Finding the Kool Mixx: how Brown & Williamson used music marketing to sell cigarettes.
To describe the history of Kool's music-themed promotions and analyse the role that music played in the promotion of the brand. Analysis of previously secret tobacco industry documents, legal documents, and promotional materials. Brown & Williamson started Kool sponsorship of musical events in 1975 with Kool Jazz concerts. Music was considered to be an effective marketing tool because: (1) music helped consumers make emotional connections with the brand; (2) music concerts were effective for targeted marketing; (3) music tied together an integrated marketing campaign; and (4) music had potential to appeal widely to a young audience. Brown & Williamson's first music campaigns successfully targeted young African-American male audiences. Subsequent campaigns were less effective, exploring different types of music to achieve a broader young adult appeal. This case study suggests Brown & Williamson used music most successfully for targeted marketing, but they failed to develop a wider audience using music because their attempts lacked consistency with the Kool brand's established identity. The 2004 "Kool Mixx" campaign both returned to Brown & Williamson's historic practice targeting young African-American males, and also exploited a musical genre with much more potential to bring Kool more universal appeal, as hip-hop music is increasingly popular among diverse audiences. Tobacco control efforts led by African-American community activists to oppose these marketing strategies should continue; expanding these coalitions to include the hip-hop community may further increase their effectiveness.


Prevalence, incidence, and risk factors of primary open-angle glaucoma - a cohort study based on longitudinal data from a German public health insurance.
This study estimates the prevalence and incidence rates of primary open -angle glaucoma (POAG) as well as risk factors based on a dataset from the largest German health insurance company. A random sample of 250,000 persons at age 50+ of the Allgemeine Ortskrankenkasse (AOK) from 2010 to 2013 was used. Selected risk factors of POAG incidence were analyzed using multivariate Cox proportional hazard models. The age-standardized prevalence of POAG at age 50+ in 2010 was 2.79% (95%-CI: 2.72-2.85%). The age-standardized total incidence rate was 0.38 (0.36-0.39) per 100 person-years. Sex differences were significant for total prevalence and total incidence rates, with higher prevalence and incidence rates for women compared to men. The Cox model revealed a strong age effect, a significantly 19% higher incidence for women (p ≤ 0.001), injuries of the eye and orbit (175%, p ≤ 0.001), degeneration of iris and ciliary body (155%, p = 0.022), myopia (155%, p ≤ 0.001), retinal vascular occlusions (134%, p ≤ 0.001), hypertension (13%, p ≤ 0.001) and diabetes mellitus (23%, p ≤ 0.001). Health claims data are an important data source for estimating POAG occurrence and help overcome the problems of small sample sizes. These results may help to understand the causal pathways of POAG and to develop intervention strategies to increase the awareness of patients and physicians with the aim of reducing POAG incidence.


Modulation of Amygdala Response by Cognitive Conflict in Adolescents with Conduct Problems and Varying Levels of CU Traits.
Adolescents with conduct problems and low callous-unemotional traits are characterised by high levels of reactive aggression. Prior studies suggest that they can have exaggerated neural and behavioural responses to negative emotional stimuli, accompanied by compromised affect regulation and atypical engagement of prefrontal areas during cognitive control. This pattern may in part explain their symptoms. Clarifying how neurocognitive responses to negative emotional stimuli can be modulated in this group has potential translational relevance. We present fMRI data from a cognitive conflict task in which the requirement to visually scan emotional (vs. calm) faces was held constant across low and high levels of cognitive conflict. Participants were 17 adolescent males with conduct problems and low levels of callous-unemotional traits (CP/LCU); 17 adolescents with conduct problems and high levels of callous-unemotional traits (CP/HCU, who typically show blunted reactivity to fear), and 18 typically developing controls (age range 10-16). Control participants showed typical attenuation of amygdala response to fear relative to calm faces under high (relative to low) conflict, replicating previous findings in a healthy adult sample. In contrast, children with CP/LCU showed a reduced (left amygdala) or reversed (right amygdala) attenuation effect under high cognitive conflict conditions. Children with CP/HCU did not differ from controls. Findings suggest atypical modulation of amygdala response as a function of task demands, and raise the possibility that those with CP/LCU are unable to implement typical regulation of amygdala response when cognitive task demands are high.


[Dual arterial infusion chemotherapy, continuous hyperthermic peritoneal perfusion, and total parietal peritonectomy for peritoneal dissemination in gastric cancer--a case report].
A 36-year-old man developed massive ascites, of which cytology proved Class V, and upper gastrointestinal endoscopy disclosed Borrmann type 4 gastric cancer. We performed dual arterial infusion chemotherapy (DAIC) through the celiac axis and superior mesenteric artery, followed by the operation including continuous hyperthermic peritoneal perfusion, total gastrectomy, subtotal colectomy, massive intestinal resection, splenectomy, cholecystectomy, appendectomy, and total parietal peritonectomy (TPP). Ascites disappeared and the CA125 level was normalized by DAIC. This operation was well tolerated. Though the histopathological study revealed multiple peritoneal disseminations on the visceral peritoneum of stomach, small intestine, colon, and parietal peritoneum such as Douglas' pouch, there were denatured cancer cells in the visceral peritoneum to which blood supply under DAIC was distributed. These results suggested the effect of neoadjuvant DAIC and the significance of TPP.


Recognizing the allergic individual.
Patients with respiratory tract allergy present certain auditory and visual signs which, when correlated with the history, aid substantially in arriving at a conclusive diagnosis. The physician should be alert to the signs that indicate allergic disease. Early recognition followed by modern allergy management will help to prevent progression of the allergic process.


The use of blood products in paediatric oncology units in the UK.
The clinical practice group of the Royal College of Nursing paediatric oncology nurses' forum carried out an exploratory study to examine practice in administration of blood products in children's cancer centres across the UK to identify any variances in practice. A questionnaire covering the use and administration of red cells, platelets and other supportive measures was distributed to each of the 22 UK Children's Cancer Study Groups centres of which 14 responded (63 per cent). Variations among the units were found in all aspects of blood product administration including decisions about when to transfuse, methods of transfusion, treatment of adverse reactions and use of supportive products. There were some differences between the practices reported and guidance for transfusion in neonates and older children published by the British Committee for Standards in Haematology Transfusion Task Force (2004); many of these differences were attributable to the specific needs of oncology patients. The development of national guidance or minimum safe standards specifically for paediatric oncology patients could assist in reducing practice variations. This study was undertaken in children's cancer units where administration of blood products is a daily occurrence. Variations in practice that were identified here are likely to be found in non oncology/haematology settings.


Assessing impacts of unconventional natural gas extraction on microbial communities in headwater stream ecosystems in Northwestern Pennsylvania.
Hydraulic fracturing and horizontal drilling have increased dramatically in Pennsylvania Marcellus shale formations, however the potential for major environmental impacts are still incompletely understood. High-throughput sequencing of the 16S rRNA gene was performed to characterize the microbial community structure of water, sediment, bryophyte, and biofilm samples from 26 headwater stream sites in northwestern Pennsylvania with different histories of fracking activity within Marcellus shale formations. Further, we describe the relationship between microbial community structure and environmental parameters measured. Approximately 3.2 million 16S rRNA gene sequences were retrieved from a total of 58 samples. Microbial community analyses showed significant reductions in species richness as well as evenness in sites with Marcellus shale activity. Beta diversity analyses revealed distinct microbial community structure between sites with and without Marcellus shale activity. For example, operational taxonomic units (OTUs) within the Acetobacteracea, Methylocystaceae, Acidobacteriaceae, and Phenylobacterium were greater than three log-fold more abundant in MSA+ sites as compared to MSA- sites. Further, several of these OTUs were strongly negatively correlated with pH and positively correlated with the number of wellpads in a watershed. It should be noted that many of the OTUs enriched in MSA+ sites are putative acidophilic and/or methanotrophic populations. This study revealed apparent shifts in the autochthonous microbial communities and highlighted potential members that could be responding to changing stream conditions as a result of nascent industrial activity in these aquatic ecosystems.


Effects of nifedipine on psychosis and tardive dyskinesia in schizophrenic patients.
In an open label study, two fixed doses of nifedipine (30 mg and 60 mg daily) were added to the usual antipsychotic drug treatments of 10 patients suffering from chronic schizophrenia. While no patient experienced significant improvements, statistically significant falls in Brief Psychiatric Rating Scales scores were observed. A significant reduction in Abnormal Involuntary Movement Scale scores was observed in those patients with tardive dyskinesia. After the addition of nifedipine, four of the 10 patients showed large increases in plasma neuroleptic activity (radioreceptor assay) that decreased to baseline levels within two weeks. The possibility that this represents competitive inhibition and subsequent induction of the liver metabolism of the antipsychotic drugs is discussed. Adverse effects encountered are also discussed.


Dynein light chain LC8 negatively regulates NF-kappaB through the redox-dependent interaction with IkappaBalpha.
Redox regulation of nuclear factor kappaB (NF-kappaB) has been described, but the molecular mechanism underlying such regulation has remained unclear. We recently showed that a novel disulfide reductase, TRP14, inhibits tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation, and we identified the dynein light chain LC8, which interacts with the NF-kappaB inhibitor IkappaBalpha, as a potential substrate of TRP14. We now show the molecular mechanism by which NF-kappaB activation is redox-dependently regulated through LC8. LC8 inhibited TNFalpha-induced NF-kappaB activation in HeLa cells by interacting with IkappaBalpha and thereby preventing its phosphorylation by IkappaB kinase (IKK), without affecting the activity of IKK itself. TNFalpha induced the production of reactive oxygen species, which oxidized LC8 to a homodimer linked by the reversible formation of a disulfide bond between the Cys(2) residues of each subunit and thereby resulted in its dissociation from IkappaBalpha. Butylated hydroxyanisol, an antioxidant, and diphenyleneiodonium, an inhibitor of NADPH oxidase, attenuated the phosphorylation and degradation of IkappaBalpha by TNFalpha stimulation. In addition LC8 inhibited NF-kappaB activation by other stimuli including interleukin-1beta and lipopolysaccharide, both of which generated reactive oxygen species. Furthermore, TRP14 catalyzed reduction of oxidized LC8. Together, our results indicate that LC8 binds IkappaBalpha in a redox-dependent manner and thereby prevents its phosphorylation by IKK. TRP14 contributes to this inhibitory activity by maintaining LC8 in a reduced state.


Semi-Jailing Technique Using a Neuroform3 Stent for Coiling of Wide-Necked Intracranial Aneurysms.
The semi-jailing technique (SJT) provides stent-assisted remodeling of the aneurysm neck during coil embolization without grasping the coil delivery microcatheter. We retrospectively evaluated the efficacy and safety of SJT using a Neuroform3 stent for coiling of wide-necked intracranial aneurysms. We collected the clinical and radiological data between January 2009 and June 2015 of the wide-necked aneurysms treated with SJT using a Neuroform3 stent. SJT using a Neuroform3 stent was attempted in 70 wide-necked aneurysms (68 patients). There were 56 unruptured and 14 ruptured aneurysms. The size of aneurysm ranged from 1.7 to 28.1 mm (mean 6.1 mm). The immediate angiographic results were complete occlusion in 55 aneurysms (78.6%), neck remnant in 7 (10.0%), and aneurysm remnant in 8 (11.4%). Overall, periprocedural complications occurred in 13 patients (19.1%), including asymptomatic thromboembolism in 7 (10.3%), symptomatic thromboembolism in 4 (5.9%), and symptomatic hemorrhagic complications in 2 (2.9%). Conventional angiography follow-up was obtained in 55 (78.6%) of 70 aneurysms (mean, 10.9 months). The result showed progressive occlusion in 7 aneurysms (12.7%) and recanalization in 1 aneurysm (1.8%). At the end of the observation period (mean, 17.5 months), all 54 patients without subarachnoid hemorrhage showed excellent clinical outcomes (modified Rankin Scale [mRS] 0), except two (mRS 1 or 2) and seven of 14 patients with subarachnoid hemorrhage remained symptom-free (mRS 0). In this report of 70 aneurysms, SJT using a Neuroform3 stent for coiling of wide-necked intracranial aneurysms showed good technical safety, as well as favorable clinical and angiographic outcomes.


Incidental finding of renal cell carcinoma with histological regressive aspects in a pregnant woman.
A renal cell carcinoma was incidentally discovered with sonography in a 32-year-old pregnant woman. Magnetic resonance imaging was used to provide further information about tumor stage without causing adverse effects on the fetus. The patient underwent radical nephrectomy at the third month of pregnancy and subsequently delivered a normal full-term child. Pathology revealed regressive aspects which can be possibly ascribed to high progesterone levels during pregnancy.


[Metabolism of potassium in preterm infants].
During the first days of life, hyperkalemia can affect 30 to 60% of very low birth weight infants free of acute renal insufficiency (i.e. nonoliguric hyperkalemia). The place of the kidney in the regulation of the potassium homeostasis of VLBW remains badly specified. To evaluate the rate and the mechanisms of hyperkalemia in infants born at less than 32 weeks' gestation. A prospective study was conducted in 33 preterm infants (BW=1289+/-382 g; GA=28.8+/-1.7 weeks). Fifteen consecutive 8-hour urine collections were performed for each infant from the 8th hour of life (495 periods). A plasma sample was obtained at the end of each urine collection. Sodium, potassium and creatinine were measured in urine and blood samples as often as possible. Plasma potassium concentrations varied significantly over the 15 successive periods with an initial value (P1) of 4.55+/-0.80 mmol/l, a peak on P3 (4.94+/-0.81 mmol/l) and the lowest value on P13 (3.88+/-0.42 mmol/l). Hyperkalemia (plasma potassium>6.0 mmol/l) was observed in 4 infants (12%) and in 1.2% of the periods. The cumulative potassium balance (output-input) was negative over the first 7 periods (-1.97 mmol/kg), and afterwards became positive (from P8 to P15:+1.57 mmol/kg). Over the first 3 days, plasma potassium concentrations were positively correlated (p<0.01) with urinary excretion of potassium, clearance of potassium, fractional excretion of potassium, and negatively with endogenous creatinine clearance. In the first days of life, very low birth weight infants present an increase in kalemia associated with a negative potassium balance indicating a intracellular to extracellular potassium shift rather than a lower renal potassium excretion.


Stimulation of adipogenesis, peroxisome proliferator-activated receptor-gamma (PPARgamma), and thyrotropin receptor by PPARgamma agonist in human orbital preadipocyte fibroblasts.
The symptoms and signs of Graves' ophthalmopathy (GO) result from both an accumulation of hydrated hyaluronan in the orbital muscles and connective tissues and an expansion of the orbital adipose tissues. Recent studies have suggested a link between the stimulation of adipogenesis within the orbit in GO and the expression in these tissues of TSH receptor (TSHR), the putative orbital autoantigen. To further investigate this association, we treated orbital fibroblasts from patients with GO with rosiglitazone, a thiazolidinedione agonist of the PPARgamma receptor that stimulates adipocyte differentiation. We found this compound to be a potent stimulator of functional TSHR expression as well as TSHR and PPARgamma mRNA levels in differentiated cultures. In addition, rosiglitazone treatment stimulated recruitment and differentiation of a subset of cells within these cultures into mature lipid-laden adipocytes. These results suggest that TSHR expression in GO orbital preadipocyte fibroblasts is linked to adipogenesis, and that ligation of the PPARgamma receptor results in differentiation of these cells. It is possible that endogenous PPARgamma ligands play a role in stimulating orbital adipogenesis in GO, and that future treatments may be aimed at antagonism of various components of the PPARgamma signaling system.


Subcutaneous Sparganosis of the Breast.
A 77-year-old African American woman presented to the dermatologist with two pruritic lumps in her right breast. She reported traveling to Mexico on a cruise ship two years prior to the onset of her lesions, but denied a history of previous breast masses or malignancy. Despite former radiographic evaluation by her internist revealing benign growths, and despite dermatologic treatment with intralesional steroid injections, a third new, firm nodule developed in her right breast. One such nodule eventually formed into an ulcer, and a punch biopsy revealed thin-walled vascular channels in loose inflamed stroma, coarse fibrosis, calcareous corpuscles, and an elongated parasite. Further review confirmed the parasite to be Sparganum, which is the larval stage of cestodes in the genus Spirometra. Sparganosis is a rare parasitic infection caused by the plerocercoid larva of the diphyllobothroid tapeworm. Though subcutaneous sparganosis of the breast is exceedingly rare, clinicians should consider this infection in their differential of nodular breast masses.


Understanding the relationship between suicidality, current depressed mood, personality, and cognitive factors.
Links between suicidality and depressed mood are well established. There is, however, little information about the emotional regulation processes that underlie the relationship between suicidality and current low mood, and how these processes differ between groups of never-suicidal (NS), suicidal ideators, and suicide attempters. As suicidality and depression are heterogeneous constructs, this study aimed to conduct within- and between-group comparisons of known suicide risk factors that are associated with emotion regulation (neuroticism, trait aggression, brooding, impulsivity, and overgeneral autobiographical memories). Correlational design using between- and within-group comparisons from self-report measures. Inter- and intragroup differences were identified using Pearson's correlation coefficients and tests of difference. An analysis of indirect effects was used to investigate whether the relationship between suicidality and current low mood was mediated by neuroticism, trait aggression, brooding, impulsivity, and overgeneral autobiographical memories, and if this relationship varied according to group type. Brooding appeared to be a consistent feature of all three groups and was closely related to current low mood. Compared to the NS group, the relationship between suicide attempts and current low mood showed greater associations with brooding, trait aggression, and overgeneral autobiographical memories. Compared to the NS group, the suicidal ideation group showed stronger associations with neuroticism and impulsivity, but these factors did not correlate with low mood. These results suggest a need for larger studies to focus on heterogeneity within suicidal populations and consider how different combinations of risk factors may heighten or reduce suicide risk. It is well known that the severity and intensity of suicide and depressed presentations vary because of underlying dispositional and contextual factors (Fried & Nesse, ) which, in turn, affect how events are interpreted and responded to. Despite this, there is little research about how these mechanisms operate in different types of suicide groups, and their influence on the relationship between suicidality and current low mood. Understanding interrelationships that affect current low mood is of clinical significance because past suicidal history and deteriorations in already negative mood are linked to repeated suicide attempts and completion. Our findings show that ruminative brooding, defined as a tendency to repeatedly think about emotional aspects of an event, consistently correlates with current low mood across different types of suicidal groups (NS, suicidal ideators, and suicide attempters), and across analyses. Findings also show that suicidal ideation and attempt groups were associated with specific personality characteristics that increased the propensity of emotional responding and interpretation compared to the NS group. The relationship between suicide attempt and current low mood had a higher propensity to be influenced by trait aggression, brooding, and overgenerality compared to the NS group. In contrast, although the suicidal ideation group correlated more strongly with neuroticism and impulsivity, these factors did not influence current low mood. In terms of clinical practice, these findings imply that specific styles of interpretation and thinking may maintain the relationship between suicidality and current low mood. Given the cross-sectional nature of the study, however, it is not possible to imply causality. Nevertheless, the findings obtained provide some support for transdiagnostic models of cognitive-behavioural processes that could be developed further.


Pilot-scale demonstration of dissolved organic nitrogen removal from an advanced water reclamation facility using enhanced coagulation.
Most wastewater treatment facilities that satisfy stricter discharge restrictions for nutrients, remove dissolved inorganic nitrogen (DIN) species efficiently, leaving dissolved organic nitrogen (DON) to be present at a higher proportion (up to 85 %) of total nitrogen (TN) in the effluent. Discharged DON promotes algae growth in receiving water bodies and is a growing concern in effluent potable reuse applications considering its potential to form hazardous nitrogenous disinfection byproducts (N-DBPs). Enhanced coagulation is an established process in the advanced water treatment train for most potable reuse applications. However, so far, no information has been collected at the pilot scale to address DON removal efficiency and process implications by enhanced coagulation under real conditions. This study performed a comprehensive evaluation of DON removal from the effluent of the Truckee Meadows Water Reclamation Facility (TMWRF) by enhanced coagulation over the course of 11 months at the pilot scale. Three different coagulants (aluminum sulfate (alum), poly‑aluminum chloride (PACl), ferric chloride (FC)) and a cationic polymer coagulant aid (Clarifloc) were used. Optimum doses for each coagulant and polymer and ideal pH were determined by jar tests and applied at the pilot. Alum (24 mg/L) resulted in highly variable DON removal (6 % - 40 %, 21 % on average), which was enhanced by the addition of polymer, leading to 32 % DON removal on average. PACl (40 mg/L) and FC (100 mg/L) resulted in more consistent DON removal (on average 45 % and 57 %, respectively); however, polymer addition exerted minimal enhancement for these coagulants. Overall, enhanced coagulation effectively reduced DON in the tertiary effluent at the pilot scale. The treatment showed auxiliary benefits, including dissolved organic carbon (DOC) and orthophosphate removal.


Serum-Free Thyroxine Levels Were Associated with Pulmonary Hypertension and Pulmonary Artery Systolic Pressure in Euthyroid Patients with Coronary Artery Disease.
The aim of this study was to evaluate the association between thyroid hormone levels, pulmonary hypertension (PH), and pulmonary artery systolic pressure (PASP) in euthyroid patients with coronary artery disease (CAD). A cross-sectional study was conducted in individuals who underwent coronary angiography and were diagnosed as CAD from March 2013 to November 2013. 811 subjects (185 women and 626 men) were included in this study. PASP was measured by transthoracic Doppler echocardiography. 86 patients were diagnosed as PH and had significantly higher free thyroxine (FT4) levels than those without PH. Multiple logistic regression analysis demonstrated an independent association of FT4 levels with PH after adjustment of gender, age, body mass index, systolic blood pressure, left ventricular ejection fraction, hypertension, and medication use of calcium channel blockers, ACE inhibitors, angiotensin II receptor antagonists, and nitrates. Serum-free triiodothyronine (FT3) and thyroid-stimulating hormone (TSH) were not associated with PH. Furthermore, multivariate linear regression analysis showed that FT4 levels emerged as an independent predictor for PASP, while FT3 and TSH levels were not associated with PASP. Our study demonstrated that, in euthyroid patients with CAD, FT4 was an independent risk factor for PH, and FT4 levels were independently associated with PASP.


Methylglyoxal-induced AMPK activation leads to autophagic degradation of thioredoxin 1 and glyoxalase 2 in HT22 nerve cells.
Methylglyoxal (MGO) is a major glycating agent that reacts with basic residues of proteins and promotes the formation of advanced glycation end products which are believed to play key roles in a number of pathologies, such as diabetes, Alzheimer's disease, and inflammation. We previously showed that MGO treatment targets the thioredoxin and the glyoxalase systems, leading to a decrease in Trx1 and Glo2 proteins in immortalized mouse hippocampal HT22 nerve cells. Here, we propose that autophagy is the underlying mechanism leading to Glo2 and Trx1 loss induced by MGO. The autophagic markers p62, and the lipidated and active form of LC3, were increased by MGO (0.5mM). Autophagy inhibition with bafilomycin or chloroquine prevented the decrease in Trx1 and Glo2 at 6 and 18h after MGO treatment. Proteasome inhibition by MG132 exacerbated the effect of MGO on Trx1 and Glo2 degradation (18h), further suggesting a role for autophagy. ATG5 small interfering RNA protected Trx1 and Glo2 from MGO-induced degradation, confirming Trx1 and Glo2 loss is mediated by autophagy. In the search for the signals that control autophagy, we found that AMPK activation, a known autophagy inducer, was markedly increased by MGO treatment. AMPK activation was confirmed by increased acetyl coenzyme A carboxylase phosphorylation, a direct AMPK substrate and by decreased mTOR phosphorylation, an indirect marker of AMPK activation. To confirm that MGO-mediated Trx1 and Glo2 degradation was AMPK-dependent, AMPK-deficient mouse embryonic fibroblasts (MEFs) were treated with MGO. Wildtype MEFs presented the expected decrease in Trx1 and Glo2, while MGO was ineffective in decreasing these proteins in AMPK-deficient cells. Overall, the data indicate that MGO activates autophagy in an AMPK-dependent manner, and that autophagy was responsible for Trx1 and Glo2 degradation, confirming that Trx1 and Glo2 are molecular targets of MGO.


Imaging Diagnosis of a Rare Presacral Tumour.
Primary tumors in the presacral (retrorectal) space are extremely rare in adults, with an estimated incidence of 0.0025 to 0.014 in large referral centers. Congenital varieties are most common and comprise two thirds of these tumors. Primary retroperitoneal sarcomas in the pelvic region are extremely rare. We report the ultrasound and the corresponding Computed Tomography (CT) features of a rare presacral fibrosarcoma in an adult woman, in whom the diagnosis was confirmed by a CT-guided biopsy. A 54-year-old woman presented with a history of lumbar and perineal pain and painful defecation. Rectal examination revealed a hard mass in the retrorectal space. The patient was referred for imaging and a laboratory evaluation with a clinical diagnosis of a presacral mass. An abdominal ultrasound was followed by laboratory evaluation of routine hematological and hepato-renal parameters, abdomino-pelvic CT and a CT-guided biopsy. The imaging studies showed a presacral solid mass with nodular calcifications. There was conspicuous absence of cystic or adipose contents and of sacral erosion/destruction. However, hepatic metastasis was present. All imaging features suggested a retroperitoneal sarcoma in the pelvic region with metastases to the liver. The diagnosis was confirmed by CT-guided biopsy. We are reporting a new case of a very rare entity, a presacral fibrosarcoma. The imaging approach and the analysis leading to an appropriate differential diagnosis and final diagnosis is highlighted in our case report.


The role of the new penicillins and cephalosporins in the management of infection in granulocytopenic patients.
Overall, the use of the new cephalosporins has not so far been a major breakthrough in the empire therapy of febrile episodes and infections in granulocytopenic patients. In the only controlled large study available so far (EORTC), the cefotaxime-containing regimen was definitely not the best among the combinations tested. It remains to be seen whether other cephalosporins such as cefoperazone or ceftazidime would perform better in the future; especially with ceftazidime alone or in combination with aminoglycosides, the early results appear to be very promising. Whether single drug therapy with one of these new cephalosporins, which usually results in a high serum bactericidal activity, will eventually prove to be as good as combination therapy will await evaluation of more patients over extended periods of time, with a special attention to the possible emergence of resistant pathogens.


Attenuation caused by infrequently updated covariates in survival analysis.
This paper deals with hazard regression models for survival data with time-dependent covariates consisting of updated quantitative measurements. The main emphasis is on the Cox proportional hazards model but also additive hazard models are discussed. Attenuation of regression coefficients caused by infrequent updating of covariates is evaluated using simulated data mimicking our main example, the CSL1 liver cirrhosis trial. We conclude that the degree of attenuation depends on the type of stochastic process describing the time-dependent covariate and that attenuation may be substantial for an Ornstein-Uhlenbeck process. Also trends in the covariate combined with non-synchronous updating may cause attenuation. Simple methods to adjust for infrequent updating of covariates are proposed and compared to existing techniques using both simulations and the CSL1 data. The comparison shows that while existing, more complicated methods may work well with frequent updating of covariates the simpler techniques may have advantages in larger data sets with infrequent updatings.


Portable Sequentially Shifted Excitation Raman spectroscopy as an innovative tool for in situ chemical interrogation of painted surfaces.
We present the first validation and application of portable Sequentially Shifted Excitation (SSE) Raman spectroscopy for the survey of painted layers in art. The method enables the acquisition of shifted Raman spectra and the recovery of the spectral data through the application of a suitable reconstruction algorithm. The technique has a great potentiality in art where commonly a strong fluorescence obscures the Raman signal of the target, especially when conventional portable Raman spectrometers are used for in situ analyses. Firstly, the analytical capability of portable SSE Raman spectroscopy is critically discussed using reference materials and laboratory specimens, comparing its results with other conventional high performance laboratory instruments (benchtop FT-Raman and dispersive Raman spectrometers with an external fiber optic probe); secondly, it is applied directly in situ to study the complex polychromy of Italian prestigious terracotta sculptures of the 16(th) century. Portable SSE Raman spectroscopy represents a new investigation modality in art, expanding the portfolio of non-invasive, chemically specific analytical tools.


Changes in high-density lipoprotein-cholesterol subfractions with exercise training may be dependent on cholesteryl ester transfer protein (CETP) genotype.
We sought to determine if a cholesteryl ester transfer protein (CETP) gene locus variation contributes to the variability in the responses of plasma high-density lipoprotein-cholesterol (HDL-C) and its subfractions to endurance exercise training. Middle- to older-aged men and women with at least 1 lipoprotein-lipid risk factor underwent 6 months of endurance exercise training while on a low-fat diet. Plasma lipid levels were measured by nuclear magnetic resonance (NMR). Initial age, body composition, lipoprotein-lipid profiles, and VO(2)max did not differ between the 2 CETP genotype groups (B1B1, n = 16; B1B2, n = 14). With exercise training, VO(2)max increased, and body weight, total body fat, and computed tomographic (CT) intra-abdominal visceral fat decreased similarly in both CETP genotype groups. Plasma total cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels did not change significantly with training in either genotype group. HDL(2NMR)-C levels increased with exercise training in CETP B1B1 (P <.05), but did not change in CETP B1B2 genotype individuals. HDL(3NMR)-C levels tended to decrease with training in CETP B1B1 persons and HDL(4NMR)-C levels tended to increase with training somewhat more in CETP B1B2 individuals, but these differences were not significant. HDL(5NMR)-C levels increased similarly with exercise training in the 2 groups. The integrated HDL(3-5NMR)-C levels increased with exercise training in CETP B1B2 (P <.05), but did not change in CETP B1B1 genotype individuals. Apolipoprotein E (APO E) or lipoprotein lipase (LPL) PvuII genotype did not associate with HDL-C subfraction changes with training. Thus, CETP genotype may contribute to the interindividual differences in plasma HDL-C subfraction changes occurring with endurance exercise training in sedentary middle- to older-aged men and women.


Myelopathy due to spinal metastasis from adenocarcinoma of the gallbladder.
The first case of a gallbaldder carcinoma with metastasis to dura and epidural space causing myelopathy is described. The mode of metastasis remains obscure because there was no involvement of liver or retroperitoneal veins. It is possible that the spread was by the vertebral venous plexus, which could account for a spinal metastasis in the absence of liver involvement.


Serum and transforming growth factor beta regulate glial fibrillary acidic protein in serum-free-derived mouse embryo cells.
Serum-free mouse embryo (SFME) cells, derived in medium in which serum is replaced with growth factors and other supplements, display distinctive properties: (i) SFME cells do not lose proliferative potential or show gross chromosomal aberration upon extended culture, (ii) these cells depend on epidermal growth factor for survival; and (iii) SFME cell proliferation is reversibly inhibited by serum. Treatment of SFME cells with serum or transforming growth factor beta led to the appearance of glial fibrillary acidic protein, a specific marker for astrocytes. The appearance of glial fibrillary acidic protein in cultures was reversed upon removal of transforming growth factor beta or serum. Cells with properties similar to SFME cells were also isolated from adult mouse brain. These results suggest a role for transforming growth factor beta in astrocyte differentiation in developing organisms and in response to injury and identify the cell type that has the unusual properties of SFME cells.


Anti-phospholipid antibodies restore mesenteric ischemia/reperfusion-induced injury in complement receptor 2/complement receptor 1-deficient mice.
Complement receptor 2-deficient (Cr2(-/-)) mice are resistant to mesenteric ischemia/reperfusion (I/R) injury because they lack a component of the natural Ab repertoire. Neither the nature of the Abs that are involved in I/R injury nor the composition of the target Ag, to which recognition is lacking in Cr2(-/-) mice, is known. Because anti-phospholipid Abs have been shown to mediate fetal growth retardation and loss when injected into pregnant mice, we performed experiments to determine whether anti-phospholipid Abs can also reconstitute I/R injury and, therefore, represent members of the injury-inducing repertoire that is missing in Cr2(-/-) mice. We demonstrate that both murine and human monoclonal and polyclonal Abs against negatively charged phospholipids can reconstitute mesenteric I/R-induced intestinal and lung tissue damage in Cr2(-/-) mice. In addition, Abs against beta2 glycoprotein I restore local and remote tissue damage in the Cr2(-/-) mice. Unlike Cr2(-/-) mice, reconstitution of I/R tissue damage in the injury-resistant Rag-1(-/-) mouse required the infusion of both anti-beta2-glycoprotein I and anti-phospholipid Ab. We conclude that anti-phospholipid Abs can bind to tissues subjected to I/R insult and mediate tissue damage.


One-pot procedure for diazo transfer and azide-alkyne cycloaddition: triazole linkages from amines.
[reaction: see text] A one-pot reaction for Cu(II)-catalyzed diazo transfer and Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition (sometimes called click reaction) is reported. 1,4-Disubstituted 1,2,3-triazoles are obtained in excellent yields from a variety of readily available amines without the need for isolation of the azide intermediates. The reaction has a broad scope and is especially practical for the synthesis of multivalent structures because compounds substituted with multiple azides are potentially unstable.


Plasma selenium decrease during pregnancy is associated with glucose intolerance.
There is an increased requirement for selenium during pregnancy, presumably for fetal growth, which manifests as decreasing maternal blood and tissue selenium concentrations. These decreases are greater in pregnant women with gestational or preexisting diabetes. We measured selenium status and glucose tolerance between wk 12 and 34 of gestation in 22 pregnant women. We found that the increase in blood glucose in response to an oral glucose challenge at 12 wk gestation and the increase in fasting glucose during pregnancy were inversely correlated with plasma selenium concentration. Women with lower plasma glutathione peroxidase activities during pregnancy also tended to have higher fasting glucose levels. These inverse relationships between selenium status and glucose tolerance are consistent with earlier observations that suggest a link between selenium and glucose metabolism. The observation that changes in serum glucose were not accompanied by changes in insulin suggests that selenium may affect glucose metabolism downstream from insulin, or through independent energy regulatory pathways such as thyroid hormone.


In vitro chemotherapy testing of transitional cell carcinoma.
The chemotherapeutic drug sensitivity of live cells freshly isolated from two human bladder tumors was studied. Substantial differences in the sensitivities of the two tumors to various chemotherapeutic drugs as well as different sensitivities of a given tumor to different drugs were found. Such data could be valuable clinically. The therapeutic value of cyclophosphamide, thiotepa and methotrexate was questionable for these two tumors because an increase in thymidine incorporation was seen after treatment with these drugs. A similar increase was observed after treatment with 5-fluorouracil in cells of a tissue-culture cell line derived from a human bladder tumor. Pretreatment of the cells with 5-fluorouracil reduced this effect. Even after 12 to 18 hours of exposure to 5-fluorouracil, the cells formed a confluent monolayer within 9 days. A similar treatment with doxorubicin hydrochloride resulted in detachment of the cells and formation of aggregates. The aggregated cells excluded trypan blue for at least 9 days after the doxorubicin hydrochloride was removed.


Combinatorial bulk ceramic magnetoelectric composite libraries of strontium hexaferrite and barium titanate.
Bulk ceramic combinatorial libraries were produced via a novel, high-throughput (HT) process, in the form of polycrystalline strips with a gradient composition along the length of the library. Step gradient ceramic composite libraries with 10 mol % steps of SrFe12O19-BaTiO3 (SrM-BT) were made and characterized using HT methods, as a proof of principle of the combinatorial bulk ceramic process, and sintered via HT thermal processing. It was found that the SrM-BT libraries sintered at 1175 °C had the optimum morphology and density. The compositional, electrical and magnetic properties of this library were analyzed, and it was found that the SrM and BT phases did not react and remained discrete. The combinatorial synthesis method produced a relatively linear variation in composition. The magnetization of the library followed the measured compositions very well, as did the low frequency permittivity values of most compositions in the library. However, with high SrM content of ≥80 mol %, the samples became increasingly conductive, and no reliable dielectric measurements could be made. Such conductivity would also greatly inhibit any ferroelectricity and magnetoelectric coupling with these composites with high levels of the SrM hexagonal ferrite.


Posterior Arthroscopic Subtalar Arthrodesis: Clinical and Radiologic Review of 19 Cases.
Arthroscopic subtalar arthrodesis has recently gained popularity in the treatment of primary subtalar or post-traumatic arthritis, coalition, or inflammatory diseases with subtalar arthritis. The present study reports the clinical and radiologic results of 19 patients (19 feet) who underwent posterior arthroscopic subtalar arthrodesis using 2 posterior portals. A total of 19 posterior arthroscopic subtalar arthrodeses (minimum follow-up of 24 months) performed without a bone graft and with 2 parallel screws were prospectively evaluated. The fusion rate was 94% (mean time to fusion 9.8 weeks). Modified American Orthopaedic Foot and Ankle Society ankle-hindfoot scale score (maximum 94 points) improved significantly from 43 to 80 points and the visual analog scale for pain score improved from 7.6 to 1.2. The 12-item short-form physical and mental scores at the last follow-up point were 52.5 and 56.4, respectively. One (5.3%) patient underwent open repeat fusion for nonunion, 2 (10.5%) patients required a second procedure for implant removal, and 1 (5.3%) experienced reversible neuropraxia. In conclusion, posterior arthroscopic subtalar arthrodesis is a safe technique with a good union rate and a small number of complications in patients with no or very little hindfoot deformity.


Plutonium(IV) and (V) Sorption to Goethite at Sub-Femtomolar to Micromolar Concentrations: Redox Transformations and Surface Precipitation.
Pu(IV) and Pu(V) sorption to goethite was investigated over a concentration range of 10(-15)-10(-5) M at pH 8. Experiments with initial Pu concentrations of 10(-15) - 10(-8) M produced linear Pu sorption isotherms, demonstrating that Pu sorption to goethite is not concentration-dependent across this concentration range. Equivalent Pu(IV) and Pu(V) sorption Kd values obtained at 1 and 2-week sampling time points indicated that Pu(V) is rapidly reduced to Pu(IV) on the goethite surface. Further, it suggested that Pu surface redox transformations are sufficiently rapid to achieve an equilibrium state within 1 week, regardless of the initial Pu oxidation state. At initial concentrations >10(-8) M, both Pu oxidation states exhibited deviations from linear sorption behavior and less Pu was adsorbed than at lower concentrations. NanoSIMS and HRTEM analysis of samples with initial Pu concentrations of 10(-8) - 10(-6) M indicated that Pu surface and/or bulk precipitation was likely responsible for this deviation. In 10(-6) M Pu(IV) and Pu(V) samples, HRTEM analysis showed the formation of a body centered cubic (bcc) Pu4O7 structure on the goethite surface, confirming that reduction of Pu(V) had occurred on the mineral surface and that epitaxial distortion previously observed for Pu(IV) sorption occurs with Pu(V) as well.


Design Strategies of Stimuli-Responsive Supramolecular Hydrogels Relying on Structural Analyses and Cell-Mimicking Approaches.
Stimuli-responsive hydrogels are intriguing biomaterials useful for spatiotemporal controlled release of drugs, cells, and biological cues, cell engineering for various applications, and medical diagnosis. To date, many physical and chemical stimuli-responsive polymer hydrogels have been developed by chemical modification of polymer chains and cross-linking points. In particular, conjugation with biomolecules to polymers produced promising biomolecule-responsive hydrogels. These examples clearly indicate high potentials of stimuli-responsive hydrogels as promising biomaterials. In addition to polymer hydrogels, supramolecular hydrogels formed by the assembly of small molecules (hydrogelators) via noncovalent interactions have also been regarded as unique and promising soft materials due to their flexible programmability in rendering them stimuli-responsive with the larger macroscopic change (i.e., gel-sol transition). This Account describes our strategies for the rational design of stimuli-responsive supramolecular hydrogels and their biological applications. Following the detailed structural analysis of a lead hydrogelator that clearly indicates the appropriate sites for incorporation of stimuli-responsive modules, we designed supramolecular hydrogels capable of responding to simple physical (thermal and light) and chemical (pH and metal ions) stimuli. More importantly, biomolecule-responsive hydrogels were successfully developed by supramolecularly mimicking the complex yet well-ordered structures and functions of live cells containing multiple components (a cell-mimicking approach). Development of biomolecule-responsive supramolecular hydrogels has been difficult as the conventional strategy relies on the chemical incorporation of stimuli-responsive modules, owing to the lack of modules that can effectively respond to structurally diverse and complicated biomolecules. Inspired by natural systems where functional compartments (e.g., cell organelles) sophisticatedly interact with each other, we sought to integrate the two distinct microenvironments of supramolecular hydrogels (the aqueous cavity surrounded by fibers and the fluidic hydrophobic fiber domain) with other functional materials (e.g., enzymes, peptides or proteins, fluorescent chemosensors, or inorganic porous or layered nanomaterials) for biomolecule responses. In situ fluorescence microscopy imaging clearly demonstrated that chemical isolation and crosstalk are highly successful between the integrated microenvironments in supramolecular hydrogels, similar to organelles in living cells, which allow for the construction of unique optical response and sensing systems for biomolecules. Furthermore, programmed hybridization of our chemically reactive hydrogels with appropriate enzymes can provide an unprecedented universal platform for biomolecule-degradable supramolecular hydrogels. Such biomolecule-responsive hydrogels are a potentially promising tool for user-friendly early diagnostics and on-demand drug-releasing soft materials. We expect that our rational design strategies for stimuli-responsive supramolecular hydrogels by modification of chemical structures and hybridization with functional materials will inspire scientists in various fields and lead to development of novel soft materials for biological applications.


Lipid transport through the enterocytes of larval Aeshna cyanea (Insecta, Odonata).
The larval enterocytes of A. cyanea absorb lipid after luminal lipolysis in morphologically invisible form by direct membrane transport, presumably molecular diffusion. The lipolytic products are utilized for resynthesis of di- and triglyceride which become visible in the form of lipid droplets in the groundplasm. The putative site of lipid synthesis is the apical ER which locally forms highly ordered complexes. Lipid transport occurs in the form of matrix lipid so that the enterocytes of dragonfly larvae resemble in this respect the lipid-secreting mammocytes rather than the lipid-absorbing mammalian enterocytes. Lipid release involves partial lipolysis and direct membrane transport, possibly including membrane delamination, again in contrast to exocytosis in mammalian enterocytes and apocrine extrusion in mammocytes, which are both indirect membrane transport mechanisms.


Single-particle tracking of murine polyoma virus-like particles on live cells and artificial membranes.
The lateral mobility of individual murine polyoma virus-like particles (VLPs) bound to live cells and artificial lipid bilayers was studied by single fluorescent particle tracking using total internal reflection fluorescence microscopy. The particle trajectories were analyzed in terms of diffusion rates and modes of motion as described by the moment scaling spectrum. Although VLPs bound to their ganglioside receptor in lipid bilayers exhibited only free diffusion, analysis of trajectories on live 3T6 mouse fibroblasts revealed three distinct modes of mobility: rapid random motion, confined movement in small zones (30-60 nm in diameter), and confined movement in zones with a slow drift. After binding to the cell surface, particles typically underwent free diffusion for 5-10 s, and then they were confined in an actin filament-dependent manner without involvement of clathrin-coated pits or caveolae. Depletion of cholesterol dramatically reduced mobility of VLPs independently of actin, whereas inhibition of tyrosine kinases had no effect on confinement. The results suggested that clustering of ganglioside molecules by the multivalent VLPs induced transmembrane coupling that led to confinement of the virus/receptor complex by cortical actin filaments.


[Gender differences in chronic kidney diseases : myth or reality ?]
Chronic kidney disease (CKD) concerns about 10 % of the population in Switzerland. Epidemiological studies suggest that women are less prone to the development of CKD than men, and progress less rapidly to end stage renal disease. This protection seems lost when entering menopause. The reasons for this finding may stem from hormonal, structural or hemodynamic differences, yet the precise underlying mechanisms are so far incompletely understood. Some animal studies suggest a potentially beneficial effect of estrogen therapy, mainly in diabetes, yet data in humans are lacking. This article provides an overview of epidemiological data and the different hypotheses concerning gender differences in CKD, and discusses the eventual benefits of estrogen therapy to retard CKD progression.


Magnetoelectrically coupled polariton excitation in a plasmonic crystal composed of nanorod dimers.
In this work, the long wavelength optical properties of a plasmonic crystal, composed of gold nanorod dimers arranged parallel, have been studied. Due to the strong coupling between incident light and the oscillation of free electrons inside nanorod dimers, the magnetically induced and/or magnetoelectrically coupled plasmonic polaritons can be excited. A theoretical demonstration has been proposed and coupled equations that show similar profiles to the Huang-Kun equations for ionic crystals have been deduced, indicating the constitutive abnormalities and polaritonic bandgap effect. The analogy between the magnetoelectrically coupled metamaterials and ionic crystals may shed light on physical explanations, as well as constitutive parameter retrieval, for the magnetoelectric metamaterials.


Upregulated long non-coding RNA SBF2-AS1 promotes proliferation in esophageal squamous cell carcinoma.
Esophageal cancer is one of the most common types of malignant tumors located within the digestive system, with >50% of esophageal cancer cases worldwide occurring in China. Recent studies have demonstrated that long non-coding RNAs (lncRNAs) are frequently dysregulated in cancer; however, few lncRNAs have been characterized in esophageal squamous cell carcinoma (ESCC). In the present study, a novel lncRNA, SET-binding factor 2 (SBF2) antisense RNA1 (SBF2-AS1) was exhibited in ESCC. Expression levels of SBF2-AS1 in ESCC and adjacent non-cancerous tissues were detected using the reverse transcription-quantitative polymerase chain reaction. SBF2-AS1 was knocked down, and proliferation, migration, invasion, apoptosis and the cell cycle were examined in ESCC cells. Results identified that SBF2-AS1 was significantly upregulated in ESCC compared with adjacent non-cancerous tissues (fold increase, 8.82; P=0.023). The SBF2-AS1 expression level was significantly increased in patients who had a smoking (9.927 vs. 4.507; P=0.030) and/or drinking (10.938 vs. 4.232; P=0.032) history. Patients with a large tumor size exhibited increased SBF2-AS1 expression (≥4 vs. <4 cm, 14.898 vs. 5.435; P=0.018). Patients with advanced ESCC exhibited increased upregulation of SBF2-AS1 [tumor-node-metastasis (TNM) I-II vs. TNM III-IV, 1.302 vs. 15.475; P<0.01]. SBF2-AS1 was also silenced using small interfering RNA. Cell proliferative and invasive ability were significantly inhibited (P<0.05) following SBF2-AS1 silencing, the cell cycle was arrested in the G2 phase; however, there was no significant difference in the proportion of apoptotic cells. Gene Set Enrichment Analysis revealed that genes associated with cell cycle biological processes, including the cancer suppressor gene cyclin-dependent kinase 1A (CDKN1A), were significantly associated with SBF2-AS1 in ESCC tissues. Further validation confirmed that CDKN1A expression levels were increased in ECA-109 cells following SBF2-AS1 silencing. The results of the present study demonstrate that SBF2-AS1 is significantly upregulated in ESCC, and that silencing of SBF2-AS1 inhibits the proliferative and invasive ability of ESCC cells. SBF2-AS1 may be a novel biomarker and therefore a potential therapeutic target for ESCC.


In Silico Models for Design and Optimization of Science-Based Listeria Environmental Monitoring Programs in Fresh-Cut Produce Facilities.
Food facilities need time- and cost-saving methods during the development and optimization of environmental monitoring for pathogens and their surrogates. Rapid virtual experimentation through in silico modeling can alleviate the need for extensive real-world, trial-and-error style program design. Two agent-based models of fresh-cut produce facilities were developed as a way to simulate the dynamics of Listeria in the built environment by modeling the different surfaces of equipment and employees in a facility as agents. Five sampling schemes at three time points were evaluated in silico on their ability to locate the presence of Listeria contamination in a facility with sample sites for each scheme (i.e., scenario, as modeled using scenario analysis) based on the following: the facilities' current environmental monitoring program (scenario 1), Food and Drug Administration recommendations (scenario 2), random selection (scenario 3), sites exclusively from zone 3 (i.e., sites in the production room but not directly adjacent to food contact surfaces) (scenario 4), or model prediction of elevated risk of contamination (scenario 5). Variation was observed between the scenarios on how well the Listeria prevalence of the virtually collected samples reflected the true prevalence of contaminated agents in the modeled operation. The zone 3 only (scenario 4) and model-based (scenario 5) sampling scenarios consistently overestimated true prevalence across time, suggesting that those scenarios could provide a more sensitive approach for determining if Listeria is present in the operation. The random sampling scenario (scenario 3) may be more useful for operations looking for a scheme that is most likely to reflect the true prevalence. Overall, the developed models allow for rapid virtual experimentation and evaluation of sampling schemes specific to unique fresh-cut produce facilities. IMPORTANCE Programs such as environmental monitoring are used to determine the state of a given food facility with regard to the presence of environmental pathogens, such as Listeria monocytogenes, that could potentially cross-contaminate food product. However, the design of environmental monitoring programs is complex, and there are infinite ways to conduct the sampling that is required for these programs. Experimentally evaluating sampling schemes in a food facility is time-consuming, costly, and nearly impossible. Therefore, the food industry needs science-based tools to aid in developing and refining sampling plans that reduce the risk of harboring contamination. Two agent-based models of two fresh-cut produce facilities reported here demonstrate a novel way to evaluate how different sampling schemes can be rapidly evaluated across multiple time points as a way to understand how sampling can be optimized in an effort to locate the presence of Listeria in a food facility.


Dynamic catch-bonding generates the large stall forces of cytoplasmic dynein.
Cytoplasmic dynein is an important molecular motor involved in the transport of vesicular and macromolecular cargo along microtubules in cells, often in conjunction with kinesin motors. Dynein is larger and more complex than kinesin and the mechanism and regulation of its movement is currently the subject of intense research. While it was believed for a long time that dynein motors are relatively weak in terms of the force they can generate, recent studies have shown that interactions with regulatory proteins confer large stall forces comparable to those of kinesin. This paper reports on a theoretical study which suggests that these large stall forces may be the result of an emergent, ATP-dependent, bistability resulting in a dynamic catch-bonding behavior that can cause the motor to switch between high and low load-force states.


Pulmonary mucosa-associated lymphoid tissue type lymphoma with increased accumulation of fluorine 18-fluorodeoxyglucose on positron emission tomography.
Mucosa-associated lymphoid tissue (MALT) type lymphoma has generally been thought not to show increased fluorine 18-fluorodeoxyglucose (FDG) accumulation on positron emission tomography (PET), based on previous research. Only a limited numbers of articles have been published on this topic, however, involving a small number of cases. Although positive FDG PET results might be uncommon in this entity, a case of increased FDG accumulation in a case of MALT type lymphoma of the lung is presented.


Biology and management of acquired severe aplastic anemia.
Severe aplastic anemia (SAA) is a life-threatening bone marrow failure disorder characterized by pancytopenia and a hypocellular marrow. Drugs, chemical exposure, radiation, and viruses are implicated as etiologic agents, although the majority of community-acquired SAA is idiopathic. Regardless of the inciting event, most cases of SAA result from immune-mediated destruction of bone marrow progenitor cells, which spares pluripotent hematopoietic stem cells. SAA is treated by either allogeneic bone marrow transplantation (BMT) or immunosuppressive therapy. BMT restores normal hematopoiesis and cures the disease in 60% to 80% cases, with the major causes of failure being graft rejection and graft-versus-host disease. Most patients treated with immunosuppressive therapy recover hematopoiesis sufficiently to not require transfusions and are free of infection, although in many, recovery is incomplete. Moreover, up to 50% of SAA patients successfully treated with immunosuppressive therapy relapse or develop a secondary clonal disorder, such as paroxysmal nocturnal hemoglobinuria, myelodysplastic syndrome, or leukemia. High-dose cyclophosphamide without BMT is capable of restoring normal hematopoiesis with little or no risk of relapse or secondary clonal disorders. A number of effective treatment options for the treatment of SAA are now available. The optimal approach for definitive management of SAA continues to evolve.


Molecular structures reveal synergistic rescue of Δ508 CFTR by Trikafta modulators.
The predominant mutation causing cystic fibrosis, a deletion of phenylalanine 508 (Δ508) in the cystic fibrosis transmembrane conductance regulator (CFTR), leads to severe defects in CFTR biogenesis and function. The advanced therapy Trikafta combines the folding corrector tezacaftor (VX-661), the channel potentiator ivacaftor (VX-770), and the dual-function modulator elexacaftor (VX-445). However, it is unclear how elexacaftor exerts its effects, in part because the structure of Δ508 CFTR is unknown. Here, we present cryo-electron microscopy structures of Δ508 CFTR in the absence and presence of CFTR modulators. When used alone, elexacaftor partially rectified interdomain assembly defects in Δ508 CFTR, but when combined with a type I corrector, did so fully. These data illustrate how the different modulators in Trikafta synergistically rescue Δ508 CFTR structure and function.


Incorporating Observed Physiological Data to Personalize Pediatric Vital Sign Alarm Thresholds.
Bedside monitors are intended as a safety net in patient care, but their management in the inpatient setting is a significant patient safety concern. The low precision of vital sign alarm systems leads to clinical staff becoming desensitized to the sound of the alarm, a phenomenon known as alarm fatigue. Alarm fatigue has been shown to increase response time to alarms or result in alarms being ignored altogether and has negative consequences for patient safety. We present methods to establish personalized thresholds for heart rate and respiratory rate alarms. These thresholds are first chosen based on patient characteristics available at the time of admission and are then adapted to incorporate vital signs observed in the first 2 hours of monitoring. We demonstrate that the adapted thresholds are similar to those chosen by clinicians for individual patients and would result in fewer alarms than the currently used age-based thresholds. Personalized vital sign alarm thresholds can help to alleviate the problem of alarm fatigue in an inpatient setting while ensuring that all critical vital signs are detected.


Targeting the MYC and PI3K pathways eliminates leukemia-initiating cells in T-cell acute lymphoblastic leukemia.
Disease relapse remains the major clinical challenge in treating T-cell acute lymphoblastic leukemia (T-ALL), particularly those with PTEN loss. We hypothesized that leukemia-initiating cells (LIC) are responsible for T-ALL development and treatment relapse. In this study, we used a genetically engineered mouse model of Pten(-/-) T-ALL with defined blast and LIC-enriched cell populations to demonstrate that LICs are responsible for therapeutic resistance. Unlike acute and chronic myelogenous leukemia, LICs in T-ALL were actively cycling, were distinct biologically, and responded differently to targeted therapies in comparison with their differentiated blast cell progeny. Notably, we found that T-ALL LICs could be eliminated by cotargeting the deregulated pathways driven by PI3K and Myc, which are altered commonly in human T-ALL and are associated with LIC formation. Our findings define critical events that may be targeted to eliminate LICs in T-ALL as a new strategy to treat the most aggressive relapsed forms of this disease.


Effect of prompt revascularization on outcomes in diabetic patients with stable ischemic heart disease and previous myocardial infarction in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) trial.
Survivors of a myocardial infarction (MI) are at a considerable risk of developing further cardiovascular events, including recurrent MI, heart failure, stroke, and death. Patients with type 2 diabetes mellitus and stable ischemic heart disease (SIHD) have worse outcomes than their nondiabetic counterparts, and those with previous MI may be at particularly high risk. Yet, little is known about the effect of adding prompt revascularization to intensive medical therapy in this high-risk group. We carried out a post-hoc analysis of the Bypass Angioplasty Revascularization Investigation 2 Diabetes trial, which randomized patients with type 2 diabetes mellitus and SIHD to prompt revascularization with percutaneous coronary intervention or coronary artery bypass grafting in addition to intensive medical therapy or intensive medical therapy alone. Previous MI status was defined by a history of MI or pathologic Q-waves. The primary endpoints were death, nonfatal or fatal MI, nonfatal or fatal stroke, congestive heart failure, and a composite of death/MI/stroke. Of the 2280 patients with evaluable data, 936 had previous MI. In these patients, there were no differences in the 5-year event-free rates of all-cause death, MI, stroke, congestive heart failure, or death/MI/stroke between those who were randomized to prompt revascularization in addition to intensive medical therapy and those who were randomized to intensive medical therapy alone. In diabetic patients with SIHD and previous MI, adding prompt revascularization to intensive medical therapy yielded no benefit compared with intensive medical therapy alone. These findings underscore the importance of intensive medical therapy in mitigating further ischemic events.


Impact of Oxygen Supplementation on Brachial Artery Hemodynamics and Vascular Function During Ascent to 5,050 m.
Vizcardo-Galindo, Gustavo A., Connor A. Howe, Ryan L. Hoiland, Howard H. Carter, Christopher K. Willie, Philip N. Ainslie, and Joshua C. Tremblay. Impact of oxygen supplementation on brachial artery hemodynamics and vascular function during ascent to 5,050 m. High Alt Med Biol. 24:27-36, 2023.-High-altitude trekking alters upper limb hemodynamics and reduces brachial artery vascular function in lowlanders. Whether these changes are reversible with the removal of hypoxia is unknown. We investigated the impact of 20 minutes of oxygen supplementation (O2) on brachial artery hemodynamics, reactive hyperemia (RH; microvascular function), and flow-mediated dilation (FMD; endothelial function). Participants (aged 21-42 years) were examined before and with O2 at 3,440 m (n = 7), 4,371 m (n = 7), and 5,050 m (n = 12) using Duplex ultrasound (days 4, 7, and 10 respectively). At 3,440 m, O2 decreased brachial artery diameter (-5% ± 5%; p = 0.04), baseline blood flow (-44% ± 15%; p < 0.001), oxygen delivery (-39 ± 16; p < 0.001), and peak RH (-8% ± 8%; p = 0.02), but not RH normalized for baseline blood flow. Elevated FMD (p = 0.04) with O2 at 3,440 m was attributed to the reduction in baseline diameter. At 5,050 m, a reduction in brachial artery blood flow (-17% ± 22%; p = 0.03), but not oxygen delivery, diameter, RH, or FMD occurred with O2. These findings suggest that during early trekking at high altitude, O2 causes vasoconstriction in the upper limb along the arterial tree (conduit and resistance arteries). With incremental high-altitude exposure, O2 reduces blood flow without compromising oxygen delivery, RH, or FMD, suggesting a differential impact on vascular function modulated by the duration and severity of high-altitude exposure.


Relationship between Gestational Weight Gain Rate Trajectory and Overweight in Offspring at Three Years of Age.
Background: The incidence of childhood obesity has increased rapidly, and its relationship with adult diseases is constantly being revealed. Maternal factors have been shown to play an important role in the growth and development of newborns. In this article, we explored the relationship between the gestational weight gain (GWG) rate and overweight/obesity in offspring at 3 years of age. Methods: A total of 5146 pregnant women and their children registered between January 2010 and December 2018 were studied by a retrospective cohort study. The Group-based Trajectory Model was used to distinguish the GWG rate patterns. Overweight/obesity was diagnosed by the weight-for-height Z-score at 3 years of age. Logistic regression was used to analyze the association between GWG rate patterns and outcomes. Odds ratio (OR) and 95% confidence interval (95% CI) were calculated to analyze the association between GWG rate patterns and overweight/obesity in offspring at 3 years of age. Results: Three GWG rate growth patterns were identified in this study. The incidence of offspring overweight/obesity in the low-stable, high-stable, and low-sharp patterns was 8.33%, 3.68%, and 6.03% respectively. After adjusting covariates, compared with the low-stable pattern, the high-stable pattern increased the risk for offspring to be overweight/obesity at 3 years of age, with OR of 2.26 (95% CI, 1.31-3.90). However, the low-sharp pattern was not associated with overweight/obesity in offspring at 3 years of age. Conclusions: The high-stable increasing pattern of the GWG rate is a risk factor for overweight/obesity in offspring at 3 years of age.


Brewing yeast genomes and genome-wide expression and proteome profiling during fermentation.
The genome structure, ancestry and instability of the brewing yeast strains have received considerable attention. The hybrid nature of brewing lager yeast strains provides adaptive potential but yields genome instability which can adversely affect fermentation performance. The requirement to differentiate between production strains and assess master cultures for genomic instability has led to significant adoption of specialized molecular tool kits by the industry. Furthermore, the development of genome-wide transcriptional and protein expression technologies has generated significant interest from brewers. The opportunity presented to explore, and the concurrent requirement to understand both, the constraints and potential of their strains to generate existing and new products during fermentation is discussed.


Creatine Supplementation: An Update.
Creatine is a popular and widely used ergogenic dietary supplement among athletes, for which studies have consistently shown increased lean muscle mass and exercise capacity when used with short-duration, high-intensity exercise. In addition to strength gains, research has shown that creatine supplementation may provide additional benefits including enhanced postexercise recovery, injury prevention, rehabilitation, as well as a number of potential neurologic benefits that may be relevant to sports. Studies show that short- and long-term supplementation is safe and well tolerated in healthy individuals and in a number of patient populations.


State of the Art - Rectal Cancer Surgery.
In an aging society, the incidence and relevance of rectal cancer as one of the most frequent gastrointestinal cancers gains in importance. Excellent surgery and up-to-date multimodal treatments are essential for adequate oncological results and good quality of life. In this review, we describe modern developments in rectal cancer surgery and its embedment in modern multimodal therapy concepts. Distinguished interdisciplinary cooperation combined with an outstanding surgical expertise is the basic requirement for an optimal treatment of rectal cancer. Thus, high standards of oncological outcome and patient's quality of life can be achieved.


Role of Combination Antimicrobial Therapy for Vancomycin-Resistant Enterococcus faecium Infections: Review of the Current Evidence.
Enterococcus species are the second most common cause of nosocomial infections in the United States and are particularly concerning in critically ill patients with preexisting comorbid conditions. Rising resistance to antimicrobials that were historically used as front-line agents for treatment of enterococcal infections, such as ampicillin, vancomycin, and aminoglycosides, further complicates the treatment of these infections. Of particular concern are Enterococcus faecium strains that are associated with the highest rate of vancomycin resistance. The introduction of antimicrobial agents with specific activity against vancomycin-resistant Enterococcus (VRE) faecium including daptomycin, linezolid, quinupristin-dalfopristin, and tigecycline did not completely resolve this clinical dilemma. In this review, the mechanisms of action and resistance to currently available anti-VRE antimicrobial agents including newer agents such as oritavancin and dalbavancin will be presented. In addition, novel combination therapies including β-lactams and fosfomycin, and the promising results from in vitro, animal studies, and clinical experience in the treatment of VRE faecium will be discussed.


Comparison of younger and elderly patients with pulmonary tuberculosis.
A comparison of the clinical features, predisposing factors, drug-induced adverse effects and diagnostic approach in pulmonary tuberculosis in 37 younger and 35 elderly men was carried out. Elderly patients had a higher number of underlying diseases, including cardiovascular diseases and hypertension, than younger patients. The classic symptoms and signs of tuberculosis, such as productive cough, fever and general fatigue, were observed in relatively high proportions of both patients, whereas weight loss (43 vs. 16%) and crackles in the lung fields (49 vs. 16%) were significantly higher in the elderly patients than the younger ones. As for roentgenographic abnormalities, a higher involvement of middle and lower lung fields was seen in the elderly patients than in the younger. Although leukocytosis was noted in a significantly lower proportion of the elderly patients, neutropenia due to drug treatment was significantly higher (23%) than in younger patients (5%). In a mass survey, the detection of pulmonary tuberculosis in elderly men was significantly lower (23%) than that in younger men (54%), suggesting that an extensive mass survey for pulmonary tuberculosis in elderly men should be done.


Emerging role of exosomes in vascular diseases.
Exosomes are biological small spherical lipid bilayer vesicles secreted by most cells in the body. Their contents include nucleic acids, proteins, and lipids. Exosomes can transfer material molecules between cells and consequently have a variety of biological functions, participating in disease development while exhibiting potential value as biomarkers and therapeutics. Growing evidence suggests that exosomes are vital mediators of vascular remodeling. Endothelial cells (ECs), vascular smooth muscle cells (VSMCs), inflammatory cells, and adventitial fibroblasts (AFs) can communicate through exosomes; such communication is associated with inflammatory responses, cell migration and proliferation, and cell metabolism, leading to changes in vascular function and structure. Essential hypertension (EH), atherosclerosis (AS), and pulmonary arterial hypertension (PAH) are the most common vascular diseases and are associated with significant vascular remodeling. This paper reviews the latest research progress on the involvement of exosomes in vascular remodeling through intercellular information exchange and provides new ideas for understanding related diseases.


Guideline-recommended secondary prevention drug therapy after acute myocardial infarction: predictors and outcomes of nonadherence.
Guideline-recommended pharmacotherapy after myocardial infarction (MI) has been shown to reduce cardiovascular morbidity and mortality. Our objectives were to determine factors of, and to measure outcomes associated with nonadherence after MI. Multicentre, prospective, observational study (Acute Coronary Syndromes Registry). We analyzed data of 11,823 consecutive hospital survivors of acute MI and evaluated their discharge medication with the five following drugs: acetyl salicylic acid, clopidogrel, β-blocker, angiotensin-converting enzyme inhibitor/sartan and statin. Patients receiving less than four drugs (group 1, n=3439, 29.1%) were compared with those receiving 4-5 drugs (group 2, n=8384, 70.9%). The impact of clinical, demographic and treatment factors on not prescribing each of these five drugs at discharge was investigated by using multiple logistic regression models. Patients of group 1 were older, had more comorbidities, more frequently suffered a nonST elevation MI and less often received reperfusion therapy. In the multivariate analysis, group 1 was associated with an increased risk for death at 1-year follow-up [odds ratio (OR): 1.6, 95% confidence interval (CI): 1.4-1.9]. After adjustment for confounding variables chronic oral anticoagulation was the strongest predictor for not receiving acetyl salicylic acid (OR: 19.6, 95% CI: 15.9-24.0) at discharge, no percutaneous coronary intervention within 48 h for not receiving statin (OR: 2.1, 95% CI: 1.9-2.4) and clopidogrel (OR: 10.4, 95% CI: 9.4-11.5), chronic obstructive lung disease for not receiving β-blocker (OR: 4.2, 95% CI: 3.6-4.9) and chronic renal insufficiency for not receiving angiotensin-converting enzyme inhibitor/sartan (OR: 2.8, 95% CI: 2.2-3.5). In clinical practice guideline-adherent secondary prevention drug therapy is linked with an improved 1-year survival. Comorbidities and no interventional treatment were strong negative predictors for guideline-adherent discharge medication.


Correlation between asthma severity and serum IgE in asthmatic children sensitized to Dermatophagoides pteronyssinus.
We undertook this study to test the possible correlation between serum concentration of total and specific IgE antibodies and asthma severity in asthmatic children sensitized to the house dust mite Dermatophagoides pteronyssinus. The study included 157 asthmatic children aged 5-15 years (8 +/- 3 years). Clinical diagnosis was based on personal and family history, physical examination, pulmonary function testing and skin tests. Asthma severity was determined according to GINA guidelines. In vitro tests included serum concentration of total and specific IgE. All asthmatic children had elevated serum concentration of total IgE. The children with elevated serum concentration of total IgE also showed an increased serum concentration of specific IgE. Asthma of higher higher severity was present in patients with total IgE concentration >288.0 kIU/L (AUC = 0.736) and specific IgE to Dermatophagoides pteronyssinus >44.1 kIUA/L (AUC = 0.843). Intermittent asthma was present in 76.9% of children with specific IgE concentration <44.1 kIUA/L. The positive predictive value suggested with 79.2% probability that a child with a concentration of specific IgE to Dermatophagoides pteronyssinus >44.1 kIUA/L would have a more severe form of asthma. Asthmatic children with higher asthma severity have a higher serum concentration of both total IgE (>288.0 kIU/L) and specific IgE to Dermatophagoides pteronyssinus (>44.1 kIUA/L), respectively.


Effects of Climate Change on Epidemics of Powdery Mildew in Winter Wheat in China.
Powdery mildew is a highly destructive winter wheat pathogen in China. Since the causative agent is sensitive to changing weather conditions, we analyzed climatic records from regions with previous wheat powdery mildew epidemics (1970 to 2012) and investigated the long-term effects of climate change on the percent acreage (PA) of the disease. Then, using PA and the pathogen's temperature requirements, we constructed a multiregression model to predict changes in epidemics during the 2020s, 2050s, and 2080s under representative concentration pathways RCP2.6, RCP4.5, and RCP8.5. Mean monthly air temperature increased from 1970 to 2012, whereas hours of sunshine and relative humidity decreased (P < 0.001). Year-to-year temperature changes were negatively associated with those of PA during oversummering and late spring periods of disease epidemics, whereas positive relationships were noted for other periods, and year-to-year changes in relative humidity were correlated with PA changes in the early spring period of disease epidemics (P < 0.001). Our models also predicted that PA would increase less under RCP2.6 (14.43%) than under RCP4.5 (14.51%) by the 2020s but would be higher by the 2050s and 2080s and would increase least under RCP8.5 (14.37% by the 2020s). Powdery mildew will, thus, pose an even greater threat to China's winter wheat production in the future.


The effect of 17-methoxyl-7-hydroxy-benzene-furanchalcone isolated from Millettia pulchra on myocardial ischemia in vitro and in vivo.
The effect of 17-methoxyl-7-hydroxy-benzene-furanchalcone isolated from the roots of Millettia pulchra (Benth.) Kurz var. Laxior (Dunn) Z. Wei on rat myocardial ischemia has been investigated. An in vitro cardiocyte apoptosis model and an in vivo myocardial ischemia model were used to elucidate the mechanism of 17-methoxyl-7-hydroxy-benzene-furanchalcone. In contrast to hydrogen peroxide (H2O2, 100 µmol/L), 17-methoxyl-7-hydroxy-benzene-furanchalcone in vitro (255 and 510 µmol/L) increased the quantity of total superoxide dismutase and the protein expression of B cell lymphoma/leukemia-2, while it inhibited cardiocyte apoptosis, the release of malondialdehyde and tumor necrosis factor α, and protein expression of nuclear factor κ Bp65 and Bcl-2-associated X protein. Furthermore, pretreatment with MHBFC in vivo (10 and 20 mg/kg) decreased heart rate, systolic pressure, diastolic pressure, average pressure, left ventricular systolic pressure, the largest upstroke velocity of the left ventricular pressure (+ dp/dtmax), total antioxidative capability, myoglobin isoenzyme of creatine kinase, and inducible nitric oxide synthase, while it increased endothelial nitric oxide synthase, ATPases, left ventricular diastolic pressure, left ventricular end-diastolic pressure, the largest descendent velocity of the left ventricular pressure (-dp/dtmax) and the interval from the beginning of left ventricular contraction to +dp/dtmax (t - dp/dtmax), all in a dose-dependent manner. Our present results suggest that 17-methoxyl-7-hydroxy-benzene-furanchalcone is an attractive antimyocardial ischemia agent mostly because of its negative heart rate and negative inotropic effects, the reduction in myocardial oxidative damage, and the modulating expression of genes associated with apoptosis, which improves diastolic function.


Probing infinity in bounded two-dimensional electrostatic systems.
The total electrostatic energy of systems of identical particles of equal charge is studied in configurations bounded in space, but divergent in the number of charges. This approach shall guide us to unveil a non-linear, functional form specifying the divergent nature of system energy. We consider fractals to be physical entities, with charges located in their vertices or nodes. This description is interesting since features, such as the corresponding fractal dimension, can characterize the total energy EN. Finally, at local length scales, we describe how energy diverges at charge accumulation points in the fractal, that is, almost everywhere by definition.


Short-term outcomes of neoadjuvant hormonal therapy versus neoadjuvant chemotherapy in breast cancer: systematic review and meta-analysis of randomized controlled trials.
Estrogen receptor positive (ER+) breast cancer (BC) is highly hormonal therapy-responsive. The choice between neoadjuvant hormonal therapy (NHT) and neoadjuvant chemotherapy (NCT) remains controversial. The aim of this meta-analysis was to evaluate benefits and safety of NHT compared with NCT for operable BC patients. Areas covered: Electronic databases were searched to identify randomized clinical trials (RCTs) comparing NHT and NCT for treatment of invasive and immunohistochemically ER+ BC. Major outcomes were clinical response rate, pathologic complete response (pCR), operation methods, recurrence, and adverse events. Five RCTs were included. The clinical response rates between NHT and NCT were not statistically different overall, or in ER-rich patients or postmenopausal women. Compared with NCT, NHT had a significant reduction of complete response rate and an increment in progressive disease rate. NHT increased rates of breast conserving surgery (BCS) and wide local excision (WLE) compared with NCT. All the other parameters were comparable. Patients receiving NHT had better tolerance than those undergoing NCT. Expert commentary: When treating BC, NHT was well tolerated, and contributed to more BCS and WLE cases, especially in ER-rich postmenopausal patients. While for those who are eligible for chemotherapy, NCT might be better recommended due to higher response rates.


Synthesis of α-carboxyphosphinopeptides derived from norleucine.
In the present study, we describe in detail the synthesis of a relatively rare class of phosphorus compounds, α-carboxyphosphinopeptides. We prepared several norleucine-derived α-carboxyphosphinic pseudopeptides of the general formula Nle-Ψ[PO(OH)]-Gly. These compounds could have important applications as transition state-mimicking inhibitors for methionine or leucine aminopeptidases or other enzymes. For the preparation of the key α-carboxyphosphinate protected precursors, we investigated, compared and improved two different synthetic methods described in literature: the Arbuzov reaction of a silylated N-protected phosphinic acid with a bromoacetate ester and the nucleophilic addition of a mixed O-methyl S-phenyl N-protected phosphonic acid or a methyl N-protected phosphonochloridate with tert-butyl lithioacetate. We also prepared two N-Fmoc protected synthons, Fmoc-Nle-Ψ[PO(OH)]-Gly-COOH and Fmoc-Nle-Ψ[PO(OAd)]-Gly-COOH, and demonstrated that these precursors are suitable building blocks for the solid-phase synthesis of α-carboxyphosphinopeptides.


Similar symptoms and confounding conditions: benign prostatic hyperplasia versus hyperglycemia.
The traditional approach to diagnosing men with symptoms associated with benign prostatic hyperplasia (BPH) based on the American Urological Association symptom index may be limiting. There are often concurrent conditions that may be responsible for the urinary complaints of men with BPH, namely hyperglycemia. Both conditions manifest many of the same symptoms and complaints by patients, but treatment of one can lead to a missed diagnosis of the other.


[Determination of free catecholamines in the urine using high efficiency liquid chromatography with an electrochemical detector].
The authors describe electrochemical detector high-pressure liquid chromatography (EDHPLC) technique for measuring nanogram amounts of catecholamines in human urine. Alumina-treated samples are layered onto a reverse-phase column for the separation of catecholamines, with a monochloracetate buffer/acetonitrile mixture containing 75 mg of sodium octyl sulfate as the mobile phase. Electrochemical detector was employed for the quantitative detection of catecholamines. Catecholamine levels of up to 1000 ng are detectable with the use of electrochemical detector. EDHPLC is a highly suitable method for clinical investigations.


Weekly patterns of suicide and the influence of alcohol consumption in an urban sample.
The weekly fluctuation in suicide rates is influenced by several factors including sex, psychiatric illness and alcohol dependence. The purpose of this study is to explore the impact of current alcohol use on suicid. Data on sex, date of death, results of blood and/or urine alcohol tests and history of alcohol dependence in suicide victims over the 1997-2002 period were retrieved from a forensic database in two cities in Chuvash Republic. Over the six-year study period, 1,379 suicides were committed, 59% of them under the influence of alcohol. The peak incidence for men and women regardless of previous alcohol consumption was on Wednesdays and Mondays, respectively. The overall suicide rate was highest on Mondays and lowest on Thursdays. Both sexes were less likely to commit suicide during holidays than on weekends or workdays while intoxicated with alcohol. In this urban sample, the distribution of suicide across weekdays only partly followed the international pattern. The peak incidence of suicide showed sex difference, with the highest incidence for women on Mondays and for men on Wednesdays. The higher suicide rate on workdays might be accounted for by work-related stress, while the lower rate on weekends could be explained that people usually drink alcohol in the comforting company of family or friends, which reduces psychological tension and suicidal ideation. The majority of men consumed alcohol before committing suicide, regardless of the day of the week, while this observation was true for women only on Fridays and Sundays. Alcohol consumption greatly contributes to suicidal behavior in Chuvash Republic.


Effect of elevated dietary tryptophan on protein synthesis in rat liver.
This study investigated whether rats force-fed for three days an elevated (1%) tryptophan diet compared to a control (0.2% tryptophan) diet had changes in hepatic protein metabolism. Earlier, we showed that a single administration of L-tryptophan to fasted rats caused a rapid increase in hepatic protein synthesis. In the present study rats force-fed a high tryptophan diet for 3 days and killed the fourth morning had increased rats of hapatic protein synthesis, cytochrome P-450 and b5 activities, in vitro nuclear RNA release (cell sap and nuclear effects) and nuclear envelope nucleoside triphosphatases activity compared to animals force-fed the control diet. We noted little or no change in hapatic total polyribosomal aggregation patterns or plasma and hepatic free amino acid levels.


Metabolomic approach to understand the acute and chronic hepatotoxicity of Veratrum nigrum extract in mice based on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.
Veratrum nigrum L. (VN) is a poisonous traditional Chinese medicine herb present since thousands of years in China. Clinical studies have shown that VN has the ability to cause hepatotoxicity, which severely limits its clinical use. The mechanism of its hepatotoxicity has not been fully elucidated. The purpose of this study was to develop and characterize a model of acute and chronic hepatotoxicity induced by Veratrum nigrum L. extract (VNE) to understand the mechanism of liver tissue metabolomics approach using on ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOFMS). Mice were administered with VNE in the acute and chronic phases. Histopathologic inspections and biochemistry analysis disclosed severe liver damage after exposure to VNE. A partial least-squares discriminant analysis (PLS-DA) of the metabolomic profiles of rat liver tissues highlighted a number of metabolic disturbances induced by VNE, focusing on purine and pyrimidine metabolism, tryptophan metabolism, phospholipid metabolism, sphingolipid metabolism and fatty acid metabolism. These findings could well explain VNE-induced acute and chronic hepatotoxicity and reveal several potential biomarkers associated with this toxicity. This indicates that UHPLC-Q-TOFMS-based metabolomics approach demonstrated its feasibility and allowed a better understanding of VNE-induced liver toxicity dynamically.


Interpersonal Relationship, Knowledge Characteristic, and Knowledge Sharing Behavior of Online Community Members: A TAM Perspective.
With the rapid development of information science and technology, online communities are attracting an increasing number of participants, who can share information, create original content, and offer emotional support, thus communicating and spreading knowledge frequently within the community. To develop a model of influencing factors for the knowledge sharing behavior of online community members, this study employs the technology acceptance model (TAM) as a moderator variable based on the social exchange theory. In this study, the influencing factors model for knowledge sharing behavior of online community members was tested using PLS-SEM. The results show that knowledge sharing is motivated by trust and quality of knowledge; the interaction term of perceived usefulness and knowledge quality of the user has a significant negative correlation with the knowledge sharing behavior of online community users; perceived usefulness significantly positively moderates the correlation between knowledge tacitness and knowledge sharing behavior of users; perceived ease of use significantly positively moderates the relationship between knowledge quality and knowledge sharing behavior; perceived ease of use significantly negatively moderates the relationship between knowledge tacit and knowledge sharing behavior. In order to maximize the activity and stickiness of the online community platform, the platform must focus on maintaining and enhancing the platform's credibility and knowledge quality. On the other hand, the online community platform extols its professional utility and ease of operation, which are conducive to the generation of behavior that is conducive to knowledge sharing.


Automated tracking and classification of the settlement behaviour of barnacle cyprids.
A focus on the development of nontoxic coatings to control marine biofouling has led to increasing interest in the settlement behaviour of fouling organisms. Barnacles pose a significant fouling challenge and accordingly the behaviour of their settlement-stage cypris larva (cyprid) has attracted much attention, yet remains poorly understood. Tracking technologies have been developed that quantify cyprid movement, but none have successfully automated data acquisition over the prolonged periods necessary to capture and identify the full repertoire of behaviours, from alighting on a surface to permanent attachment. Here we outline a new tracking system and a novel classification system for identifying and quantifying the exploratory behaviour of cyprids. The combined system enables, for the first time, tracking of multiple larvae, simultaneously, over long periods (hours), followed by automatic classification of typical cyprid behaviours into swimming, wide search, close search and inspection events. The system has been evaluated by comparing settlement behaviour in the light and dark (infrared illumination) and tracking one of a group of 25 cyprids from the water column to settlement over the course of 5 h. Having removed a significant technical barrier to progress in the field, it is anticipated that the system will accelerate our understanding of the process of surface selection and settlement by barnacles.


Equilibrium partitioning of chlorinated solvents in the vadose zone: low f(oc) geomedia.
A series of gas (vapor)-advecting water-unsaturated column experiments using a low organic content (f(oc)) silica sand was conducted to determine mass distributions of chlorinated-volatile hydrophobic organic compounds (C-VHOCs) in a natural sorbent system. C-VHOCs used were trichloroethene (TCE), tetrachloroethene (PCE), chlorobenzene (CB), and 1,3-dichlorobenzene (DCB). Four volumetric water contents (theta(w) = 0.07, 0.12, 0.17, 0.20) and several influent gas-phase C-VHOC (solute) concentrations were considered. The method of temporal first moments was applied to complete breakthrough curve data to determine total C-VHOC gas-phase retardation and associated gas-phase C-VHOC mass fraction. Results were compared to an equilibrium partitioning advective-dispersive formulation of total gas-phase retardation. Literature-derived values of Henry's law constants and independent measurements of gas/water interface areal extent and interface phase adsorption allowed quantification of C-VHOC mass fractions in the aqueous and gas/water interface phases. Unaccounted C-VHOC mass, derived from comparison of measured C-VHOC retardation to independent phase prediction, was attributed to solid-phase sorption. Results indicate that for all conditions tested, gas/water interfacial adsorption exhibited only a small effect on C-VHOC vapor retardation (accounting for < or = 10% of the total C-VHOC distributions). Solid-phase association was the dominant uptake mechanism, accounting for 46-91% of the total C-VHOC mass in the porous system. Evaluation of the solid-phase C-VHOC uptake results in terms of a modified form of the Dubinin-Radushkevich (DR) isotherm equation provided strong evidence supporting the mechanism of pore-filling in this natural, low f(oc) sorbent.


Triggering of T cell-mediated immune responses by allogenic tumor cell vaccine in patients with oral cancer.
We investigated the immunomodulatory activity of allogenic whole tumor cell vaccine in oral cancer patients in vitro by two-color flow cytometry. Vaccine treatment significantly increased the expression of CD69 and HLA-DR in CD3+ T-cell subsets. The frequency of Interferon-gamma and Interleukin (IL)-2 expressing CD4+/CD8+ T-cell subsets was significantly higher with a concomitant reduction in IL-4 and IL-10 expressing T-cells in the vaccine treated group as compared with the untreated controls. Vaccine treatment significantly increased T-cell receptor (TCR), Vbeta3, Vbeta5 and Vbeta8 usage. The results indicate that the allogenic whole tumor cell vaccine is able to trigger T-cell mediated immunity in patients with intraoral squamous cell carcinoma.