Consequences of flower heliotropism for reproduction in an alpine buttercup (Ranunculus adoneus).
The flowers of the alpine snow buttercup Ranunculus adoneus track the sun's movement from early morning until mid-afternoon. Individual blooms last up to a week: younger female stage flowers show greater solar tracking fidelity than older hermaphrodite or dehisced flowers. Flowers aligned parallel to the sun's rays reach mean internal temperatures several degrees Celsius above ambient air temperature. As a flower's angle of deviation from the sun increases beyond 45 degrees, internal flower temperature is significantly reduced. Fly pollinators are seen disproportionately often on flowers aligned with the sun; this is due, in part, to their greater residence time on tracking flowers. Fly visitation is important to fecundity. When flies were excluded from flowers, some selfed seeds were matured, but total seed production was much less than in either handoutcrossed or open-pollinated flowers. Flowers that were tethered at random angles to prevent solar tracking set fewer, smaller seeds than unmanipulated control flowers. Reductions in seed weight were statistically consistent at different times in the season, but tethering influenced seed number per flower most strongly in the early season. Effects of tethering on maternal reproduction could be due to either pollinator diserimination, post-pollination developmental processes, or both. In a second series of experiments using fluorescent dye particles as pollen analogs, tethered donor flowers dispersed dye to as many recipients as paired control flowers, suggesting that solar tracking fidelity may have little effect upon this component of male reproduction.


Effects of carbon monoxide exposure in patients with documented cardiac arrhythmias.
This study was designed to determine whether carbon monoxide has proarrhythmic effects at rest and during upright exercise in patients with myocardial ischemia and moderate baseline ectopic activity. Exposure of patients with documented myocardial ischemia to low levels of carboxyhemoglobin (COHb) alters the myocardial response to exercise. Anecdotal reports from patients with myocardial ischemia have noted the development of arrhythmias related to carbon monoxide exposure. Increased frequency of arrhythmias related to carbon monoxide exposure in patients performing supine bicycle exercise has been recently reported. Twenty-eight nonsmoking men and five nonsmoking women with documented coronary artery disease and a minimum of 30 ventricular ectopic beats/h over a 20-h period were studied. Subjects were exposed in a randomized double-blind fashion to either room air or sufficient carbon monoxide to elevate their COHb concentration to 3% or 5% in 1 h, followed by a maintenance exposure to carbon monoxide. The subjects then left the laboratory and resumed their normal daily activity to determine changes in ventricular ectopic beats after carbon monoxide exposure. There was no significant change in the frequency of single ventricular ectopic beats at rest from 115 +/- 28 (in room air) to 121 +/- 31 at 3% COHb to 94 +/- 23 at 5% COHb. Exercise itself increased the frequency of ventricular ectopic beats, but there was no additional effect of carbon monoxide exposure on the exercise-induced increase in isolated ectopic beats or complex ectopic waveforms. Analysis of the data based on grouping of the subjects by the severity of disease (ventricular ectopic beat frequency, ejection fraction, presence of exercise-induced ischemia) indicated no proarrhythmic effect of carbon monoxide. In patients with frequent ventricular ectopic activity (> or = 30 ectopic beats/h), exposure to carbon monoxide producing either 3% or 5% COHb does not increase arrhythmia frequency of single or multiple beats during rest or exercise.


Improvements in the primary culture of neonate rat myocardial cells by study of the mechanism of endoplasmic reticulum stress.
We previously found that endoplasmic reticulum stress (ERS) might be exhibited in the conventional protocol of the primary culture of neonate rat myocardial cells (NRMCs) and that the high glucose concentration (25 mmol/L) in the culture medium might be the cause. Here, we investigated if the high concentration of glucose might influence ERS in myocardial cells during culture. GRP78 expression (ERS marker) was similar in groups with tunicamycin (TM) and without TM in high glucose cultured cells (p > 0.01). Different glucose concentrations elicited different GRP78 expressions according to analyses of protein and RNA levels, which showed ERS in H/H groups. Finally, we found that GRP78 expression was higher in TM groups compared with M/M groups (p < 0.01). The conventional high-glucose culture media during primary culture of NRMCs induced ERS. We propose that medium-glucose culture media should be used and describe an improved protocol for the primary culture of NRMCs.


Renal dysfunction as a consequence of acute liver damage by bile duct ligation in cirrhotic rats.
Renal failure is a common complication in patients with alcohol-induced cirrhosis who undergo a superimposed severe alcoholic hepatitis. Our aim was to evaluate renal dysfunction established as a consequence of acute liver damage (ALD) induced by bile duct ligation (BDL) in cirrhotic rats. Hepatic and renal functional assays were performed. Hyperbilirubinemia and increased alanine aminotransferase and aspartate aminotransferase (p<0.05) in rats with BDL were observed since the first day of bile obstruction in cirrhotic rats. Urinary volume and urinary sodium concentration showed a significant reduction (p<0.05) on days 3 and 5 after BDL. Plasma renin activity, plasma renin concentration, serum creatinine, and BUN values increased (p<0.05) from day 1 to day 7 after BDL. Glomerular filtration rate was substantially decreased from day 1 to day 7. Histological changes became apparent since day 3 after BDL in which glomeruli with mesangial hypercellularity took place in the absence of tubular necrosis; with portal inflammation and proliferation of biliar conduits. Results of the present work demonstrate that ALD induced by BDL in cirrhotic rats produces changes in renal function. In conclusion, this experimental model demonstrates that an ALD of variable etiology, either surgical or induced by CCl(4), can cause important damage that eventually results in renal function deterioration. This experimental model may be suitable, to study the physiopathology of this syndrome, as well as for the evaluation of different pharmacological therapies.


Uptake of macromolecules into neurons from a focal vasogenic cerebral edema and subsequent axonal spread to other brain regions. A preliminary study in the mouse with horseradish peroxidase as a tracer.
Intravenously (i.v.) injected horseradish peroxidase (HRP) which has leaked out of the vessels in a cryogenic cortical injury of adult mice is taken up into a large number of neurons resulting in two different forms of labeling. Diffuse neuronal labeling of the type previously reported in many conditions with vasogenic brain edema occurred particularly within the primary lesion. The other and more frequent type, here called granular neuronal labeling, was present in a wide zone immediately outside the injury. Such neurons contained HRP in numerous cytoplasmic granules and had the same characteristics as normal neurons accumulating HRP after retrograde axonal transport. By using highly sensitive histochemical methods for demonstration of HRP we could also follow bundles of labeled axons out from the primary lesion. Some of them passed the corpus callosum to the fronto-parietal cortex of the contralateral hemisphere. With this report we would like to put emphasize on certain phenomena occurring in neurons which previously have not been particularly recognized in studies on vasogenic brain edema. It can be assumed that in a focal brain lesion components from the edematous fluid and other "would substances" can be taken up into nerve cell processes and then be intracellularly transported in different directions. In this way, nerve cell populations located in other brain areas and even in the contralateral hemisphere may be influenced by components from the primary injury.


Pediatric narcolepsy: clinical and therapeutical approaches.
Narcolepsy occurs during childhood in combination with cataplexy in one-third of the subjects. Symptoms may develop rapidly over a few weeks or months, with excessive daytime sleepiness and cataplexy being the most dramatic and observable symptoms. It can be secondary to brain tumors or several rare diseases, but in most cases narcolepsy with or without cataplexy is a primary condition, better explained by the selective loss of hypocretin neurons in posterolateral hypothalamus. A specific HLA allele, HLA-DQB1*0602, is involved and the disease is thought to be autoimmune. Tribbles 2-specific antibodies have been identified. Recent medications have greatly improved the symptoms and wellbeing of young patients. However, these treatments are delivered off-label in the pediatric population. There is an absolute necessity for well-conducted clinical trials in order to improve treatment in children and adolescents with narcolepsy and to evaluate clinical efficacy and good tolerance of medications. Nonpharmacological approaches are certainly helpful and should be promoted systematically, especially in very young children. Narcolepsy of recent onset in children or adolescents should be considered a therapeutic emergency, even though immunotherapy is still controversial.


Association between cumulative joint loading from occupational activities and knee osteoarthritis.
To determine the associations between cumulative occupational physical load (COPL) and 3 definitions of knee osteoarthritis (OA). Cross-sectional analyses were performed from 2 population-based cohorts (n = 327). Eligible symptomatic participants were those with pain, aching, or discomfort in or around the knee on most days of a month at any time in the past and any pain in the past 12 months. Asymptomatic participants responded "no" to both knee pain questions. Self-reported COPL was calculated over each participant's lifetime and then categorized into quarters (QCOPL). Radiographic OA (ROA) and symptomatic OA (SOA) were defined by Kellgren/Lawrence grade ≥2, with SOA also including pain. Magnetic resonance imaging (MRI) OA was defined using criteria by Hunter et al. Logistic regression, adjusted with population weights, examined the associations between QCOPL and each of ROA, SOA, and MRI-OA after controlling for covariates and two-way interactions. Participants had a mean ± SD age of 58.5 ± 11.0 years and a mean ± SD body mass index of 26.3 ± 4.7 kg/m(2) . Of those, 109 (33.3%) had ROA, 102 (31.2%) had SOA, and 131 (40.1%) had MRI-OA. Compared with QCOPL-1, increased odds of ROA were found for QCOPL-4 (odds ratio [OR] 3.15, 95% confidence interval [95% CI] 1.02-9.70) and QCOPL-3 (OR 4.19, 95% CI 1.55-11.34). Statistically significant relationships were found in SOA (QCOPL-4: OR 8.16, 95% CI 1.89-35.27; QCOPL-3: OR 5.73, 95% CI 1.36-24.12) and MRI-OA (QCOPL-4: OR 9.54, 95% CI 2.65-34.27; QCOPL-3: OR 9.04, 95% CI 2.65-30.88; QCOPL-2: OR 7.18, 95% CI 2.17-23.70). Occupational activity is associated with knee OA, with dose-response relationships observed in SOA and MRI-OA.


Collateral impact of the COVID-19 pandemic on the use of healthcare resources among people with disabilities.
We assessed the collateral impact of the COVID-19 pandemic on healthcare service use among people with disabilities. We utilized the COVID-19 database from the Korean National Health Insurance Service claims from 2015 until June 2020. We included 5,850 people with disabilities and matched 5,850 without disabilities among those who were neither tested nor diagnosed with COVID-19. We used a quasi-experimental setting with a COVID-19 outbreak as an external event in a difference-difference estimation with matching controls. Participants with disabilities recorded a larger decrease in the number of claims for total services (2.1 claims per 5 months) upon the COVID-19 pandemic's onset compared to those without disabilities (1.6 claims), and the difference-in-difference estimates were statistically significant (0.46 claims). The decline was driven by outpatient and emergency visits. The extent of the decline was large for the severe disability group overall. By disability type, those with a physical disability showed a statistically significant decline in the number of claims. The COVID-19 pandemic has had a collateral impact on people with disabilities' use of healthcare services. Continued assessment is needed regarding whether the collateral impact has been sustained or is following a different path.


Effect of lower dose of oral conjugated equine estrogen on size and oxidative susceptibility of low-density lipoprotein particles in postmenopausal women.
Estrogen replacement therapy (ERT) has an antioxidant effect that opposes the oxidation of LDL. Oral ERT-induced increases in plasma triglyceride, however, are associated with decreased LDL size, which may counteract this antioxidant effect. Because lower doses of oral estrogen do not affect plasma triglyceride concentrations, LDL size might not change, and the antioxidant effect of estrogen might be preserved. We investigated whether a lower dose of oral estrogen could eliminate the adverse effects of high-dose oral ERT on the size and oxidative susceptibility of LDL in postmenopausal women. Postmenopausal women received no treatment or were treated with oral conjugated equine estrogen (CEE) 0.625 or 0.3125 mg/d for 3 months. CEE at a dose of 0.625 mg/d significantly increased plasma triglyceride concentrations and decreased LDL diameter, but the concentrations of LDL-derived thiobarbituric acid reactive substances (TBARS) and lag time for conjugated diene formation did not change. In contrast, 0.3125 mg of CEE did not affect plasma triglyceride concentrations or LDL diameter and significantly decreased LDL-derived TBARS concentrations and significantly prolonged LDL lag time. Estrogen-induced changes in LDL diameter correlated negatively with changes in plasma triglyceride (r=-0.44, P<0.01) and LDL-derived TBARS (r=-0.57, P<0.001) but positively with changes in LDL lag time (r=0.42, P<0.01). Because oral CEE at a dose of 0.3125 mg/d does not elevate plasma triglyceride, resulting in unchanged size of LDL particles that are resistant to oxidation, the antioxidant effect of estrogen can be preserved.


Review article: mild to moderate Crohn's disease--defining the basis for a new treatment algorithm.
Previously, clinicians have had few choices in treating mild to moderate Crohn's disease. They currently treat these Crohn's disease patients with oral mesalamine and antibiotics. This treatment approach is based on the safety of these agents, and the perception that they are effective. This perception regarding efficacy may be influenced by publication bias. This review examines the efficacy and safety data of the conventional corticosteroids, mesalamine, sulfasalazine, budesonide and antibiotics for inducing the remission of mild to moderate Crohn's disease from randomized controlled trials, and proposes an evidence-based treatment approach. Sulfasalazine has demonstrated modest efficacy when Crohn's disease is confined to the colon. Mesalamine has no clear benefit over placebo in treating active Crohn's disease. Conventional corticosteroids effectively induce remission but are associated with unwanted adverse effects. Budesonide has similar efficacy to conventional steroids with far fewer adverse effects. Antibiotics have not consistently demonstrated efficacy. We propose a new evidence-based approach which suggests inducing remission of mild to moderate Crohn's disease with budesonide 9 mg/day for patients with ileal and/or right colonic involvement; sulfasalazine for those with disease limited to the colon; and conventional steroids for high disease activity, those who failed budesonide and those with left-sided disease who are allergic or intolerant to sulfasalazine.


Effect of combined interferon-alpha induction therapy and ribavirin on chronic hepatitis C virus infection: a randomized multicentre study.
The efficacy of interferon-alpha (IFN) induction in combination with ribavirin for chronic hepatitis C virus (HCV) infection is not known. A total of 256 treatment-naive HCV RNA-positive patients with biopsy-confirmed chronic hepatitis were enrolled in a randomized multicentre study. The patients received either standard combination therapy with 3 MIU interferon-alpha2b thrice weekly for 26 weeks or 6 MIU interferon-alpha2b daily for 4 weeks and 3 MIU 3/7 days for 22 weeks. All patients received ribavirin 1000 mg or 1200 mg (weight dependent) daily during the 26-week treatment period. Patients were monitored for HCV RNA during and following treatment. The sustained virological response rates (26 weeks after end of treatment) were 54% and 47% for patients receiving IFN induction/ribavirin and standard IFN/ribavirin, respectively (P = 0.35). Among patients infected with genotype 1a/1b, the sustained response rates were 32% and 35%. In patients infected with genotype 2b/3a IFN induction/ribavirin led to a sustained response rate of 80% as compared to 65% in the standard combination therapy group (P = 0.073). Steatosis was more frequently seen in liver biopsies from patients infected with genotype 3a as compared to genotypes la/lb. Among genotype 1a/1b infected patients. steatosis was a highly significant predictor of failure to achieve sustained virological response. Logistic regression analysis (multivariate analysis) showed that independent predictors of sustained virological response were low age, female gender, genotype 2b/3a and HCV RNA negativity at 2 weeks. IFN induction in combination with ribavirin does not increase the sustained virological response rate among patients infected with HCV. Absence of steatosis is an independent predictor of sustained virological response in patients infected with genotypes 1a/1b.


Preventive effects of vitamin D treatment on bleomycin-induced pulmonary fibrosis.
Patients with pulmonary fibrosis often have low vitamin D levels, the effects of which are largely unknown. We here report that early vitamin D supplementation significantly reduced the severity of pulmonary fibrosis and inflammatory cell accumulationin in the bleomycin-induced pulmonary fibrosis mouse model on supplementary days 14, 21 and 28 (P < 0.001). Vitamin D supplementation also prevented some ultrastructural changes in response to bleomycin administration, including basement membrane thickening, interstitial fibrin deposition and microvilli flattening or disappearance on days 14, 21 and 28, and lamellar body swelling or vacuolation on days 21 and 28. The bleomycin group had rising hydroxyproline level on days 14, 21 and 28, whereas the vitamin D treatment group showed consistently lower hydroxyproline level but still higher than that of the control group (P < 0.001). Our immunohistochemistry and densitometry analyses showed less staining for α-smooth muscle actin, a myofibroblast marker, in the vitamin D group compared to the bleomycin group (P < 0.001). Thus, vitamin D treatment could prevent bleomycin-induced pulmonary fibrosis by delaying or suppressing ultrastructural changes, as well as attenuating hydroxyproline accumulation and inhibiting myofibroblastic proliferation. These data further our understanding of the roles of vitamin D in pulmonary fibrogenesis and in the treatment of pulmonary fibrosis.


Influence of age upon the metabolism of zinc in livers of C57BL/6J mice.
The kinetics of accumulation and loss of zinc from the liver following subcutaneous administration of 10 mg of zinc per kg were examined in young adult (6 months old) and old (24 months old) male C57BL/6J mice. After zinc treatment, total liver zinc concentrations rose equally in both groups and returned to basal levels at 96 h post treatment. However, differences were found in the subcellular distribution of zinc in these two age groups. The concentration of zinc in the cytosolic fraction (104,000 g supernate) prepared from the livers of old mice attained its maximum at 24 h post treatment. In contrast, the concentration of zinc in the cytosolic fraction of liver from young adult mice peaked at 48 h post treatment. This difference in accumulation of zinc in the cytosol was reflected by differences in the binding of zinc to metallothionein, a cytosolic transition metal binding protein. In old mice the highest amounts of zinc bound to metallothionein were found at 24 h post treatment: in young adults the maximal zinc binding to this protein occurred at 48 h post treatment. Examination of the relationship between cytosolic zinc contents and the binding of zinc to metallothionein in young adult and old mice suggested similar regulatory processes in the two age groups. Thus, age-dependent differences in accumulation and loss of zinc from the cytosolic fraction of liver probably reflect factors other than differences in regulation of the synthesis of metallothionein by this essential metal.


Distribution of HLA class I and II genes in ankylosing spondylitis patients from Morocco.
In Morocco, the patients affected by ankylosing spondylitis (AS) presents a high frequency of coxitis. Our study reports, for the first time, the polymorphism of Human Leukocyte Antigen (HLA) class I and class II molecules in the Moroccan patients. Forty-six patients diagnosed with an AS and coxitis were compared to a group of 183 healthy controls matched by age, sex and ethnic origin. The HLA typing was performed using microlymphocytotoxicity for the class I (-A, -B) and PCR-SSP for the class II (-DR, -DQ). We found a significant increase of the HLA-B27 antigen frequency (P<0.0001, RR=20.9) in AS patients (29.3%) compared to the controls (3.2%) and a significant decrease in the frequency of HLA-B12 and HLA-B18 antigens. Examination of HLA class II distribution shows a significant increase of the HLA-DRB1*11 allele frequency in patients (P<0.0001). Concerning HLA-DQB1* alleles, no significant difference between patients and controls was appreciable. The HLA-B27 antigen is involved in the predisposition to the AS with coxitis in the Moroccan population. However, the low frequency observed in our population suggests the existence of other genetic and/or environmental factors. Other HLA genes seem to confer a predisposing effect (DRB*11) or a protective effect (B12 and B18) against the disease.


An examination of the initial cancer consultation of medical and radiation oncologists using the Cancode interaction analysis system.
This study provides an analysis of the structure of the initial cancer consultation, the consultation styles of medical and radiation oncologists, and their effect on patient outcomes. One hundred and fifty-five cancer patients attending their first consultation with either a medical or radiation oncologist were audiotaped and the transcripts were analysed using the Cancode computer interaction analysis system. Findings revealed that medical oncologists allowed patients and their families more input into the consultation and were rated as warmer and more patient-centred compared with radiation oncologists. However, radiation oncologists spent a longer period discussing, and were more likely to bring up, social support issues with patients. Both medical and radiation oncologists varied their consultation style according to the patient's gender, age, anxiety levels, prognosis, and education. Patients seeing an oncologist who was rated as warmer and discussed a greater number of psychosocial issues had better psychological adjustment and reduced anxiety after consultation. These findings provide current evidence that may be used to inform improvements of communication skills training for oncologists and highlight the need for future communication research to separately consider oncologists from different disciplines.


Contributions of the hippocampus and the striatum to simple association and frequency-based learning.
Using fMRI and a learning paradigm, this study examined the independent contributions of the hippocampus and striatum to simple association and frequency-based learning. We scanned 10 right-handed young adult subjects using a spiral in/out sequence on a GE 3.0 T scanner during performance of the learning paradigm. The paradigm consisted of 2 cues that predicted each of 3 targets with varying probabilities. Simultaneously, we varied the frequency with which each target was presented throughout the task, independent of cue associations. Subjects had shorter response latencies to frequently occurring and highly associated target stimuli and longer response latencies to infrequent target stimuli, indicating learning. Imaging results showed increased caudate activity to infrequent relative to frequent targets and increased hippocampal activity to infrequent relative to frequent cue-target associations. This work provides evidence of different neural mechanisms underlying learning based on simple frequencies versus associations within a single paradigm.


Activation of interferon response genes and of plasmacytoid dendritic cells in HIV-1 positive subjects with GB virus C co-infection.
GB virus C (GBV-C) coinfection has a protective role in Human Immunodeficiency Virus (HIV) infection, and increases the duration of suppression of HIV-1 viremia in patients under Highly Active Anti-Retroviral Therapy (HAART). Since innate antiviral response may be involved in the protection, we analyzed the possible role of GBV-C as activator of innate immunity. To this aim, we measured the extent of activation of the interferon (IFN) system and of circulating Dendritic Cells (DC) in vivo, and the ability of GBV-C to activate these functions in vitro. Activation of IFN system and of circulating DC was compared in GBV-positive and -negative HIV-1 co-infected patients with HAART-driven suppression of HIV-1 viremia. Endogenous levels of IFN-gamma and RNA-dependent protein kinase (PKR) mRNA were significantly higher in peripheral blood mononuclear cells (PBMC) from GBV-C-positive when compared to GBV-C-negative patients. IFN-gamma expression was correlated with all the Interferon response genes (IRGs) and with GBV-C viremia. The frequency of circulating plasmacytoid DC (pDC) expressing the CD80 activation marker was increased in GBV-C-positive patients, and was correlated with GBV-C viral load. In vitro experiments indicated that GBV-C is able to induce IFN-gamma expression in PBMC. In addition, in PBMC cultures GBV-C induced an increase of CD80 expression by pDC, that was reduced by antibody to IFN-gamma. Our data indicate that in HIV-positive patients GBV-C coinfection promotes the activation of IFN-gamma and downstream IRG expression, as well as with the activation/maturation of circulating pDC. GBV-C-driven IFN-gamma activation is, at least in part, responsible for the increased maturation of pDC. This crosstalk may suggest a role for GBV-C coinfection in boosting the innate antiviral response to HIV infection.


[A quantitative evaluation of the changes in the proliferation of a human lymphocyte culture after mutagen exposure at the G0 stage].
Cell cycle delay of human lymphocytes treated with mutagens at G0 stage has been studied using a mathematical model. Cell cycle delay depends on entry cells into the first S phase and is independent on the cell cycle duration.


Out on campus: sexual orientation and academic climate in a university context.
Although lesbian, gay, and bisexual (LGB) students often "come out" in university settings, empirical studies have demonstrated that these environments are often hostile toward them. The current paper posits that such hostile contexts adversely affect their educational experiences. Results from a survey of a stratified random sample of 1,927 undergraduate and graduate students on a scale measuring perceptions of academic climate (General Campus Climate) supported this claim: LGB students had more negative perceptions of a variety of campus factors. In addition, a scale measuring perceptions of Lesbian, Gay, and Bisexual Campus Climate found that LGB students were more likely than heterosexuals to perceive the campus as inhospitable to LGB people. Women and racial and ethnic minorities were also more likely to rate the LGB climate as hostile. Finally, data from two scales measuring attitudes believed to influence these perceptions yielded gender, racial/ethnic, religious, and sexual orientation differences in theoretically meaningful directions. Results indicate that LGB students often experience the university in more negative ways than heterosexual students, and that certain campus communities--particularly women and racial/ethnic minorities--are more aware of this negativity and contribute to it less because of their relatively more progay attitudes. Implications for how to improve LGB students' experiences are discussed.


Acquired multi-azole resistance in Candida tropicalis during persistent urinary tract infection in a dog.
Multi-azole resistance acquisition by Candida tropicalis after prolonged antifungal therapy in a dog with urinary candidiasis is reported. Pre- and post-azole treatment isolates were clonally related and had identical silent mutations in the ERG11 gene, but the latter displayed increased azole minimum inhibitory concentrations. A novel frameshift mutation in ERG3 was found in some isolates recovered after resistance development, so it appears unlikely that this mutation is responsible for multi-azole resistance.


Green fiscal policy and enterprise green innovation: evidence from quasi-natural experiment of China.
We aim to study the impact of green fiscal policy on enterprise green innovation by applying a time-varying difference-in-difference (DID) model, and treat the comprehensive demonstration city of fiscal policy for energy conservation and emission reduction (CPEE) in China as a quasi-natural experiment. The results show that the CPEE can significantly improve enterprise's green innovation performance of pilot area. This net policy effect is valid after a series of robustness tests to control for various potential confounding factors. Heterogeneity analysis reveals that the effect of CPEE is stronger for state-owned enterprises and enterprises in high energy consumption industries or industries with higher industrial concentration. In addition, the effect of CPEE is various among different categories of green patents, which is stronger for the types of alternative energy production category, waste management category, administrative supervision and design category. The mechanism test indicates that the CPEE can improve the green innovation performance by increasing enterprise' investment in research and development, promoting territorial industrial transformation and upgrading, and enhancing enterprise executives' environmental awareness. To achieve the carbon peaking and carbon neutrality goals, the green enabling role of fiscal reform pilot policy in transition economies and the applicability of localized policies should be excavated.


Wnt-Notch Signaling Interactions During Neural and Astroglial Patterning of Human Stem Cells.
The human brain formation involves complicated processing, which is regulated by a gene regulatory network influenced by different signaling pathways. The cross-regulatory interactions between elements of different pathways affect the process of cell fate assignment during neural and astroglial tissue patterning. In this study, the interactions between Wnt and Notch pathways, the two major pathways that influence neural and astroglial differentiation of human induced pluripotent stem cells (hiPSCs) individually, were investigated. In particular, the synergistic effects of Wnt-Notch pathway on the neural patterning processes along the anterior-posterior or dorsal-ventral axis of hiPSC-derived cortical spheroids were explored. The human cortical spheroids derived from hiPSCs were treated with Wnt activator CHIR99021 (CHIR), Wnt inhibitor IWP4, and Notch inhibitor (N-[N-(3,5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester [DAPT]) individually, or in combinations (CHIR + DAPT, IWP4 + DAPT). The results suggest that CHIR + DAPT can promote Notch signaling, similar or higher than CHIR alone, whereas IWP4 + DAPT reduces Notch activity compared to IWP4 alone. Also, CHIR + DAPT promoted hindbrain marker HOXB4 expression more consistently than CHIR alone, while IWP4 + DAPT promoted Olig2 expression, indicating the synergistic effects distinctly different from that of the individual small molecule. In addition, IWP4 simultaneously promoted dorsal and ventral identity. The patterned neural spheroids can be switched for astroglial differentiation using bone morphogenetic protein 4. This study should advance the derivations of neurons, astroglial cells, and brain region-specific organoids from hiPSCs for disease modeling, drug screening, as well as for hiPSC-based therapies. Impact Statement Wnt signaling plays a central role in neural patterning of human pluripotent stem cells. It can interact with Notch signaling in defining dorsal-ventral and rostral-caudal (or anterior-posterior) axis of brain organoids. This study investigates novel Wnt and Notch interactions (i.e., Wntch) in neural patterning of dorsal forebrain spheroids or organoids derived from human induced pluripotent stem cells. The synergistic effects of Wnt activator or inhibitor with Notch inhibitor were observed. This study should advance the derivations of neurons, astroglial cells, and brain region-specific organoids from human stem cells for disease modeling and drug screening, as well as for stem cell-based therapies. The results can be used to establish better in vitro culture methods for efficiently mimicking in vivo structure of central nervous system.


Sleep and epilepsy.
The intimate relationship between sleep and epilepsy has long been recognized, yet our understanding of the relationship is incomplete. In this article we address four key issues in this area. First, we consider the reciprocal interaction between sleep and epilepsy. Sleep state clearly influences seizure onset, particularly in certain epilepsy syndromes. The converse is also true; epilepsy may disrupt sleep, either directly through seizures and epileptiform activity, or indirectly through medication-related effects. Unraveling the influences of sleep stage, epilepsy syndrome, and drug effects is challenging, and the current state of knowledge is reviewed. Secondly, accurate diagnosis of sleep-related epilepsy can be difficult, particularly the distinction of nocturnal frontal lobe epilepsy (NFLE) from arousal parasomnias. The challenges in this area, along with work from the authors, are discussed. Thirdly, we will explore the putative relationship between obstructive sleep apnea (OSA) and epilepsy, including the effect of OSA on quality of life; this will lead us to a brief exploration of the effects of OSA on neuroendocrine function. Finally, we will review the evidence surrounding the role of sleep in sudden unexpected death in epilepsy (SUDEP).


Long-term outcome after the original and simple modified technique of valve-sparing aortic root reimplantation in Marfan-based population, David V University of Tokyo modification.
In valve-sparing aortic root replacement (VSARR), how to reproduce Valsalva sinus has been an issue. In the original David V procedure, they put plication stitches at sinotubular junction level, although the reefing effect is limited and distal graft remains larger than native. Other modified techniques are two-grafts technique and ready-made Valsalva graft. However, the former needs graft-graft anastomosis and may not be cost-effective, while in the latter, the shape of sinus is fixed and minor adjustment is difficult. David V University of Tokyo modification (David V-UT) is our original solution to that, creating pseudosinus with one straight graft by longitudinal size-reduction running sutures above each pseudosinus. The purpose of the present study is to investigate long-term outcome of David V-UT. We analyzed 59 David V-UT patients from February 2004 to February 2013 and long-term outcomes were investigated by Kaplan-Meier methods. Risk factors for adverse events "death or recurrent aortic insufficiency (AI) with or without aortic valve reoperation" were analyzed by using Cox proportional hazard models. Mean age was 33.1±14.5 years, and 38 patients (64%) were male. Marfan syndrome (MFS) accounts for 47 patients (80%). Only one patient was with bicuspid aortic valve. No in-hospital mortality was observed. Mean follow-up was 4.9±2.4 years. Estimated survival was 94.0±3.4% at 5 years. Freedoms from aortic valve reoperation and recurrent AI greater than mild were 95.7±3.0% and 88.9±4.7% at 5 years, respectively. In Cox proportional hazard analysis, preoperative AI greater than mild and Z score of annular diameter were significant risks for adverse events (p=0.027 and 0.045, hazard ratio 6.084 and 1.432, 95% C.I. 1.225-30.21 and 1.008-2.035, respectively). Even in Marfan-characterized population, David V-UT provided satisfactory long-term outcome, comparable to other VSARR modifications. It is simple but can freely reproduce trilobed sinus with one straight graft.


Hepatic arterial and portal venous complications after adult and pediatric living donor liver transplantation, risk factors, management and outcome (A retrospective cohort study).
Hepatic arterial (HA) and portal venous (PV) complications of recipients after living donor liver transplantation(LDLT) result in patient loss. The aim of this study was to analyze these complications. We retrospectively analyzed HA and/or PV complications in 213 of 222 recipients underwent LDLT in our centre. The overall male/female and adult/pediatric ratios were 183/30 and 186/27 respectively. The overall incidence of HA and/or PV complications was 19.7% (n = 42), while adult and pediatric complications were 18.3% (n = 39) and 1.4% (n = 3) respectively. However early (<1month) and late (>1month) complications were 9.4% (n = 20) and 10.3% (n = 22) respectively. Individually HA problems (HA stenosis, HA thrombosis, injury and arterial steal syndrome) 15% (n = 32), PV problems (PV thrombosis and PV stenosis) 2.8% (n = 6) and simultaneous HA and PV problems 1.9% (n = 4). 40/42 of complications were managed by angiography (n = 18), surgery (n = 10) or medically (Anticoagulant and/or thrombolytic) (n = 12) where successful treatment occurred in 18 patients. 13/42 (31%) of patients died as a direct result of these complications. Preoperative PVT was significant predictor of these complications in univariate analysis. The 6-month, 1-, 3-, 5- 7- and 10-year survival rates in patients were 65.3%, 61.5%, 55.9%, 55.4%, 54.5% and 54.5% respectively. HA and/or PV complications specially early ones lead to significant poor outcome after LDLT, so proper dealing with the risk factors like pre LT PVT (I.e. More intensive anticoagulation therapy) and the effective management of these complications are mandatory for improving outcome.


Dual modulation of synaptic inhibition by distinct metabotropic glutamate receptors in the rat hippocampus.
1. The effects of metabotropic glutamate receptor (mGluR) activation on synaptic inhibition were examined using whole-cell recordings of spontaneous and miniature inhibitory synaptic currents from CA3 pyramidal cells in rat hippocampal slices. 2. The mGluR agonist (1S,3R)trans-1-aminocyclopentane-1,3-dicarboxylic acid (tACPD) increased spontaneous IPSC (spIPSC) frequency by up to 5-fold. At doses above 5 microM the increase was transient (15-45 s) and was followed by a decline to control frequency. In these conditions, elevating external K+ from 2 to 8 mM could still increase spIPSC frequency. 3. Miniature IPSCs (mIPSCs) were recorded in the presence of 1 microM TTX, 5 mM Mg2+ and nominally zero Ca2+. At concentrations above 50 microM, tACPD induced a sustained, reversible reduction in mIPSC frequency by up to 43%. 4. Quisqualate, at doses as low as 50 nM, increased spIPSC frequency, but did not affect mIPSC frequency at concentrations up to 10 microM. 5. The specific mGluR2 and 3 agonist (2S,1'R,2'R,3'R)-2-(2,3-dicarboxycyclopropyl)glycine (DCG-IV, 3 microM) reduced mIPSC frequency by 40 +/- 4% but did not increase spIPSC frequency. 6. The putative mGluR antagonist L-2-amino-3-phosphonopropionate (L-AP3, 1 mM) blocked the effect of tACPD on mIPSC but not spIPSC frequency. The broad-spectrum antagonist (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG, 500 microM) blocked both responses. 7. mGluR activation also had dual effects on IPSCs evoked by focal extracellular stimulation. Application of 5 microM tACPD increased the mean amplitude of evoked IPSCs by 112 +/- 9%, largely by reducing the proportion of response failures. In contrast, IPSC amplitude was reduced to 44 +/- 1% of control values by 3 microM DCG-IV. 8. These results suggest hippocampal inhibitory cells express two distinct mGluR subtypes. One receptor (possibly mGluR1 or 5) is located on somato-dendritic membrane and enhances cell excitability. Another (mGluR2 or 3) is present at inhibitory terminals and reduces the probability of GABA release.


Relationship between plasma anti-Müllerian hormone concentrations during the rearing period and subsequent embryo productivity in Japanese black cattle.
To use plasma anti-Müllerian hormone (AMH) concentrations as early-stage markers for donor cow selection, we investigated the relationship between plasma AMH concentrations in Japanese black heifers and subsequent embryo productivity following superovulation treatment. Plasma AMH and nonesterified fatty acid (NEFA) concentrations in 6 heifers were evaluated once per month from 3 mo before successful AI for primiparity to 3 mo postpartum. Following calving, embryo collection by superovulation treatment was performed at 3- to 4-mo intervals. There were no significant differences in plasma AMH concentrations between the time points throughout the study period. There were, however, significant inter-animal differences in plasma AMH concentrations (P < 0.05). These findings suggest that plasma AMH concentrations were stable over time and individually specific. There were significant positive correlations between plasma AMH concentrations before AI and embryo productivity variables, including the number of ova/embryos (number of transferable embryos, degenerated embryos, and unfertilized oocytes) and numbers/proportions of fertilized and transferable embryos. There was no significant correlation between plasma AMH and NEFA concentrations throughout the study period. These findings reveal that plasma AMH concentrations during the rearing period can be used to predict subsequent embryo productivity following superovulation treatment, suggesting that these concentrations are useful early-stage markers for selecting donor cows.


Resin-based composite materials: elution and pollution.
Pollution arises from all human activity and the provision of oral healthcare using resin-based composite restorative materials (RBCs) should be considered. This paper aims to provide a comprehensive review of the potential pollutant risk to the environment from the chemical compounds found in resin-based restorative materials, by including: 1) the principal pollutant compounds present in the resin matrix; 2) the degradation process of RBCs and its consequences; 3) the methods used for the detection and quantification of monomer elution and RBC microparticles; and 4) a review of the release mechanisms of eluates and RBC microparticles into the environment.RBCs are pollutants by virtue of the compounds created during the degradation processes. These are in the form of the constituent eluted monomers and microparticles. Their impact on the environment and biodiversity is unknown. These materials are currently one of the main direct-placement restorative materials and their success is unquestionable when used and maintained correctly. Mitigation strategies for reducing the impact of pollution on the environment should be considered and implemented by all stakeholders and processes in the supply chain, from manufacturing, clinical use and waste management.


Simultaneous isolation of xanthomegnin, viomellein, rubrosulphin, viopurpurin, and brevianamide A by preparative HPLC.
A method for the isolation of xanthomegnin, viomellein, rubrosulphin, viopurpurin, and brevianamide A from Penicillium viridicatum (DSM 2447) is described. After extraction, HPLC was performed with a preparative silicagel column, eluted with toluene / ethyl acetate / formic acid (27/9/1, v/v/v) and dichloromethane / acetic acid (9/1, v/v). The toxins were detected with a UV-monitor. It was possible to isolate them in an absolutely pure state. The described method is operationally simple and very efficient.


Differences in blood pressure level and hypertension in three ethnic groups of northeastern India.
A cross sectional study on hypertension was done on 294 subjects aged 30 years and above. 150 households were selected randomly representing 50 households from each locality inhabited exclusively by the rural Mizos, indigenous rural Assamese and the tea-garden workers respectively, in the northeastern region of India. Blood pressure was measured by sphygmo-manometer in sitting posture. Anthro-pometric measurements were taken using standard procedure for measuring height, weight, waist and hip girth. Information on age, sex, ethnicity, literacy, alcohol intake, smoking pattern, physical activity, occupation, amount of salt consumption was collected using a standard and pre-tested questionnaire. Significant differences were observed in both the systolic and diastolic blood pressure levels among the three different ethnic groups selected for this study (p < 0.0001). Multiple regression analyses indicated that in Mizos, age, waist circumference and alcohol intake were independently associated with increase in systolic blood pressure whereas smoking was found to be negatively associated with systolic blood pressure (R2 = 0.391, p < 0.001). Factors, which were the best predictors of diastolic blood pressure, were age and body mass index [(kg/m2) (R2 = 0.227, p < 0.001)]. In the rural Assamese population, the best predictors of systolic blood pressure were age and waist circumference (R2 = 0.263, p = 0.018). For the diastolic blood pressure, age, alcohol intake and body mass index were important correlates (R2 = 0.131, p < 0.001). In the tea garden community, important predictors of systolic blood pressure were age, gender and marital status (R2 = 0.187, p < 0.001). On the other hand, age and alcohol intake were best predictors for diastolic blood pressure (R2 = 0.09, p < 0.001).


Efficacy of a single application of a 12.5% pyriprole topical solution against laboratory infestations with ticks (Ixodes ricinus, Dermacentor reticulatus, and Rhipicephalus sanguineus) on dogs.
In three separate studies, the efficacy of a single treatment with a 12.5% pyriprole spot-on solution was investigated against induced infestation with Ixodes ricinus, Dermacentor reticulatus and Rhipicephalus sanguineus on dogs (both sexes; Beagles in Studies 1 and 2, mixed-breed in Study 3). For each tick species, one group of 8 dogs left untreated (Studies 1 and 2) or treated with a placebo solution (Study 3) was compared with another group treated once with the spot-on solution at a dose rate of at least 12.5mg/kg. The dogs were infested with 50 unfed adult ticks of the respective species at various time-points before and after treatment and the surviving attached and unattached ticks were recorded 48 h after re-infestation. For each tick species, efficacy was assessed for each time-point and cumulatively for the whole evaluation period. The dogs were submitted to general health observations and clinical assessments during the study. Efficacy against I. ricinus and R. sanguineus was 100% during the whole evaluation period of 30 days. For D. reticulatus cumulative efficacy for the 30 days after treatment was 98.9%. The product was well tolerated by all the animals.


Using spaced education to teach interns about teaching skills.
Despite limited preparation and knowledge base, surgical interns have important teaching responsibilities. Nevertheless, few faculty development programs are aimed at interns. Succinct teaching skill content was electronically distributed over time (spaced education) to interns in academic year 2010/2011. The interns in the previous year served as historic controls. Electronic surveys were distributed for program evaluation. Fifteen of 24 (62.5%) interns and 35 of 49 (71.4%) students responded to the surveys in academic year 2009/2010 and 16 of 27 (59.3%) interns and 38 of 52 (73%) students responded in academic year 2010/2011. Surveys showed improved attitudes toward teaching by interns as well as a higher estimation of interns' teaching skills as rated by students for those interns who received the spaced education program. Using spaced education to improve interns' teaching skills is a potentially powerful intervention that improves interns' enthusiasm for teaching and teaching effectiveness. The changes are mirrored in students' ratings of interns' teaching skills and interns' attitudes toward teaching.


Assessment of Pelvic-Lumbar-Thigh Biomechanics to Optimize The Childbirth Position: An "In Vivo" Innovative Biomechanical Study.
The study aimed to assess the associations between the pelvis orientation, lumbar curve and thigh postures throughout pregnancy in a population of healthy women. Additionally, optimal mechanical birth conditions in terms of the pelvic inlet and lumbar curve were researched. The individuals' posture was assessed with three-dimensional motion analysis and the lumbar curve with the Epionics SPINE system. The association between the hip joint angles (flexion and abduction), the pelvis external conjugate, and lumbar curve position was assessed with a generalized linear mixed model (GLMM) adjusted to individuals' characteristics. Joint laxity was assessed with a modified Jobbin's extensometer. For all of the subjects, hip flexion and hip abduction were significantly associated with the angle between the external conjugate and spine, with higher correlation in the multivariate regression model. The association between hip flexion and the lumbar curve was less significant in multivariate than univariate regression analysis. Optimal birth conditions were never reached. The findings contribute to the understanding of the association between the hip position (flexion and abduction), pelvic orientation, and lumbar curve adjusted for joint laxity in healthy pregnant women. They lay the groundwork for future research in the field of obstetrical biomechanics.


Improving paramedic responses for patients dying at home: a theory of change-based approach.
Paramedics are increasingly being called to attend patients dying from advanced incurable conditions. However, confidence to deal with such calls varies, with many feeling relatively unskilled in this aspect of their role. A number of interventions have been piloted to improve their skills in end-of-life care (EoLC) but without a fully specified theoretical model. Theory of Change models can provide theoretical and testable links from intervention activities to proposed long-term outcomes and indicate the areas for assessment of effectiveness. This study aimed to develop an intervention for improving paramedic EoLC for patients in the community. A Theory of Change approach was used as the overarching theoretical framework for developing an intervention to improve paramedic end-of-life skills. Nine stakeholders - including specialist community paramedics, ambulance call handlers and palliative care specialists - were recruited to five consecutive online workshops, ranging between 60 and 90 min. Each workshop had 2-3 facilitators. Over multiple workshops, stakeholders decided on the desired impact, short- and long-term outcomes, and possible interventions. During and between these workshops a Theory of Change model was created, with the components shared with stakeholders. The stakeholders agreed the desired impact was to provide consistent, holistic, patient-centred, and effective EoLC. Four potential long-term outcomes were suggested: (1) increased use of anticipatory and regular end-of-life medications; (2) reduced end-of-life clinical and medication errors; (3) reduced unnecessary hospitalisations; (4) increased concordance between patient preferred and actual place of death. Key interventions focused on providing immediate information on what to do in such situations including: appraising the situation, developing an algorithm for a treatment plan (including whether or not to convey to hospital) and how to identify ongoing support in the community. A Theory of Change approach was effective at identifying impact, outcomes, and the important features of an end-of-life intervention for paramedics. This study identified the need for paramedics to have immediate access to information and resources to support EoLC, which the workshop stakeholders are now seeking to develop as an intervention.


Middle Latency Auditory Evoked Potential (MLAEP) in Workers with and without Tinnitus who are Exposed to Occupational Noise.
Tinnitus is an important occupational health concern, but few studies have focused on the central auditory pathways of workers with a history of occupational noise exposure. Thus, we analyzed the central auditory pathways of workers with a history of occupational noise exposure who had normal hearing threshold, and compared middle latency auditory evoked potential in those with and without noise-induced tinnitus. Sixty individuals (30 with and 30 without tinnitus) underwent the following procedures: anamnesis, immittance measures, pure-tone air conduction thresholds at all frequencies between 0.25-8 kHz, and middle latency auditory evoked potentials. Quantitative analysis of latencies and amplitudes of middle latency auditory evoked potential showed no significant differences between the groups with and without tinnitus. In the qualitative analysis, we found that both groups showed increased middle latency auditory evoked potential latencies. The study group had more alterations of the "both" type regarding the Na-Pa amplitude, while the control group had more "electrode effect" alterations, but these alterations were not significantly different when compared to controls. Individuals with normal hearing with or without tinnitus who are exposed to occupational noise have altered middle latency auditory evoked potential, suggesting impairment of the auditory pathways in cortical and subcortical regions. Although differences did not reach significance, individuals with tinnitus seemed to have more abnormalities in components of the middle latency auditory evoked potential when compared to individuals without tinnitus, suggesting alterations in the generation and transmission of neuroelectrical impulses along the auditory pathway.


Physical prognostic factors predicting outcome following lumbar discectomy surgery: systematic review and narrative synthesis.
Success rates for lumbar discectomy are estimated as 78-95% patients at 1-2 years post-surgery, supporting its effectiveness. However, ongoing pain and disability is an issue for some patients, and recurrence contributing to reoperation is reported. It is important to identify prognostic factors predicting outcome to inform decision-making for surgery and rehabilitation following surgery. The objective was to determine whether pre-operative physical factors are associated with post-operative outcomes in adult patients [≥16 years old] undergoing lumbar discectomy or microdiscectomy. A systematic review was conducted according to a registered protocol [PROSPERO CRD42015024168]. Key electronic databases were searched [PubMed, CINAHL, EMBASE, MEDLINE, PEDro and ZETOC] using pre-defined terms [e.g. radicular pain] to 31/3/2017; with additional searching of journals, reference lists and unpublished literature. Prospective cohort studies with ≥1-year follow-up, evaluating candidate physical prognostic factors [e.g. leg pain intensity and straight leg raise test], in adult patients undergoing lumbar discectomy/microdiscectomy were included. Two reviewers independently searched information sources, evaluated studies for inclusion, extracted data, and assessed risk of bias [QUIPS]. GRADE determined the overall quality of evidence. 1189 title and abstracts and 45 full texts were assessed, to include 6 studies; 1 low and 5 high risk of bias. Meta-analysis was not possible [risk of bias, clinical heterogeneity]. A narrative synthesis was performed. There is low level evidence that higher severity of pre-operative leg pain predicts better Core Outcome Measures Index at 12 months and better post-operative leg pain at 2 and 7 years. There is very low level evidence that a lower pre-operative EQ-5D predicts better EQ-5D at 2 years. Low level evidence supports duration of leg pain pre-operatively not being associated with outcome, and very low-quality evidence supports other factors [pre-operative ODI, duration back pain, severity back pain, ipsilateral SLR and forward bend] not being associated with outcome [range of outcome measures used]. An adequately powered low risk of bias prospective observational study is required to further investigate candidate physical prognostic factors owing to existing low/very-low level of evidence.


Pre-Hematopoietic Stem Cell Transplantation Rituximab for Epstein-Barr Virus and Post-Lymphoproliferative Disorder Prophylaxis in Alemtuzumab Recipients.
Epstein-Barr virus (EBV) reactivation and EBV-related post-transplantation lymphoproliferative disorder (PTLD) are often fatal complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The risk of EBV reactivation may be mitigated by depletion of B cells with rituximab. Starting in January 2020, allo-HSCT recipients undergoing T-cell depletion with alemtuzumab received 1 dose of rituximab before transplantation. The objective of this study was to evaluate the cumulative incidence of EBV reactivation and EBV-PTLD in recipients of allo-HSCT and in vivo T-cell depletion with alemtuzumab who received pre-HSCT rituximab compared to patients who did not. This was a single-center retrospective analysis of adult patients who consecutively received an HLA-identical allo-HSCT between January 2019 and May 2021 and in vivo T-cell depletion with alemtuzumab. Patients were included in the rituximab cohort if they received rituximab within 6 months before their transplantation. The primary endpoint was incidence of EBV reactivation at day 180 among those receiving pre-HSCT rituximab versus those not receiving rituximab. Secondary endpoints included cumulative incidence of EBV-PTLD at 1 year, time to engraftment, immune reconstitution, and incidence of infections and acute graft-versus-host disease (aGVHD) at day 180. Eighty-six consecutive patients who received an allo-HSCT with alemtuzumab T-cell depletion were reviewed; 43 patients who received pre-HSCT rituximab after our protocol modification were compared to 43 patients who did not receive pre-HSCT rituximab before this change. Median age was 57 (interquartile range [IQR] 40-69) years, and the majority of patients had acute myeloid leukemia or myelodysplastic syndrome. Baseline characteristics were similar between the cohorts. EBV reactivation at day 180 occurred in 23 (53%) patients without prior rituximab exposure versus 0 patients with pre-HSCT rituximab exposure (P < .0001). Similarly, 6 patients without prior rituximab exposure developed PTLD at 1 year compared to no cases of PTLD among patients receiving pre-HSCT rituximab. There was no difference in neutrophil engraftment, incidence of infections, or aGVHD at day 180 between the 2 cohorts. There was a delay in time to platelet engraftment in the rituximab cohort (median 16 [IQR 15-20] days versus 15 [IQR 14-17] days; P = .04). Administration of pre-HSCT rituximab before allo-HSCT in patients receiving T-cell depletion with alemtuzumab was associated with a significant decrease in the risk for EBV reactivation and EBV-PTLD, without increasing aGVHD or infection rates.


Infiltrating retiform perineurioma: a case report.
Retiform perineurioma is a rare distinct histologic subtype of benign soft tissue perineurioma. We report 1 case of retiform perineurioma with a superficial invasion of the adjacent skeletal muscle. The patient was a 34-year-old woman with a neoplasm located between the deltoid muscle and the biceps. Histologically, the tumor was nonencapsulated, composed exclusively of perineurial cells without cytologic and tissue atypia. There were focal areas in which the neoplastic cells infiltrated the muscle tissue, widely separating the bundles. This case may represent a diagnostic pitfall as it can be confused with a malignant perineurioma.


Electrically switchable van der Waals magnon valves.
Van der Waals magnets have emerged as a fertile ground for the exploration of highly tunable spin physics and spin-related technology. Two-dimensional (2D) magnons in van der Waals magnets are collective excitation of spins under strong confinement. Although considerable progress has been made in understanding 2D magnons, a crucial magnon device called the van der Waals magnon valve, in which the magnon signal can be completely and repeatedly turned on and off electrically, has yet to be realized. Here we demonstrate such magnon valves based on van der Waals antiferromagnetic insulator MnPS3. By applying DC electric current through the gate electrode, we show that the second harmonic thermal magnon (SHM) signal can be tuned from positive to negative. The guaranteed zero crossing during this tuning demonstrates a complete blocking of SHM transmission, arising from the nonlinear gate dependence of the non-equilibrium magnon density in the 2D spin channel. Using the switchable magnon valves we demonstrate a magnon-based inverter. These results illustrate the potential of van der Waals anti-ferromagnets for studying highly tunable spin-wave physics and for application in magnon-base circuitry in future information technology.


Monitoring of mycotoxin biomarkers in the Czech Republic.
AFM1 was determined in 72 (72%) samples of human urine, range 19-6064 pg/g creatinine, mean 367 pg/g creatinine, median 158 pg/g creatinine and 90% percentile 755 pg/g creatinine in 1997. AFM1 was determined in 46 (43.8%) samples of human urine, range 21-19219 pg/g creatinine, mean 414 pg/g creatinine, median 96 pg/g creatinine and 90% percentile 415 pg/g creatinine in 1998. OTA was determined in 2077 (94.2%) samples of human serum, range 0.1-13.7 μg/L, mean 0.28 μg/L, median 0.2 μg/L and 90% percentile 0.5 μg/L in 1994-2002. OTA was determined in 12 (40%) samples of human kidneys, range 0.1-0.2 μg/kg, mean 0.07 μg/kg, and median 0.05 μg/kg in 2001.


Chemical and biochemical characterisation of biochar-blended composts prepared from poultry manure.
The aim of this study was to assess the effect of a 2% (v/v) addition of biochar on the quality of a composting mixture prepared with poultry manure and different local organic wastes (rice husk and apple pomace). Compost quality was evaluated in terms of typical stabilisation indices, the microbial biomass and selected enzymatic activities related to the C, N and P cycles. The main effects of biochar were a 10% increase in C captured by humic substance extraction and a 30% decrease of water-soluble C, due to an enhanced degradation rate and/or the sorption of these labile compounds into the biochar. The urease, phosphatase and polyphenol oxidase activities of the biochar-blended compost were enhanced by 30-40% despite the lower amount of microbial biomass. Denaturing gradient gel electrophoresis revealed a higher diversity of fungi in biochar-amended compost, suggesting a change in microbial composition compared to the unamended compost.


Assessing the reliability and cross-sectional and longitudinal validity of fifteen bioelectrical impedance analysis devices.
The purpose of this investigation was to expand upon the limited existing research examining the test-retest reliability, cross-sectional validity and longitudinal validity of a sample of bioelectrical impedance analysis (BIA) devices as compared with a laboratory four-compartment (4C) model. Seventy-three healthy participants aged 19-50 years were assessed by each of fifteen BIA devices, with resulting body fat percentage estimates compared with a 4C model utilising air displacement plethysmography, dual-energy X-ray absorptiometry and bioimpedance spectroscopy. A subset of thirty-seven participants returned for a second visit 12-16 weeks later and were included in an analysis of longitudinal validity. The sample of devices included fourteen consumer-grade and one research-grade model in a variety of configurations: hand-to-hand, foot-to-foot and bilateral hand-to-foot (octapolar). BIA devices demonstrated high reliability, with precision error ranging from 0·0 to 0·49 %. Cross-sectional validity varied, with constant error relative to the 4C model ranging from -3·5 (sd 4·1) % to 11·7 (sd 4·7) %, standard error of the estimate values of 3·1-7·5 % and Lin's concordance correlation coefficients (CCC) of 0·48-0·94. For longitudinal validity, constant error ranged from -0·4 (sd 2·1) % to 1·3 (sd 2·7) %, with standard error of the estimate values of 1·7-2·6 % and Lin's CCC of 0·37-0·78. While performance varied widely across the sample investigated, select models of BIA devices (particularly octapolar and select foot-to-foot devices) may hold potential utility for the tracking of body composition over time, particularly in contexts in which the purchase or use of a research-grade device is infeasible.


Vein and artery growth after anastomosis with vascular closure staple clips vs interrupted polypropylene suture: application in pediatric vascular surgery.
Alternatives are still being sought in vascular surgery to address the problem of arrested growth after anastomosis in growing vessels, and opinions differ widely regarding the most suitable technique. This study compared vascular growth and permeability after anastomosis using the latest-generation vascular closure staple (VCS) system and the conventional suture technique to ascertain which approach yielded better results. Thirty 55-day-old lambs underwent end-to-end anastomosis of the carotid artery and jugular vein. Serial ultrasonography and angiography were carried out over the ensuing 6-month growth period, after which lambs were euthanized. Both VCS clips and polypropylene suture allowed longitudinal and transverse vessel growth; however, longitudinal growth was significantly greater in clip-closed vessels than in either sutured or untreated vessels. The results obtained for vascular growth and permeability suggest that VCS clips may provide a suitable alternative to conventional suture in pediatric vascular surgery.


Challenges in scaling up of special care newborn units--lessons from India.
Neonatal mortality rate in India is high and stagnant. Special Care Newborn Units (SCNUs) are being set up to provide quality level II newborn care services in district hospitals of several districts to meet this challenge. The units are located in some of the remotest districts where the burden of neonatal deaths and accessibility to special care is a concern. A recently concluded evaluation of these units indicates that it is possible to provide quality level II newborn care in district hospitals. However, there are critical constraints such as availability and skills of human resources, maintenance of equipment and bed occupancy. It is not the SCNU alone but an active network of SCNU (level II care), neonatal stabilization units (level I care) and newborn care corners can impact neonatal mortality rate reduction higher. Number of beds is also not sufficient to cater to the increasing demand of such services. Available number of nurses is a problem in many such units. An effective and sustainable system to maintain and repair the equipment is essential. Scaling up these units would require squarely addressing these issues.


Extracellular to Intracellular Water Ratio Determined by Bioimpedance is Associated with Mortality in Patients Admitted for Diabetic Foot Ulcers.
An increased extracellular water/intracellular water (ECW/ICW) ratio determined by bioimpedance has been related to mortality in patients undergoing hemodialysis. We aimed to evaluate the impact of body water distribution in patients with diabetes-related foot ulcers. Seventy-six patients were evaluated with bioimpedance, handgrip strength, and laboratory examinations. The ECW/ICW ratio is a prognostic factor for early mortality.


Claus Schwechheimer.
Interview with Claus Schwechheimer, who studies the roles of auxin and gibberellin in the regulation of plant growth.


Robotic versus open pancreatectomy: a systematic review and meta-analysis.
Robotic surgery is gaining momentum with advantages for minimally invasive management of pancreatic diseases. The objective of this meta-analysis is to compare the clinical and oncologic safety and efficacy of robotic versus open pancreatectomy. A systematic review of the literature was performed to identify studies comparing robotic pancreatectomy and open pancreatectomy. Postoperative outcomes, intraoperative outcomes, and oncologic safety were evaluated. Meta-analysis was performed using a random-effect model. Seven studies matched the selection criteria, including 137 (40 %) cases of robotic pancreatectomy and 203 (60 %) cases of open pancreatectomy. None of the included studies were randomized. Overall complication rate was significantly lower in robotic group [risk difference (RD) = -0.12, 95 % confidence interval (CI) -0.22 to -0.01, P = 0.03], as well as reoperation rate (RD = -0.12; CI -0.2 to -0.03, P = 0.006) and margin positivity (RD = -0.18; 95 % CI -0.3 to -0.06, P = 0.003). There was no significant difference in postoperative pancreatic fistula (POPF) incidence and mortality. The median (range) conversion rate was 10 % (0-12 %). The results of this meta-analysis suggest that robotic pancreatectomy is as safe and efficient as, if not superior to, open surgery for patients with benign or malignant pancreatic diseases. However, the evidence is limited and more randomized controlled trials are needed to further clearly define this role.


Changes in left ventricular morphology and function after mitral valve surgery.
Degenerative mitral valve disease is the leading cause of mitral regurgitation in North America. Surgical intervention has hinged on the symptoms and ventricular changes that develop as compensatory ventricular remodeling occurs. In the present study, we sought to characterize the temporal response of left ventricular (LV) morphology and function to mitral valve surgery for degenerative disease and to identify the preoperative factors that influence reverse remodeling. From 1986 to 2007, 2,778 patients with isolated degenerative mitral valve disease underwent valve repair (n = 2,607 [94%]) or replacement (n = 171 [6%]) and had ≥1 postoperative transthoracic echocardiogram; 5,336 transthoracic echocardiograms were available for analysis. Multivariate longitudinal repeated-measures analysis was performed to identify the factors associated with reverse remodeling. The LV dimensions decreased in the first year after surgery (end-diastolic from 5.7 ± 0.80 to 4.9 ± 1.4 cm; end-systolic from 3.4 ± 0.71 to 3.1 ± 1.4 cm). The LV mass index decreased from 139 ± 44 to 112 ± 73 g/m(2). The reduction in LV hypertrophy was less pronounced in patients with greater preoperative left heart enlargement (p <0.0001) and a greater preoperative LV mass (p <0.0001). The postoperative LV ejection fraction initially decreased from 58 ± 7.0% to 53 ± 20%, increased slightly during the first postoperative year, and was negatively influenced by preoperative heart failure symptoms (p <0.0001) and a lower preoperative LV ejection fraction (p <0.0001). The risk-adjusted response of LV morphology and function to valve repair and replacement was similar (p >0.2). In conclusion, a positive response toward normalization of LV morphology and function after mitral valve surgery is greatest in the first year. The best response occurs when surgery is performed before left heart dilation, LV hypertrophy, or LV dysfunction develop.


Subjective and objective symmetry in perception of form.
A new quantitative measure of the physical symmetry of 2-dimensional shapes is proposed which relates it to the proportion of translational and rotational (TR) overlap between a figure and its mirror image. Category ratings of the apparent vertical symmetry of distorted diamond figures correlate highly with this measure while it is also an important contributor in the prediction of the apparent symmetry and geometricity of random polygons.


Occurrence, outcomes and predictors of portal hypertension in cystic fibrosis: A longitudinal prospective birth cohort study.
The reported prevalence of portal hypertension (PH) in Cystic Fibrosis is variable, incidence rates rarely provided and the utility of liver function tests (LFT's) early in life to predict PH is questionable. The aims were to (1) determine PH prevalence (P) and incidence rate (IR) and combined mortality transplant (MTX) data in PH vs non-PH patients and (2) to assess association of LFTs in early life with liver disease and PH. (1) A double centre longitudinal cohort study of 577 CF patients diagnosed by newborn screening (NBS) with annual examinations for PH up to 18.5 years of age (max) was performed over 28 years for P, IR, and MTX data; (2) Cox proportional hazard models were used to assess the association of elevated LFTs on 2 or more occasions over 0-6.5 years and PH. 51/577(8.8%) developed PH with an average IR of near 3/1000 patient years per 5 year interval representing young, mid and late childhood respectively in patients 3-18 years of age. Combined mortality/liver transplant occurred in 12/51 (23.5%) PH and 25/526 (4.8%) non-PH (p < 0.001). Elevated enzymes particularly GGT (HR:5.71, 95% CI 3.11-10.47); ALT/GGT (HR: 5.56, 95% CI 2.82-10.98); and ALP/GGT (HR: 5.74, 95% CI 2.78-11.86) were associated with the onset of PH. This birth cohort with annual examination for PH provides an accurate assessment of the prevalence, and IR of PH and MTX of PH vs non-PH. Early elevated LFTs are associated with onset of MBC/PH.


Principles and application of internal fixation in cattle.
The principles of bone healing and vascular and periosteal responses are considered in relation to different methods of fracture fixation and complications. Advantages and disadvantages of the available internal fixation devices are reviewed for the fractures that most commonly occur in the different age groups.


From genes to brain oscillations: is the visual pathway the epigenetic clue to schizophrenia?
Molecular data and gene expression data and recently mitochondrial genes and possible epigenetic regulation by non-coding genes is revolutionizing our views on schizophrenia. Genes and epigenetic mechanisms are triggered by cell-cell interaction and by external stimuli. A number of recent clinical and molecular observations indicate that epigenetic factors may be operational in the origin of the illness. Based on the molecular insights, gene expression profiles and epigenetic regulation of gene, we went back to the neurophysiology (brain oscillations) and found a putative role of the visual experiences (i.e. visual stimuli) as epigenetic factor. The functional evidences provided here, establish a direct link between the striate and extrastriate unimodal visual cortex and the neurobiology of the schizophrenia. This result support the hypothesis that 'visual experience' has a potential role as epigenetic factor and contribute to trigger and/or to maintain the progression of the schizophrenia. In this case, candidate genes sensible for the visual 'insult' may be located within the visual cortex including associative areas, while the integrity of the visual pathway before reaching the primary visual cortex is preserved. The same effect can be perceived if target genes are localised within the visual pathway, which actually, is more sensitive for 'insult' during the early life than the cortex per se. If this process affects gene expression at these sites a stably sensory specific 'insult', i.e. distorted visual information, is entering the visual system and expanded to fronto-temporo-parietal multimodal areas even from early maturation periods. The difference in the timing of postnatal neuroanatomical events between such areas and the primary visual cortex in humans (with the formers reaching the same development landmarks later in life than the latter) is 'optimal' to establish an abnormal 'cell- communication' mediated by the visual system that may further interfere with the local physiology. In this context the strategy to search target genes need to be rearrangement and redirected to visual-related genes. Otherwise, psychophysics studies combining functional neuroimage, and electrophysiology are strongly recommended, for the search of epigenetic clues that will allow to carrier gene association studies in schizophrenia.


Relationship between antithrombotic drugs and postoperative outcomes in patients with gastric cancer after gastrectomy: a propensity matching analysis.
As there is no consensus on the impact of antithrombotic drugs on post-gastrectomy outcomes in gastric cancer patients, this study aimed to investigate the impact of antithrombotic drugs on postoperative outcomes in these patients after gastrectomy. Patients with Stage I-III primary gastric cancer who underwent radical gastrectomy between April 2005 and May 2022 were included. We performed propensity score matching to adjust for patient background and compared bleeding complications. Multivariate analysis with logistic regression analysis was performed to identify risk factors associated with bleeding complications. Of the 6798 patients, 310 (4.6%) were in the antithrombotic group and 6488 (95.4%) were in the non-antithrombotic group. Twenty-six patients (0.38%) experienced bleeding complications. After matching, the number of patients in each group was 300, with insignificant differences in any factor. A comparison of postoperative outcomes showed no difference in bleeding complications (P = 0.249). In the antithrombotic group, 39 (12.6%) continued drugs, and 271 (87.4%) discontinued them before surgery. After matching, there were 30 and 60 patients, respectively, with no differences in patient background. A comparison of postoperative outcomes showed no differences in bleeding complications (P = 0.551). In multivariate analysis, antithrombotic drug use and continuation of antiplatelet agents were not risk factors for bleeding complications. Antithrombotic drugs and its continuation may not worsen bleeding complications in patients with gastric cancer after radical gastrectomy. Bleeding complications were rare, and further studies are needed on risk factors for bleeding complications in larger databases.


Mycobacterium tuberculosis-induced apoptotic neutrophils trigger a pro-inflammatory response in macrophages through release of heat shock protein 72, acting in synergy with the bacteria.
Mycobacterium tuberculosis (Mtb) survive inside macrophages by manipulating microbicidal functions such as phago-lysosome fusion, production of reactive oxygen species and nitric oxide, and by rendering macrophages non-responsive to IFN-gamma. Mtb-infected lung tissue does however not only contain macrophages, but also significant numbers of infiltrating polymorphonuclear neutrophils (PMN). These are able to phagocytose and kill ingested Mtb, but are short-lived cells that constantly need to be removed from tissues to avoid tissue damage. Phagocytosis of aged or UV-induced apoptotic PMN by macrophages induce an anti-inflammatory response in macrophages. However, in the present study, we show that engulfment of Mtb-induced apoptotic PMN by macrophages initiates secretion of TNF-alpha from the macrophages, reflecting a pro-inflammatory response. Moreover, Mtb-induced apoptotic PMN up-regulate heat shock proteins 60 and 72 (Hsp60, Hsp72) intracellularly and also release Hsp72 extracellularly. We found that both recombinant Hsp72 and released Hsp72 enhanced the pro-inflammatory response to both Mtb-induced apoptotic PMN and Mtb. This stimulatory effect of the supernatant was abrogated by depleting the Hsp72 with immunoprecipitation. These findings indicate that released Hsp72 from Mtb-infected PMN can trigger macrophage activation during the early stage of Mtb infections, thereby creating a link between innate and adaptive immunity.


Parameterisation of Respiratory Impedance in Lung Cancer Patients From Forced Oscillation Lung Function Test.
This study aims to analyze the contribution and application of forced oscillation technique (FOT) devices in lung cancer assessment. Two devices and corresponding methods can be feasible to distinguish among various degrees of lung tissue heterogeneity. The outcome respiratory impedance Zrs (in terms of resistance Rrs and reactance Xrs) is calculated for FOT and is interpreted in physiological terms by being fitted with a fractional-order impedance mathematical model (FOIM). The non-parametric data obtained from the measured signals of pressure and flow is correlated with an analogous electrical model to the respiratory system resistance, compliance, and elastance. The mechanical properties of the lung can be captured through Gr to define the damping properties and Hr to describe the elastance of the lung tissue, their ratio representing tissue heterogeneity ηr. We validated our hypotheses and methods in 17 lung cancer patients where we showed that FOT is suitable for non-invasively measuring their respiratory impedance. FOIM models are efficient in capturing frequency-dependent impedance value variations. Increased heterogeneity and structural changes in the lungs have been observed. The results present inter- and intra-patient variability for the performed measurements. The proposed methods and assessment of the respiratory impedance with FOT have been demonstrated useful for characterizing mechanical properties in lung cancer patients. This correlation analysis between the measured clinical data motivates the use of the FOT devices in lung cancer patients for diagnosis of lung properties and follow-up of the respiratory function modified due to the applied radiotherapy treatment.


An image-based mapping of significance and relevance of facial skin colour changes of females living in Thailand.
There are methods to evaluate skin colour on defined areas over the face but no approach automatically and accurately evaluates skin colour variations on large facial areas, comparing subjects, treatments and/or time points. We propose such an image-based approach to visualize quickly the outcome of clinical studies on colour variations. Among 54 Asian women, one group applied a vehicle twice daily, during 28 days, and the other group an anti-ageing emulsion, taking facial images at baseline and after treatment. Changes in L*a*b* values were studied on four pre-selected facial regions. We also reconstructed average facial images from which the L*a*b* parameters were extracted for every pixel, computing relevance (ΔE) and significance data. Using colour gradients, we mapped these results onto the average facial images. After treatment, L*a*b* parameters show no statistically relevant colour changes in the vehicle group. In the 'active' group, skin was lighter at the upper cheek and, overall, redness decreased. Relevance and significance maps confirmed no visible colour changes in the vehicle group. In the 'active' group, the mapping approach revealed colour changes and their location. Skin became lighter below the eye, cheek and forehead. It was less red below the eyes, on the cheek, jawline and forehead, and generally more yellow. Our image-based mapping approach proves to be powerful. It enables us to identify precise facial regions of relevant and statistically significant colour changes after a topical treatment, regions that would have otherwise been undetected.


Effects of ionic liquid and nanogold particles on high-performance liquid chromatography-electrochemical detection and their application in highly efficient separation and sensitive analysis of five phenolic acids in Xuebijing injection.
A novel high performance liquid chromatography-electrochemical detector (HPLC-ECD) analytical system was developed in this study by integratedly utilizing ionic liquid (IL) of 1-butyl-3-methylimidazolium bromide and an additive of gold nanoparticles. The resulted pilot study was first performed to assess the effects of 1-butyl-3-methylimidazolium bromide and gold nanoparticles on the chromatographic characteristics of five phenolic acids in Xuebijing injection, including danshensu (DSS), protocatechuic acid (PA), protocatechuic aldehyde (PAH), hydroxy safflower yellow A (HSYA) and ferulic acid (FA). It was notable to observe that retainability of the phenolic acids were markly lowered by IL addition. Compared with the cases without IL addition, the retention times of DSS, PA, PAH, HSYA and FA have decreased 2.851, 1.532, 1.53, 0.818 and 0.552 min, respectively when 0.6% IL in the mobile phase. In addition, the corresponding theoretical plate numbers and peak areas for these compounds were significantly increased. Area response for DSS, PA, PAH, HSYA and FA were enhanced by 772%, 628%, 584%, 703% and 600%, respectively. It was observed that nano-gold catalysis power enabled peak areas of DSS, PAH, FA and PA to enhance 5.7, 6.2, 8.5 and 66.5 times relative to the case with addition of IL. Altogether, the optimized HPLC-ECD system was successfully applied to the pharmacokinetics study of Xuebijing injection with underlying applicability to in vivo and in vitro analysis of a variety of natural product from Chinese medicine plants, TCM formulae and associated patent TCM preparation.


La-doping induced localized excess electrons on (BiO)2CO3 for efficient photocatalytic NO removal and toxic intermediates suppression.
Photocatalysis technology has been extensively adopted to abate typical air pollutants. Nevertheless, it is a challenge to develop photocatalysts aiming to simultaneously improve photocatalytic selectivity and efficiency. In this study, to improve the photocatalytic selectivity and the performance of (BiO)2CO3 in the oxidation of NO to target products (NO2- /NO3-), we developed a novel method to construct La-doped (BiO)2CO3 (La-BOC) for forming localized excess electrons (Ex) on (BiO)2CO3 surface. The results indicate that the Ex could effectively accelerate the activation of reactants and promote charge separation and transfer. Under visible light, the gas molecules could capture the Ex and get activated to produce reactive oxygen species (ROS) with high oxidation ability, which enables complete oxidation of NO to target products instead of producing other toxic by-products. Due to the functionality of the Ex, the photocatalytic selectivity and efficiency of La-BOC have been synchronously improved. Combining experimental and theoretical methods, this work unravels the pathway of charge carriers transportation/transformation and elucidates the photocatalytic NO oxidation mechanism. The present work could provide a novel method to improve photocatalytic selectivity and activity for safe air pollutant abatement.


Trends in referral patterns to presurgical evaluation at a European reference center.
To determine if growing evidence for epilepsy surgery as an early treatment option is reflected in the decrease of latencies between epilepsy onset and referral for presurgical evaluation METHODS: Retrospective analysis of latencies in 1646 patients (children and adults) from the time of epilepsy diagnosis to first presurgical workup in the period from 1999 to 2019 based on electronic patient charts at a tertiary epilepsy center. Time spans 1999-2009 and 2010-2019, prior to and following the ILAE definition of pharmacoresistance, and the role of etiological factors were assessed. Over the whole period, the mean latency between diagnosis and a presurgical workup was 15.3 y. There was a significant reduction in the latencies between the periods 1999-2009 (16.9 y) and 2010-2019 (13.4 y), (p < 0.0001). In a linear regression analysis, the latency decreased by 2.6 months/year from 17.4 in 1999 to 13.1 y in 2019 (p < 0.001). Subgroup analyses showed significant decreases in latency to presurgical evaluation in patients with hippocampal sclerosis from 24.4 to 19.5 y, in malformations of cortical development from 16.4 to 13.2 y, and in nonlesional patients from 18.1 to 12.8 y, in contrast to patients with MR evidence for brain tumors with similar latencies across time (10.5 vs. 9.5 y, n.s.). The reduction of the time span to a first presurgical evaluation was highly significant over time, yet moderate in its degree. Overall, the aim of early diagnostic evaluation for epilepsy surgery options after established pharmacoresistance was only achieved for a minority of patients.


Combining THz laser excitation with resonant soft X-ray scattering at the Linac Coherent Light Source.
This paper describes the development of new instrumentation at the Linac Coherent Light Source for conducting THz excitation experiments in an ultra high vacuum environment probed by soft X-ray diffraction. This consists of a cantilevered, fully motorized mirror system which can provide 600 kV cm(-1) electric field strengths across the sample and an X-ray detector that can span the full Ewald sphere with in-vacuum motion. The scientific applications motivated by this development, the details of the instrument, and spectra demonstrating the field strengths achieved using this newly developed system are discussed.


Functional analysis of the interaction between the mismatch repair protein MutS and the replication processivity factor β clamp in Pseudomonas aeruginosa.
Interaction between MutS and the replication factor β clamp has been extensively studied in a Mismatch Repair context; however, its functional consequences are not well understood. We have analyzed the role of the MutS-β clamp interaction in Pseudomonas aeruginosa by characterizing a β clamp binding motif mutant, denominated MutSβ, which does not interact with the replication factor. A detailed characterization of P. aeruginosa strain PAO1 harboring a chromosomal mutSβ allele demonstrated that this mutant strain exhibited mutation rates to rifampicin and ciprofloxacin resistance comparable to that of the parental strain. mutSβ PAO1 was as proficient as the parental strain for DNA repair under highly mutagenic conditions imposed by the adenine base analog 2-aminopurine. In addition, using a tetracycline resistance reversion assay to assess the repair of a frameshift mutation, we determined that the parental and mutSβ strains exhibited similar reversion rates. Our results clearly indicate that the MutS-β clamp interaction does not have a central role in the methylation-independent Mismatch Repair of P. aeruginosa.


Clinical features and outcomes of patients with myasthenia gravis admitted to an intensive care unit: A 20-year retrospective study.
There are limited data on the clinical characteristics and outcomes of patients with myasthenia gravis (MG) admitted to the intensive care unit (ICU) at Charlotte Maxeke Johannesburg Academic Hospital (CMJAH). The aim was to study the clinical characteristics and outcomes of patients with MG admitted to the CMJAH over two decades. A retrospective study was undertaken of patients with MG admitted to the multidisciplinary ICU of CMJAH over a 20-year period, from 1998 to 2017. Demographic data, clinical features, management and outcomes of patients were assessed and reviewed from the case records. Thirty-four patients with MG were admitted to the ICU during this period: 24 female and 10 male. The mean age ± SD was 37.4 ± 13.0 years, with a range of 16 - 66 years. Four patients were human immunodeficiency virus (HIV)-positive. The mean length of stay (LOS) in ICU was 10.6 ± 20.1 days, ranging from 1 to 115 days. Two patients were diagnosed with MG in the ICU after failure to wean from the ventilator. Overall, 22 patients were intubated and ventilated on admission. Morbidities included self-extubation, aspiration pneumonia and iatrogenic pneumothorax. History of thymectomy was present in 12 patients. The treatments received for MG included pyridostigmine (73.5%), corticosteroids (55.9%), azathioprine (35.3%), plasmapheresis (26.5%) and intravenous immunoglobulin (8.8%). The overall mortality in the ICU was 5.9%. MG is a serious disorder with considerable morbidity and mortality. It is, however, a potentially manageable disease, provided that appropriate ICU resources are available. This study provides further insight into the characteristics and outcomes of myasthenia gravis patients in ICU, within a South African context.


Electromyographic activity of voluntarily activated trunk flexor and extensor muscles in post-stroke hemiparetic subjects.
To study the EMG activity of selected trunk muscles during self-initiated voluntary flexion and extension of the trunk in post-stroke hemiparetic subjects, and to compare measurement results to corresponding findings in control subjects. Using a sample of 50 patients and 30 control subjects, bilateral EMG activity of the rectus abdominis (RA) and external oblique (EO) muscles was studied during direct trunk flexion, and activity of the lumbar erector spinae (ES) and latissimus dorsi (LD) was studied during straight trunk extension. Variables of timing, magnitude, and temporal synchronization between muscle activity on the paretic and non-paretic sides of the body in the patient group were compared with the same measurements taken from the left and right sides of the body in the control group. Activity of the RA and LD muscles on the affected side of the body was reduced and delayed relative to the unaffected side in the patients and relative to the control subjects. Some deterioration was also observed in the function of the EO muscle, whereas the lumbar ES displayed normal activity on both sides of the body. Trunk velocity during both flexion and extension was slower in the patients than in the controls. Despite the existence of ipsilateral as well as contralateral higher inputs to axial and to a lesser extent also to more lateral trunk muscles, the function of the superficial abdominal muscles and of the LD muscle is adversely affected by a contralateral stroke. Conversely, the lumbar ES, which can be categorized as local trunk extensors, seem to normally fulfill their anti-gravitational task on both sides of the body.


Clinical and Economic Outcomes in Patients with Persistent Asthma Who Attain Healthcare Effectiveness and Data Information Set Measures.
Attainment of asthma-specific US Healthcare Effectiveness Data and Information Set (HEDIS) quality measures may be associated with improved clinical outcomes and reduced economic burden. We examined the relationship between the attainment of HEDIS measures asthma medication ratio (AMR) and medication management for people with asthma (MMA) on clinical and economic outcomes. This retrospective claims database analysis linked to ambulatory electronic medical records enrolled US patients aged ≥5 years with persistent asthma between May 2015 and April 2017. The attainment of AMR ≥0.5 and MMA ≥75% was determined over a 1-year premeasurement period. Asthma exacerbations and asthma-related health care costs were evaluated during the subsequent 12-month measurement period, comparing patients attaining 1 or both measures with those not attaining either. In total, 32,748 patients were included, 75.2% of whom attained AMR (n = 24,388) and/or MMA (n = 12,042) during the premeasurement period. Fewer attainers of 1 or more HEDIS measures had ≥1 asthma-related hospitalizations, emergency department visit, corticosteroid burst, or exacerbation (4.9% vs 7.3%; 9.6% vs 18.2%; 43.8% vs 51.6%; 14.3% vs 23.3%, respectively; all P < .001) compared with nonattainers. In adjusted analyses, HEDIS attainment was associated with a lower likelihood of exacerbations (odds ratio: 0.63, [95% confidence interval: 0.60-0.67]; P < .001). The attainment of ≥1 HEDIS measures lowered total and asthma-related costs, and asthma exacerbation-related health care costs per patient relative to nonattainers (cost ratio: 0.87, P < .001; 0.96, P = .02; and 0.59, P < .001, respectively). Overall and asthma-specific costs were lower for patients attaining AMR, but not MMA. HEDIS attainment was associated with significantly improved asthma outcomes and lower asthma-specific costs.


A new species of Dactyloa from eastern Panama, with comments on other Dactyloa species present in the region.
Giant anoles of the genus Dactyloa have been considered to be represented in eastern Panama by six species. In this contribution, we describe a seventh species that is restricted to the Majé, San Blas, Darién, and Piedras-Pacora mountain ranges. The new species resembles D. ibanezi, D. limon, and D. purpurescens in external morphology but differs from these species in dewlap coloration, dorsal color pattern, morphometrics, and scalation. The recognition of the new species is further supported by DNA barcoding (genetic distances >2.7% in 16S and >7.8% in COI between the new species and all other species of Dactyloa). We discuss the taxonomic identity of D. purpurescens, and, based on morphological evidence, we place D. chocorum in the synonymy of the former species. An identification key for all 11 Dactyloa species occurring in Panama is provided.


The latent period of the Limulus lateral eye receptor potential: action of chlorobutanol.
Excised lateral eye retinular cells of Limulus polyphemus exposed to chlorobutanol were examined using microelectrode techniques. The effects observed were: (1) a marked shortening of the receptor potential latent period; (2) a decrease in the effective input resistance of retinular cells to hyperpolariziog currents; and (3) a reduction in magnitude of retinular cell receptor and membrane potential. The magnitude of the changes were concentration dependent and reversible and were only produced by chlorobutanol and closely related compounds. Chlorobutanol does not alter the sodium permeability of the receptor cell membrane but it may increase the rate of the process or processes occurring during the latent period of the receptor potential.