services to families with young children. The curriculum is delivered by interprofessional facilitator dyads: a family physician and another professional. The content covers areas such as newborn assessment, developmental screening and referrals, parenting issues, pregnancy, preconception, and prevention, and is supported by case studies, videos, and community resources. Based on casual feedback and formal evaluations, we conclude that the overall goal of launching the Early Years Program-to address previously identified gaps-has been achieved. We continue to improve the program to meet the challenges of the ever changing undergraduate health science education.


Effects of complete androgen blockade for 12 and 24 weeks on the pathological stage and resection margin status of prostate cancer.
To compare the pathological stage and surgical margin status in patients undergoing either immediate radical prostatectomy or 12 and 24 weeks of neoadjuvant hormonal treatment (NHT) in a prospective, randomised study. Whole mount sections of 393 radical prostatectomy specimens were evaluated: 128 patients had immediate surgery, 143 were treated for 12 weeks and 122 for 24 weeks with complete androgen blockade. Histopathology revealed organ confined tumours in 40.4% of patients with clinical stage B disease in the immediate surgery group, whereas 12 and 24 weeks of NHT increased the number of organ confined tumours to 54.6% and 64.8%, respectively. Among patients with clinical stage C tumours, pathological staging found organ confined disease in 10.4%, 31.4%, and 61.2% in the immediate surgery, 12 weeks of NHT, and 24 weeks of NHT groups, respectively. Preoperative NHT caused a significant decrease in positive margins both in patients with clinical stage B and C disease. The extent of margin involvement was not influenced by preoperative treatment. Neoadjuvant androgenic suppression is effective in reducing both the pathological stage and the positive margin rate in patients with stage B and C prostatic cancer undergoing radical surgery. Some beneficial effects are evident in those patients treated for 24 weeks, and it is reasonable to assume that the optimal duration of NHT is longer than three months.


Fluorescence molecular tomography in the second near-infrared window.
Fluorescence molecular tomography (FMT), an in vivo noninvasive imaging technology, can provide localization and quantification information for deep fluorophores. Light at wavelengths in the near-infrared (NIR-I) window from 650 nm to 950 nm has conventionally been chosen for FMT. In this study, we introduced longer NIR wavelengths within the 1100 nm to 1400 nm range, known as the "second NIR spectral window" (NIR-II). A singular-value analysis method was used to demonstrate the utility and advantages of using the NIR-II for FMT, and experiments showed an improvement in the spatial resolution in phantom studies.