Lung function and cytokine levels in professional athletes.
Previous studies have demonstrated that exercise-induced asthma and bronchial hyperresponsiveness commonly occur in athletes. The present study investigates pulmonary function and cytokine levels in professional athletes to explore the impact of various sports on respiratory system function and to evaluate the possible role of systemic anaphylaxis. Lung function was measured at rest in professional athletes without a history of smoking. Athletes were recruited from 10 different sports including swimming, water ballet, shooting, volleyball, softball, football, kickboxing, fencing, judo, and track and field. Measurements included forced vital capacity (FVC), forced expiratory volume in one second (FEV(1)), vital capacity (VC), peak expiratory flow (PEF), maximal mid-expiratory flow curve (MMEF), and forced expiratory flow rate (FEF(25-75)%). In addition, the medical history of all athletes was recorded. Correlations between lung function measurements and the different sports, age, gender, height and weight were analyzed. In some athletes, serum was sampled to detect IL-4 and IL-10 concentrations. In these subjects, the correlation between pulmonary function and cytokine levels was analyzed. A total of 147 professional athletes and 30 healthy volunteers were enrolled in the study. Allergic rhinitis and asthma were detected only in swimmers with an incidence of 56.52% (13/23) and 8.70% (2/23), respectively. Lung function measures were significantly correlated with sport, age, gender, height, and weight. Ventilation functions (including FVC, FEV(1), FEV(1)/FVC, and MMV) in male athletes were superior to those in females, and the ventilation functions in swimmers were superior to those in others. However, the small airway functions (MMEF, FEF(50), FEF(75)) in swimmers and in track and field athletes were lower than predicted (swimmers: 72%, 70%, and 78%, respectively; track and field athletes: 79%, 75%, and 99%, respectively). Serum analyses for IL-4 and IL-10 revealed that IL-4 concentrations were higher in swimmers 69.34 +/- 22.4 pg/mL relative to non-swimmers (p = 0.000). By contrast IL-10 concentrations were lower in swimmers 34.94 +/- 9.71 pg/mL than that in the static group (44.69 +/- 16.32 pg/mL; p = 0.027). IL-4 levels were negatively correlated with FEV(1)%, FEF(25)%, FEF(50)%, and MMEF%. By contrast, IL-10 levels were not correlated with any of these measures. The lung function measurements were correlated with sport, age, gender, height, and weight in the various athletes. The lung capacity of swimmers was greater than that of other athletes. Small airway dysfunction was observed in some swimmers and endurance athletes. We observed an association between systemic anaphylaxis and small airway dysfunction after prolonged regular training, particularly following swimming and endurance training.


Surgical management of severe acute lower extremity ischemia.
Seventy-four patients (70 men [95%], 4 women [5%], mean age, 63 years) with severe, acute lower limb ischemia (acute clinical deterioration and absent pedal Doppler signals) caused by either arterial thrombosis (n = 68) or embolism (n = 6) underwent urgent surgical management consisting of operative revascularization with or without amputation in 67 patients (91%) and primary amputation alone in 7 patients (9%). Sixty-one patients (82%) had severely threatened limb viability, and 13 (18%) had major irreversible ischemic limb changes at presentation. Eighty-six percent of patients were initially anticoagulated with heparin. Seventy percent underwent preoperative angiography. Surgical revascularization included 42 inflow and 20 outflow arterial reconstructions and 9 thrombectomy or embolectomy procedures. Mean follow-up was 17 months (range, 0 to 64). Life-table primary patency at 36 months for arterial reconstructions was 81% for inflow and 78% for outflow procedures. Cumulative limb salvage was 70% at 1 month and 68% at 36 months. Patient survival was 85% at 1 month and 51% at 36 months. No death was directly attributable to complications related to limb reperfusion, and no patient required dialysis for myoglobinuria. We conclude that management of severe, acute lower limb ischemia with early amputation of nonviable limbs and heparinization, angiography, and prompt operative revascularization for threatened but viable extremities minimizes morbidity and mortality rates, while maximizing limb salvage. These results may be useful for comparison with comparable groups of patients treated with thrombolytic or endovascular modalities.


Gambling in Young Adults Aged 17-24 Years: A Population-Based Study.
A large contemporary UK cohort study, the Avon Longitudinal Study of Parents and Children, was used to investigate gambling behavior and to explore the antecedents of regular gambling in the 17-24-year age group. Participants completed computer-administered gambling surveys in research clinics, on paper, and online. The sample sizes were 3566 at age 17 years, 3940 at 20 years, and 3841 at 24 years; only 1672 completed all three surveys. Participation in gambling in the last year was reported by 54% of 17-year-olds, rising to 68% at 20 years, and 66% at 24 years, with little overall variance. Regular (weekly) gambling showed a strong gender effect, increasing among young men from 13% at 17 years to 18% at 20 years, and 17% at 24 years. Although gambling frequency increased between the ages of 17 and 20 years, gambling behaviors showed little variance between 20 and 24 years, except online gambling and betting on horseraces. The commonest forms of gambling were playing scratchcards, playing the lottery, and private betting with friends. Gambling on activities via the internet increased markedly between 17 and 24 years, especially among males. In the fully adjusted model, individual antecedents of regular gambling were being male, and having a low IQ, an external locus of control, and high sensation seeking scores. Parental gambling behavior and maternal educational background were associated with regular gambling in both sexes. Regular gambling was associated with smoking cigarettes and frequent and harmful use of alcohol, but no associations with depression were found.


Effects of storage temperature and time on canine plasma ammonia concentrations.
Stability of ammonia in canine plasma was determined, with regard to temperature and time of storage. Heparinized venous blood samples were collected from 8 healthy dogs, immediately placed in an ice water bath, and centrifuged at 5 C. Plasma was harvested from the blood samples, and the initial analysis of each sample for plasma ammonia was performed within 30 minutes after collection. Separate aliquots of the plasma from each dog were stored at 21 C, 4 C, -15 C, or -40 C. Ammonia concentrations of the aliquots stored at the various temperatures were determined at 24, 48, and 96 hours after collection. Statistical analysis of the data from each dog did not indicate a significant relationship between the initial concentration of plasma ammonia and subsequent determinations. Correlation or significance was not found among samples stored at similar temperatures and evaluated at similar times.


A comparative evaluation of tibial component designs of total knee prostheses.
Three-dimensional finite-element stress analyses were used to compare the fixation of tibial component configurations of surface-replacement-type total knee prostheses, bases on the stresses in the cancellous bone, in the polymethylmethacrylate, and at the bone cement-bone interface. The results indicate that, in general, metal components provide lower system stresses than polyethylene components, particularly in the methacrylate and the cancellous bone, and that one-piece designs give lower bone cement-bone interface stresses compared with those with separated condylar components. Of the designs considered, a single-post, metal-backed design provided the lowest system stresses over-all. a great and confusing variety of tibial component design exists today, with more in the process of development. Short of long term clinical trials, there are few objective methods by which these designs can be evaluated and long-term performance predicted. There is evidence from clinical results that excessively high stresses in the systems can lead to loosening of the tibial component. The finite-element method provides a method for comparing prosthetic designs using system stresses a s a design criterion. On this basis, we analyzed the stress distribution for several types of tibial components and discuss the advantages and disadvantages of their designs.


Crystal structure of quinolinic acid phosphoribosyltransferase from Mmycobacterium tuberculosis: a potential TB drug target.
. Mycobacterium tuberculosis is the single most deadly human pathogen and is responsible for nearly three million deaths every year. Recent elucidation of the mode of action of isoniazid, a frontline antimycobacterial drug, suggests that NAD metabolism is extremely critical for this microorganism. M. tuberculosis depends solely on the de novo pathway to meet its NAD demand. Quinolinic acid phosphoribosyltransferase (QAPRTase), a key enzyme in the de novo biosynthesis of NAD, provides an attractive target for designing novel antitubercular drugs. . The X-ray crystal structure of the M. tuberculosis QAPRTase apoenzyme has been determined by multiple isomorphous replacement at 2.4 A resolution. Structures of the enzyme have also been solved in complex with the substrate quinolinic acid (QA), the inhibitory QA analog phthalic acid (PA), the product nicotinate mononucleotide (NAMN), and as a ternary complex with PA and a substrate analog, 5-phosphoribosyl-1-(beta-methylene)pyrophosphate (PRPCP). The structure of the nonproductive QAPRTase-PA-PRPCP Michaelis complex reveals a 5-phosphoribosyl-1-pyrophosphate-binding site that is different from the one observed in type I phosphoribosyltransferases (PRTases). The type II PRTase active site of QAPRTase undergoes conformational changes that appear to be important in determining substrate specificity and eliciting productive catalysis. . QAPRTase is the only known representative of the type II PRTase fold, an unusual alpha/beta barrel, and appears to represent convergent evolution for PRTase catalysis. The active site of type II PRTase bears little resemblance to the better known type I enzymes.


The proneural gene ASCL1 governs the transcriptional subgroup affiliation in glioblastoma stem cells by directly repressing the mesenchymal gene NDRG1.
Achaete-scute homolog 1 gene (ASCL1) is a gene classifier for the proneural (PN) transcriptional subgroup of glioblastoma (GBM) that has a relevant role in the neuronal-like differentiation of GBM cancer stem cells (CSCs) through the activation of a PN gene signature. Besides prototypical ASCL1 PN target genes, the molecular effectors mediating ASCL1 function in regulating GBM differentiation and, most relevantly, subgroup specification are currently unknown. Here we report that ASCL1 not only promotes the acquisition of a PN phenotype in CSCs by inducing a glial-to-neuronal lineage switch but also concomitantly represses mesenchymal (MES) features by directly downregulating the expression of N-Myc downstream-regulated gene 1 (NDRG1), which we propose as a novel gene classifier of MES GBMs. Increasing the expression of ASCL1 in PN CSCs results in suppression of self-renewal, promotion of differentiation and, most significantly, decrease in tumorigenesis, which is also reproduced by NDRG1 silencing. Conversely, both abrogation of ASCL1 expression in PN CSCs and enforcement of NDRG1 expression in either PN or MES CSCs induce proneural-to-mesenchymal transition (PMT) and enhanced mesenchymal features. Surprisingly, ASCL1 overexpression in MES CSCs increases malignant features and gives rise to a neuroendocrine-like secretory phenotype. Altogether, our results propose that the fine interplay between ASCL1 and its target NDRG1 might serve as potential subgroup-specific targetable vulnerability in GBM; enhancing ASCL1 expression in PN GBMs might reduce tumorigenesis, whereas repressing NDRG1 expression might be actionable to hamper the malignancy of GBM belonging to the MES subgroup.


Gigabar spherical shock generation on the OMEGA laser.
This Letter presents the first experimental demonstration of the capability to launch shocks of several-hundred Mbar in spherical targets--a milestone for shock ignition [R. Betti et al., Phys. Rev. Lett. 98, 155001 (2007)]. Using the temporal delay between the launching of the strong shock at the outer surface of the spherical target and the time when the shock converges at the center, the shock-launching pressure can be inferred using radiation-hydrodynamic simulations. Peak ablation pressures exceeding 300 Mbar are inferred at absorbed laser intensities of ∼3×10(15) W/cm2. The shock strength is shown to be significantly enhanced by the coupling of suprathermal electrons with a total converted energy of up to 8% of the incident laser energy. At the end of the laser pulse, the shock pressure is estimated to exceed ∼1 Gbar because of convergence effects.


Identification and Validation of a Potent Multi-miRNA Signature for Prediction of Prognosis of Osteosarcoma Patients.
BACKGROUND Osteosarcoma, the most common solid malignancy, has high incidence and mortality rates. We constructed a miRNA-based signature that can be used to assess the prognosis of osteosarcoma patients. MATERIAL AND METHODS The miRNA profile was derived from the Gene Expression Omnibus (GEO) website, with matched clinical records. The miRNA-based overall survival (OS)-predicting signature was established by LASSO Cox regression analysis. Receiver operating characteristic (ROC) curve and Kaplan-Meier (K-M) analyses were performed to examine the stability and discriminatory ability of the OS-predicting signatures. Pathway enrichment analyses were performed to uncover potential mechanisms. RESULTS Three miRNAs (miR-153, miR-212, and miR-591) independently related to the OS were extracted to build a risk score formula. The ROC curve and K-M analyses revealed good discrimination ability of the OS signature for osteosarcoma patients in both the training cohort (P=0.00015, AUC=0.962) and the validation cohort (P=0.0065, AUC=0.793). As shown in multivariate analysis, the classifier showed favorable predictive accuracy similar to the recurrence status to be an independent risk factor for osteosarcoma. Furthermore, the nomogram showed a synergistic effect by combining the clinicopathological features with our classifier. Also, the enrichment analyses of the target genes may contribute to improved treatment of osteosarcoma. CONCLUSIONS The 3-miRNA-based classifier serves as an effective prognosis-predicting signature for osteosarcoma patients.


Is there a role for growth hormone replacement in adults to control acute and post-acute COVID-19?
The SARS-CoV-2 pandemic created a multitude of medical crossroads requiring real time adaptations of best practice covering preventative and interventional aspects of care. Among the many discoveries borne from efforts to address the myriad clinical presentations across multiple organ systems was a common impact on tissues with cells that express the ACE-2 receptor. The vast majority of acute infections began and often ended in the respiratory tract, but more recent evaluations have confirmed significant extrapulmonary manifestations including symptom clusters that extend beyond the acute phase of infection collectively referred to as "post-acute sequelae SARS-CoV-2 infection" (PASC) or more commonly as "long (-haul) COVID". Both acute SARS-CoV-2 infection and PASC are associated with gut microbiome dysbiosis and alterations in the gut-brain and HPA-axis in a subset of the infected. Mounting evidence suggests these extrapulmonary manifestations may ultimately lead to reduced growth hormone (GH) secretion as demonstrated following stimulation tests. Disrupted GH secretion could cause or exacerbate long lasting neuropsychological symptoms as seen in other similar manifesting conditions. Ongoing clinical research has shown promising improvement in PASC patients with fatigue and cognition complaints can be achieved via GH replacement therapy. GH stimulation testing should be considered in PASC workups and future research should delve deeper into the mechanistic effects of GH on acute COVID and PASC.


Does WeChat use intensity influence Chinese college students' mental health through social use of WeChat, entertainment use of WeChat, and bonding social capital?
Previous research notes that the usage of WeChat is significantly related to individuals' mental health, but the underlying mechanism is still not completely discovered. The present study aimed to explore the sequential mediating roles of WeChat use motivations and bonding social capital on the effects of WeChat use intensity on mental health in Chinese college students. The present study adopted an online survey with a total of 487 Chinese college students. Correlation analysis and serial mediation analysis were measured by process regarding the hypothesis. The study presented findings indicating that WeChat use intensity had both direct and indirect impacts on the levels of life satisfaction and loneliness experienced by college students in China. Specifically, the utilization of WeChat for social motivation and entertainment motivation was found to have a suppressive effect on the relationship between the intensity of WeChat usage and individuals' life satisfaction. The association between the intensity of WeChat usage and mental health outcomes (life satisfaction and loneliness) was found to be mediated by bonding social capital. Furthermore, the association between the intensity of WeChat usage and mental health was found to be mediated by the sequential mediation effects of using WeChat for social motivation and bonding social capital, as well as the sequential mediation effects of using WeChat for entertainment motivation and bonding social capital. Our findings provide implications for policymakers and social workers regarding renovating the perceptions of the relationships between WeChat use intensity and overall mental health. Specifically, practical online activities and services of SNSs are recommended to be designed for meeting social and recreational gratifications and boosting bonding social capital, which in turn promotes psychological wellbeing.


"Frozen" transition States: pentavalent carbon et Al.
Organic ligands have been designed for the stabilization of specific geometries of compounds of nonmetallic elements. These ligands have made possible the isolation, or direct observation, of large numbers of trigonal bipyramidal organo-nonmetallic species. Many of these species are analogs of transition states for nucleophilic displacement reactions and have been stabilized by the ligands to such a degree that they have become ground-state energy minima. Ideas derived from research on these species have been applied to carbon species to generate a molecule that is an analog of the transition state for the associative nucleophilic displacement reaction. The molecule is a pentavalent carbon species that has been observed by nuclear magnetic resonance spectroscopy.


"INTERMED": a method to assess health service needs. II. Results on its validity and clinical use.
The validity and clinical use of a recently developed instrument to assess health care needs of patients with a physical illness, called INTERMED, is investigated. The INTERMED combines data reflecting patients' biological, psychological, and social characteristics with information on health care utilization characteristics. An example of a patient population in which such an integral assessment can contribute to the appropriateness of care, are patients with low back pain of degenerative or unknown origin. It supports the validity and the clinical usefulness of the INTERMED when clinically relevant subgroups in this heterogeneous population can be identified and described based on their INTERMED scores. The INTERMED was utilized in a group of patients (N = 108) having low back pain who vary on the chronicity of complaints, functional status, and associated disability. All patients underwent a medical examination and responded to a battery of validated questionnaires assessing biological, psychological, and social aspects of their life. In addition, the patients were assessed by the INTERMED. It was studied whether it proved to be possible to form clinically meaningful groups of patients based on their INTERMED scores; for this, a hierarchical cluster analysis was performed. In order to clinically describe them, the groups of patients were compared with the data from the questionnaires. The cluster analysis on the INTERMED scores revealed three distinguishable groups of patients. Comparison with the questionnaires assessing biological, psychological, and social aspects of disease showed that one group can be characterized as complex patients with chronic complaints and reduced capacity to work who apply for a disability compensation. The other groups differed explicitly with regard to chronicity, but also on other variables. By means of the INTERMED, clinically relevant groups of patients can be identified, which supports its use in clinical practice and its use as a method to describe case mix for scientific or health care policy purposes. In addition, the INTERMED is easy to implement in daily clinical practice and can be of help to ease the operationalization of the biopychosocial model of disease. More information on its validity in different patient populations is necessary.


Association of rheumatoid arthritis with a dominant DR1/Dw4/Dw14 sequence motif, but not with T cell receptor beta chain gene alleles or haplotypes.
HLA-DR, HLA-DQ, and T cell receptor beta (TCR beta) chain gene polymorphisms were investigated in 43 patients with rheumatoid arthritis (RA), in 10 patients with Felty's syndrome (FS), and in 5 RA multicase families. RA was found to be strongly associated with a DRB1 gene sequence motif present in DR1, DR4-Dw4, and DR4-Dw14 alleles. Ninety-three percent of RA patients were positive for at least 1 of these alleles, providing strong support for the "shared epitope hypothesis." The frequency distribution of this sequence motif suggests a dominant mode of inheritance. All 10 FS patients were DR4-Dw4 positive. Different DR-DQ associations among DR4 positive RA and FS patients indicate heterogeneity in the genetic susceptibility to these 2 disease entities. Furthermore, analyses of TCR V beta 8, V beta 11, and C beta gene polymorphisms did not support the notion of an influence of TCR beta germline allotypes on RA susceptibility.


Adaptive filtering in ECG monitoring of the fetal heart rate.
There has long been an interest in noninvasively monitoring the fetal electrocardiogram (ECG). In the past twenty years a clinical need has developed to monitor the instantaneous fetal heart rate (FHR) and changes in the heart rate from one beat to the next, i.e., beat-to-beat FHR variability as well as an interest in understanding the development of cardiac arrhythmias. The purpose of this paper is to present initial results obtained from an Electrocardiographic Adaptive Processor (EAP) to noninvasively monitor in real-time continuous tracings of the fetal ECG, FHR, and FHR variability. Twenty-five sets of noninvasive fetal ECG data were collected from pregnant subjects during the third trimester of pregnancy using maternal abdominal paste-on electrodes. The fetal QRS amplitude and shape varied from 5 to 30 microvolts with fetal position, gestational age, and relative electrode configuration. Results have been obtained in three specific areas: 1) The development and initial testing of a microprocessor based Electrocardiographic Adaptive Processor (EAP) implemented as an FHR monitor has been completed. The EAP has been implemented to adaptively cancel, in real-time, the maternal ECG component from maternal abdominal ECG leads to provide a continuous tracing of the fetal ECG complex, or FHR and FHR variability. 2) Maternal and thoracic ECG data stored on computer disk were used to test the adaptive techniques to cancel the strong interfering maternal ECG. Studies continue to effectively reduce background electromyographic (EMG) noise. 3) Tracings of the fetal QRS complex, instantaneous FHR, and short term FHR variability have been obtained in real-time.(ABSTRACT TRUNCATED AT 250 WORDS)


High feasibility and antileukemic efficacy of fludarabine, cytarabine, and idarubicin (FLAI) induction followed by risk-oriented consolidation: A critical review of a 10-year, single-center experience in younger, non M3 AML patients.
About 105 consecutive acute myeloid leukemia (AML) patients treated with the same induction-consolidation program between 2004 and 2013 were retrospectively analyzed. Median age was 47 years. The first induction course included fludarabine (Flu) and high-dose cytarabine (Ara-C) plus idarubicin (Ida), with or without gemtuzumab-ozogamicin (GO) 3 mg/m(2) (FLAI-5). Patients achieving complete remission (CR) received a second course without fludarabine but with higher dose of idarubicin. Patients not achieving CR received an intensified second course. Patients not scheduled for early allogeneic bone marrow transplantation (HSCT) where planned to receive at least two courses of consolidation therapy with Ara-C. Our double induction strategy significantly differs from described fludarabine-containing regimens, as patients achieving CR receive a second course without fludarabine, to avoid excess toxicity, and Ara-C consolidation is administrated at the reduced cumulative dose of 8 g/m(2) per cycle. Toxicity is a major concern in fludarabine containing induction, including the recent Medical Research Council AML15 fludarabine, cytarabine, idaraubicin and G-CSF (FLAG-Ida) arm, and, despite higher anti-leukemic efficacy, only a minority of patients is able to complete the full planned program. In this article, we show that our therapeutic program is generally well tolerated, as most patients were able to receive subsequent therapy at full dose and in a timely manner, with a 30-day mortality of 4.8%. The omission of fludarabine in the second course did not reduce efficacy, as a CR rate of 83% was achieved and 3-year disease-free survival and overall survival (OS) were 49.6% and 50.9%, respectively. Our experience shows that FLAI-5/Ara-C + Ida double induction followed by risk-oriented consolidation therapy can result in good overall outcome with acceptable toxicity. Am. J. Hematol. 91:755-762, 2016. © 2016 Wiley Periodicals, Inc.


[Ecological aspects between Contracaecum sp. (Nematoda, Anisakidae) and the host Serrasalmus spilopleura Kner, 1860 (Pisces, Characidae) in natural populations of northeastern Argentina].
From February 1987 to February 1989, the populational biology of Contraceacum sp. (larvae) in its paratenic host, the fish Serrasalmus spilopleura Kner, 1860, was studied in two ponds in a subtropical permanent habitat northeastern of Argentina. Fishes from Ramada Paso pond presented 80% of prevalence and 1 to 132 larvae per fish while fishes from Aeroclub pond presented 63% of prevalence and 1 to 184 larvae per fish. Fishes collected from Aeroclub pond have shown a high prevalence of infection during the first period of study (1987), diminishing the following year. In fishes from Ramada Paso pond the prevalence varied not significatively during the two years. Prevalence and mean intensity of infection increase with body length and weight of the hosts. Sex of hosts is not an influential factor in parasitic level. The lenitic "closed" environmental (Ramada Paso pond) evidenced the greatest larvae mean intensity and prevalence. Although, the lenitic "open" environmental (Aeroclub pond) showed the greatest parasitic number of individuals in an infrapopulation. The spatial dispersion in both ponds were aggregated and fit well a negative binomial model. Nevertheless, the Aeroclub pond presented the greatest overdispersion.


Sustained Effectiveness of Pfizer-BioNTech and Moderna Vaccines Against COVID-19 Associated Hospitalizations Among Adults - United States, March-July 2021.
Real-world evaluations have demonstrated high effectiveness of vaccines against COVID-19-associated hospitalizations (1-4) measured shortly after vaccination; longer follow-up is needed to assess durability of protection. In an evaluation at 21 hospitals in 18 states, the duration of mRNA vaccine (Pfizer-BioNTech or Moderna) effectiveness (VE) against COVID-19-associated hospitalizations was assessed among adults aged ≥18 years. Among 3,089 hospitalized adults (including 1,194 COVID-19 case-patients and 1,895 non-COVID-19 control-patients), the median age was 59 years, 48.7% were female, and 21.1% had an immunocompromising condition. Overall, 141 (11.8%) case-patients and 988 (52.1%) controls were fully vaccinated (defined as receipt of the second dose of Pfizer-BioNTech or Moderna mRNA COVID-19 vaccines ≥14 days before illness onset), with a median interval of 65 days (range = 14-166 days) after receipt of second dose. VE against COVID-19-associated hospitalization during the full surveillance period was 86% (95% confidence interval [CI] = 82%-88%) overall and 90% (95% CI = 87%-92%) among adults without immunocompromising conditions. VE against COVID-19- associated hospitalization was 86% (95% CI = 82%-90%) 2-12 weeks and 84% (95% CI = 77%-90%) 13-24 weeks from receipt of the second vaccine dose, with no significant change between these periods (p = 0.854). Whole genome sequencing of 454 case-patient specimens found that 242 (53.3%) belonged to the B.1.1.7 (Alpha) lineage and 74 (16.3%) to the B.1.617.2 (Delta) lineage. Effectiveness of mRNA vaccines against COVID-19-associated hospitalization was sustained over a 24-week period, including among groups at higher risk for severe COVID-19; ongoing monitoring is needed as new SARS-CoV-2 variants emerge. To reduce their risk for hospitalization, all eligible persons should be offered COVID-19 vaccination.


Associations of Microvascular Complications With the Risk of Cardiovascular Disease in Type 1 Diabetes.
We examined whether the presence of microvascular complications was associated with increased subsequent risk of cardiovascular disease (CVD) among participants with type 1 diabetes in the Diabetes Control and Complications Trial and Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study followed for >35 years. Standardized longitudinal data collection included: 1) stereoscopic seven-field retinal fundus photography centrally graded for retinopathy stage and clinically significant macular edema; 2) urinary albumin excretion rate (AER) and estimated glomerular filtration rate (eGFR); 3) cardiovascular autonomic neuropathy (CAN) reflex testing; and 4) adjudicated CVD events, including death from CVD, nonfatal myocardial infarction, stroke, subclinical myocardial infarction on electrocardiogram, confirmed angina, or coronary artery revascularization. Cox proportional hazards models assessed the association of microvascular complications with subsequent risk of CVD. A total of 239 participants developed CVD, including 120 participants who suffered major adverse cardiovascular events (MACE) defined as nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. The presence of microvascular disease (diabetic retinopathy, kidney disease, or CAN) was associated with increased risk of subsequent CVD and MACE (hazard ratios 1.86 to 3.18 and 2.09 to 3.63, respectively), associations that remained significant after adjusting for age and HbA1c. After adjustment for traditional CVD risk factors, however, only sustained AER ≥30 mg/24 h occurring alone and/or with eGFR <60 mL/min/1.73 m2 and the presence of both retinal and kidney disease remained associated with CVD. Advanced microvascular disease, especially moderate to severe albuminuria or eGFR <60 mL/min/1.73 m2, conveyed an increased risk of subsequent cardiovascular disease in the DCCT/EDIC cohort.


Phosphatidic acid and phosphatidylinositol labelling in adipose tissue. Relationship to the metabolic effects of insulin and insulin-like agents.
Exposure to phospholipase C increased the incorporation of [32P]Pi into phosphatidate, CMP-phosphatidate and phosphatidylinositol in rat adipose tissue and isolated adipocytes. A similar effect was observed in response to insulin and oxytocin. Theophylline, 3-isobutyl-1-methylxanthine and adenosine deaminase decreased [32P]Pi incorporation, and adenosine and N6-phenylisopropyladenosine reversed these effects. As with insulin, exposure of adipose tissue to phospholipase C stimulated oxidation of glucose, pyruvate and leucine and activated pyruvate dehydrogenase. Oxytocin and adenosine also mimicked the effects of insulin on leucine oxidation and pyruvate dehydrogenase. However, only insulin stimulated glycogen synthase activity, indicating that the regulation of synthase may be achieved by intracellular events distinct from those regulating changes in phospholipid metabolism, sugar transport and mitochondrial enzyme activities. It is postulated that exposure to phospholipase C forms diacylglycerol, which is phosphorylated to yield phosphatidate. The increased labelling of CMP-phosphatidate and phosphatidylinositol results from the conversion of phosphatidate into these lipids. The correlation between the effects of phospholipase C on phosphatidate synthesis and changes in adipose-tissue metabolism suggests the possibility that increased phosphatidate may directly or indirectly produce changes in membrane transport and enzyme activities. The pattern of phospholipid labelling produced by insulin, adenosine and oxytocin suggests that these stimuli may also increase phosphatidate synthesis, and, if so, changes in phospholipid metabolism could account for some of the metabolic actions of these stimuli.


Giant sialolith of submandibular gland: report of a case†.
Sialolithiasis is one of the most common diseases of salivary glands in middle-aged patients. Sialoliths are localized in submandibular glands in nearly 80% of the reported cases and they are classified as 'giant' in case any dimension exceeds 15 mm. Giant sialolith in submandibular gland is a rare disorder. Here, an unusual case of giant sialolith in submandibular gland is reported. A 42-year-old man referred with complaints of recurrent pain and swelling in the left submandibular area. Computerized tomography revealed a calcified mass of 42 × 17 mm size within the submandibular gland. Excision was performed in the submandibular gland and a giant sialolith of 35 mm length localized in the body of the gland was detected. The postoperative period was uneventful and the patient fully recovered.


Accurate diagnosis of bullous pemphigoid requires multiple health care visits.
Accurate use of diagnostic codes is crucial for epidemiological and genetic research based on electronic health record (EHR) data. This retrospective study validated the International Classification of Diseases (ICD)-10 diagnostic code L12.0 for bullous pemphigoid (BP) using EHR data from two Finnish university hospitals. We found 1225 subjects with at least one EHR entry of L12.0 between 2009 and 2019. BP diagnosis was based on clinical findings characteristic of BP and positive findings on direct immunofluorescence (DIF), BP180-NC16A enzyme-linked immunosorbent assay (ELISA) or indirect immunofluorescence (IIF) assay. True BP was found in 901 patients; the positive predictive value (PPV) for L12.0 was 73.6% (95% CI 71.0-76.0). L12.0 was more accurately registered in dermatology units than any specialized health care units (p<0.001). Including patients with multiple L12.0 registrations (≥3), increased the accuracy of the L12.0 code in both dermatology units and other settings. One diagnostic code of L12.0 is not enough to recognize BP in a large epidemiological data set; including only L12.0 registered in dermatology units and excluding cases with <3 L12.0 record entries markedly increases the PPV of BP diagnosis.


Screening for autologous blood transfusions.
The ratio between the amount of hemoglobin in the mature erythrocyte population and the reticulocytes (RBCHb:RetHb ratio) has previously been suggested as a marker to screen for EPO-abuse. We speculated that the reinfusion of blood would lead to a marked increase in this ratio, making it a valuable parameter in the screening for autologous blood doping. Three bags of blood (approximately 201+/-11 g of Hb) were withdrawn from 16 males and stored at either -80 degrees C (-80 T, n=8) or +4 degrees C (+4 T, n=8) and reinfused 10 weeks or 4 weeks later, respectively. Seven subjects served as controls. Different erythrocyte parameters were measured on a hematological analyzer serially throughout and during a 4 week wash-out period. By using RBCHb:RetHb ratio cut-off limits of 145.7 (1:100) ('suspicious') and 182.9 (1:1000) ('positive'), 35.4% (-80 T) and 19.6% (+4 T) of all samples obtained during a 4 week wash-out period were identified as 'suspicious', and 18.8% (-80 T) and 4.3% (+4 T) as 'positive'. In total, 7 out of 16 (43.8%) subjects had at least one sample exceeding 182.9. Compared to the currently used indirect parameters, the RBCHb:RetHb ratio is the best indicator of autologous blood doping after reinfusion, and the parameter could be used in a testing setting, once stability validation has been performed.


A novel isophorone-based red-emitting fluorescent probe for selective detection of sulfide anions in water for in vivo imaging.
The sulfide anion is significant in industrial processes, biology and environmental science. Hence, robust fluorescent sensors for sulfide which are water soluble and biocompatible are highly desirable. Here, we developed a novel red-emitting fluorescent probe (SP1) for the sulfide anion based on cleaving the dinitrobenzenesulfonate ester to restore the fluorescence, accompanied by a long wavelength emission at 644 nm. The detection process took place in 100% PBS buffer, which suggested it had excellent water solubility. Most importantly, the ability of SP1 to detect sulfide anions in living cells (MCF-7 cells) and zebrafish has also been proven.


Patellar dislocation following total knee replacement.
The reported incidence of patellar problems after total knee replacement has ranged from 5 to 30 per cent. Patellar dislocation is infrequent but can cause disabling symptoms. Between January 1974 and May 1982, eleven patients (twelve knees) with symptomatic lateral dislocation of the patella after total knee replacement were treated at The Hospital for Special Surgery by realignment of the extensor mechanism. All of the patients were women. Their average age was sixty-two years and average weight, eighty-seven kilograms. The diagnosis was osteoarthritis in seven knees and rheumatoid arthritis in five. Most of the patients had had preoperative valgus deformity (average, 18 degrees). The cause of dislocation was trauma in three knees, incorrect tracking of the patella after replacement in six, and malrotation of the tibial component in three. Four different prosthetic designs had been used. The design of the implant did not appear to be a factor causing dislocation in this group. The patellar dislocation was treated by proximal realignment of the quadriceps in ten knees, lateral retinacular release alone in one, and revision of the tibial and femoral components combined with proximal realignment in one. After an average follow-up of thirty-four months (range, twenty-four to fifty-seven months), the results according to The Hospital for Special Surgery knee-rating scale were excellent in ten knees and good in two, and there had been no redislocations.


Notch signaling and inherited disease syndromes.
The Notch signaling pathway is an evolutionarily conserved, intercellular signaling mechanism essential for proper embryonic development in organisms as diverse as insects, nematodes, echinoderms and mammals. Disruptions in conserved developmental pathways frequently result in inherited congenital anomalies in humans. Mutations in genes encoding Notch pathway components underlie three inherited human diseases: Alagille syndrome, spondylocostal dysostosis, and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. Mouse models for these three diseases have been developed, and are leading to novel insights into the pathology of these diseases in humans.


[Interrelation of nuclear envelope with cell organelles in peritoneal cells during ontogenesist and in experimental pathology].
Visceral and parietal peritoneum was studied by electron microscopy in albino mice both in the process of ontogenesis and after its injury induced by the the intraperitoneal injection of 0.5% novocaine solution. It was shown that during the early stages of intrauterine development (Day 13) most of the mesotheliocytes and mesenchymal cells contained predominantly free ribosomes (polysomes) in their cytoplasm while other organelles were rare and were located near the nuclear envelope. Subsequently, the number of membranous organelles increased while that of polysomes decreased. One day after the injury of the mesothelium, undifferentiated mesotheliocytes containing numerous polysomes in their cytoplasm appeared at the margin of wound surface. In these cells the protrusion 9f membranes of nuclear envelope and their association with the membranous organelles (endoplasmic reticulum, Golgi complex, mitochondria) were detected. The observed interrelations between the nuclear envelope and the membranous cytoplasmic organelles is considered to be a possible way of their formation in the undifferentiated cells. Rare occurrence of this phenomenon in adults animals under the pathological condition and its absence during the physiological regeneration is considered as a manifestation of the law of histogenetic recapitulation.


In vitro reaction to orthopaedic biomaterials by macrophages and lymphocytes isolated from patients undergoing revision surgery.
Periprosthetic tissues observed at sites of loose total joint implants exhibit abundant macrophages, lymphocytes, fibroblasts and particulate debris. Macrophages phagocytose orthopaedic debris and release proinflammatory cytokines, chemokines, matrix metalloproteinases and other substances. In addition, other cell types present in tissues harvested from the bone-implant interface are thought to influence periprosthetic bone resorption. The present study examined the effects of polymethylmethacrylate (PMMA), cobalt chrome molybdenum alloy (CoCr), and titanium-alloy particle challenge on macrophages co-cultured with lymphocytes in vitro. Potential synergistic effects of lymphocytes on macrophage activation were determined by measuring interleukin-6 and tumor necrosis factor-alpha release following exposure to orthopaedic biomaterial particles. Exposure of macrophages or macrophages co-cultured with lymphocytes to all three types of particles resulted in increased release of interleukin-6 and tumor necrosis factor-alpha at 48 h, when compared to macrophages or macrophages co-cultured with lymphocytes, respectively, cultured in the absence of particles. Lymphocytes isolated from periprosthetic tissues secreted increased basal levels of cytokines relative to peripheral blood lymphocytes. Higher doses of PMMA and titanium-alloy particles stimulated increased levels of cytokine release in the macrophage and macrophage/lymphocyte groups. In contrast, a higher dose of CoCr particles (0.075% v/v) was not as effective as the 0.015% v/v dose, indicating probable CoCr toxicity. The macrophage/lymphocyte co-culture did not show synergism between the two types of cells with respect to cytokine release. T-cells at the bone-implant interface may alter the biological response to particulate debris.


Effects of magnesium sulfate in kainic acid-induced status epilepticus.
Because magnesium has antiseizure effects in some animal models of epilepsy, and possible neuroprotective effects in some models of neuronal injury, we aimed to investigate its effects in the kainic acid (KA) model of status epilepticus (SE) in prepubescent rats. This age was chosen because it is a common age for onset of epilepsy and of SE in humans. Three groups of P35 rats were studied: Group I (MgKA) received magnesium sulfate MgSO4 (270 mg/kg then 27 mg/kg every 20 minutes for 5 hours) and 10 mg/kg KA. Group II (KA) received saline instead of MgSO4 and 10 mg/kg KA. Group III (control) received saline injections only. The dose we used has been shown previously to have anticonvulsant activity in another seizure model. Rats were recorded for their acute behavioral seizures directly after KA, and underwent the handling and Morris Water Maze (MWM) tests on P96-97 and P102-106 respectively. The MgKA and the KA groups did not differ in their acute seizures and both showed similar histologic lesions in CA3/CA4 and CA1 hippocampal subfields, and were more aggressive on the handling test than control rats. The MgKA group took more time to reach the platform in MWM than controls, while the KA group scores were intermediate between the two groups. Using the dose of 540 mg/kg MgSO4 and 54 mg/kg every 20 min showed the similar result of lack of protection against impairment in long-term memory. We conclude that (1) Magnesium did not manifest acute behavioral antiseizure effects in the KA P35 model of SE. (2) Magnesium did not prevent the tested long-term behavioral and histological consequences of SE in this model.


Deep Convolutional Neural Network Regularization for Alcoholism Detection Using EEG Signals.
Alcoholism is attributed to regular or excessive drinking of alcohol and leads to the disturbance of the neuronal system in the human brain. This results in certain malfunctioning of neurons that can be detected by an electroencephalogram (EEG) using several electrodes on a human skull at appropriate positions. It is of great interest to be able to classify an EEG activity as that of a normal person or an alcoholic person using data from the minimum possible electrodes (or channels). Due to the complex nature of EEG signals, accurate classification of alcoholism using only a small dataset is a challenging task. Artificial neural networks, specifically convolutional neural networks (CNNs), provide efficient and accurate results in various pattern-based classification problems. In this work, we apply CNN on raw EEG data and demonstrate how we achieved 98% average accuracy by optimizing a baseline CNN model and outperforming its results in a range of performance evaluation metrics on the University of California at Irvine Machine Learning (UCI-ML) EEG dataset. This article explains the stepwise improvement of the baseline model using the dropout, batch normalization, and kernel regularization techniques and provides a comparison of the two models that can be beneficial for aspiring practitioners who aim to develop similar classification models in CNN. A performance comparison is also provided with other approaches using the same dataset.


Bacterial and archaeal amoA gene distribution covaries with soil nitrification properties across a range of land uses.
Ammonia-oxidizing bacteria and ammonia-oxidizing archaea are commonly found together in soils, yet the factors influencing their relative distribution and activity remain unclear. We examined archaeal and bacterial amoA gene distribution, and used a novel bioassay to assess archaeal and bacterial contributions to nitrification potentials in soils spanning a range of land uses (forest, pasture, cultivated and long-term fallowed cropland) along a 10 km transect. The assay, which quantifies the extent to which acetylene-inactivated soil nitrification potential recovers (RNP) in the presence of bacterial protein synthesis inhibitors, indicated a significant archaeal contribution to the nitrification potentials of the pasture and long-term fallowed soils. Archaeal amoA gene abundance did not vary significantly among the soils, but bacterial amoA gene abundance did, resulting in archaeal : bacterial amoA abundance ratios ranging from 1.1 ± 0.8 in cultivated soils to 396 ± 176 in pasture soils. Both archaeal and bacterial amoA gene compositions were heterogeneous across the landscape, but differed in their patterns of variability. Archaeal amoA gene distributions were distinct among each of the three main land-use types: forest, pasture and cropland soils. In contrast, bacterial amoA gene composition was distinct in forest and in cultivated cropland, while pasture and long-term fallowed cropland soils were similar. In both pasture and long-term fallowed cropland soils, one phylotype of Nitrosospira cluster 3a was highly abundant. This distinct bacterial amoA gene fingerprint correlated with significant contributions of archaea to RNP of both soils, despite differences in archaeal amoA gene composition between the pasture and fallowed soils. This observation suggests that the factors driving the development of ammonia-oxidizing bacteria community composition might influence the extent of archaeal contribution to soil nitrification.


13C-n.m.r. of the cyanylated apoflavodoxin and flavodoxin from Clostridium pasteurianum.
The thiol group of the flavodoxin from Clostridium pasteurianum has been cyanylated in a single step using [cyanato-13C]2-nitro-5-thiocyanatobenzoic acid. This chemical modification increases the dissociation constant of the apoflavodoxin-FMN complex 10-fold from 0.33 +/- 0.15 nM to 2.9 +/- 1.3 nM. The thiocyanate carbons of the cyanylated cysteine residue of apoflavodoxin and flavodoxin had chemical shift values of 114.7 and 112.3 p.p.m. respectively. From these chemical shifts we conclude that the binding of FMN by the cyanylated apoflavodoxin causes a decrease in the polarity and/or hydrogen bonding capacity of the environment of the thiocyanate group. We compare these results with those obtained from similar studies on the cyanylated apoflavodoxin and flavodoxin from Megasphaera elsdenii and we discuss how FMN binding and cyanylation perturb the structures of apoflavodoxins from Megasphaera elsdenii and Clostridium pasteurianum.


Structure of the Anti-C60 Fullerene Antibody Fab Fragment: Structural Determinants of Fullerene Binding.
The structure of the anti-C60 fullerene antibody Fab fragment (FabC60) was solved by X-ray crystallography. The computer-aided docking of C60 into the antigen-binding pocket of FabC60 showed that binding of C60 to FabC60 is governed by the enthalpy and entropy; namely, by π-π stacking interactions with aromatic residues of the antigen-binding site and reduction of the solvent-accessible area of the hydrophobic surface of C60. A fragment of the mobile CDR H3 loop located on the surface of FabC60 interferes with C60 binding in the antigen-binding site, thereby resulting in low antibody affinity for C60. The structure of apo-FabC60 has been deposited with pdbid 6H3H.


Clinical Impact of COVID-19 Outbreak on Cancer Patients: A Retrospective Study.
Coronavirus disease (COVID-19), an acute respiratory syndrome caused by a novel severe acute respiratory syndrome coronavirus (SARS-CoV-2), has rapidly spread worldwide, significantly affecting the outcome of a highly vulnerable group such as cancer patients. The aim of the present study was to evaluate the clinical impact of COVID-19 infection on outcome and oncologic treatment of cancer patients. We retrospectively enrolled cancer patients with laboratory and/or radiologic confirmed SARS-CoV-2 infection, admitted to our center from February to April 2020. Descriptive statistics were used to summarize the clinical data and univariate analyses were performed to investigate the impact of anticancer treatment modifications due to COVID-19 outbreak on the short-term overall survival (OS). Among 61 patients enrolled, 49 (80%) were undergoing anticancer treatment and 41 (67%) had metastatic disease. Most patients were men; median age was 68 years. Median OS was 46.6 days (40% of deaths occurred within 20 days from COVID-19 diagnosis). Among 59 patients with available data on therapeutic course, 46 experienced consequences on their anticancer treatment schedule. Interruption or a starting failure of the oncologic therapy correlated with significant shorter OS. Anticancer treatment delays did not negatively affect the OS. Lymphocytopenia development after COVID was significantly associated with worst outcome. COVID-19 diagnosis in cancer patients may affect their short-term OS, especially in case of interruption/starting failure of cancer therapy. Maintaining/delaying cancer therapy seems not to influence the outcome in selected patients with recent COVID-19 diagnosis.


Response of cells persistently infected with arenaviruses to superinfection with homotypic and heterotypic viruses.
Vero cell cultures persistently infected with the arenaviruses Junin, Pichinde, Tacaribe, and Tamiami were established and designated Vero-Jun, Vero-Pic, Vero-Tac, and Vero-Tam, respectively. Two types of carrier cultures could be easily distinguished: Vero-Jun and Vero-Tac systems were characterized by a lack of infectious virus production after a few cell transfers, whereas a more productive state with continuous release of virus was observed in Vero-Pic and Vero-Tam cultures. These differences appeared to be related to resistance of the culture to viral superinfection. In fact, Vero-Jun and Vero-Tac cultures totally excluded only the replication of the serologically more closely related arenaviruses Amapari, Junin, or Tacaribe, while the refractoriness of Vero-Pic and Vero-Tam cultures was extended to most of the virus group members. The resistance of Vero-Jun cells to superinfection by Junin or Tacaribe virus could be ascribed to the production of specific uv-resistant Junin interfering particles, which showed a specific range of interference against Junin and Tacaribe viruses. Interfering particles against homotypic and heterotypic arenaviruses were isolated from Vero-Pic cultures. However, the degree of interference developed by these Pic-interfering particles was not enough to fully explain reinfecting virus exclusion from Vero-Pic cultures. Viral susceptibility of persistent cultures is proposed as a useful tool to examine relationships of members of the arenavirus group.


Diagnostic Approach to Benign and Malignant Calcifications in the Abdomen and Pelvis.
Intra-abdominal calcifications are common. Multiple pathologic processes manifest within the abdomen and pelvis in association with calcifications, which can be benign, premalignant, or malignant. Although calcium deposition in the abdomen can occur secondary to various mechanisms, the most common cau se is cellular injury that leads to dystrophic calcifications. The authors provide a summary of various common and uncommon calcifications in the abdomen and pelvis, primarily using location to illuminate diagnostic significance. Six broad categories of calcifications in the abdomen and pelvis are recognized: mesenteric, peritoneal, retroperitoneal, organ-based, vascular, and musculoskeletal. In addition to site, the various patterns and morphology of calcifications encountered in various conditions can be helpful for diagnosis, especially those depicted on radiographs. For example, some patterns diagnostic for various conditions include round or oval stones in the biliary or urothelial tracts, curvilinear calcifications associated with cysts or neoplasms, and sheetlike calcifications along peritoneal surfaces in the setting of chronic peritoneal dialysis or metastatic disease. Organ encrustation with calcium may be a premalignant finding (eg, porcelain gallbladder). In addition, the development of calcium after initiation of treatment can be used as an indicator of response in conditions such as tuberculosis, lymphoma, and hydatid disease. As calcifications are almost invariably detected at imaging, it is imperative for radiologists to be aware of their diagnostic implications and use the presence of calcification in an organ, mass, or other anatomic location for problem solving. ©RSNA, 2020.


Optimum acetabular component fixation.
Acetabular pressfit fixation depends on rigid initial fixation, subchondral bone preservation, and close apposition to allow biologic interface incorporation. A hemispherical cup with a 1 to 2 mm pressfit offers optimal fixation and adjunct fixation with screws or pegs appears to be limited. Pressfit continues to be the ideal fixation choice for most patients.


"Phospholipids of virus-induced membranes in cytoplasm of Escherichia coli.
Infection of Escherichia coli with amber mutants of phage fd, in contrast to infection with wild-type phage, leads to cell death and the proliferation of intracytoplasmic membranes observed in electron micrographs at the poles of the cells. The accumulation of membranes correlates with changes in structural phospholipids, especially a marked increase in the apparent rate of formation and total amount of cardiolipin (from 4 to 20% of total radioactive phospholipids), and a compensating decline in phosphatidylethanolamine.


Olfactory rule learning-induced enhancement in intrinsic neuronal excitability is maintained by shutdown of the cholinergic M-current.
Training rats in a particularly difficult olfactory discrimination task initiates a period of accelerated learning, manifested as a dramatic increase in the rats' capacity to discriminate between pairs of odors once they have learned the discrimination task, implying that rule learning has taken place. At the cellular biophysical level, rule learning is maintained by reduction in the conductance of the slow current (sIAHP) simultaneously in most piriform cortex layer II pyramidal neurons. Such sIAHP reduction is expressed in attenuation of the post-burst afterhyperpolarization (AHP) potential and thus in enhanced repetitive action potential firing. Previous studies have shown that a causal relationship exists between long-lasting post-burst AHP reduction and rule learning. A specific channel through which the sIAHP flows has not been identified. The sIAHP in pyramidal cells is critically dependent on membrane phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)]. PtdIns(4,5)P(2) regulates the calcium sensitivity of the sIAHP by acting downstream from the rise in intracellular calcium. These findings led to the interesting hypothesis that PtdIns(4,5)P(2) activates a variety of potassium channels. Thus, the sIAHP would not represent a unitary ionic current but the embodiment of a generalized potassium channel gating mechanism. We thus hypothesized that the learning-induced increase in intrinsic excitability is mediated by reduced conductance of one or more of the currents that contribute to the sIAHP. Here we first show, using current-clamp recordings, that the post-burst AHP in piriform cortex pyramidal neurons is also mediated by the Ih, and the contribution of this current to the post-burst AHP is also affected by learning. We also show, using whole-cell patch-clamp recordings, that the sIAHP in neurons from trained rats is not sensitive to blocking membrane phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)], and to the blocking of the current mediated by the cholinergic muscarinic acetylcholine receptor (M-current). Further current-clamp recordings also show that blocking PtdIns(4,5)P(2) synthesis and application of a specific IKCa blocker have no effect on the post-burst AHP in neurons from trained as well as control rats. Taken together with results from our previous studies, these data suggest that rule learning-induced long-lasting enhancement in intrinsic neuronal excitability results from reduced conductance of the M-current and thus the slow potassium currents, which control repetitive spike firing.


A cytochrome cd1-type nitrite reductase isolated from the marine denitrifier Pseudomonas nautica 617: purification and characterization.
Nitrite reductase (cytochrome cd1) was purified to electrophoretic homogeneity from the soluble extract of the marine denitrifying bacterium Pseudomonas nautica strain 617. Cells were anaerobically grown with 10 mM nitrate as final electron acceptor. The soluble fraction was purified by four successive chromatographic steps and the purest cytochrome cd1 exhibited an A280 nm(oxidized)/A410nm(oxidized) coefficient of 0.90. In the course of purification, cytochrome cd1 specific activity presented a maximum value of 0.048 units/mg of protein. This periplasmic enzyme is a homodimer and each 60 kDa subunit contains one heme c and one heme d1 as prosthetic moieties, both in a low spin state. Redox potentials of hemes c and d1 were determined at three different pH values (6.6, 7.6 and 8.6) and did not show any pH dependence. The first 20 amino acids of the NH2-terminal region of the protein were identified and the sequence showed 45% identity with the corresponding region of Pseudomonas aeruginosa nitrite reductase but no homology to Pseudomonas stutzeri and Paracoccus denitrificans enzymes. Spectroscopic properties of Pseudomonas nautica 617 cytochrome cd1 in the ultraviolet-visible range and in electron paramagnetic resonance are described. The formation of a heme d1 -nitric-oxide complex as an intermediate of nitrite reduction was demonstrated by electron paramagnetic resonance experiments.


Combined effects of land reclamation, channel dredging upon the bioavailable concentration of polycyclic aromatic hydrocarbons (PAHs) in Victoria Harbour sediment, Hong Kong.
The up-to-date concentration of polycyclic aromatic hydrocarbons (PAHs) in sediment materials of Victoria Harbour was investigated so as to evaluate the pollution potential associated with the reclamation projects in Hong Kong. A total of 100 sediment samples were collected at 20 locations. Except the control point in reservoir, the PAHs concentrations were detectable levels all sites (131-628.3ng/g, dw) and such values were higher than Dutch Target and Intervention Values (the New Dutch standard in 2016). The PAHs concentration indicating that construction waste and wastewater discharges were the main pollutant sources. Results of correlation in single cell gel electrophoresis assay (comet assay) studies also revealed that the PAHs concentration was highly correlated (<0.01) with DNA migration (i.e. the length of tail moment of fish cells) in 5mg/ml of PAHs. The above observation indicates that the PAHs present in the sediment may substantially effect the marine ecosystem. Although the dredged sediment can be a useful sea-filling material for land reclamation; however, the continuing leaching of PAHs and its impact on the aquatic environment need to be studied further.


Carcinoma of the urachus: the role of computed tomography.
Carcinoma of the urachus is a rare entity with poor prognosis. Calcification, a deformed bladder apex, and lateral ureteral displacement have been described as radiographic findings, although radiology has been considered to be of limited value in establishing the diagnosis. Two cases are reported in which computed tomography (CT) contributed to the diagnosis and management. The association of a calcified suprapubic mass on CT together with a history of the passage of blood and mucus per urethra is suggestive of the diagnosis.


Incomplete abscission and cytoplasmic bridges in the evolution of eukaryotic multicellularity.
The textbook view of cell division terminates with the final separation of the two daughter cells in the process called abscission. However, in contrast to this classical view, a variety of cell types in multicellular organisms are connected through cytoplasmic bridges, which most often form by incomplete abscission or - more rarely - by local fusion of plasma membranes. In this review, we survey the distribution, function, and formation of cytoplasmic bridges across the eukaryotic tree of life. We find that cytoplasmic bridges are widespread, and were likely ancestrally present, in almost all lineages of eukaryotes with clonal multicellularity - including the five 'complex multicellular' lineages: animals, fungi, land plants, red algae, and brown algae. In animals, cytoplasmic bridges resulting from incomplete abscission are ubiquitous in the germline and common in pluripotent cell types. Although cytoplasmic bridges have been less studied than other structural mediators of multicellularity (such as adhesion proteins and extracellular matrix), we propose that they have played a pivotal role in the repeated evolution of eukaryotic clonal multicellularity - possibly by first performing a structural role and later by allowing exchange of nutrients and/or intercellular communication, which notably buffered cell-cell competition by averaging gene expression. Bridges were eventually lost from many animal tissues in concert with the evolution of spatial cell differentiation, cell motility within the organism, and other mechanisms for intercellular distribution of signals and metabolites. Finally, we discuss the molecular basis for the evolution of incomplete abscission and examine the alternative hypotheses of single or multiple origins.


[Protective effect of purple sweet potato flavonoids on CCL4-induced acute liver injury in mice].
To investigate the protective effect of purple sweet potato flavonoids (PSPF) on CCl4-induced acute liver injury in mice. Sixty mice were randomly divided into six groups (n=10 in each): blank group, model group, PSPF groups (400 mg*kg(-1), 200 mg*kg-1 and 100 mg*kg(-1)) and positive control group (DDB 150 mg*kg(-1)). Acute liver injury was induced by administration of peanut oil with 0.1% CCl4 (10 mg*kg(-1)) in mice. The viscera index, serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH) were measured, and the activities of superoxide dismutase (SOD) and the contents of malondialdehyde (MDA) in hepatic tissues were also measured. The pathological changes of liver were observed with microscopy. PSPF significantly decreased serum ALT, AST and LDH levels (P<0.05 or P<0.01) and MDA content in hepatic tissues (P<0.01), increased the activities of SOD (P<0.01). Purple sweet potato total flavonoids can prevent CCl4-induced acute liver injury in mice, which may be related to inhibition of lipid peroxidation and reduction of oxygen free radicals.


Volatile organic compounds (VOCs) produced by biocontrol yeasts.
The Volatile organic compounds (VOCs) produced by biocontrol yeast strains which belong to the Wickerhamomyces anomalus, Metschnikowia pulcherrima, Aureobasidium pullulans and Saccharomyces cerevisiae species were identified by solid phase microextraction (SPME) coupled with Gas Chromatography-Mass Spectrometry (GC-MS). Alcohols (ethyl alcohol, 3-methyl-1-butanol and phenylethyl alcohol) and esters (ethyl acetate and isoamyl acetate) were found to be the main VOCs emitted by the yeast strains, which had different production rate over a 16-day period. In addition, the tested yeast strains showed a remarkable ability to consume oxygen and to produce high percentages of carbon dioxide over a 5 days incubation period in a model system. The yeast strains, which were proven to very efficiently suppress in vivo the growth of postharvest fungal by VOCs, also quickly produced high percentages of ethyl acetate and carbon dioxide. . For all these reasons, we believe that the level of yeast biocontrol efficacy through the production of volatiles could be the result of a synergistic effect between VOCs and carbon dioxide in the packaging environment.


Smoking cessation in primary care: Exploration of barriers and solutions in current daily practice from the perspective of smokers and healthcare professionals.
Evidence based recommendations for smoking cessation are not followed in routine primary care. A better understanding is needed why smoking cessation treatment is still underutilized. To explore barriers and solutions of smoking cessation treatment, from the perspective of smokers and healthcare professionals in Dutch primary care. Focus groups were conducted with 14 smokers (smokers and ex-smokers) and semi-structured individual interviews with nine healthcare professionals (general practitioners and practice nurses). Data was analysed using the Constant Comparative Method. Barriers that prevented successful smoking cessation treatment were the lack of awareness regarding the available smoking cessation treatments at the healthcare centre among smokers and the resistance against preventive tasks among healthcare professionals. Nonetheless, general practitioners (GPs) did not fear jeopardizing the doctor-patient relationship by discussing smoking. Quitting was regarded as the smokers' own responsibility and GPs felt that merely using medication was no guarantee for successful quitting. Even so, practice nurses and smokers preferred medication use. Proposed solutions were that GPs should advise smokers to quit, whereas someone else should deliver intensive behavioural support, preferably the practice nurse. Smokers and healthcare professionals seem to wait for each other to start smoking cessation. GPs should know that they could discuss smoking cessation with every patient without jeopardizing the doctor-patient relationship, preferably followed by referral to a practice nurse for intensive behavioural support. Furthermore, more patients should know that they could receive pharmacological treatment as well as behavioural support for smoking cessation in their healthcare centre.


[Improvement of medical care of workers engaged in oil extraction in Siberia].
Complex clinical and functional examination of 662 workers engaged into oil extraction revealed unfavorable influence of shifted expedition work mode on the health state. Chronic diseases were diagnosed in 47% of the examinees. Structure of chronic diseases among the examinees presented prevalent disorders of central nervous system and vegetative regulation. The authors necessitated differentiated screening among the shifted expedition workers in accordance with their health grade groups. Expert committees for this examination should include psychiatrist, narcology expert and ophthalmologist.


Development and validation of a laser-induced breakdown spectroscopic method for ultra-trace determination of Cu, Mn, Cd and Pb metals in aqueous droplets after drying.
The present study reports a fast and accurate methodology for laser-induced breakdown spectroscopic, LIBS, analysis of aqueous samples for environmental monitoring purposes. This methodology has two important attributes: one is the use of a 300nm oxide coated silicon wafer substrate (Si+SiO2) for the first time for manual injection of 0.5 microliter aqueous metal solutions, and two is the use of high energy laser pulses focused outside the minimum focus position of a plano convex lens at which relatively large laser beam spot covers the entire droplet area for plasma formation. Optimization of instrumental LIBS parameters like detector delay time, gate width and laser energy has been performed to maximize atomic emission signal of target analytes; Cu, Mn, Cd and Pb. Under the optimal conditions, calibration curves were constructed and enhancements in the LIBS emission signal were obtained compared to the results of similar studies given in the literature. The analytical capability of the LIBS technique in liquid analysis has been improved. Absolute detection limits of 1.3pg Cu, 3.3pg Mn, 79pg Cd and 48pg Pb in 0.5 microliter volume of droplets were obtained from single shot analysis of five sequential droplets. The applicability of the proposed methodology to real water samples was tested on the Certified Reference Material, Trace Metals in Drinking Water, CRM-TMDW and on ICP multi-element standard samples. The accuracy of the method was found at a level of minimum 92% with relative standard deviations of at most 20%. Results suggest that 300nm oxide coated silicon wafer has an excellent potential to be used as a substrate for direct analysis of contaminants in water supplies by LIBS and further research, development and engineering will increase the performance and applicability of the methodology.


Fifty years of the double helix and its impact on psychiatry.
To discuss the impact of Watson and Crick's double helix discovery on the field of psychiatry. Psychiatric research studies using molecular genetic techniques are summarized. The implications of these findings in terms of our understanding and treatment of mental illness are discussed. There now exists growing evidence of candidate gene sites for a variety of psychiatric disorders ranging from schizophrenia to reading disability. The field of psychiatric genetics has become one of the most vital and productive areas of psychiatric research. New findings are continually coming to light, bringing us ever closer to understanding these complex disorders at a molecular level. Such knowledge could lead to improved drug treatments, screening of at-risk individuals and even a reduction in the stigma attached to psychiatric disorders.


Contractile activity is required for sarcomeric assembly in phenylephrine-induced cardiac myocyte hypertrophy.
Agonist-induced hypertrophy of cultured neonatal rat ventricular myocytes (NRVM) has been attributed to biochemical signals generated during receptor activation. However, NRVM hypertrophy can also be induced by spontaneous or electrically stimulated contractile activity in the absence of exogenous neurohormonal stimuli. Using single-cell imaging of fura 2-loaded myocytes, we found that low-density, noncontracting NRVM begin to generate intracellular Ca2+ concentration ([Ca2+]i) transients and contractile activity within minutes of exposure to the alpha 1-adrenergic agonist phenylephrine (PE; 50 microM). However, NRVM pretreated with verapamil and then stimulated with PE failed to elicit [Ca2+]i transients and beating. We therefore examined whether PE-induced [Ca2+]i transients and contractile activity were required to elicit specific aspects of the hypertrophic phenotype. PE treatment (48-72 h) increased cell size, total protein content, total protein-to-DNA ratio, and myosin heavy chain (MHC) isoenzyme content. PE also stimulated sarcomeric protein assembly and prolonged MHC half-life. However, blockade of voltage-gated L-type Ca2+ channels with verapamil, diltiazem, or nifedipine (10 microM) blocked PE-induced total protein and MHC accumulation and prevented the time-dependent assembly of myofibrillar proteins into sarcomeres. Inhibition of actin-myosin cross-bridge cycling with 2,3-butanedione monoxime (7.5 mM) also prevented PE-induced total protein and MHC accumulation, indicating that mechanical activity, rather than [Ca2+]i transients per se, was required. In contrast, blockade of [Ca2+]i transients and contractile activity did not prevent the PE-induced increase in cell surface area, activation of the mitogen-activated protein kinases ERK1 and ERK2, or upregulation of atrial natriuretic factor gene expression. Thus contractile activity is required to elicit some but not all aspects of the the hypertrophic phenotype induced by alpha 1-adrenergic receptor activation.


Look before you leap: the role of negative urgency in appraisals of ambiguous and unambiguous scenarios in individuals high in generalized anxiety disorder symptoms.
Negative interpretation bias, the propensity to make threatening interpretations of ambiguous information, is associated with symptoms of generalized anxiety disorder (GAD). Apart from its relationship with intolerance of uncertainty (IU), little is known about what explains the presence of this cognitive bias in GAD. One factor may be negative urgency (NU), the tendency to take rash action when distressed, which is related to GAD symptoms and to cognitive biases in nonclinical populations. The aim of the present study was to examine the relationship between NU and interpretation bias in individuals high in GAD symptoms (N = 111). IU, trait anxiety, and other forms of impulsivity were examined concurrently as competing correlates of interpretation bias. Greater NU and IU were found to be unique correlates of greater threatening interpretations of ambiguous scenarios. Greater NU was also a unique correlate of greater threatening interpretations of negative and positive scenarios. No other forms of impulsivity were uniquely related to interpretation bias. The findings suggest that greater NU may have a role in the tendency for individuals high in GAD symptoms to make threatening interpretations in response to ambiguous scenarios, overtly threatening situations, and situations without indication of threat or danger. Theoretical implications of these findings are discussed.


Two-Stream Deep Hashing With Class-Specific Centers for Supervised Image Search.
Hashing has been widely used for large-scale approximate nearest neighbor search due to its storage and search efficiency. Recent supervised hashing research has shown that deep learning-based methods can significantly outperform nondeep methods. Most existing supervised deep hashing methods exploit supervisory signals to generate similar and dissimilar image pairs for training. However, natural images can have large intraclass and small interclass variations, which may degrade the accuracy of hash codes. To address this problem, we propose a novel two-stream ConvNet architecture, which learns hash codes with class-specific representation centers. Our basic idea is that if we can learn a unified binary representation for each class as a center and encourage hash codes of images to be close to the corresponding centers, the intraclass variation will be greatly reduced. Accordingly, we design a neural network that leverages label information and outputs a unified binary representation for each class. Moreover, we also design an image network to learn hash codes from images and force these hash codes to be close to the corresponding class-specific centers. These two neural networks are then seamlessly incorporated to create a unified, end-to-end trainable framework. Extensive experiments on three popular benchmarks corroborate that our proposed method outperforms current state-of-the-art methods.


Percutaneous tracheostomy.
The purpose of this review is to discuss the various techniques of percutaneous tracheostomy and to assess their safety and efficacy profile, indications and contraindications, early and late complications. Literature was reviewed from Medline and MD Consult databases. Early techniques by Sheldon, toye and Schachner have been abandoned due to their high complication rates. Percutaneous dilational tracheostomy using the Ciaglia kit (Wiliam Cook Europe Bjaeverskov) and a Griggs kit (Portex PDT kit, POrtex, Hythe, Kent, UK) has been used most often. Griggs guide Wire Dilator Forceps kit (SIMS, Portex, Hythe, Kent, UK) is the next most common in use but its long-term studies are few. Fantoni (TLT set, Mallinckrodt Medical) and PercuTwist device (Riisch, Kernen, Germany) are two new techniques currently under study. Percutaneous dilational tracheostomy and conventional surgical tracheostomy are still competing methods to provide an airway for intensive care patient requiring assisted ventilation. Review of literature shows that percutaneous tracheostomy is safe, cost-effective and compares favourably with the open surgical tracheostomy. Many intensive care units now use the percutaneous tracheostomy as a procedure of choice. Percutaneous tracheostomy has a learning curve and requires appropriate case selection and meticulous attention to the technique by all those who want to use this method.


Interactive impacts of microplastics and arsenic on agricultural soil and plant traits.
The ability of microplastics (MPs) to interact with environmental pollutants is currently of great concern due to the increasing use of plastic. Agricultural soils are sinks for multipollutants and the safety of biodegradable MPs in field conditions is questioned. However, still few studies have investigated the interactive effects between MPs and metals on the soil-plant system with agricultural soil and testing crops for human consumption. In this work, we tested the effect on soil and plant parameters of two common MPs, non-degradable plastic low-density polyethylene and biodegradable polymer polylactic acid at two different sizes (<250 μm and 250-300 μm) in association with arsenic (As). Lettuce (Lactuca sativa L.) was used as a model plant in a small-scale experiment lasting 60 days. Microplastics and As explained 12 % and 47 % of total variance, respectively, while their interaction explained 21 %, suggesting a higher toxic impact of As than MPs. Plant growth was promoted by MPs alone, especially when biodegradable MPs were added (+22 %). However, MPs did not affect nutrient concentrations in roots and leaves. The effect of MPs on enzyme activities was variable depending on the time of exposure (with larger effects immediately after exposure), the type and size of the MPs. On the contrary, the co-application of MP and As, although it did not change the amount of bioavailable As in soil in the short and medium term, it resulted in a significant decrease in lettuce biomass (-19 %) and root nutrient concentrations, especially when polylactic acid was applied. Generally, MPs in association with As determined the plant-soil toxicity. This work provides insights into the risk of copollution of MPs and As in agricultural soil and its phytotoxic effect for agricultural crops. However, the mechanisms of the joint effect of MP and As on plant toxicity need further investigation, especially under field conditions and in long-term experiments.


Low phase noise operation of microwave oscillator circuits.
In this paper, we describe a theoretical basis, leading to new results, on the general conditions to be fulfilled by oscillator circuits to achieve a very low phase noise. Three main conditions must be fulfilled by a transistor oscillator circuit to reach the minimum phase noise. The energy stored in the resonator must be maximum. Its transfer to the controlling voltage port of the transistor current source must be first maximized. A possible conversion noise at the transistor output port will be also minimized by maximizing the energy transferred to that port. The proposed method has been applied to an experimental oscillator set up with a PHEMT transistor. A state-of-the-art phase noise of -80 dBc/Hz at 100 Hz offset from carrier with a 1/f(3) slope has been measured at room temperature with a 9.2 GHz, oscillator. The application of these new results to free-running oscillator circuits with one-stage then multistage transistor amplifiers demonstrate clearly the validity of the design method. The efficiency of this design method and its ease of use represent a real breakthrough in the field of low noise transistor oscillator circuit design.


Are serious games too serious? Diffusion of wearable technologies and the creation of a diffusion of serious games model.
Today globally, more people die from chronic diseases than from war and terrorism. This is not due to aging alone but also because we lead unhealthy lifestyles with little or no exercise and typically consume food with poor nutritional content. This paper proffers the design science research method to create an artefact that can help people study the diffusion of serious games. The ultimate goal of the study is to create a serious game that can help people to improve their balance in physical exercise, nutrition and well-being. To do this, first we conducted 97 interviews to study if wearables can be used for gathering health data. Analysis indicates that designers, manufacturers, and developers of wearables and associated software and apps should make their devices reliable, relevant, and user friendly. To increase the diffusion, adoption, and habitual usage of wearables key issues such as privacy and security need to be addressed as well. Then, we created a paper prototype and conducted a further 32 interviews to validate the first prototype of the game, especially with respect to the diffusion possibilities of the game. Results are positive from a formal technology acceptance point of view showing relevance and usefulness. But informally in the open questions some limitations also became visible. In particular, ease of use is extremely important for acceptance and calling it a game can in fact be an obstruction. Moreover, the artefact should not be patronizing and age differences can also pose problems, hence the title not to make the serious game too serious. Future research plans to address these problems in the next iteration while the future implementation plan seeks for big platforms or companies to diffuse the serious game. A key theoretical contribution of this research is the identification of habit as a potential dependent variable for the intention to use wearables and the development of a diffusion model for serious games. The hedonic perspective is added to the model as well as trust and perceived risks. This model ends the cycle of critical design with an improvement of theory as result contributing to the societal goal of decreasing Obesities and Diabetes.


Identification and quantification of polystyrene microplastics in marine sediments facing a river mouth through NMR spectroscopy.
Accurate identification and quantification of microplastic pollution in marine sediments are crucial for assessing their ecological impact. In this study, we explored the potential of Nuclear Magnetic Resonance (NMR) spectroscopy as an analytical tool for the analysis of microplastics in complex environmental matrices such as marine sediments. Two common plastic polymers, polystyrene (PS) and acrylonitrile butadiene styrene (ABS), were investigated. The marine sediments facing the Tiber River mouth (Italy) were collected according to a bathymetric gradient. Results demonstrated the successful detection and quantification of PS in all sediment samples (within a range of 12.3-64.6 μg/L), while no ABS significant signals were found. An increment trend with depth was observed in the PS signal, relatable to its physicochemical properties and the Tiber River plume hydrodynamic characteristics. The NMR's non-destructive nature and minimal sample preparation represent a promising avenue for standardizing protocols to assess the microplastic distribution and impact in marine sediments.


Scenes unseen: the parahippocampal cortex intrinsically subserves contextual associations, not scenes or places per se.
The parahippocampal cortex (PHC) has been implicated in both place/scene processing and episodic memory. We proposed that this region should instead be seen as intrinsically mediating contextual associations and not place/scene processing or episodic memory exclusively. Given that place/scene processing and episodic memory both rely on associations, this modified framework provides a platform for reconciling what seemed like different roles assigned to the same region. Comparing scenes with scenes, we show here that the PHC responds significantly more strongly to scenes with rich contextual associations compared with scenes of equal visual qualities but less associations. This result adds unequivocal support to the view that the PHC mediates contextual associations in general rather than places or scenes proper, and necessitates a revision of the current view that the PHC contains a dedicated place/scenes "module."


Crystalline architectures of C84 with tunable morphology and linearly polarized red emission.
Fullerene-based micro/nano-architectures (FMNAs) with remarkable photoluminescence (PL) emissions have attracted considerable interest as potential building blocks for optical and biolabeling applications, by virtue of their low toxicity and environmentally friendly nature. Nevertheless, the PL polarization properties of FMNAs have rarely been explored. Herein, we demonstrate the preparation of highly crystalline architectures of C84, which exhibit polymorphism depending on the preparation conditions but possess similar hexagonal close-packed (hcp) structures. The PL data demonstrate that the as-prepared carambola-like hexagonal microprisms (c-HPs) show enhanced red emission compared to regular hexagonal microprisms (r-HPs). More importantly, the linear polarization of the PL emission is verified and estimated through single-prism spectroscopy, which changes from 0.42 (r-HP) to 0.58 (c-HP), comparable to those of traditional rod-like semiconductors. Thus, we demonstrate a significant correlation between the morphology and emission characteristics of C84-based microprisms, highlighting the possibility of controlling the photophysical properties of FMNAs by finely tailoring their external morphologies. This study expands the range of carbon materials with linearly polarized emissions and offers potential for use in polarization-based micro-scale sensors or detectors.


Comprehensive genomic characterization of five canine lymphoid tumor cell lines.
Leukemia/lymphoma cell lines have been critical in the investigation of the pathogenesis and therapy of hematological malignancies. While human LL cell lines have generally been found to recapitulate the primary tumors from which they were derived, appropriate characterization including cytogenetic and transcriptional assessment is crucial for assessing their clinical predictive value. In the following study, five canine LL cell lines, CLBL-1, Ema, TL-1 (Nody-1), UL-1, and 3132, were characterized using extensive immunophenotyping, karyotypic analysis, oligonucleotide array comparative genomic hybridization (oaCGH), and gene expression profiling. Genome-wide DNA copy number data from the cell lines were also directly compared with 299 primary canine round cell tumors to determine whether the cell lines represent primary tumors, and, if so, what subtype each most closely resembled. Based on integrated analyses, CLBL-1 was classified as B-cell lymphoma, Ema and TL-1 as T-cell lymphoma, and UL-1 as T-cell acute lymphoblastic leukemia. 3132, originally classified as a B-cell lymphoma, was reclassified as a histiocytic sarcoma based on characteristic cytogenomic properties. In combination, these data begin to elucidate the clinical predictive value of these cell lines which will enhance the appropriate selection of in vitro models for future studies of canine hematological malignancies.


Aminergic innervation of the hypothalamus.
Anatomical aspects of aminergic neurons contained within or projecting to the hypothalamus have been studied with the Falck-Hillarp fluorescence method, the glycoxylic acid technique, Palkovits' "punch-out" system with radioenzymatic assays, electron microscopy (EM), and immunocytochemical localization of the synthesizing enzymes with the light microscope and EM. Dopaminergic (DA) neurons include the tuberoinfundibular and incertohypothalamic groups. Serotonergic (5-HT) neurons project largely from the raphe nuclei, but there are indications of some intrinsic 5-HT cells. Noradrenergic input to the hypothalamus comes almost completely from lateral tegmental brain stem neurons via the ventral adrenergic bundle, but the paraventricular, dorsomedial, supraoptic and periventricular nuclei receive some fibers directly from the locus coeruleus through the dorsal bundle. EM studies reveal aminergic boutons wiwh dense cored vesicles, but specific synaptic profiles with thickened postsynaptic membranes appear to be limited in number, and it has been proposed that the amines may commonly be released from boutons without true synaptic endings. Electrophysiological studies related to neuroendocrine phenomena reveal stimulatory and inhibitory responses to amines and to activated aminergic neurons. These effects may be transmitted via inhibitory interneurons. Functional recovery from the chronic loss of 85% of hypothalamic norepinephrine suggests that the catecholamine may serve as a modulator rather than as an essential link in the chain of neuroendocrine cause-effect relationships.


Papillomaviruses and interferon.
Papillomaviruses are infectious agents which cause benign tumours, or warts, of cutaneous, uterine cervical and laryngeal epithelia. These infections are very common, yet no uniformly effective therapy exists. Current treatments do not selectively inhibit viral processes but destroy the infected epithelial cells. Since interferons have antiviral effects in vivo and in vitro, it was hypothesized that they might be useful for treating papillomavirus-induced conditions. Interferons have now been demonstrated to be effective in several forms of papillomavirus infection. In vitro, chronic treatment of bovine papillomavirus-transformed cells led to the loss of the papillomavirus genomes and return of the cells to a normal morphology. In humans, interferons have been used for treating laryngeal papillomatosis, cutaneous and anogenital warts and epidermodysplasia verruciformis. Partial and total remissions have been achieved with both intralesional and systemic administration. Ongoing studies aim to identify which conditions are most responsive, the optimal dosage and regimen and the most effective class of interferon. The mechanisms by which these responses occur are unknown, but are thought to depend on interferon inducing specific cellular proteins.


[Dental implantation and prosthetics in Sjögren's syndrome].
The author discusses the methods and conditions for the successful outcome of implantation in patients with Sjögren's syndrome. Considers it no alternative orthopedic and psychological rehabilitation of the patient with objective xerostomia. Examines implantation in patients with Sjögren's syndrome as a specialized form of surgical care.


Women's experience of sexuality after radical cystectomy - a qualitative study.
The aim of this study was to explore how women experienced sexuality after radical cystectomy due to bladder cancer. We performed an interview study with qualitative design with content analysis. Inclusion criteria were age below 75 years. In total 10 women, with a median age of 64 years at surgery, were interviewed at median 24 months post radical cystectomy. The 10 women described sexual life as affected after surgery but they all tried to find ways to overcome the new situation together with their partner. The overall theme was 'A balance between emotional and physical closeness' emerged from 30 codes that were condensed into five subcategories and two categories: 'A sensual relationship' and 'A sexual relationship'. The first category constituted the subcategories 'Feeling of intimacy' and 'The importance of the relationship'. The category 'A sexual relationship' was revealed from the subcategories 'Reluctance to engage in sexual activity' and 'Partner inability to engage in sexual activity', and 'Acting for sexual rehabilitation'. The uncertainty that the women felt about their anatomical changes after radical cystectomy created a sexual anxiety and reluctance to resume intercourse. Even though the surgery had a major impact on their sexual life, the women tried to be sexually active. However, the meaning of sexual life was not just having sexual activity but also included closeness, affirmation, affection, and feeling attractive. Sexual counseling at an appropriate timepoint is essential to assure a balance between emotional and physical closeness, i.e. to regain sexual health.