Follow-up after post-partum psychiatric emergency department visits: an equity-focused population-based study in Canada.
Emergency department visits for a psychiatric reason in the post-partum period represent an acute need for mental health care at a crucial time, but little is known about the extent of timely outpatient follow-up after these visits or how individual and intersecting social determinants of health influence this outcome. This study aimed to examine outpatient mental health care follow-up by a physician in the 30 days after an individual attended the emergency department for a psychiatric reason in the post-partum period and understand how social determinants of health affect who receives follow-up care. In this population-based cohort study, routinely collected health data from Ontario, Canada were accessed through ICES to identify all post-partum individuals whose sex was listed as female on their health card and who had attended an emergency department in Ontario before the COVID-19 pandemic for a psychiatric reason. Individuals admitted to hospital at the time of the emergency department visit, who died during the visit, or who left without being seen were excluded from the study. Ethnicity data for individuals were not collected. The primary outcome was the proportion of individuals with any outpatient physician (psychiatrist or family physician) visit for a mental health reason within 30 days of the index emergency department visit. Family physician mental health visits were identified using a validated algorithm for Ontario Health Insurance Plan-billed visits and mental health diagnostic codes for community health centre visits. We examined the associations between social determinants of health (age, neighbourhood income, community size, immigration, neighbourhood ethnic diversity) and who received an outpatient mental health visit. We used modified Poisson regression adjusting for the other social determinants of health, clinical, and health services characteristics to examine independent associations with follow-up, and conditional inference trees to explore how social determinants of health intersect with each other and with clinical and health services characteristics in relation to follow-up. We analysed data collected between April 1, 2008, and March 10, 2020, after exclusions we identified 12 158 people who had attended the emergency department for a psychiatric reason in the post-partum period (mean age 26·9 years [SD 6·2]; range 13-47); 9848 individuals lived in an urban area, among these 1518 (15·5%) were immigrants and 2587 (26·3%) lived in areas with high ethnic diversity. 5442 (44·8%) of 12 158 individuals received 30-day follow-up. In modified Poisson regression models, younger age, lower neighbourhood income, smaller community size, and being an immigrant were associated with a lower likelihood of follow-up. In the CTREE, similar variables were important, with several intersections between social determinants of health and between social determinants of health and other variables. Fewer than half of emergency department visits for a psychiatric reason in the post-partum period were followed by timely outpatient care, with social-determinants-of-health-based disparities in access to care. Improvements in equitable access to post-emergency department mental health care are urgently needed in this high-risk post-partum population. Department of Psychiatry, University of Toronto; Canadian Institutes of Health Research.


Effect of low blood glucose on plasma CRF, ACTH, and cortisol during prolonged physical exercise.
The effects of low blood glucose concentration during low-intensity prolonged physical exercise on the hypothalamus-pituitary-adrenocortical axis were investigated in healthy young men. In experiment 1, six subjects who had fasted for 14 h performed bicycle exercise at 50% of their maximal O2 uptake until exhaustion. At the end of the exercise, adrenocorticotropic hormone (ACTH) and cortisol increased significantly. However, this hormonal response was totally abolished when the same subjects exercised at the same intensity while blood glucose concentrations were maintained at the preexercise level. In experiment 2, in addition to ACTH and cortisol, the possible changes in plasma concentration of corticotropin-releasing factor (CRF) were investigated during exercise of the same intensity performed by six subjects. As suggested by a previous study (Tabata et al. Clin. Physiol. Oxf. 4: 299-307, 1984), when the blood glucose concentrations decreased to less than 3.3 mM, plasma concentrations of CRF, ACTH, and cortisol showed a significant increase. At exhaustion, further increases were observed in plasma CRF, ACTH, and cortisol concentrations. These results demonstrate that decreases in blood glucose concentration trigger the pituitary-adrenocortical axis to enhance secretion of ACTH and cortisol during low-intensity prolonged exercise in humans. The data also might suggest that this activation is due to increased concentration of CRF, which was shown to increase when blood glucose concentration decreased to a critical level of 3.3 mM.


Molecular characterization of the type-specific gamma-determinant located on the adenovirus fiber.
The fiber knob carries the type-specific gamma-antigen which can be demonstrated in hemagglutination inhibition tests. In order to characterize the gamma-determinant we selected subgenus DI adenovirus serotypes 9 and 19 (Ad9 and Ad19) which exhibited 29 amino acid exchanges in the knob domain. Like all subgenus DI adenoviruses they showed a complete hemagglutination pattern with rat and human erythrocytes. We constructed a total of 14 chimeric Ad9/Ad19 and Ad19/Ad9 fiber proteins, which possessed fiber knobs with progressively exchanged Ad9 and Ad19 amino acids. Furthermore, we created 39 fiber proteins with distinct amino acid exchanges in the knob regions by primer-directed mutagenesis. The proteins were expressed in Escherichia coli and tested in hemagglutination and hemagglutination inhibition tests. From our results we can conclude that the type-specific gamma-determinant is not restricted to a distinct region on the adenovirus fiber knob but is composed of at least 17 amino acids. Most of the amino acids contributing to the Ad9 and Ad19 gamma-determinants are located on the fiber knob loops.


Impact of infectious diseases service consultation on diagnosis of infective endocarditis.
The infectious diseases (ID) consultation service is a new clinical entity in Japan. We examined the impact of ID consultation on the diagnosis of infective endocarditis (IE) at a large teaching hospital in Japan. Routine consultation with an ID service for cases of positive blood culture was implemented at Kameda Medical Center in November 2004. In addition, ID service doctors started to give lectures on ID to doctors and also provided local guidelines on ID. We compared the incidence of IE during a 3-y and 10-month period before intervention with that during a 5-y and 2-month period after intervention. The modified Duke criteria were used to confirm the diagnosis of definite IE. Patients who fulfilled the criteria for definite IE were included in the analysis. Twenty-seven cases of IE were diagnosed before the implementation of routine consultation, and 76 cases after. The respective incidences of IE were 48.7 and 84.8 per 100,000 patients discharged from the hospital (p = 0.01). The relapse rate of IE within 6 months was significantly lower in patients who underwent routine consultation (22.2% vs 2.2%; p = 0.02). Routine consultation with an ID service for cases of positive blood culture, together with consecutive lecturing and local guidelines by ID specialists, resulted in improved detection of IE and a reduced relapse rate within 6 months. Timely consultation with an ID specialist in bacteraemia cases may be beneficial for improving the outcomes of patients in this setting.


The role of antidepressants in the management of fibromyalgia syndrome: a systematic review and meta-analysis.
The role of antidepressants in the management of fibromyalgia syndrome (FMS) still needs to be determined. The objective of this study was to provide a quantitative analysis (meta-analysis) of the efficacy and harms of antidepressants in the management of adult FMS patients. The data sources used were the databases MEDLINE, SCOPUS and the Cochrane Central Register of Controlled Trials (until December 30, 2010), the reference lists of included articles, and the websites of the US National Institutes of Health (NIH) and the Pharmaceutical Research and Manufacturers of America (PhRMA). Studies with a randomized controlled trial (RCT) design comparing any types of antidepressants with pharmacological placebo or head-to-head comparisons of different types of antidepressants in FMS patients were included. RCTs in which antidepressants were combined with any other defined treatment or antidepressants were tested against anything but drug placebo were excluded. Patients diagnosed with FMS according to predefined criteria of any age were included. To be included, studies had to assess at least one key domain of FMS (pain, sleep, fatigue, health-related quality of life [HRQOL]) as outcomes of efficacy and report total treatment discontinuation rates and/or dropout rates due to adverse events as outcomes for harms. Data were extracted according to protocols of previous systematic reviews on antidepressants in FMS. Methodology quality was assessed by the van Tulder score. Standardized mean differences (SMD) were calculated for continuous outcomes by means and standard deviations and relative risks (RR) for 30% pain reduction and total dropout rate for comparisons of antidepressants with placebo. Examination of the combined results was performed by a random effects model. We used Cohen's categories to evaluate the magnitude of the effect size, calculated by SMD. Heterogeneity was tested by the I2 statistic. Thirty-five studies were included in the meta-analysis. The SMDs of serotonin noradrenaline (norepinephrine) reuptake inhibitors (SNRIs) on pain, sleep, fatigue, depression and HRQOL were significant. Based on Cohen's categories, the effect size on pain was small and the ones on sleep, fatigue, depression and HRQOL were not substantial. 1481/3528 (42.0%) patients with SNRIs and 737/2304 (32.0%) patients with placebo reported a 30% pain reduction (number needed to treat [NNT] 10.0; 95% CI 8.00, 13.4; I2 = 4%). The RR of dropouts due to adverse events was 1.83 (95% CI 1.53, 2.18; I2 = 33%). The SMDs of selective serotonin reuptake inhibitors (SSRIs) on pain, sleep, depression and HRQOL were significant. Based on Cohen's categories, the effect sizes on pain, depression and HRQOL were small and the one on sleep not substantial. 72/198 (36.4%) patients with SSRIs and 40/194 (20.6%) patients with placebo reported a 30% pain reduction (NNT 6.3; 95% CI 4.1, 14.1). The RR of dropouts due to adverse events was 1.60 (95% CI 0.84, 3.04; I2 = 0%). The SMDs of tricyclic antidepressants (TCAs) on pain, sleep, fatigue and HRQOL were significant. Based on Cohen's categories, the effect sizes on pain and sleep were moderate and the ones on fatigue and HRQOL were small. 140/290 (48.3%) patients with TCAs and 70/252 (27.8%) patients with placebo reported a 30% pain reduction (NNT 4.9; 95% CI 3.5, 8.0). The RR of dropouts due to adverse events was 0.84 (95% CI 0.46, 1.52; I2 = 0%). The TCA amitriptyline and the SNRIs duloxetine and milnacipran are first-line options for the treatment of FMS patients. Physicians and patients should be realistic about the potential benefits of antidepressants in FMS. A small number of patients experience a substantial symptom relief with no or minor adverse effects. However, a remarkable number of patients dropout of therapy because of intolerable adverse effects or experience only a small relief of symptoms, which does not outweigh the adverse effects.


NLRP3: A Promising Therapeutic Target for Inflammatory Bowel Disease.
Inflammatory bowel disease (IBD), which includes Crohn's disease and ulcerative colitis, is an intestinal disease with complicated pathological mechanisms. The incidence of IBD has been increasing in recent years, which has a significant negative impact on the lives of patients. Therefore, it is particularly important to find new therapeutic targets and innovative drugs for the development of IBD. Recent studies have revealed that NLRP3 inflammatory vesicles can play an important role in maintaining intestinal homeostasis and sustaining the intestinal immune response in IBD. On the one hand, aberrant activation of NLRP3 inflammatory vesicles may cause excessive immune response by converting caspase-1, proIL-18, and proIL-1β to their active forms and releasing pro-inflammatory cytokines to stimulate the development and progression of IBD, and we can improve IBD by targeting blockade of NLRP3 activation. On the other hand, NLRP3 may also play an enter protective role by maintaining the homeostasis of the intestinal immune system. In this paper, we reviewed the activation mechanism of NLRP3 inflammasome, and the effects of NLRP3 inflammasome activation on IBD are discussed from two different perspectives: pathology and protection. At the same time, we listed the effects of direct inhibitors, indirect inhibitors, and natural inhibitors of NLRP3 inflammasome on IBD in combination with cutting-edge advances and clinical practice results, providing new targets and new ideas for the clinical treatment of IBD.


Synthesis of ZnO nanowires with supercritical carbon dioxide and post heat treatment.
Zinc oxide (ZnO) nanowires are used in applications such as gas sensors and solar cells. This work presents a novel synthesis route for ZnO nanowires using supercritical carbon dioxide (scCO2) and post heat treatment. The method used scCO2 and a precursor solution as reactants to form nanowires on a galvanized surface. After the scCO2 treatment, the substrate was heat-treated. The surfaces were characterized with SEM, TEM, EDS, FTIR, XRD and optical spectroscopy. The FTIR results showed that the surface structure had changed from zinc hydroxycarbonate to ZnO during the heat treatment. The nanowires were slightly bent due to the heat treatment according to the SEM images. The presence of ZnO was further confirmed with XRD. The bandgap of the structure was determined by reflectance measurements and showed a value of 3.23 eV. The synthesis method presented in this study offers a unique approach into the formation of ZnO nanowires in a facile, rapid and environmentally friendly process.


Molecular Dynamics Simulation of Polyacrylamide Adsorption on Calcite.
In poorly consolidated carbonate rock reservoirs, solids production risk, which can lead to increased environmental waste, can be mitigated by injecting formation-strengthening chemicals. Classical atomistic molecular dynamics (MD) simulation is employed to model the interaction of polyacrylamide-based polymer additives with a calcite structure, which is the main component of carbonate formations. Amongst the possible calcite crystal planes employed as surrogates of reservoir rocks, the (1 0 4) plane is shown to be the most suitable surrogate for assessing the interactions with chemicals due to its stability and more realistic representation of carbonate structure. The molecular conformation and binding energies of pure polyacrylamide (PAM), hydrolysed polyacrylamide in neutral form (HPAM), hydrolysed polyacrylamide with 33% charge density (HPAM 33%) and sulfonated polyacrylamide with 33% charge density (SPAM 33%) are assessed to determine the adsorption characteristics onto calcite surfaces. An adsorption-free energy analysis, using an enhanced umbrella sampling method, is applied to evaluate the chemical adsorption performance. The interaction energy analysis shows that the polyacrylamide-based polymers display favourable interactions with the calcite structure. This is attributed to the electrostatic attraction between the amide and carboxyl functional groups with the calcite. Simulations confirm that HPAM33% has a lower free energy than other polymers, presumably due to the presence of the acrylate monomer in ionised form. The superior chemical adsorption performance of HPAM33% agrees with Atomic Force Microscopy experiments reported herein.


Hepatitis C virus and human immunodeficiency virus: a dangerous dealing.
It is estimated that, in the United States and Europe, 15-30% of people with human immunodeficiency virus (HIV) are coinfected with hepatitis C virus (HCV). Among these patients, approximately 80% are intravenous drug users (IVDU), 71% are hemophiliacs, and around 20% are homosexual/bi-sexual men. HIV infection accelerates the natural history of HCV infection. On the contrary, highly active antiretroviral therapy reduces the rate of mortality due to liver disease by immune restoration. Since having HIV implies being at risk also for HCV as both infections can be acquired in similar ways, all individuals with the former should be screened for the latter. Loss of antibodies against HCV in HIV-seropositive IVDU has been shown. Thus, quantitative tests determining HCV-RNA levels in blood are currently being employed for diagnosis confirmation in case of an obvious ''risk group''. Since HIV can progress more rapidly than HCV, it may be preferable to treat HIV first. The 2007 recommendations from HCV-HIV International Panel indicate current treatment of HCV in coinfected patients with pegylated formulation of interferon at standard doses plus weight based ribavirin. The treatment duration should be evaluated on the basis of HCV genotype. Liver transplantation is a most debated issue when dealing with HCV/HIV coinfected subjects. Mortality among HIV-infected liver transplant recipients is similar to that of age and race-matched HIV-negative controls. The present concise review attempts to highlight on the current clinical situation on HIV/HCV coinfection.


Clinical approach to genetic cardiomyopathy in children.
Cardiomyopathy (CM) remains one of the leading cardiac causes of death in children, although in the majority of cases, the cause is unknown. To have an impact on morbidity and mortality, attention must shift to etiology-specific treatments. The diagnostic evaluation of children with CM of genetic origin is complicated by the large number of rare genetic causes, the broad range of clinical presentations, and the array of specialized diagnostic tests and biochemical assays. We present a multidisciplinary diagnostic approach to pediatric CM of genetic etiology. We specify criteria for abnormal left ventricular systolic performance and structure that suggest CM based on established normal echocardiographic measurements and list other indications to consider an evaluation for CM. We provide a differential diagnosis of genetic conditions associated with CM, classified as inborn errors of metabolism, malformation syndromes, neuromuscular diseases, and familial isolated CM disorders. A diagnostic strategy is offered that is based on the clinical presentation: biochemical abnormalities, encephalopathy, dysmorphic features or multiple malformations, neuromuscular disease, apparently isolated CM, and pathological specimen findings. Adjunctive treatment measures are recommended for severely ill patients in whom a metabolic cause of CM is suspected. A protocol is provided for the evaluation of moribund patients. In summary, we hope to assist pediatric cardiologists and other subspecialists in the evaluation of children with CM for a possible genetic cause using a presentation-based approach. This should increase the percentage of children with CM for whom a diagnosis can be established, with important implications for treatment, prognosis, and genetic counseling.


Research Progress of Titanium-Based High Entropy Alloy: Methods, Properties, and Applications.
With the continuous progress and development in the biomedicine field, metallic biomedical materials have attracted the considerable attention of researchers, but the related procedures need to be further developed. Since the traditional metal implant materials are not highly compatible with the human body, the modern materials with excellent mechanical properties and proper biocompatibility should be developed urgently in order to solve any adverse reactions caused by the long-term implantations. The advent of the high-entropy alloy (HEA) as an innovative and advanced idea emerged to develop the medical implant materials through the specific HEA designs. The properties of these HEA materials can be predicted and regulated. In this paper, the progression and application of titanium-based HEAs, as well as their preparation and biological evaluation methods, are comprehensively reviewed. Additionally, the prospects for the development and use of these alloys in implant applications are put forward.


A New Stochastic Kriging Method for Modeling Multi-Source Exposure-Response Data in Toxicology Studies.
One of the most fundamental steps in risk assessment is to quantify the exposure-response relationship for the material/chemical of interest. This work develops a new statistical method, referred to as SKQ (stochastic kriging with qualitative factors), to synergistically model exposure-response data, which often arise from multiple sources (e.g., laboratories, animal providers, and shapes of nanomaterials) in toxicology studies. Compared to the existing methods, SKQ has several distinct features. First, SKQ integrates data across multiple sources and allows for the derivation of more accurate information from limited data. Second, SKQ is highly flexible and able to model practically any continuous response surfaces (e.g., dose-time-response surface). Third, SKQ is able to accommodate variance heterogeneity across experimental conditions and to provide valid statistical inference (i.e., quantify uncertainties of the model estimates). Through empirical studies, we have demonstrated SKQ's ability to efficiently model exposure-response surfaces by pooling information across multiple data sources. SKQ fits into the mosaic of efficient decision-making methods for assessing the risk of a tremendously large variety of nanomaterials and helps to alleviate safety concerns regarding the enormous amount of new nanomaterials.


p38 Mitogen-activated protein kinase- and HuR-dependent stabilization of p21(Cip1) mRNA mediates the G(1)/S checkpoint.
Activation of p38 mitogen-activated protein kinase (MAPK) plays an important role in the G(2)/M cell cycle arrest induced by DNA damage, but little is known about the role of this signaling pathway in the G(1)/S transition. Upregulation of the cyclin-dependent kinase inhibitor p21(Cip1) is thought to make a major contribution to the G(1)/S cell cycle arrest induced by gamma radiation. We show here that inhibition of p38 MAPK impairs p21(Cip1) accumulation and, as a result, the ability of cells to arrest in G(1) in response to gamma radiation. We found that p38 MAPK induces p21(Cip1) mRNA stabilization, without affecting its transcription or the stability of the protein. In particular, p38 MAPK phosphorylates the mRNA binding protein HuR on Thr118, which results in cytoplasmic accumulation of HuR and its enhanced binding to the p21(Cip1) mRNA. Our findings help to understand the emerging role of p38 MAPK in the cellular responses to DNA damage and reveal the existence of p53-independent networks that cooperate in modulating p21(Cip1) levels at the G(1)/S checkpoint.


Responsive Emulsions for Sequential Multienzyme Cascades.
Multienzyme cascade biocatalysis is an efficient synthetic process, avoiding the isolation/purification of intermediates and shifting the reaction equilibrium to the product side.. However, multienzyme systems are often limited by their incompatibility and cross-reactivity. Herein, we report a multi-responsive emulsion to proceed multienzyme reactions sequentially for high reactivity. The emulsion is achieved using a CO2 , pH, and thermo-responsive block copolymer as a stabilizer, allowing the on-demand control of emulsion morphology and phase composition. Applying this system to a three-step cascade reaction enables the individual optimal condition for each enzyme, and a high overall conversion (ca. 97 % of the calculated limit) is thereby obtained. Moreover, the multi-responsiveness of the emulsion allows the facile and separate yielding/recycling of products, polymers and active enzymes. Besides, the system could be scaled up with a good yield.


Lesion of the pedunculopontine tegmental nucleus in rat augments cortical activation and disturbs sleep/wake state transitions structure.
The pedunculopontine tegmental nucleus (PPT) represents a major aggregation of cholinergic neurons in the mammalian brainstem, which is important in the generation and maintenance of REM sleep. We investigated the effects of unilateral and bilateral PPT lesions on sleep and all the conventional sleep-state related EEG frequency bands amplitudes, in an attempt to find the EEG markers for the onset and progression of PPT cholinergic neuronal degeneration. The experiments were performed on 35 adult male Wistar rats, chronically implanted for sleep recording. During the surgical procedure for EEG and EMG electrodes implantation, the unilateral or bilateral PPT lesion was produced under ketamine/diazepam anesthesia, by the stereotaxically guided microinfusion of 100 nl 0.1M ibotenic acid (IBO) into PPT. We applied Fourier analysis to signals acquired throughout 6h of recordings, and each 10s epoch was differentiated as a Wake, NREM or REM state. We also calculated the group probability density estimates (PDE) of all Wake, NREM and REM conventional EEG frequency amplitudes, and the number of all the transition states using MATLAB 6.5. Our results show that the unilateral or bilateral PPT lesions did not change the sleep/wake architecture, but did change the sleep/wake state transitions structure and the sleep/state related "EEG microstructure". Unilateral or bilateral PPT lesions sustainably increased Wake/REM and REM/Wake transitions from 14 to 35 days after lesions. This was followed by decreased NREM/REM and REM/NREM transitions from 28 days only in the case of the bilateral PPT lesion. The unilateral PPT lesion augmented both Wake theta and REM beta while it also attenuated the relative amplitude of the Wake delta frequency, with a delay of one week. Following a bilateral PPT lesion there was augmentation of the relative amplitude of the Wake, NREM, and REM beta and REM gamma frequency which occurred simultaneously to NREM and Wake delta attenuation. We have shown that the PPT cholinergic neuronal loss sustainably increased the number of the Wake/REM and REM/Wake transitions and augmented sleep-states related cortical activation that was simultaneously expressed by the high frequency amplitude augmentation, as well as Wake and NREM delta frequency attenuation.


Cloning and expression of a Helicobacter bilis immunoreactive protein.
In an effort to identify immunoreactive Helicobacter bilis antigens with potential for serodiagnosis, sera from mice experimentally infected with H. bilis were used to screen an H. bilis genomic DNA expression library. Among 17 immunoreactive clones, several contained sequences that encoded a predicted 167-kDa protein (P167). Five overlapping P167 peptides (P167A to P167E) of approximately 40 kDa each were generated and tested. Immune sera reacted with fragments P167C and P167D at dilutions of 1:1,600 and 1:6,400, respectively, and reacted with an H. bilis membrane extract at a dilution of 1:800 in an enzyme-linked immunosorbent assay. Sera from mice experimentally infected with H. hepaticus did not react with P167C and P167D. Sera from mice naturally infected with H. bilis but not sera from mice naturally infected with H. hepaticus reacted with P167C and P167D. Hyperimmune sera against P167C peptide reacted with recombinant P167C and with a 120-kDa band in H. bilis lysates but did not react with a protein of the same size on immunoblots prepared from H. hepaticus, H. muridarum, or unrelated Borrelia burgdorferi and Campylobacter jejuni whole-cell lysates. Nevertheless, the P167A, P167B, P167C, and P167D primers, but not the P167E primers, amplified DNA from H. hepaticus, and all five primer sets amplified DNA from H. muridarum. These results suggest that P167 is an immunodominant, H. bilis-specific antigen that may have potential for use in serodiagnosis.


Lowering cholesterol, blood pressure, or both to prevent cardiovascular events: results of 8.7 years of follow-up of Heart Outcomes Evaluation Prevention (HOPE)-3 study participants.
Rosuvastatin (10 mg per day) compared with placebo reduced major adverse cardiovascular (CV) events by 24% in 12 705 participants at intermediate CV risk after 5.6 years. There was no benefit of blood pressure (BP) lowering treatment in the overall group, but a reduction in events in the third of participants with elevated systolic BP. After cessation of all the trial medications, we examined whether the benefits observed during the active treatment phase were sustained, enhanced, or attenuated. After the randomized treatment period (5.6 years), participants were invited to participate in 3.1 further years of observation (total 8.7 years). The first co-primary outcome for the entire length of follow-up was the composite of myocardial infarction, stroke, or CV death [major adverse cardiovascular event (MACE)-1], and the second was MACE-1 plus resuscitated cardiac arrest, heart failure, or coronary revascularization (MACE-2). In total, 9326 (78%) of 11 994 surviving Heart Outcomes Prevention Evaluation (HOPE)-3 subjects consented to participate in extended follow-up. During 3.1 years of post-trial observation (total follow-up of 8.7 years), participants originally randomized to rosuvastatin compared with placebo had a 20% additional reduction in MACE-1 [95% confidence interval (CI), 0.64-0.99] and a 17% additional reduction in MACE-2 (95% CI 0.68-1.01). Therefore, over the 8.7 years of follow-up, there was a 21% reduction in MACE-1 (95% CI 0.69-0.90, P = 0.005) and 21% reduction in MACE-2 (95% CI 0.69-0.89, P = 0.002). There was no benefit of BP lowering in the overall study either during the active or post-trial observation period, however, a 24% reduction in MACE-1 was observed over 8.7 years. The CV benefits of rosuvastatin, and BP lowering in those with elevated systolic BP, compared with placebo continue to accrue for at least 3 years after cessation of randomized treatment in individuals without cardiovascular disease indicating a legacy effect. NCT00468923.


Unsuspected gonorrhea and chlamydia in patients of an urban adult emergency department: a critical population for STD control intervention.
Urban emergency departments (EDs) providing services to patients at high risk for sexually transmitted infection may be logical sites for intervention. To determine the prevalence of gonorrhea (GC) and chlamydia (CT) in an adult ED patient population, and to assess risk factors for infection. Cross-sectional study of patients aged 18 to 44 in an urban ED, seeking care of any medical nature. Main outcome was positive for GC or CT by urine ligase chain reaction assay. Test results for GC and/or CT were positive in 13.6% of 434 18 to 31 year-olds and in 1.8% of 221 32 to 44 year-olds. Of 63 infected individuals identified by the study, 15 (23.8%) were treated at the ED visit. Age < or =31 detected 88% of infections. Among 18- to 31-year-old patients, predictive risk factors by multivariate analysis included age <25, >1 sex partner in the past 90 days, and a history of sexually transmitted disease. This study identified a high prevalence of GC and CT in patients seeking ED services. Many of these infections were clinically unsuspected. These data demonstrate that the ED is a high-risk setting and may be an appropriate site for routine GC and CT screening in 18- to 31-year-old patients.


Lessons learnt from an international intercomparison of national network systems used to provide early warning of a nuclear accident.
As part of the European Research Council's Fourth Framework Programme, the EURADOS Action Group on Monitoring of External Exposures held an intercomparison of national network systems. This took place during May/June 1999 at the Risø Natural Enviromental Radiation Measurement Station in Denmark and at the Underground Laboratory for Dosimetry and Spectrometry (UDO) of the Physikalisch-Technische Bundesanstalt (PTB) in Germany. The network systems are used continuously to monitor radiation levels throughout a country in order to give early warning of nuclear accidents having transboundary implications. The radiation levels measured are used to estimate the radiation risks to people arising from the accident. Seven European countries participated in the intercomparison with detector systems used in their national network systems as well as with detectors being developed for future use. Since different radiation quantities were measured by the systems (namely exposure, air kerma and ambient dose equivalent), the initial analysis of the intercomparison results was made in terms of the quantity air kerma rate. This report completes the analysis of the results and these are given in terms of air kerma rate in order to be consistent with the preliminary report. In addition, in some cases the results are also given in terms of the quantity measured by each national network system. The experience gained from this intercomparison is used to help organise a follow-up intercomparison to be held at the PTB Braunschweig in September 2002 and in which a further seven or eight countries from Europe will participate.


[Compatibility of the results of ultrasound-guided fine needle aspiration biopsy with the histological findings in assessment of focal breast lesions among woman attending the outpatient breast clinic].
Continuous increase of morbidity and mortality rate due to breast cancer has led to development of new diagnostic methods that are aimed at detecting neoplastic and preneoplastic lesions in their early, yet asymptomatic stages. Development of modern imaging techniques (ultrasonography, mammography, magnetic resonance) and invasive diagnostic procedures (fine needle aspiration biopsy, core needle biopsy, stereotactically guided biopsy) allows to detect lesions not exceeding 1 cm in diameter, and therefore may provide a complete cure. The aim of this study was to estimate diagnostic usefulness of ultrasound-guided fine needle aspiration biopsy in detecting benign breast dysplasia (with and without proliferation of ductal epithelial cells), benign neoplastic lesions and breast cancer, as well as to determine compatibility between US-guided FNAB results and subsequent histological findings. The study group consisted of 213 female patients. The obtained results were subject for statistical analyses that revealed a high degree of compatibility between US-guided FNAB and histological results (93.6-95.5%), and also confirmed high sensitivity of US-guided FNAB. This method has proved to be an efficient diagnostic tool for early detection of benign breast dysplasia, benign neoplasms and breast cancer, making early surgical treatment possible in most cases and permitting omission of an intra-operative histological examination.


[Recent advances and perspective in the study of the molecular imprinting of proteins].
Molecular imprinting technique (MIT) involves the synthesis of polymer in the presence of a template to produce complementary binding sites in terms of its size, shape, and functional group orientation. Such kind of polymer possesses specific recognition ability towards its template molecule. Despite the rapid development of MIT over the years, the majority of the template molecules that have been studied are small molecules, while molecular imprinting of proteins remains a significant yet challenging task due to their large size, structural flexibility and complex conformation. In this review, we summarize the research findings over the past five years, and discuss the characteristics of the technique, the most recent progress and the perspective in the field of molecular imprinting of proteins.


Spatial variation of gain and saturation in a fast axial flow CO(2) laser amplifier.
The spatial variation of gain and saturation is analyzed in weakly and heavily saturated cases for a fast axial flow (FAF) CO(2) laser amplifier with laser gas in laminar and turbulent flow regions. Expressiong the laser parameters by fourth-order even functions of the radial distance, the development of the amplified radiation is predicted and compared successfully to the experimental results for the 10P(18) line. The distinctive feature of a FAF system is enhancement of the gain and saturation irradiance as well as the mode volume. The condition of spatial soliton is also discussed in a heavily saturated case.


The comb jelly opsins and the origins of animal phototransduction.
Opsins mediate light detection in most animals, and understanding their evolution is key to clarify the origin of vision. Despite the public availability of a substantial collection of well-characterized opsins, early opsin evolution has yet to be fully understood, in large part because of the high level of divergence observed among opsins belonging to different subfamilies. As a result, different studies have investigated deep opsin evolution using alternative data sets and reached contradictory results. Here, we integrated the data and methods of three, key, recent studies to further clarify opsin evolution. We show that the opsin relationships are sensitive to outgroup choice; we generate new support for the existence of Rhabdomeric opsins in Cnidaria (e.g., corals and jellyfishes) and show that all comb jelly opsins belong to well-recognized opsin groups (the Go-coupled opsins or the Ciliary opsins), which are also known in Bilateria (e.g., humans, fruit flies, snails, and their allies) and Cnidaria. Our results are most parsimoniously interpreted assuming a traditional animal phylogeny where Ctenophora are not the sister group of all the other animals.


Effect of pallidotomy on postural control and motor function in Parkinson disease.
To investigate the effects of pallidotomy on postural reactions and other motor parkinsonian deficits. Comparison of performance by patients before and after pallidotomy on tests of balance and function. A Parkinson disease Center of Excellence and Center for Human Performance Testing at a university hospital and research center. Twenty-nine patients with Parkinson disease undergoing pallidotomy. Performance results on the United Parkinson's Disease Rating Scale (UPDRS), activities of daily living and motor subscales (parts II and III). and posturography (sensory organization test), which were collected before and 3 and 6 months after surgery with patients in the practically defined off state (medication withheld for at least 12 hours). Data were analyzed with a paired Wilcoxon and Spearman correlation. There was a significant improvement in mean +/- SD UPDRS motor subscale score after pallidotomy (before surgery, 52.43+/-13.46; after surgery, 43.93+/-15.15; z= 3.63; P=.003). There were no significant changes in the UPDRS activities of daily living subscale or average stability scores when the group was examined as a whole. However, examination of individual data revealed that 9 (56%) of 16 patients who could stand independently before surgery showed improvement in either the number of falls or the average stability score. No patient who was unable to stand independently before surgery was able to stand independently after it. Pallidotomy helped improve overall motor function in patients with parkinsonism and, for some patients, also improved postural stability.


Sleep slow oscillation and plasticity.
It is well documented that sleep contributes to memory consolidation and it is also accepted that long-term synaptic plasticity plays a critical role in memory formation. The mechanisms of this sleep-dependent memory formation are unclear. Two main hypotheses are proposed. According to the first one, synapses are potentiated during wake; and during sleep they are scaled back to become available for the learning tasks in the next day. The other hypothesis is that sleep slow oscillations potentiate synapses that were depressed due to persistent activities during the previous day and that potentiation provides physiological basis for memory consolidation. The objective of this review is to group information on whether cortical synapses are up-scaled or down-scaled during sleep. We conclude that the majority of cortical synapses are up-regulated by sleep slow oscillation.


[Medical errors and conflicts in clinical practice].
The number of medical errors is increasing. Medical errors have negative impact on the professional activities of physicians. Analysis of the causes and incidence of medical errors and conflicts in clinical practice of foreign and domestic doctors is presented based on the author's observations and didactic materials recommended for training doctors to prevent conflict situations in their professional work and for developing a common strategy for the prevention of medical errors.


Vascular endothelial growth factor-induced retinal permeability is mediated by protein kinase C in vivo and suppressed by an orally effective beta-isoform-selective inhibitor.
Increased vascular permeability and excessive neovascularization are the hallmarks of endothelial dysfunction, which can lead to diabetic macular edema and proliferative diabetic retinopathy in the eye. Vascular endothelial growth factor (VEGF) is an important mediator of ocular neovascularization and a known vasopermeability factor in nonocular tissues. In these studies, we demonstrate that intravitreal injection of VEGF rapidly activates protein kinase C (PKC) in the retina at concentrations observed clinically, inducing membrane translocation of PKC isoforms alpha, betaII, and delta and >threefold increases in retinal vasopermeability in vivo. The effect of VEGF on retinal vascular permeability appears to be mediated predominantly by the beta-isoform of PKC with >95% inhibition of VEGF-induced permeability by intravitreal or oral administration of a PKC beta-isoform-selective inhibitor that did not inhibit histamine-mediated effects. These studies represent the first direct demonstration that VEGF can increase intraocular vascular permeability through activation of PKC in vivo and suggest that oral pharmacological therapies involving PKC beta-isoform-selective inhibitors may prove efficacious for the treatment of VEGF-associated ocular disorders such as diabetic retinopathy.


RENISUS Plants and Their Potential Antitumor Effects in Clinical Trials and Registered Patents.
Cancer is a significant cause of morbidity and mortality. Scientific advances, coupled with potential flaws in current treatments, are driving research into the discovery of new bioactive molecules. This systematic review focused on scientific studies with clinical trials and patents registered on the National Relation of Medicinal Plants of Interest to the Unified Health System (RENISUS) plants (or derivative compounds) with antitumor potential. Studies with 19 different forms of cancer were found, the prostate being the organ with the highest research incidence and the species Glycine max, Curcuma longa, and Zingiber officinale, beside the phytochemicals curcumin and soy isoflavone were the most tested in clinical trials/patents.


[Congenital gastroschisis--prenatal diagnosis and perinatal management].
The birth prevalence of gastroschisis is increasing world-wide. This situation applies particularly to young, slim women who smoke. At a first glance this is a paradox in light of the ever-increasing age of pregnant women among whom there are fewer and fewer smokers. In numerous studies it has been clearly demonstrated that not only (nutritional) teratogenic substances and environmental factors but also epidemiological causes can be held responsible for this phenomenon. Nowadays gastroschisis is detected prenatally in up to 90% of all foetuses. Advantages of a prenatal diagnosis include the identification of associated disorders and the determination of a high-risk constellation (IUGR, intraabdominal bowel dilatation or vanishing gut). This is essential for an adequate interdisciplinary counseling for the afflicted parents together with obstetricians, paediatric surgeons and neonatalogists. The efficacy of serial amnioexchanges with regard to a better neonatal outcome has as yet not been unambiguously clarified. The possibilities for surgical procedures on the foetus are limited and can at present only be considered as experimental attempts in animal models. From an obstetrical perspective the in utero transport and elective Caesarean section before completion of the 36 (th) week of gestation in a tertiary centre with appropriate facilities (paediatric surgery, neonatalogy) seem to be the course recommended by most authors in spite of inconclusive data. The survival rates for babies with gastroschisis after operative treatment (primary defect closure, silotechnique) are considerably high (>90%).


Cognitive-behavioural therapy for adolescents with bulimic symptomatology: the acceptability and effectiveness of internet-based delivery.
The evidence base for the treatment of adolescents with bulimia nervosa (BN) is limited. To assess the feasibility, acceptability, and clinical outcomes of a web-based cognitive-behavioural (CBT) intervention for adolescents with bulimic symptomatology. 101 participants were recruited from eating disorders clinics or from beat, a UK-wide eating disorders charity. The programme consisted of online CBT sessions ('Overcoming Bulimia Online'), peer support via message boards, and email support from a clinician. Participants' bulimic symptomatology and service utilisation were assessed by interview at baseline and at three and six months. Participants' views of the treatment package were also determined. There were significant improvements in eating disorder symptoms and service contacts from baseline to three months, which were maintained at six months. Participants' views of the intervention were positive. The intervention has the potential for use as a first step in the treatment of adolescents with bulimic symptomatology.


[The correlation between pulmonary hypertension and histological findings of the pulmonary vessels in congenital heart disease (author's transl)].
In nearly 100 infants the hämodynamic and histological findings of pulmonary hypertension in congenital heart diseases are correlated when a banding-procedure was done. There were: 45 ventricle septal defects, 10 atrio-ventricular canals, 13 transpositions of the great arteries, 16 patent ductus arteriosus and 7 miscellaneous. A hämodynamic hypertension was more frequent than the histological hypertension; but there was a difference in the different heart diseases: The patients with patent ductus arteriosus and hypertension show only in a few cases histological alterations; in infants with VSD the correlation was much more better. Whether a banding procedure of the pulmonary artery is able to provide the progress of pulmonary sclerosis may be discussed after a second excision of lung-tissue when the correction of the heart disease is done.


Assessing neuroprotective effects of diroximel fumarate and siponimod via modulation of pacemaker channels in an experimental model of remyelination.
Cuprizone (CPZ)-induced alterations in axonal myelination are associated with a period of neuronal hyperexcitability and increased activity of hyperpolarization-activated and cyclic nucleotide-gated (HCN) channels in the thalamocortical (TC) system. Substances used for the treatment of multiple sclerosis (MS) have been shown to normalize neuronal excitability in CPZ-treated mice. Therefore, we aimed to examine the effects of diroximel fumarate (DRF) and the sphingosine 1-phospate receptor (S1PR) modulator siponimod on action potential firing and the inward current (Ih) carried by HCN ion channels in naive conditions and during different stages of de- and remyelination. Here, DRF application reduced Ih current density in ex vivo patch clamp recordings from TC neurons of the ventrobasal thalamic complex (VB), thereby counteracting the increase of Ih during early remyelination. Siponimod reduced Ih in VB neurons under control conditions but had no effect in neurons of the auditory cortex (AU). Furthermore, siponimod increased and decreased AP firing properties of neurons in VB and AU, respectively. Computational modeling revealed that both DRF and siponimod influenced thalamic bursting during early remyelination by delaying the onset and decreasing the interburst frequency. Thus, substances used in MS treatment normalize excitability in the TC system by influencing AP firing and Ih.


Long-term potentiation in the reciprocal corticohippocampal and corticocortical pathways in the chronically implanted, freely moving rat.
The hippocampus and adjacent cortical structures, including the entorhinal, perirhinal, and parahippocampal cortices, appear to serve as an integrated memory system. This extended hippocampal system is believed to influence memory and consolidation through an extensive set of reciprocal connections with widespread areas of the neocortex. Long-term potentiation (LTP) has been well-examined in the intrinsic connections of the hippocampus and neocortex. However, LTP in the pathways and structures thought to convey information between the hippocampus and neocortex has received little attention. If these pathways and structures are involved in information storage, and if LTP reflects a general synaptic encoding mechanism, then these systems are also likely to support LTP. In this paper we discuss a series of experiments aimed at investigating LTP in the efferents between the hippocampus and neocortex in chronically implanted animals. In the first experiment, the efferents of the perirhinal cortex were stimulated. LTP in the dentate gyrus (DG) reached asymptote more slowly than is typically seen following perforant path stimulation, whereas the frontal area (M1) reached asymptote more quickly than reported following corticocortical stimulation. The DG and M1 LTP was long-lasting, but entorhinal cortex LTP had decayed to baseline levels after a week. In the second experiment, the hippocampal efferents were stimulated. The perirhinal, entorhinal, and frontal cortex showed a similar slow potentiation, with only the perirhinal cortex levels returning to baseline after a week. In the third experiment, the projections from M1 were tested. The perirhinal cortex and hippocampus showed a long-lasting LTP. Although LTP was found in all pathways examined, there were differences in the induction and decay rate, and these properties may correspond to differences in learning rate and longevity of information storage.


Trends in frequency and duration of tobacco habit in relation to potentially malignant lesion: A 3 years retrospective study.
Oral cancer is one of the most debilitating and disfiguring of all malignancies; it is one of the most frequently occurring cancers in the body. The high incidence of oral cancer in India has been attributed to widespread tobacco usage among the population either in chewable or smoked form. In the current study, we retrospectively analyzed 191 cases (2007-2009) of potentially malignant oral lesions, which had been biopsied in our hospital, in order to assess their relationship with tobacco usage. Based on the histopathology, these lesions were classified as high-risk lesions (HRL), low-risk lesions, and questionable risk lesions. The data obtained were then analyzed to find out the correlation between the occurrence of risk level with various demographic parameters such as age and gender as well as with type, frequency, and duration of tobacco habit. Out of 191 cases, 122 patients reported with tobacco habit (chewers, smokers, and both) and frequency (<5 and >5 packets/day) were seen in 109 cases and duration (<5 and >5 years) seen in 99 cases. These parameters were correlated with histopathological diagnosis and results showed that both the groups came under the high-risk category. Further analysis of decategorized group (age and gender) was also done. Analysis showed that overall histopathologically diagnosed HRLs were seen more in males and smokers compared to female and chewers, respectively.


Bovine leukaemia-virus infection in Costa Rica.
The geographical distribution of bovine leukaemia-virus (BLV)-infected herds in Costa Rica and the isolation of BLV from cases of enzootic bovine leukosis are presented. It was found that BLV is prevalent throughout the country, affecting mostly dairy cattle (Bos taurus) located in the highlands around the central valley of Costa Rica. By contrast, beef cattle (Bos indicus) raised in the lowlands were affected to a lesser extent. One out of four isolates of BLV obtained from local cattle with lymphosarcomatous tumours was analysed and had similar physical, serological and biological characteristics to a reference strain of BLV isolated in the USA. However, different patterns of recognition of BLV-protein p24 were observed among naturally infected cattle using the western-blotting technique.


Ablation therapy of non-colorectal cancer lung metastases: retrospective analysis of tumour response post-laser-induced interstitial thermotherapy (LITT), radiofrequency ablation (RFA) and microwave ablation (MWA).
To retrospectively compare the local tumour response and survival rates in patients with non-colorectal cancer lung metastases post-ablation therapy using laser-induced thermotherapy (LITT), radiofrequency ablation (RFA) and microwave ablation (MWA). Retrospective analysis of 175 computed tomography (CT)-guided ablation sessions performed on 109 patients (43 males and 66 females, mean age: 56.6 years). Seventeen patients with 22 lesions underwent LITT treatment (tumour size: 1.2-4.8 cm), 29 patients with 49 lesions underwent RFA (tumour size: 0.8-4.5 cm) and 63 patients with 104 lesions underwent MWA treatment (tumour size: 0.6-5 cm). CT scans were performed 24-h post-therapy and on follow-up at 3, 6, 12, 18 and 24 months. The overall-survival rates at 1-, 2-, 3- and 4-year were 93.8, 56.3, 50.0 and 31.3% for patients treated with LITT; 81.5, 50.0, 45.5 and 24.2% for patients treated with RFA and 97.6, 79.9, 62.3 and 45.4% for patients treated with MWA, respectively. The mean survival time was 34.14 months for MWA, 34.79 months for RFA and 35.32 months for LITT. In paired comparison, a significant difference could be detected between MWA versus RFA (p = 0.032). The progression-free survival showed a median of 23.49 ± 0.62 months for MWA,19.88 ± 2.17 months for LITT and 16.66 ± 0.66 months for RFA (p = 0.048). The lowest recurrence rate was detected in lesions ablated with MWA (7.7%; 8 of 104 lesions) followed by RFA (20.4%; 10 of 49 lesions) and LITT (27.3%; 6 of 22 lesions) p value of 0.012. Pneumothorax was detected in 22.16% of MWA ablations, 22.73% of LITT ablations and 14.23% of RFA ablations. LITT, RFA and MWA may provide an effective therapeutic option for non-colorectal cancer lung metastases with an advantage for MWA regarding local tumour control and progression-free survival rate.


Combined Graph/Relational Database Management System for Calculated Chemical Reaction Pathway Data.
Presently, quantum chemical calculations are widely used to generate extensive data sets for machine learning applications; however, generally, these sets only include information on equilibrium structures and some close conformers. Exploration of potential energy surfaces provides important information on ground and transition states, but analysis of such data is complicated due to the number of possible reaction pathways. Here, we present RePathDB, a database system for managing 3D structural data for both ground and transition states resulting from quantum chemical calculations. Our tool allows one to store, assemble, and analyze reaction pathway data. It combines relational database CGR DB for handling compounds and reactions as molecular graphs with a graph database architecture for pathway analysis by graph algorithms. Original condensed graph of reaction technology is used to store any chemical reaction as a single graph.


Biology of diesel exhaust effects on respiratory function.
In recent decades, clinicians and scientists have witnessed a significant increase in the prevalence of allergic rhinitis and asthma. The factors underlying this phenomenon are clearly complex; however, this rapid increase in the burden of atopic disease has undeniably occurred in parallel with rapid industrialization and urbanization in many parts of the world. Consequently, more people are exposed to air pollutants than at any point in human history. Worldwide, increases in allergic respiratory disease have mainly been observed in urban communities. Epidemiologic and clinical investigations have suggested a strong link between particulate air pollution and detrimental health effects, including cardiopulmonary morbidity and mortality. The purpose of this review is to provide an evidence-based summary of the health effects of air pollutants on asthma, focusing on diesel exhaust particles (DEPs) as a model particulate air pollutant. An overview of observational and experimental studies linking DEPs and asthma will be provided, followed by consideration of the mechanisms underlying DEP-induced inflammation and a brief discussion of future research and clinical directions.


Lower rate of mpox vaccination hesitancy and medical consultation among Chinese men who have sex with men living with HIV in comparison with those living without HIV: A national observational study.
This anonymous cross-sectional study aimed to investigate the relationships between HIV infection and mpox-related focus issues among Chinese men who have sex with men (MSM). This study involved in 27 MSM social organizations and was conducted from July 31 to August 4, 2023. Mpox vaccination hesitancy was defined as the proportion of participants who expressed unwillingness to receive self-funded and free vaccines. Logistic regression models were employed to estimate odds ratios (OR) and 95% confidence interval (95%CI). Of 7196 MSMs, the prevalence of mpox differed between people living with HIV (PLWH) (1.04%, 20/1920) and people living without HIV (PLWoH) (0.55%, 29/5276) (P = .037). However, after adjusting for all covariates, there was no significant association between HIV status and mpox (aOR = 1.17; 95%CI = 0.58, 2.39; P = .658). Furthermore, the crude rates of vaccination hesitation (PLWoH: 5.91%, PLWH: 4.11%; P = .004) and consultation hesitation (PLWoH: 16.22%, PLWH: 10.78%; P < .001) were both lower in the PLWH. Compared with PLWoH, PLWH had lower odds ratios of vaccination hesitation (aOR = 0.70; 95%CI = 0.53, 0.92; P = .011) and consultation hesitation (aOR = 0.74; 95%CI = 0.60, 0.90; P = .003) among MSM. The estimate of association between HIV status and consultation hesitation was even smaller among MSM who reported hepatitis C infection or uncertainty (aOR = 0.30; 95%CI = 0.15, 0.56), compared with those without hepatitis C (aOR = 0.73; 95%CI = 0.60, 0.89) (P for interaction = .037). MSM living with HIV in China demonstrated a greater willingness to accept mpox vaccination and medical consultation. In the future, it is recommended that medical institutions establish good medical environment to control the mpox epidemic, especially for PLWH.


Amino acid transport by the filamentous fungus Arthrobotrys conoides.
Uptake of l-valine by germinated spores of Arthrobotrys conoides has all the characteristics of a system of transport that requires an expenditure of energy by the cells. It is dependent on temperature and has an energy of activation of 16,000 cal/mole. Uptake is optimal at pH 5 to 6. l-Valine accumulated against a concentration gradient and is not lost from the cells by leakage or exchange. The process requires energy supplied by the metabolic reactions that are inhibited by catalytic amounts of 2,4-dinitrophenol and azide. The kinetics of the system are consistent with a mechanism of transport that depends on a limited number of sites on the cell surface, and the Michaelis constant for the system is 1.5 x 10(-5) to 7.5 x 10(-5)m. Modification of the amino or carboxyl group abolishes l-valine uptake. The process is competitively inhibited by d-valine, glycine, and other neutral amino acids (K(i) = 1.5 x 10(-5) to 4.0 x 10(-5)m), indicating a lack of stereospecificity, and also indicating that aliphatic side chain is not required for binding with the carrier. The transport system has less affinity for acidic amino acids (glutamic and aspartic acids) than neutral amino acids, and a greater affinity for basic amino acids (histidine, lysine, and arginine). The range of affinity is in the order of 100, as measured in terms of K(i) values for various compounds. The data presented provide suggestive evidence that the uptake by A. conoides of all amino acids except proline is mediated by a single carrier system that possesses an overall negative charge.


Nonadiabatic dynamics of uracil: population split among different decay mechanisms.
Nonadiabatic dynamics simulations performed at the state-averaged CASSCF method are reported for uracil. Supporting calculations on stationary points and minima on the crossing seams have been performed at the MR-CISD and CASPT2 levels. The dominant mechanism is characterized by relaxation into the S(2) minimum of ππ* character followed by the relaxation to the S(1) minimum of nπ* character. This mechanism contributes to the slower relaxation with a decay constant larger than 1.5 ps, in good agreement with the long time constants experimentally observed. A minor fraction of trajectories decay to the ground state with a time constant of about 0.7 ps, which should be compared to the experimentally observed short constant. The major part of trajectories decaying with this time constant follows the ππ* channel and hops to the ground state via an ethylenic conical intersection. A contribution of the relaxation proceeding via a ring-opening conical intersection was also observed. The existence of these two latter channels together with a reduced long time constant is responsible for a significantly shorter lifetime of uracil compared to that of thymine.


Sexually dimorphic responses to neonatal basal forebrain lesions in mice: II. Cortical morphology.
Previous studies in the mouse have shown that neonatal lesions to the cholinergic basal forebrain (nBM) areas result in transient cholinergic depletion of neocortex and precipitate altered cortical morphogenesis. Lesion-induced morphological alterations in cortex persist into adulthood and are accompanied by behavioral changes, including spatial memory deficits. The current study investigated whether neonatal nBM lesions affect male and female mice differently in adulthood. Quantitative morphometry of cortical layer width was employed to assess alterations in cytoarchitecture in neonatally nBM-lesioned and littermate control mice of both sexes following behavioral testing. Our results showed significant decreases in cortical layer IV and V widths across somato/motor cortex in neonatally nBM lesioned mice of both sexes. Sexually dimorphic responses were observed in cortical layer II/III and total cortical width, limited to the area containing the "barrel cortex" representation of the whisker hairs. In lesioned females, layer II/III and total cortical width were decreased relative to female controls, and in lesioned males, layer II/III was increased relative to controls, whereas total cortical width was unchanged. In male but not female mice we observed significant correlations between decreased widths in layer IV and V and impaired performance on a spatial memory task. The current data further support a role of developing cholinergic cortical afferents in the modulation of cortical morphogenesis and cortical circuits involved in cognitive behaviors. In addition, our observations provide further evidence for sexually dimorphic development and function in cognitive centers of the rodent brain.


Mitotic quiescence in hepatic cancer stem cells: An incognito mode.
Hepatocellular carcinoma represents one of the most aggressive cancers with high recurrence rates. The high recurrence is a major problem in the management of this disease. Cancer stem cells (CSCs) are often regarded as the basis of cancer recurrence. The anti-proliferative therapy kills the proliferating cells but induces mitotic quiescence in CSCs which remain as residual dormant CSCs. Later on, withdrawal of treatment reactivates the residual CSCs from dormancy to produce new cancer cells. The proliferation of these newly formed cancer cells initiates new tumor formation in the liver leading to tumor recurrence. HCC cells evade the immune surveillance via modulating the key immune cells by alpha feto-protein (AFP) secreted from CSCs or hepatic progenitor cells. This AFP mediated immune evasion assists in establishing new tumors by cancer cells in the liver. In this review, we will summarise the CSC mechanisms of recurrence, mitotic quiescence, dormancy and reactivation of CSCs, metastasis and immune evasion of hepatocellular carcinoma.


Fluorescein angiography of the choroid in health and disease.
Fluorescein angiography of the normal fundus reveals the segmental nature of the choroidal vascular bed. Despite the presence of anatomically demonstrable anastomoses, a segmental distribution is present in vivo up to the choriocapillaris level. Choroidal vascular diseases manifest by localized of diffuse delayed or incomplete filling of the choroid and by the involvement of the overlying retinal pigment epithelium. In the acute phase of choroidal arterial occlusive disease, ophthalmoscopy reveals localized or diffuse edema. Fluorescein angiography of such cases initially shows a delayed perfusion of the involved area followed later on by fluorescein leakage. This late diffusion of the dye is probably related to alterations of the retinal pigment epithelial barrier. The extent of the lesion after resolution of the edema mainly depends on the site and the extent of the occlusion, on the development of collaterals and possibly on the involvement of the choroidal venous circulation. Ophthalmoscopy and fluorescein angiography will reveal localized or diffuse pigmentary changes, sometimes of quite characteristic aspect. This may be associated with local destruction of the choriocapillaris, although normalization of choroidal blood flow may also be observed. Chronic choroidal vascular insufficiency is a possible cause for choroidal sclerosis. Chronic choroidal ischemia is also a possible explanation for peripheral pigmentary changes seen in the elderly.


Plasma neutralization properties of the SARS-CoV-2 Omicron variant.
The Omicron SARS-CoV-2 variant has spread internationally and is responsible for rapidly increasing case numbers. The emergence of divergent variants in the context of a heterogeneous and evolving neutralizing antibody response in host populations might compromise protection afforded by vaccines or prior infection. We measured neutralizing antibody titers in 169 longitudinally collected plasma samples using pseudotypes bearing the Wuhan-hu-1 or the Omicron variant or a laboratory-designed neutralization-resistant SARS-CoV-2 spike (PMS20). Plasmas were obtained from convalescents who did or did not subsequently receive an mRNA vaccine, or naive individuals who received 3-doses of mRNA or 1-dose Ad26 vaccines. Samples were collected approximately 1, 5-6 and 12 months after initial vaccination or infection. Like PMS20, the Omicron spike protein was substantially resistant to neutralization compared to Wuhan-hu-1. In convalescent plasma the median deficit in neutralizing activity against PMS20 or Omicron was 30- to 60-fold. Plasmas from recipients of 2 mRNA vaccine doses were 30- to 180- fold less potent against PMS20 and Omicron than Wuhan-hu-1. Notably, previously infected or two-mRNA dose vaccinated individuals who received additional mRNA vaccine dose(s) had 38 to 154-fold and 35 to 214-fold increases in neutralizing activity against Omicron and PMS20 respectively. Omicron exhibits similar distribution of sequence changes and neutralization resistance as does a laboratory-designed neutralization-resistant spike protein, suggesting natural evolutionary pressure to evade the human antibody response. Currently available mRNA vaccine boosters, that may promote antibody affinity maturation, significantly ameliorate SARS-CoV-2 neutralizing antibody titers.


Connexin diversity and gap junction regulation by pHi.
The molecular mechanisms controlling pH-sensitivity of gap junctions formed of two different connexins are yet to be determined. We used a proton-sensitive fluorophore and electrophysiological techniques to correlate changes in intracellular pH (pHi) with electrical coupling between connexin-expressing Xenopus oocytes. The pH sensitivities of alpha 3 (connexin46), alpha 2 (connexin38), and alpha 1 (connexin43) were studied when these proteins were expressed as: 1) nonjunctional hemichannels (for alpha 3 and alpha 2), 2) homotypic gap junctions, and 3) heterotypic gap junctions. We found that alpha 3 hemichannels are sensitive to changes in pHi within a physiological range (pKa = 7.13 +/- 0.03; Hill coefficient = 3.25 +/- 1.73; n = 8; mean +/- SEM); an even more alkaline pKa was obtained for alpha 2 hemichannels (pKa = 7.50 +/- 0.03; Hill coefficient = 3.22 +/- 0.66; n = 13). The pH sensitivity curves of alpha 2 and alpha 3 homotypic junctions were indistinguishable from those recorded from hemichannels of the same connexin. Based on a comparison of pKa values, both alpha 3 and alpha 2 gap junctions were more pHi-dependent than alpha 1. The pH sensitivity of alpha 2-containing heterotypic junctions could not be predicted from the behavior of the two connexons in the pair. When alpha 2 was paired with alpha 3, the pH sensitivity curve was similar to that obtained from alpha 2 homotypic pairs. Yet, pairing alpha 2 with alpha 1 shifted the curve similar to homotypic alpha 1 channels. Pairing alpha 2 with a less pH sensitive mutant of alpha 1 (M257) yielded the same curve as when alpha 1 was used. However, the pH sensitivity curve of alpha 3/alpha 1 channels was similar to alpha 3/alpha 3, while alpha 3/M257 was indistinguishable from alpha 3/alpha 1. Our results could not be consistently predicted by a probabilistic model of two independent gates in series. The data show that dissimilarities in the pH regulation of gap junctions are due to differences in the primary sequence of connexins. Moreover, we found that pH regulation is an intrinsic property of the hemichannels, but pH sensitivity is modified by the interactions between connexons. These interactions should provide a higher level of functional diversity to gap junctions that are formed by more than one connexin.


The Use of Soy Isoflavones in the Treatment of Prostate Cancer: A Focus on the Cellular Effects.
A possible link between diet and cancer has long been considered, with growing interest in phytochemicals. Soy isoflavones have been associated with a reduced risk of prostate cancer in Asian populations. Of the soy isoflavones, genistein and daidzein, in particular, have been studied, but recently, equol as a derivative has gained interest because it is more biologically potent. Different mechanisms of action have already been studied for the different isoflavones in multiple conditions, such as breast, gastrointestinal, and urogenital cancers. Many of these mechanisms of action could also be demonstrated in the prostate, both in vitro and in vivo. This review focuses on the known mechanisms of action at the cellular level and compares them between genistein, daidzein, and equol. These include androgen- and estrogen-mediated pathways, regulation of the cell cycle and cell proliferation, apoptosis, angiogenesis, and metastasis. In addition, antioxidant and anti-inflammatory effects and epigenetics are addressed.


Contrast Staining may be Associated with Intracerebral Hemorrhage but Not Functional Outcome in Acute Ischemic Stroke Patients Treated with Endovascular Thrombectomy.
To evaluate the incidence of post-interventional contrast staining (PICS) in acute ischemic stroke (AIS) Chinese patients who were treated with endovascular thrombectomy (ET) and investigate potential association of PICS with functional outcome and intracerebral hemorrhage (ICH). This observational study was based on a single-center prospective registry study. AIS patients who underwent ET from January 2013 to February 2017 were recruited into this study. All patients had dual-energy CT (DECT) scan of the head at 12 to 24 hours post-ET. The primary outcome was the incidence of PICS. Secondary outcomes were total ICH, symptomatic ICH (sICH), 3-month functional outcome, and long-term functional outcome. One hundred and eighty patients were enrolled in this study. PICS was detected in 50 patients (28%) based on the post-interventional CT scan. We first used basic statistical analyses, showing that the incidence of both total ICH (60% vs. 25%, p<0.001) and sICH (18% vs. 8%, p=0.044) were higher in patients with PICS than those without, and fewer patients achieved no disability (mRS≤1) in the PICS group compared to the control group at both 3-month and long-term follow-up (p<0.01 each). However, multivariate regression analysis further revealed that PICS only increased total (adjusted odds ratio, 7.38; 95% confidence interval 1.66 to 32.9; p=0.009) but not sICH risk. Furthermore, the logistic regression analyses did not show statistical difference in good clinical outcomes or mortality between the two groups. PICS is a common phenomenon in Chinese AIS patients. It is associated with total ICH after ET, but it seems to have no effect on functional outcome and sICH. Further large-scale studies are warranted to validate these results.


Transport of H(+), Na(+) and K(+) across the posterior midgut of blood-fed mosquitoes (Aedes aegypti).
Following ingestion of a blood meal, the adult female mosquito undergoes a massive diuresis during which Na(+), Cl(-) and water are secreted at high rates by the Malpighian tubules. In the hours following completion of diuresis, digestion of the K(+)-rich blood cells provides a source of energy as well as amino acids for proteins in the developing eggs. Although the transport of inorganic ions by the Malpighian tubules of blood-fed mosquitoes has been extensively characterized, relatively little is known of the epithelial transport mechanisms responsible for movement of Na(+), H(+), and K(+) across the posterior midgut. In this paper we have used the Scanning Ion-selective Electrode Technique (SIET) to measure the basal (unstimulated) rates of transport of K(+), Na(+) and H(+) across the isolated posterior midgut at intervals after the blood meal. We have also measured luminal concentrations of Na(+) and K(+) and the transepithelial electrical potential at the same time points and have calculated the electrochemical potentials for Na(+), K(+) and H(+) across the midgut. SIET measurements reveal absorption (lumen to bath) of Na(+) and H(+) and secretion of K(+) for the first 2h after blood-feeding. By 24h after the meal, absorption of Na(+) and H(+) remains active while there is an electrochemical gradient favouring absorption of K(+). Inhibition by ouabain and Ba(2+) suggest a role for the Na(+)/K(+)-ATPase and K(+) channels in absorption of Na(+) and K(+), respectively. Inhibition of H(+) absorption by acetazolamide implicates carbonic anhydrase in transepithelial H(+) transport.


Recognition of a Nocardia transvalensis complex by resistance to aminoglycosides, including amikacin, and PCR-restriction fragment length polymorphism analysis.
Amikacin resistance, rare among nocardiae, was observed in 58 clinical isolates of nocardiae. All of these isolates hydrolyzed hypoxanthine, and 75 to 100% utilized citrate, D-galactose, and D-trehalose as sole carbon sources. Based on utilization of I-erythritol, D-glucitol, i-myo-inositol, D-mannitol, and ribitol and susceptibility to amoxicillin-clavulanic acid, the 58 isolates were separable into four groups. One group was negative for I-erythritol and ribitol and included all the isolates belonging to Nocardia asteroides complex antibiogram type IV. The remaining three groups were positive for I-erythritol and ribitol and were grouped within Nocardia transvalensis. The group that included the type strain was designated N. transvalensis sensu stricto, and the other two groups were designated new taxons 1 and 2. PCR-restriction fragment length polymorphism (RFLP) analysis of a 439-bp segment of the 65-kDa heat shock protein gene with XhoI and HinfI produced identical patterns for 53 (91%) and 58 (100%) isolates, respectively, and differentiated them from all other Nocardia taxa. NarI- and HaeIII-derived RFLP patterns clearly differentiated each of the four biochemically defined taxa. These four groups were also distinguishable by using the chromogenic substrates in Dade MicroScan test panels. By high-performance liquid chromatography, these isolates exhibited the same unique mycolic acid-ester elution patterns that differed from those of all other clinically significant nocardiae. Gas-liquid chromatographic analysis of fatty acids also produced similar patterns for all isolates that distinguished them from all other Nocardia taxa, but did not differentiate the four taxa within the complex. We propose the designation N. transvalensis complex for these four groups of nocardiae, pending further genetic evaluation.


[Evolution of breast cancer. A 5-year clinical experience at a city hospital].
In order to clarify the role that some epidemiologic factor might have on the clinical evolution of breast cancer, a retrospective study was conducted. Seventy six women diagnosed with breast cancer were selected from the population of the Hospital de Ginecobstetricia 3 del Centro Medico Nacional "La Raza" del Instituto Mexicano del Seguro Social, from 1985 to 1990. Age, medical and family history, clinical onset, diagnosis, treatment, evolution and clinical status at present were analyzed. Survival analysis and Pearson's correlation were carried out. Thirty one percent of the women were 41 to 50 years old, and thirty percent had family history of breast cancer. Other systemic condition was present in 42% of the patients and multiparity in 12%. The mean age of menopause onset was 47 +/- years. Eighty-three percent of the patients looked for medical attention due to a mammary tumor mainly in the left breast (75% of the cases). Fifty-one percent of the cases were diagnosed in advanced stages. The commonest histologic variety found was the invasive ductal carcinoma (94%). Sixty six patients underwent surgical therapy. Sixteen percent of the sample had already metastases when diagnosed; mainly at lung, bone liver or brain, in that order. Systemic therapy was administered in 63% of the cases and radiotherapy in 22 patients. About 48% of the whole sample presented recurrency and 24% progression. The overall survival at five years was 82%. Sixteen percent of these patients had tumor activity clinically apparent. In general, mortality was present in advanced stages. Survival analysis demonstrated that age and tumor persistency directly influenced survival rate in this population. Other variables' role could not be evaluated. Nevertheless variables analyzed are very helpful in actions implementation to the breast cancer management.


One-year clinical outcomes of the STENTYS Self-Apposing¨ coronary stent in patients presenting with ST-segment elevation myocardial infarction: results from the APPOSITION III registry.
The aim of APPOSITION III was to evaluate the feasibility and performance of the STENTYS Self-Apposing¨ stent (STENTYS S.A., Paris, France) in the setting of primary percutaneous coronary intervention (PCI). APPOSITION III was an international, prospective, multicentre registry. The study population consisted of 965 patients. The rate of the primary endpoint major adverse cardiac events (MACE), defined as the composite of cardiac death, recurrent target vessel myocardial infarction (TV-MI), and clinically driven target lesion revascularisation (CD-TLR), at one year was 9.3%. One-year cardiac death rate was 2.0%, TV-MI rate was 1.3%, CD-TLR rate was 7.4% and definite/probable stent thrombosis (ST) rate was 3.5% (definite ST 2.8%). An interim safety analysis of in-hospital outcomes in the first 400 patients showed higher event rates if post-dilation was not performed, and post-dilations became highly recommended in the remaining cohort. Patients undergoing post-dilation eventually showed a numerically lower one-year MACE rate (8.4% vs. 11.3%, p=0.137). One-year TV-MI (0.8% vs. 2.5%, p=0.027) and definite ST (1.9% vs. 5.0%, p=0.010) rates were significantly lower if post-dilation was performed, with the divergence occurring at <30 days. The use of the STENTYS Self-Apposing¨ stent in the setting of primary PCI was feasible and associated with acceptable cardiovascular event rates which improved when post-dilation was performed.


mRNA export and the TREX complex.
Over the past few decades, we have learned that eukaryotes have evolved sophisticated means to coordinate the nuclear export of mRNAs with different steps of gene expression. This functional orchestration is important for the maintenance of the efficiency and fidelity of gene expression processes. The TREX (TRanscription-EXport) complex is an evolutionarily conserved multiprotein complex that plays a major role in the functional coupling of different steps during mRNA biogenesis, including mRNA transcription, processing, decay, and nuclear export. Furthermore, recent gene knockout studies in mice have revealed that the metazoan TREX complex is required for cell differentiation and development, likely because this complex regulates the expression of key genes. These newly identified roles for the TREX complex suggest the existence of a relationship between mRNA nuclear biogenesis and more complex cellular processes. This review describes the functional roles of the TREX complex in gene expression and the nuclear export of mRNAs. This article is part of a Special Issue entitled: Nuclear Transport and RNA Processing.


Variable TERRA abundance and stability in cervical cancer cells.
Telomeres are transcribed into long non-coding RNA, referred to as telomeric repeat-containing RNA (TERRA), which plays important roles in maintaining telomere integrity and heterochromatin formation. TERRA has been well characterized in HeLa cells, a type of cervical cancer cell. However, TERRA abundance and stability have not been examined in other cervical cancer cells, at least to the best of our knowledge. Thus, in this study, we measured TERRA levels and stability, as well as telomere length in 6 cervical cancer cell lines, HeLa, SiHa, CaSki, HeLa S3, C-33A and SNU-17. We also examined the association between the TERRA level and its stability and telomere length. We found that the TERRA level was several fold greater in the SiHa, CaSki, HeLa S3, C-33A and SNU-17 cells, than in the HeLa cells. An RNA stability assay of actinomycin D-treated cells revealed that TERRA had a short half-life of ~4 h in HeLa cells, which was consistent with previous studies, but was more stable with a longer half-life (>8 h) in the other 5 cell lines. Telomere length varied from 4 to 9 kb in the cells and did not correlate significantly with the TERRA level. On the whole, our data indicate that TERRA abundance and stability vary between different types of cervical cancer cells. TERRA degrades rapidly in HeLa cells, but is maintained stably in other cervical cancer cells that accumulate higher levels of TERRA. TERRA abundance is associated with the stability of RNA in cervical cancer cells, but is unlikely associated with telomere length.


What influences people's responses to public health messages for managing risks and preventing infectious diseases? A rapid systematic review of the evidence and recommendations.
Individual behaviour changes, such as hand hygiene and physical distancing, are required on a population scale to reduce transmission of infectious diseases such as COVID-19. However, little is known about effective methods of communicating risk reducing information, and how populations might respond. To synthesise evidence relating to what (1) characterises effective public health messages for managing risk and preventing infectious disease and (2) influences people's responses to messages. A rapid systematic review was conducted. Protocol is published on Prospero CRD42020188704. Electronic databases were searched: Ovid Medline, Ovid PsycINFO and Healthevidence.org, and grey literature (PsyarXiv, OSF Preprints) up to May 2020. All study designs that (1) evaluated public health messaging interventions targeted at adults and (2) concerned a communicable disease spread via primary route of transmission of respiratory and/or touch were included. Outcomes included preventative behaviours, perceptions/awareness and intentions. Non-English language papers were excluded. Due to high heterogeneity studies were synthesised narratively focusing on determinants of intentions in the absence of measured adherence/preventative behaviours. Themes were developed independently by two researchers and discussed within team to reach consensus. Recommendations were translated from narrative synthesis to provide evidence-based methods in providing effective messaging. Sixty-eight eligible papers were identified. Characteristics of effective messaging include delivery by credible sources, community engagement, increasing awareness/knowledge, mapping to stage of epidemic/pandemic. To influence intent effectively, public health messages need to be acceptable, increase understanding/perceptions of health threat and perceived susceptibility. There are four key recommendations: (1) engage communities in development of messaging, (2) address uncertainty immediately and with transparency, (3) focus on unifying messages from sources and (4) frame messages aimed at increasing understanding, social responsibility and personal control. Embedding principles of behavioural science into public health messaging is an important step towards more effective health-risk communication during epidemics/pandemics.


Stage T3 prostate cancer: a nonrandomized comparison between definitive irradiation and induction hormonal manipulation plus prostatectomy.
At our institution, a Phase II trial using androgen suppression followed by surgery was completed for men with Stage T3 disease and negative laparoscopic nodal dissection. We recently reported the unfavorable biochemical outcome of that experience. Because that analysis did not include a control group of irradiated patients, the current project was undertaken to compare that Phase II experience with clinical Stage T3 patients treated at our institution with definitive irradiation during an overlapping period of time. The Phase II trial included 21 patients with T3 tumors and negative laparoscopic nodal dissections treated by 4 months of neoadjuvant hormonal treatment (leuprolide +/- flutamide) prior to radical prostatectomy. Patients who declined to participate in the study or those judged ineligible by virtue of poor surgical risk were treated with definitive irradiation (n = 29). Although the radiation portals were shaped with multileaf collimation, no attempt was made to design "conformal fields." The median dose was 68 Gy (range 66 to 72) delivered in conventional fractionation. Biochemical failure after prostatectomy was defined as prostate-specific antigen (PSA) levels exceeding 0.2 ng/mL. Biochemical failure after irradiation was defined as a rise in absolute level of PSA greater than 1.5 ng/mL, or two consecutive elevations of PSA on sequential measurements, even if the absolute level was less than 1.5 ng/mL. In univariate comparison, the freedom from biochemical relapse rate at 3 years was 41% for irradiated patients and 23% for those treated by hormones combined with surgery (P <0.05). In a multivariate regression model controlling for the prognostic factors of baseline PSA, age, clinical substage, Gleason score, and treatment modality (induction androgen suppression + prostatectomy versus radiotherapy), only low baseline PSA independently predicted improved freedom from biochemical recurrence (P = 0.04). The combination of induction hormonal treatment followed by radical prostatectomy offered no advantage over irradiation alone in this single institutional experience. Notwithstanding, the majority of men treated by definitive radiotherapy manifested biochemical failure. More innovative strategies such as conformal irradiation (either alone or combined with androgen ablation) and radiation dose escalation should be pursued to optimize outcome for this unfavorable group of patients.


Sentinel lymph node biopsy in head and neck cancer.
In the past decade, the technique of sentinel lymph node biopsy (SLNB) has been applied to a vast array of primary neoplasms, ranging from head and neck melanoma to vulvar carcinoma. At present, experience with SLNB is greatest in patients with melanoma and breast cancer. In view of the well known complications associated with cervical node dissection, it has been suspected for some time that cervical SLNB, if successful, might reduce the morbidity associated with the definitive care of patients with head and neck cancers. This report assesses the current status of SLNB in the treatment of head and neck cancers; while formal investigations of the efficacy of this technique are recommended, SLNB has not yet been demonstrated to possess the same level of utility seen in SLNB in melanoma and breast cancer patients. As a consequence, the application of SLNB to head and neck cancers remains an experimental technique--one which has not yet acquired the status of the standard of patient care.


Bioethanol production from raffinate phase of supercritical CO2 extracted Stevia rebaudiana leaves.
The extracts of Stevia rebaudiana are marketed as dietary supplements and utilized as natural sweetening agent in food products. Subsequent to extraction on industrial scale, large quantities of solid wastes are produced. The aim of this study was to investigate the bioconversion efficiency of supercritical CO(2) extracted S. rebaudiana residues. Therefore, leaves were extracted with supercritical CO(2) and ethanol mixture in order to obtain glycosides, then the raffinate phase was hydrolyzed by both dilute acid and various concentrations of cellulase and β-glucosidase cocktail. The maximum yield of reducing sugars reached 25.67 g/L under the optimal conditions of enzyme pretreatment, whereas 32.00 g/L was reached by consecutive enzymatic and acid hydrolyses. Bioethanol yield (20 g/L, 2.0% inoculum, 2 days) based on the sugar consumed was 45.55% corresponding to a productivity of 0.19 kg/m(3)h which demonstrates challenges to be utilized as a potential feedstock for the production of bioethanol.


Avascular necrosis of the femoral head following intramedullary nailing of the femur in a skeletally mature young adult: a case report.
Avascular necrosis (AVN) of the femoral head is a well-documented complication of intramedullary nailing (IMN) of femoral shaft fractures in adolescents and children (age range, 10 years to 13 years 10 months). In adults, AVN after IMN has been reported in association with femoral neck fractures, intra-articular hip injuries, steroid use, and various other medical conditions. With those factors set aside, the literature includes only 1 case of AVN after IMN in an adult. Now we report the case of a previously healthy, skeletally mature young adult male who, at age 16 years 0 month, was treated with IMN after a traumatic femoral shaft fracture and subsequently developed AVN of the femoral head.


Individual differences among cocaine users.
The present study examined whether individual differences in personality could differentiate two types of cocaine users. We hypothesized that self-medicators (SM) use cocaine as a way to alleviate their dysphoric moods, whereas sensation seekers (SS), in contrast, use cocaine primarily to engender positive mood states. Eighteen male cocaine users were classified based on two dimensions of the Tridimensional Personality Questionnaire. SM were defined by having high harm avoidance (>17) and low novelty-seeking scores (<18), and SS by high novelty-seeking (>18) and low harm-avoidance scores (<17). It was predicted that SM would report higher depression and anxiety than would SS, and would also exhibit a brain activity pattern similar to that found in clinical depression. The results showed that SM reported higher anxiety than SS, F(1, 8) = 27.5, p < .001, but did not differ in depression. SM exhibited decreased blood flow within the left frontal lobes, F(1, 10) = 6.78, p < .05, similar to what has been observed in major depressive disorder. These findings suggest the importance of attending to individual differences in the motivation for cocaine use so that treatment can be targeted more effectively.


Physiologic Effects of High-Flow Nasal Cannula in Healthy Subjects.
High-flow nasal cannula (HFNC) is increasingly used in the management of acute and chronic respiratory failure. Little is known about the optimal settings for HFNC. This study was designed to assess the dose effect of HFNC on respiratory effort indexes and respiratory patterns in spontaneously breathing adults. A randomized controlled crossover study was conducted in 10 healthy subjects. Five experimental conditions were evaluated: baseline with no therapy; 5 L/min with conventional nasal prongs; and HFNC at 20, 40, and 60 L/min. The primary outcomes were the indexes of respiratory effort (ie, esophageal pressure swing [ΔPes], esophageal pressure-time product, and work of breathing). Secondary outcomes included breathing pattern parameters and blood gases. Dead-space ventilation and washout were calculated based on minute ventilation, breathing frequency, and Radford equations. ΔPes increased from median (interquartile range [IQR] 3.2 (2.2-3.6) cm H2O at baseline to median (IQR) 5.7 (4.6-6.8) cm H2O at 60 L/min (P < .001). Neither esophageal pressure-time product nor work of breathing were modified during the tested conditions. The minute volume was significantly reduced at 40 and 60 L/min compared with baseline (P = .04), mostly driven by an important and dose-dependent reduction in breathing frequency, from median (IQR) 16 (15-18) breaths/min at baseline, to median (IQR) 8 (7-10) breaths/min at 60 L/min (P < .001). Capillary [Formula: see text] was stable in all the tested conditions. The calculated dead-space ventilation was reduced by half with HFNC. HFNC did not significantly modify work of breathing in healthy subjects. However, a significant reduction in the minute volume was achieved, capillary [Formula: see text] remaining constant, which suggests a reduction in dead-space ventilation with flows > 20 L/min. (ClinicalTrials.gov registration NCT02495675).


CASE REPORT OF IRRITABLE BOWEL SYNDROME RESPONDING TO OMALIZUMAB.
Irritable bowel syndrome (IBS) is the most commonly diagnosed gastrointestinal condition manifested by chronic abdominal pain and altered bowel habits in the absence of any organic cause. While 10% - 20% of the population has IBS, only ≈ 25% of patients with IBS seek professional health care. Due to IBS multifactorial etiology, there is no single therapeutic option available with a satisfactory efficacy; therefore, patients frequently express a high level of frustration with their current therapies. We present a case of the 42 year-old woman with IBS, who was administered Omalizumab (a recombinant DNA-derived humanized IgG1 monoclonal antibody which specifically binds to free human immunoglobulin E (IgE) in the blood) doe to concomitant antihistamine resistant chronic spontaneous urticaria and experienced significant improvement in overall IBS symptoms. If our observation will be confirmed in prospective randomized studies, Omalizumab may turn out to be a useful pharmacological tool for this common disorder.


Nicotine enhances acquisition of a T-maze visual discrimination: assessment of individual differences.
In the present report, rats' performance was assessed in five tasks designed to measure behavioral response to different novel stimuli under different experimental situations. Daily nicotine treatment (0, 0.3 or 1.0 mg / kg) began after the conclusion of the behavioral tasks and continued throughout the experiment. Training of a T-maze visual discrimination task commenced after 11 days of nicotine pretreatment. As a group, rats treated with the higher dose of nicotine (1.0 mg / kg) made fewer errors to acquire the initial T-maze discrimination than saline-treated controls. Activity induced by an inescapable novel environment (i.e. first behavioral screen) was positively correlated with the number of errors to acquire the initial discrimination in the T-maze for the two nicotine-treated groups (0.3 and 1.0 mg / kg). To examine this positive correlation further, a median split analysis was conducted on the novelty-induced activity for each group. Nicotine, especially the high dose (1.0 mg / kg), enhanced performance in rats that were less active in the inescapable novel environment. Nicotine treatment did not affect the performance of rats that were more active in that environment. After the initial visual discrimination was acquired, the reverse discrimination was trained. Nicotine treatment did not affect performance; the number of errors to acquire the reversal for nicotine- and saline-treated rats did not differ. Overall a nicotine-induced improvement in performance is demonstrated which can be predicted by a rat's reactivity to environmental novelty.