Symmetry and Rigidity for Boosting Erbium-Based Molecular Light-Upconversion in Solution.
Previously limited to highly symmetrical homoleptic triple-helical complexes [Er(Lk)3 ]3+ , where Lk are polyaromatic tridentate ligands, single-center molecular-based upconversion using linear optics and exploiting the excited-state absorption mechanism (ESA) greatly benefits from the design of stable and low-symmetrical [LkEr(hfa)3 ] heteroleptic adducts (hfa- =hexafluoroacetylacetonate anion). Depending on (i) the extended π-electron delocalization, (ii) the flexibility and (iii) the heavy atom effect brought by the bound ligand Lk, the near-infrared (801 nm) to visible green (542 nm) upconversion quantum yield measured for [LkEr(hfa)3 ] in solution at room temperature can be boosted by up to three orders of magnitude.


Paradoxical air embolism during percutaneous nephrolithotomy due to patent foramen ovale: Case report.
Paradoxical air embolism is a very rare complication associated with percutaneous nephrolithotomy (PCNL). Incidence may be higher if patients also suffer from a septal heart defect. We report the case of a 76-year old male who presented for PCNL treatment of a right kidney lower calyceal calculus. During the procedure, the patient developed signs and symptoms consistent with that of air embolism. Intraoperative echocardiography confirmed the diagnosis. Subsequent intraoperative and postoperative medical management was carried out and the patient was discharged after recovery three days later. This case highlights the importance of a rare but potentially fatal complication of PCNL.


Insights on chemical-biological correlations learned from investigations on the sulfated galactan from the marine alga Bothryocladia occidentalis.
Marine organisms have been proven to be a valuable source of bioactive compounds. Among them, we highlight the sulfated galactans (SGs) from seaweeds, which besides being massively exploited as industrial thickening and gelling agents (agarans and carrageenans), have also shown promising pharmacological properties. Investigations on the non-agaran/-carrageenan SG from the red algae Bothryocladia occidentalis (SGBo) have demonstrated clear correlations between physical-chemical features and biological activities. SGBo is composed of 2,3-disulfated (~33%) or 2-sulfated (33%) α-D-galactose linked to non- or 2-sulfated β-D-galactose repetitive disaccharide units. The notable serpin-dependent/-independent anticoagulant activity of SGBo (~130 international units [IU]/mg) is higher than those of other SGs containing less 2,3-disulfated α-D-galactose units and their low-molecular-weight derivatives, and thus is directly correlated to its high molecular mass (>200 kDa) and sulfation pattern. Although SGBo has antithrombotic efficacy equivalent to heparin and decreased bleeding potential at low-doses, high-doses substantially increase thrombus formation in animal models. Such an odd dose-dependent dual antithrombotic/prothrombotic activity has been attributed to the ability of SGBo to activate factor XII. In addition to anticoagulant properties, SGBo also exerts antimalarial, antileishmanial and antiophidic activities, and, therefore, has a remarkable potential for the research and development of novel drugs.


Origin of Subthreshold Turn-On in Quantum-Dot Light-Emitting Diodes.
The subthreshold (or sub-bandgap) turn-on for electroluminescence is one of the most discussed, but often misinterpreted, phenomena for solution-processed quantum-dot light-emitting diodes. Here, multiple techniques are applied to show that the phenomenon can be readily explained using the fundamental rules of carrier injection and transport. Evident from temperature dependent photovoltage measurements, it is found that the energy up-conversion originating from the decay of charge transfer excitons is not responsible for the subthreshold turn-on. Further analysis using electroabsorption reveals that the turn-on voltage of electroluminescence consistently correlates with the flat-band voltage of the emission layer. Under such subthreshold bias, although the device current is still limited by the depleted hole-transporting layer, field-assisted carrier injection starts to provide enough electrons and holes for detectable radiative recombination, thereby enabling distinct subthreshold turn-on.


The effect of female sex hormone supplementation on tendon in pre and postmenopausal women: A systematic review.
Oestrogen deprivation has been shown to have a negative effect on connective tissue and its turnover. A link may exist between supplemental oestrogen, preservation of tendon collagen and less tendon abnormality. The aim was to determine the effects of female sex hormone supplementation (FSHS) on tendon. A systematic search of nine key health databases; Medline, CINAHL, EMBASE, SPORTDiscus, AUSPORT and AMI, Cochrane Library, SafetyLit and PEDro was completed (to Feb 24, 2016). The search yielded 6378 records using terms relating to hormone (oestrogen, estrogen, hormone replacement therapy, HRT, estrogen therapy, oestrogen therapy, oral contraceptive pill) and tendon. Quality assessment, data extraction and data synthesis of included papers was undertaken. Low level of evidence for all outcomes; no positive or negative link between FSHS and molecular, mechanical and morphological tendon response outcomes, and the addition of exercise to FSHS, had minimal effects on tendon CSA. The effect of oestrogen supplementation on tendon is contradictory and inconsistent. This review suggests there is a need for further studies to understand the effects of FSHS on tendon tissue at a mechanical, morphological and molecular level.


Serum concentrations of topiramate in patients with epilepsy: influence of dose, age, and comedication.
Topiramate is a new antiepileptic drug (AED) approved as add-on therapy. Previous studies have shown that topiramate has only a limited effect on other AEDs, but its own metabolism can be induced by enzyme-inducing drugs. The aim of this study was to investigate the influence of topiramate dose, age, and comedication, especially of carbamazepine, phenytoin, phenobarbital, oxcarbazepine, lamotrigine, and valproic acid (VPA) on topiramate serum concentrations in patients with epilepsy. In total, 480 samples of 344 inpatients who fulfilled the inclusion criteria (e.g., trough concentration, body weight available) were investigated. The topiramate serum concentration in relation to topiramate dose per body weight (level-to-dose ratio) was calculated and compared for patients receiving topiramate monotherapy and for patients receiving topiramate plus one other AED. Analysis of covariance (using age as covariate) showed that comedication had a highly significant influence on the topiramate serum concentrations. Regression analysis including all 480 samples confirmed that in combinations with phenytoin, carbamazepine, phenobarbital, and oxcarbazepine, the topiramate concentrations were significantly lower compared with topiramate monotherapy, whereas VPA and lamotrigine had no significant influence. Moreover, regression analysis indicated that primidone and methsuximide lowered topiramate concentrations, whereas gabapentin, bromide, and sulthiame did not. In addition to comedication, the patient's age was significantly correlated with topiramate clearance. In accordance with the results of previous studies, these results indicated that infants and children had lower topiramate concentrations than adults receiving the same topiramate dose per body weight. Comedication and age should be considered in adjusting topiramate dosage. Determination of topiramate serum concentrations may be useful, especially when enzyme-inducing drugs are withdrawn or added.


Etiology and pathophysiology of portal hypertension.
Portal hypertension may result from increased resistance of the hepatic vascular bed ("backflow") and from a hyperdynamic splanchnic circulation ("forward flow" theory). Most likely, both mechanisms contribute to the formation of portal hypertension in man. The classical macroscopic terminology describes prehepatic, intrahepatic and posthepatic forms of portal hypertension. Increased splanchnic blood flow represents the predominant cause of some pre- and intrahepatic types of portal hypertension. Intrahepatic portal hypertension has been subclassified as presinusoidal, sinusoidal or postsinusoidal. However, one to one allotments of diseases to this classification may not be made. The relative contribution of each of these causes to the increased portal pressure of liver cirrhosis varies with the etiology of the disease. A new ultrastructural classification of the processes leading to portal hypertension differentiates primarily hepatocellular (e.g., increased hepatocellular size) from interstitional causes (e.g., sinusoidal capillarization). The role of the fenestrated sinusoidal endothelial cells in the regulation of intrahepatic resistance and, thus, for the generation of portal hypertension is poorly defined up to date. A thorough evaluation of the effects of prostanglandins, leukotrienes, catecholamines, serotonin and others on sinusoidal endothelial cells and hepatic microcirculation may provide the basis for new therapeutic avenues.


Poverty as an Adverse Childhood Experience.
Research demonstrates the correlation between childhood adversities linked to poverty and negative outcomes in adulthood, indicating that poverty may itself be considered an adverse childhood experience. Because child poverty is a result of family economic circumstance, policy investments promoting family financial health are imperative to protect child well-being and North Carolina's future prosperity.


Risk groups in patients with bladder cancer treated with radical cystectomy: statistical and clinical model improving homogeneity.
In this study we identified homogeneous risk groups, with no survival overlap among the subgroups that make up each risk group, in patients with transitional cell carcinoma of the bladder treated with radical cystectomy alone. Predictive factors for tumor death were analyzed with univariate and multivariate analysis among a group of 298 patients with transitional cell carcinoma of the bladder treated with radical cystectomy alone. Independent variables were progressively incorporated according to their statistical power in a stepwise process identifying a model with independent subgroups. The risk groups were identified according to different survival cutoff points including subgroups with similar survival. To search a clinical application and to check the strength of this model a new model was also set up using the weight score based on the size of hazard ratio from multivariate analysis. Univariate analysis demonstrated that lymphatic invasion status, pathological stage (P), lymph node status (N) and prostatic stroma status (St) were predictive variables for tumor death, and the latter 3 were independent variables in the multivariate analysis. By taking the most powerful, N, as the reference variable, and progressively incorporating additional variables, a model was found including 7 independent subgroups. In this model only 2 subgroups, N1 and N2-3, included more than 1 category and their survival was also calculated. Three risk groups were identified establishing different survival cutoffs. The 5-year cancer specific survival rate was 86.4% for low risk (P1-2N0St-), 64.4% (range 60.9% to 65.3%) for intermediate risk (P1-2N1St-, P3N0St-, HR = 2.7) and 28.1% (range 0% to 47.7%) for high risk (N2-3, P4, St+, N1P3, HR = 8.7). This model was also reproduced using the weight score based on the size of the hazard ratio from the multivariate analysis Three homogeneous risk groups were identified with high statistically significant survival differences among them and no survival overlap among subgroups that make up the risk groups.


Kinetic considerations for the quantitative assessment of efflux activity and inhibition: implications for understanding and predicting the effects of efflux inhibition.
Unexpected and complex experimental observations related to efflux transport have been reported in the literature. This work was conducted to develop relationships for efflux activity (PS(efflux)) as a function of commonly studied kinetic parameters [permeability-surface area product (PS), efflux ratio (ER), degree of efflux inhibition (phi(i)), 50% inhibitory concentration (IC(50)), and Michaelis-Menten constant (K(m))]. A three-compartment model (apical, cellular, and basolateral) was used to derive flux equations relating the initial rate of flux and steady-state mass transfer in the presence or absence of active efflux. Various definitions of efflux ratio (ER) were examined in terms of permeability-surface area products. The efflux activity (PS(efflux)) was expressed in terms of ER and PS. The relationships between PS(efflux) and PS, ER, phi(i), IC(50), and K(m) were solved mathematically. Simulations and examples from the literature were used to illustrate the resulting mathematical relationships. The relationships derived according to a three-compartment model differed fundamentally from commonly accepted approaches for determining PS(efflux), phi(i), IC(50) and K(m). Based on the model assumptions and mathematical derivations, currently used mathematical relationships erroneously imply that efflux activity is proportional to change in PS (i.e., flux or P(app)) and thus underestimate PS(efflux) and phi(i,) and overestimate IC(50) and K(m). An understanding of the relationship between efflux inhibition and kinetic parameters is critical for appropriate data interpretation, standardization in calculating and expressing the influence of efflux transport, and predicting the clinical significance of efflux inhibition.


Evaluation of daptomycin pharmacodynamics and resistance at various dosage regimens against Staphylococcus aureus isolates with reduced susceptibilities to daptomycin in an in vitro pharmacodynamic model with simulated endocardial vegetations.
The need to investigate novel dosing regimens and combinations is essential in combating poor treatment outcomes for Staphylococcus aureus bacteremia and endocarditis. We evaluated the impact of simulated standard- and high-dose daptomycin in combination with gentamicin or rifampin against daptomycin-susceptible and nonsusceptible matched strains of S. aureus. These strains were collected from the daptomycin bacteremia and endocarditis clinical trial and consisted of three susceptible strains (MIC, 0.25 mg/liter) and four nonsusceptible isolates (MICs, 2 to 4 mg/liter). Daptomycin regimens of 6 and 10 mg/kg of body weight daily alone and in combination with gentamicin at 5 mg/kg daily or rifampin at 300 mg every 8 h were evaluated using an in vitro model with simulated endocardial vegetations over 96 h. Rapid bactericidal activity, identified by time to 99.9% kill, was displayed in all regimens with the daptomycin-susceptible strains. Concentration-dependent activity was noted by more-rapid killing with the 10-mg/kg/day dose. The addition of gentamicin improved activity in the majority of susceptible isolates. Daptomycin 6-mg/kg/day monotherapy displayed bactericidal activity for only one of the nonsusceptible isolates and for only two isolates with increased doses of 10 mg/kg/day. Combination regimens demonstrated improvement with some but not all nonsusceptible isolates. Three isolates developed a reduction in daptomycin susceptibility with 6-mg/kg/day monotherapy, but this was suppressed with both combination therapy and high-dose daptomycin. These results suggest that high-dose daptomycin therapy and combination therapy may be reasonable treatment options for susceptible isolates; however, more investigations are needed to confirm the variability of these regimens with nonsusceptible isolates.


The road to HIV-1 integrase inhibitors: the case for supporting basic research.
AIDS has been transformed from a death sentence to a manageable disease for many patients with access to combination antiviral therapy. It is informative to look back on some of the key advances that have led to this transformation. The arsenal of tools currently available to clinicians now includes inhibitors of the viral reverse transcriptase, protease and integrase enzymes. The author discusses some of the key advances that have led to this transformation with an emphasis on the role of basic science in developing integrase inhibitors. Many of the stepping-stones could not easily have been foreseen to lead to medical advances. Treatments for diseases that are yet to emerge will likely depend on the progress made in basic science today.


Vaccenic acid and cis-9,trans-11 CLA in the rumen and different tissues of pasture- and concentrate-fed beef cattle.
The objective of present study was the comparison of trans-11 18:1 (VA) and cis-9,trans-11 CLA concentrations in the rumen and different tissues in beef cattle, and to examine the diet and breed effects on the compound concentration and deposition. Sixty-four German Holstein and German Simmental bulls were randomly assigned to two dietary treatments, based on concentrate or pasture. The concentration of cis-9,trans-11 CLA and VA in rumen, duodenal digesta and different tissues was determined by gas chromatography. The results showed that pasture relative to concentrate feeding significantly increased the concentration of VA in duodenal digesta, plasma and erythrocyte phospholipids. Pasture-based feeding resulted in a significant enrichment of cis-9,trans-11 CLA in plasma lipids and erythrocyte phospholipids, but not in rumen and duodenal digesta, compared to concentrate-fed diet. Diet did not affect the cis-9,trans-11 CLA concentrations (mg/100 g fresh tissue) in semitendinosus muscle and subcutaneous fat. There was a breed effect on the deposition of cis-9,trans-11 CLA in longissimus muscle with lower concentration in pasture-fed German Simmental bulls compared to concentrate-fed bulls. However, pasture feeding significantly increased both, the VA and cis-9,trans-11 CLA concentrations in liver and heart tissues. Both diet and breed effects on Delta(9)-desaturase index was observed in muscle and subcutaneous fat tissues. There was a linear relationship between the concentration of VA and cis-9,trans-11 CLA and the coefficients of determination (R (2)) varied between 0.29 and 0.87 from rumen to the different tissues.


Influence of positions on the incidence and severity of maxillofacial injuries in vehicular crashes [corrected].
The objective of this study was to determine the influence of positions on the incidence and severity of maxillofacial injuries in vehicular crashes. Two hundred and fifty cases of RTA were seen and studied from October 1999 to May, 2000. They comprised 72.8% males and 27.2% females with a male to female ratio of 2.7:1. The age range was 1 to 80 years with a mean age of 40 years. The most common vehicle involved in RTA was the mini bus, 34.3% followed by motorcycle, 26.5%. Middle seat passengers, drivers and motorcycle passengers and riders sustained more and severe injuries during crashes. The mandible was more frequently fractured at the symphysis (24.6%) than at any other site while the maxilla was frequently fractured at the zygomatic bone and arch (10.8%). More injuries occurred in the age range of 20-30 years and these accounted for 31.8% of the cases. Only 6 occupants of motor vehicles wore seat belts before accident while no motorcycle rider or passenger wore any helmet. In conclusion, drivers, middle seat occupants of a vehicle, motorcycle passenger and riders sustained more and severe injuries than back seat occupants.


Can you imagine this? Imagined contact as a strategy to promote positive intergroup relations.
In comparison to the extensive body of research on intergroup contact, which encompasses predictors, outcomes, and implications, there has been relatively little attention given to the role of imagined contact with diverse ethno-religious out-groups. This gap particularly exists in understanding the factors that contribute to the effectiveness of imagined contact interventions. This article aims to address this gap by presenting current research on the predictors and consequences of imagined contact. We offer an overview of the circumstances in which imagined contact proves beneficial; while focusing on research that holds relevance for designing interventions and policies promoting contact between culturally and religiously diverse groups and individuals. We also acknowledge the existing limitations within this field of study and propose potential direction for future research.


Abacavir and cardiovascular disease: A critical look at the data.
Most HIV-infected subjects will receive a treatment regimen including abacavir or tenofovir. Therefore, clarifying if there is an increased risk of acute myocardial infarction (AMI) among those exposed to abacavir is of the utmost importance. Due to the low frequency of AMI in this young population (2-5 per 1000 patients/year), efforts to clarify this have been quite controversial. While some observational cohorts have found a statistically significant association, others have not. Meta-analysis of randomized clinical trials offering the highest scientific evidence found no association at all, but with a limited statistical power to definitely rule out a small effect. A channelling or selection bias has been demonstrated in cohort studies, favouring the prescription of abacavir to subjects with or at risk for chronic kidney disease, and therefore, with an intrinsic increased cardiovascular risk. The recent NA-ACCORD cohort study does not identify an increased risk for AMI associated with recent abacavir use in a fully adjusted model (HR 1.33; 95%CI:0.96, 1.88). However, it does find an association in a second analysis restricted to treatment-naïve persons, with higher differences in baseline characteristics among compared arms. A critical review of the compiled available evidence is therefore mandatory, particularly in light of the first single-tablet regimen to receive approval that does contain abacavir.


Postoperative atypical hemolytic uremic syndrome associated with complement c3 mutation.
Atypical hemolytic uremic syndrome (aHUS) can be distinguished from typical or Shiga-like toxin-induced HUS. The clinical outcome is unfavorable; up to 50% of affected patients progress to end-stage renal failure and 25% die during the acute phase. Multiple conditions have been associated with aHUS, including infections, drugs, autoimmune conditions, transplantation, pregnancy, and metabolic conditions. aHUS in the nontransplant postsurgical period, however, is rare. An 8-month-old boy underwent surgical repair of tetralogy of Fallot. Neurological disturbances, acute renal failure, thrombocytopenia, and microangiopathic hemolytic anemia developed 25 days later, and aHUS was diagnosed. Further evaluation revealed that his complement factor H (CFH) level was normal and that anti-FH antibodies were not detected in his plasma. Sequencing of his CFH, complement factor I, membrane cofactor protein, complement factor B, and thrombomodulin genes was normal. His ADAMTS-13 (a disintegrin-like and metalloprotease with thrombospondin-1 repeats 13) activity was also normal. However, he had a potentially causative mutation (R425C) in complement component C3. Restriction fragment length polymorphism analysis revealed that his father and aunt also had this mutation; however, they had no symptoms of aHUS. We herein report a case of aHUS that developed after cardiovascular surgery and was caused by a complement C3 mutation.


Antileukemic effect of interleukin-2 on spontaneous development of leukemia after H-2-compatible allogenic bone marrow transplantation in AKR/J mice.
AKR/J mice, highly susceptible to spontaneous T cell leukemogenesis, were protected from developing the disease by H-2-compatible allogenic bone marrow transplantation (BMT) and intermittent treatment with interleukin-2(IL-2). Allogeneic BMT from C3H/HeJ mice and treatment with PBS yielded T cell leukemia in chimeras after the same latent period as that observed in normal AKR/J mice. In contrast, IL-2-treated chimeras caused an incidence of only 40% T cell leukemia. The preventing effect of IL-2 on leukemia development was not observed in one-year-treated chimeras, probably due to a lack of continuous antileukemic effects over the long term. Both LAK and NK activities in spleen cells were significantly increased in IL-2-treated chimeras. The cytotoxicity against T cell lymphoma cell line derived from AKR/J also increased in the IL-2-treated chimeras. Similarly, LPS-, PWM-, and IL-2-induced responses were increased in the IL-2-treated chimeras. TNF-alpha secretion from spleen cells also rose after IL-2-administration. IL-1 beta, IFN-gamma, and TNF-alpha mRNA became detectable in spleen cells using the PCR technique. The characteristics of leukemia cells in chimeras with overt leukemia were not directly affected by IL-2 administration. It is suggested that partial inhibition of spontaneous T cell leukemia development in AKR/J mice by allogeneic BMT and IL-2 may be due to the enhancement of graft-versus-leukemia effects. Further study may provide insights into the mechanisms involved in preventing leukemia development after allogenic BMT and IL-2 in AKR/J mice.


Prognostic Value of c-MYC Expression in Patients with Peripheral Neuroblastic Tumors.
Neuroblastic tumors are the most common solid tumors in children. The aim of this study was to explore the prognostic value of immunostaining for cellular-myelocytomatosis viral oncogene (c-MYC) expression in patients with peripheral neuroblastic tumors (NTs). A retrospective study was conducted to compare the expression of c-MYC detected by immunohistochemistry and v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) by fluorescence in situ hybridization among 177 cases of NTs and determine the associations of c-MYC and MYCN with the clinical stages, morphological types, and survival rates of NTs. The cases positive for c-MYC were mainly the favorable histology type in stage 3 or 4 with a poor NT prognosis, but no morphological changes related to the poor prognosis were observed in their samples under a microscope. The cases with positive c-MYC expression did not overlap those with MYCN amplification. Positive c-MYC expression portends a poor prognosis in patients with NTs.


First Report of Black Rot on Persimmon Fruit Caused by Diaporthe eres in China.
The fruit of persimmon (Diospyros kaki L.) is popular with consumers for its delicious taste and is widely grown in China. In September 2022, fruit rot symptoms were found on persimmons grown at the Tobacco Research Institute of Chinese Academy of Agricultural Sciences (120°26'43.879″E, 36°7'59.794″N) in Qingdao City, Shandong Province, China. Diseases incidence on fruit is 70%. Typical symptoms were small, black spots, which gradually expanded, and became rot lesions, causing fruit rot and serious losses. To isolate the pathogen, small sections (approximately 2 × 2 mm) of symptomatic tissues from five persimmon fruits were surface-sterilized in 5% NaClO, followed by 75% ethanol, rinsed with sterile distilled water, and then incubated on potato dextrose agar (PDA) plates incubated at 28℃ for 5 days. By single spore isolation method, seven dominant fungal isolates developed with similar colonies. They were initially white and gradually turned to gray after 7 d. The alpha conidia were unicellular, colorless, elliptic or fusiform, and 5.0 to 8.0 μm × 2.5 to 3.5 μm in size. Beta conidia were unicellular, colorless, filiform, often hooked at one end and 18 to 28 μm × 1.3 to 1.5 μm in size. These morphological features were consistent with Diaporthe spp (Udayanga et al. 2014). To confirm identity of the causal fungus, the internal transcribed spacer (ITS) rDNA, translation elongation factor 1-a (TEF1-a), b-tubulin (TUB), and histone H3 (HIS) genes of three representative isolates (De2, De3 and DeR2) were amplified and sequenced using primers ITS1/ITS4, EF1-728F/EF1-986R, Bt2a/Bt2b and CYLH3F/H3-1b as described by Chaisiri et al. (2021). The resulting sequences were deposited in GenBank (accession nos. OP963195, OP963386 and OP963389 for ITS; OP968958, OP968959 and OP9689600 for EF1-α; OP978141, OP978142 and OP978143 for TUB; OP968955, OP96896 and OP968957 for HIS), and showed 99-100% similarity with D. eres by NCBI blast. Phylogenetic analysis was conducted using MEGA-X software, with the NJ method. In the phylogenetic tree, the combined sequences attributed the three isolates to the D. eres. On the basis of morphological and molecular characteristics, the pathogen was identified as D. eres. The strain De2 was preserved in the Agricultural Culture Collection of China (preservation number: ACCC 35482). Pathogenicity tests were performed by wound inoculation on healthy persimmon fruit. These were surface sterilized with 75% ethanol for 1 min, rinsed in sterile water three times, and allowed to dry. A 5-mm agar disc with mycelium of the causal pathogen was placed on the surface of fruit, which was wounded with a sterile needle in advance, with the sterile PDA plugs used as control. Three persimmons were used for each treatment, repeat three times. All the treated fruits were incubated in the sterilized transparent plastic cans at 28°C and 90% RH. After 3 days inoculation, the first symptom of rot lesion appeared on the fruit with mycelial plugs, whereas the control fruit remained symptomless. The same causal pathogens were re-isolated from the lesions and identified by morphologyand confirmed to fulfill Koch's postulates. This is the first report of D. eres causing fruit rot on persimmon. This finding showed that Diaporthe eres is a causal agent of persimmon fruit rot in China.


Chronic abdominal complaints and Helicobacter pylori in a Haitian population.
The objective of this study was to examine demographic, clinical, and pathologic variables, including Helicobacter pylori infection and malignancy, associated with chronic abdominal pain in a rural Haitian population. One hundred four patients underwent esophagogastroduodenoscopy, with biopsy only in those with gross findings. Associations between demographic, clinical, and pathologic variables were examined using the chi-square test. P values less than or equal to 0.05 were considered statistically significant. The majority (n = 66; 63%) required biopsy. Of these, 62% were positive for H. pylori. The associations between (1) chest complaints and esophageal disease, (2) female gender and benign esophageal disease, and (3) chronic active gastritis and presence of H. pylori were significant. There was one malignancy. H. pylori gastritis was common; malignancy was rare. Demographic and clinical variables poorly predicted pathologic diagnosis, which is consistent with previous studies. Further study is needed to assess the influence of other variables, including the African enigma, on disease progression in this population.


Phloem Sap Sampling from Brassica napus for 3D-PAGE of Protein and Ribonucleoprotein Complexes.
Sampling the phloem of higher plants is often laborious and significantly dependent on the plant species. However, proteome studies under denaturing conditions could be achieved in different plant species. Native protein:protein and protein:nucleic acid complexes from phloem samples have as yet scarcely been analyzed, although they might play important roles in maintenance of this specialized compartment or in long-distance signaling. Large molecular assemblies can be isolated using a blue native gel electrophoresis (BN-PAGE). Their protein components can be separated by a subsequent sodium dodecyl sulfate PAGE (SDS-PAGE). However, proteins with similar molecular weights co-migrate, what can hinder protein identification by mass spectrometry. Combining BN-PAGE with two different denaturing gel electrophoresis steps, namely Tris-Tricine-urea and SDS-PAGE, enables the additional separation of proteins according to their hydrophilicity/hydrophobicity and thus increases resolution and the success of protein identification. It even allows distinguishing proteins that only differ in their posttranslational modifications. In addition, blue native northern blotting can be applied to identify the RNA components in macromolecular complexes. We show that our protocol is suitable to unravel the protein and RNA components of native protein:protein and ribonucleoprotein (RNP) complexes occurring in phloem samples. Combining a blue native PAGE with two different denaturing PAGE steps can help to separate different kinds of large protein complexes, and also enables an increased identification rate of their components by mass spectrometry. Furthermore, the protocol is robust enough to simultaneously detect potentially bound nucleic acids within single protein complexes.


[Enzootic dermonecrosis in chickens].
An enzootic of necrotic dermatosis in hen layers was described. The changes consisted in that they had constant localization and demarkated sites on the skin between the back and the neck. The disease was observed on a farm for 5000 layers in the course of two consecutive years. All birds contracted the disease and in the first year they recovered the 10 months; in second year they recovered for three months. Each bird showed symptoms for 3 weeks. The skin lesions resulted in cicatrization. The etiologic agent (a Pasteurella-like organism) was isolated from the necrotic foci. It proved pathogenic for albino mice and manifested biochemical activity and morphology characteristic of Pasteurella multocida. The disease was successfully reproduced with a broth culture applied on a scarified skin of test birds. Histopathologically, the spontaneous lesions proved undistinguishable from the experimental ones and represented coagulation necrosis of the epidermis, derm, and subcutis. It is supposed that the constant localization was due to the porte d'entrer of the infection, associated with the bad habit of picage on the neck as demonstrated on a large scale by the birds of the infected flock. This is characteristic of some lines of the White Leghorn breed.


Induced Stress and Tactile Stimulation Applied to Primiparous does and their Consequences on Maternal Behavior, Human-Animal Relationships, and Future Offspring's Sexual Disorders.
The aim of this study was to investigate whether tactile stimulation in rabbits during the gestation phase improve the maternal behavior and human-animal relationships as well as the effects on reproductive behavior of male kits when reached maturity compared to induced stress. A total of 33 primiparous New Zealand does were selected after pregnancy confirmation and allocated in a randomized complete block design. The treatments applied were as follows: (C) animals not stimulated during the experimental period; (TS) animals that received tactile stimulation; and (SS) does which were immobilized. The nest building behavior as well as the weight, sexual behavior, mortality, and semen analysis of the offspring was recorded. In addition, the novel object, flight distance, social isolation, and human-approach tests were conducted. Under the conditions of the present trial, TS animals showed more trust in the unfamiliar observer when compared to the other two treatments. The treatments applied to the females (TS and SS) were sufficient to confirm that the control group presented better values for the number of stillbirths and the proportion of deaths in the first week. Finally, the handling of does reduce the males' ejaculation and sperm presence but not inhibited sexual behavior or impaired semen quality. It is possible to conclude that TS did not impair does welfare or maternal behavior and it improved the human-animal relationship, however there was a negative impact on the litter. More studies that directly assess impact on the future reproductive capacity of the offspring are necessary.


Time-dependent and nonlinear effects of prognostic factors in nonmetastatic colorectal cancer.
The survival risk following curative surgery for nonmetastatic colorectal cancer (CRC) may be over- or underestimated due to a lack of attention to nonlinear effects and violation of the proportional hazards assumption. In this paper, we aimed to detect and interpret the shape of time-dependent and nonlinear effects to improve the predictive performance of models of prognoses in nonmetastatic CRC patients. Data for nonmetastatic CRC patients diagnosed between 2004 and 2012 were obtained from the Surveillance Epidemiology End Results registry. Time-dependent and nonlinear effects were tested and plotted. A nonlinear model that used random survival forests was implemented. The estimated 5-year cancer-specific death rate was 17.95% (95% CI, 17.70-18.20%). Tumor invasion depth, lymph node status, age at diagnosis, tumor grade, histology and tumor site were significantly associated with cancer-specific death. Nonlinear and time-dependent effects on survival were detected. Positive lymph node number had a larger effect per unit of measurement at low values than at high values, whereas age at diagnosis showed the opposite pattern. Moreover, nonproportional hazards were detected for all covariates, indicating that the contributions of these risks to survival outcomes decreased over time. The nonlinear model predicted prognoses more accurately (C-index: 0.7934, 0.7933-0.7934) than did the Fine and Gray model (C-index: 0.7550, 0.7510-0.7583). The three-dimensional cumulative incidence curves derived from nonlinear model were used to identify the change points of the risk trends. It would be useful to implement these findings in treatment plans and follow-up surveillance in nonmetastatic CRC patients.


Cheminformatics-based selection and synergism of herbal extracts with anticancer agents on drug resistance tumor cells-ACHN and A2780/cp cell lines.
The treatment of cancer usually involves lethal effect on normal body cells as side effects. Cheminformatics methodology can play a significant role in biomed/clinical scientific research. Similarity searching is a standard cheminformatics tool in drug discovery area and database design. In this study, five novel herbal extracts in combination with doxorubicin and cisplatin have been used to sensitize ACHN and A2780/cp cells. These herbal extracts have been selected on the basis of novel cheminformatics methodology and assayed for the first time. The findings confirmed predicted outcomes from the in silico research and the results introduced may bring to use the effects of these herbs in reversing of multidrug resistance (MDR) phenomenon.


Progression of early phase diabetic nephropathy in streptozotocin-induced diabetic rats: evaluation of various kidney-related parameters.
Diabetic nephropathy (DN) is one of the serious secondary complications of diabetes, which results in end-stage renal failure. Reports on the progressive nature of early phase DN especially with respect to kidney parameters such as kidney weight, type IV collagen excretion, total kidney and urinary glycosaminoglycans (GAGs) are few. This work was undertaken to determine systematically the progression of early phase DN in relation to various kidney-related parameters for a period of four months. Experimentally-induced diabetic rats were grouped based on fasting blood glucose levels. Various basic and kidney-related parameters such as kidney weight, microalbuminuria, urinary excretion of GAGs and type IV collagen, total kidney GAGs, histopathology, glomerular area and glomerular volume were examined in control and diabetic rats. There was a progressive increase in fasting blood sugar, urine sugar, kidney weight, microalbuminuria, urine glycosaminoglycans, urine type IV collagen, glomerular area and glomerular volume but there was a progressive decrease in kidney glycosaminoglycans. Glomerular sclerotic condition was aggravated with the increase in duration of diabetes from 1 to 4 months. Onset of DN in rats begins subtly after one month of diabetes but gets vitiated and more pronounced at the end of four months.


From Gut to Glucose: A Comprehensive Review on Functional Foods and Dietary Interventions for Diabetes Management.
In the realm of diabetes research, considerable attention has been directed toward elucidating the intricate interplay between the gastrointestinal tract and glucose regulation. The gastrointestinal tract, once exclusively considered for its role in digestion and nutrient assimilation, is presently acknowledged as a multifaceted ecosystem with regulatory supremacy over metabolic homeostasis and glucose metabolism. Recent studies indicate that alterations in the composition and functionality of the gut microbiota could potentially influence the regulation of glucose levels and glucose homeostasis in the body. Dysbiosis, characterized by perturbations in the equilibrium of gut microbial constituents, has been irrevocably linked to an augmented risk of diabetes mellitus (DM). Moreover, research has revealed the potential influence of the gut microbiota on important factors, like inflammation and insulin sensitivity, which are key contributors to the onset and progression of diabetes. The key protagonists implicated in the regulation of glucose encompass the gut bacteria, gut barrier integrity, and the gut-brain axis. A viable approach to enhance glycemic control while concurrently mitigating the burden of comorbidities associated with diabetes resides in the strategic manipulation of the gut environment through adapted dietary practices. This review aimed to provide a deep understanding of the complex relationship between gut health, glucose metabolism, and diabetes treatment. This study has presented an exhaustive overview of dietary therapies and functional foods that have undergone extensive research to explore their potential advantages in the management of diabetes. It looks into the role of gut health in glucose regulation, discusses the impact of different dietary elements on the course of diabetes, and evaluates how well functional foods can help with glycemic control. Furthermore, it investigates the mechanistic aspects of these therapies, including their influence on insulin sensitivity, β-cell activity, and inflammation. It deliberates on the limitations and potential prospects associated with integrating functional foods into personalized approaches to diabetes care.


N-phosphonacetyl-L-isoasparagine a potent and specific inhibitor of Escherichia coli aspartate transcarbamoylase.
The synthesis of a new inhibitor, N-phosphonacetyl-L-isoasparagine (PALI), of Escherichia coli aspartate transcarbamoylase (ATCase) is reported, as well as structural studies of the enzyme.PALI complex. PALI was synthesized in 7 steps from beta-benzyl L-aspartate. The KD of PALI was 2 microM. Kinetics and small-angle X-ray scattering experiments showed that PALI can induce the cooperative transition of ATCase from the T to the R state. The X-ray structure of the enzyme.PALI complex showed 22 hydrogen-bonding interactions between the enzyme and PALI. The kinetic characterization and crystal structure of the ATCase.PALI complex also provides detailed information regarding the importance of the alpha-carboxylate for the binding of the substrate aspartate.


Displaced radial neck fractures in children treated by closed intramedullary pinning (Metaizeau technique).
We report the retrospective results of 17 displaced radial neck fractures (O'Brien type II-III) in children aged between 6 and 16 years treated with closed intramedullary pinning according to the Metaizeau technique, from 1988 to 1992 in our Pediatric Orthopaedic Service at the Ramón y Cajal Hospital. The average follow-up was 4.1 years. Excellent results were observed in all cases except one (94%). Overgrowth of the radial head was present in three cases without functional impairment. We recommend this closed method of treatment because it is simple, easy to perform, and obtains exciting results with few complications.


Postpartum mood disorders: diagnosis and treatment guidelines.
Mood disturbance occurs commonly during the postpartum period. The symptoms may be transient and relatively mild (as in postpartum blues) or may be associated with significant impairment of functioning (as in postpartum depression and puerperal psychosis). Despite the prevalence of postpartum mood disorders, depressive symptoms that emerge during the puerperium are often overlooked. Puerperal affective illness places the mother at risk for the development of recurrent depression and has also been associated with significant long-term effects on child development and behavior. Therefore, the prompt recognition and efficacious treatment of puerperal mood disorders are essential in order to avoid adverse outcomes for both mother and infant. This article discusses the evaluation of postpartum mood disturbance and offers guidelines for the treatment of affective illness during the puerperium.


Records of chimaeroid fishes (Holocephali: Chimaeriformes) from the Pacific coast of Costa Rica, with the description of a new species of Chimera (Chimaeridae) from the eastern Pacific Ocean.
A new species of Chimaera Linnaeus 1758 is described from three specimens collected from off the Pacific coasts of Costa Rica and Peru. Chimaera orientalis n. sp., the first species of the genus described from the eastern Pacific Ocean, is distinguished from its other congeners by a combination of coloration and morphology. Additionally, new records of occurrence for another four species of chimaeroid fishes (Harriotta raleighana (Goode & Bean 1895), Rhinochimaera africana Compagno, Stehmann & Ebert 1990, Hydrolagus colliei Lay & Bennett 1839, and H. macrophthalmus de Buen 1959) previously unknown for the continental shelf of the Pacific coast of Costa Rica and Central America are reported. A key to the eastern Pacific species of the order Chimaeriformes is also presented.


4-(Benz-yloxy)phenyl 4-hexa-dec-yloxy-3-meth-oxy-benzoate.
In the title compound, C(37)H(50)O(5), the central benzene ring makes dihedral angles of 39.72 (14) and 64.43 (13)° with the benzyl and 3-meth-oxy-benzoate rings, respectively. The crystal structure is stabilized by inter-molecular C-H⋯π inter-actions involving the central benzene ring and the benzene ring closest to the aliphatic chain.


Molecular biology of the HLA-B27 locus.
The molecular biology of the HLA-B27 locus is reviewed. The HLA-B27 gene itself does not differ between healthy individuals and ankylosing spondylitis patients. Several unique features of the HLA-B27 molecule have been identified and one epitope was proposed to cross-react with bacterial proteins.


[Palliation of malignant bile duct obstruction].
Bile duct obstruction is the presenting symptom in 40-70% of cases of pancreatic cancer, and in a greater proportion of cases of cholangiocarcinoma. Since the resectability rate is very low, only a palliative procedure is suitable for most patients. In a retrospective study, the results of operative versus percutaneous biliary drainage were compared. After the latter, there were no complications, but hospital stay was longer. Until a better nonoperative palliative procedure is found, operative drainage is recommended.


Use of nonclonal serum immunoglobulin free light chains to predict overall survival in the general population.
To determine whether the free light chain (FLC) assay provides prognostic information relevant to the general population. After excluding persons with a known plasma cell disorder, we studied 15,859 Olmsted County, Minnesota, residents 50 years or older in whom unmasked data and samples for FLC testing were available. Baseline information was obtained between March 13, 1995, and November 21, 2003, and follow-up status and cause of death were identified through June 30, 2009. The κ and λ FLC sum (Σ FLC) was evaluated for its ability to predict overall survival. Specific causes of death were also investigated. In 158,003 person-years of follow-up, 4348 individuals died. A high Σ FLC was significantly predictive of worse overall survival; the risk ratio for death for those with the highest decile of Σ FLC (ie, ≥ 4.72 mg/dL) was 4.4 (95% confidence interval, 4.1-4.7) relative to the remaining study participants. Multivariate analyses demonstrated that this excess risk of death was independent of age, sex, and renal insufficiency, with a corrected risk ratio of 2.1 (95% confidence interval, 1.9-2.2). The increased mortality was not restricted to any particular cause of death because the observed-to-expected risk of death from most causes was significantly higher among those individuals with an antecedent Σ FLC of 4.72 mg/dL or higher, which is near the upper limit of normal for the test. A nonclonal elevation of Σ FLC is a significant predictor of worse overall survival in the general population of persons without plasma cell disorders.


Economic modelling of immediately sequential bilateral cataract surgery (ISBCS) in the National Health Service based on possible improvements in surgical efficiency.
To test a hypothesis that operating room (OR) productivity in the National Health Service (NHS) can be improved with the introduction of immediately sequential bilateral cataract surgery (ISBCS). Previously published time and motion data of 140 unilateral cataract surgeries conducted at five different NHS locations were reanalysed to construct a hypothetical model where only ISBCS (±one unilateral case) were conducted while maintaining time durations of all key tasks previously studied. Possible time efficiency savings were calculated for the ISBCS model and percentage increases in numbers of eyes operated per 4-hour theatre session calculated. Gains in efficiency were correlated with factors from the baseline data to predict which settings could improve efficiency most by undertaking ISBCS. Based on remodelling our time and motion study (TMS) data as hypothetical ISBCS cases, we could expect a mean 16% reduction (range 9.8%-17.8%) in the time taken for two cataract operations, translating into a mean 54% improvement (range 38%-67%) in number of cases currently performed per list and an 18% improvement (range 9%-28%) even if the number of unilateral cases per list had been fully maximised. An average number of four ISBCS cases per list (range 3-6) were required to achieve sufficient time savings to allow an extra unilateral surgery to be conducted. The introduction of routine ISBCS has the potential to improve the productivity of cataract surgery within the NHS, with efficiencies being possible in both high-volume and low-volume surgical models.


Back to the roots of modern analytical toxicology: Jean Servais Stas and the Bocarmé murder case.
In 1850 the Belgian Count Hypolyte Visart de Bocarmé was accused of having killed his brother-in-law Gustave Fougnies by poisoning with nicotine. Bocarmé had isolated nicotine from tobacco leaves (Nicotiana tabacum). J. S. Stas (1813-1891) was committed expert and managed to convince the poisoner. He was the first scientist to deproteinize organ tissues by alcohol and could successfully identify nicotine after diethyl ether extraction from the victim's organs. During court trial this identification was challenged by his mentor M. J. B. Orfila from Paris, who had stated 3 years before, that it would never be possible to isolate and identify organic poisons from organ tissues.


Reduced White Matter Fiber Density in Autism Spectrum Disorder.
Differences in brain networks and underlying white matter abnormalities have been suggested to underlie symptoms of autism spectrum disorder (ASD). However, robustly characterizing microstructural white matter differences has been challenging. In the present study, we applied an analytic technique that calculates structural metrics specific to differently-oriented fiber bundles within a voxel, termed "fixels". Fixel-based analyses were used to compare diffusion-weighted magnetic resonance imaging data from 25 individuals with ASD (mean age = 16.8 years) and 27 typically developing age-matched controls (mean age = 16.9 years). Group comparisons of fiber density (FD) and bundle morphology were run on a fixel-wise, tract-wise, and global white matter (GWM) basis. We found that individuals with ASD had reduced FD, suggestive of decreased axonal count, in several major white matter tracts, including the corpus callosum (CC), bilateral inferior frontal-occipital fasciculus, right arcuate fasciculus, and right uncinate fasciculus, as well as a GWM reduction. Secondary analyses assessed associations with social impairment in participants with ASD, and showed that lower FD in the splenium of the CC was associated with greater social impairment. Our findings suggest that reduced FD could be the primary microstructural white matter abnormality in ASD.


Normal physiologic values of neonatal pigs and the effects of isoflurane and pentobarbital anesthesia.
The newborn piglet is becoming increasingly popular as a model for neonatal studies. However, data on normal physiologic baseline values and the influence of anesthesia on these values are scarce. In this study, we describe husbandry, surgical, and experimental methods used to establish a conscious, chronically catheterized neonatal piglet model, which enabled study of unrestrained piglets recovered from surgery and anesthesia, for up to 10 days after separation from the sow. Chronic catheterization allowed repeated experiments to be performed in the same animals, reducing the number of animals needed for study. Presented herein are baseline resting hemodynamic and blood chemistry data and circulating hormone measurements of vasopressin, plasma renin activity, adrenocorticotrophic hormone, cortisol, epinephrine, norepinephrine, and dopamine for piglets in the first 2 weeks of life. Also, in two series of experiments, the effects of the gas anesthetic isoflurane and the injectable anesthetic pentobarbital on these baseline values were investigated. Results indicate that both pentobarbital and isoflurane elicit changes in blood pressure, heart rate, vasopressin, plasma renin activity and ventilatory drive that should be considered when using either of these anesthetic agents in acute studies.


Imatinib mesylate in combination with other chemotherapeutic agents for chronic myelogenous leukemia.
Imatinib therapy is an important contribution to the management of patients with chronic myelogenous leukemia (CML). Despite high rates of hematologic and cytogenetic responses to imatinib therapy, the emergence of resistance to imatinib has been recognized as a major problem in the treatment of CML. Experimental and clinical studies suggest that imatinib as a single drug may not be sufficient to eradicate BCR-ABL-positive stem cells. Therefore, whether combinations of imatinib with other agents can increase the length of molecular remission and whether such combinations can prolong survival should be determined by large-scale clinical studies. In this review, we discuss efficacious combinations for future clinical trials. These regimens combine imatinib with conventional chemotherapeutic agents or with inhibitors of other signal transduction molecules that may be preferentially activated in CML cells.


Successful control of hepatitis B surface antigenemia in a dialysis unit without geographic or machine isolation.
Persistent hepatitis B infections among patients and frequent new hepatitis B infections among both patients and staff were a major problem in our dialysis unit during its first two and one-half years of operation. During this time the mean quarterly rate of conversion to HBsAg positivity among patients ranged from 0-60% (mean 12%); in staff it ranged from 0-13%. Control efforts, including strict temporal isolation, improved sanitary measures, and use of parallel plate dialyzers without geographic or machine isolation, were begun late in 1976. After a four-month lag, new HBsAg conversions ceased among the 30 patients and staff at risk, despite continued dialysis of eight HBsAg-positive patients (at least four of whom were HBeAg-positive). Over the succeeding three years the conversion rate was zero in both patients and staff. This experience suggests that conservative control measures without geographic separation of patients may be sufficient to control an established outbreak of hemodialysis-related hepatitis B. Controlled prospective trials of this hypothesis are warranted.


Changes in hepatic nuclei induced by acetamide and thioacetamide.
Rat liver nuclei were examined following intoxication with thioacetamide or acetamide. A prompt increase in nuclear size occurred with the administration of either agent. The acetamide-related change was evanescent and, by 16 hours, the nuclei did not differ from controls. Thioacetamide produced an acute enlargement during the first eight hours and a second, more prolonged increase during the next 24 hours. The enlargement noted by microscopy was also detectable in isolated nuclei by flow spectrometry. Chemical determinations on isolated nuclei appear to sample the same size population seen in situ. An increase in RNA content of thioacetamide-treated nuclei occurred during the late phase. The temporal sequence of physical and chemical change suggests that the initial increase in nuclear volume is not the result of retained macromolecular formation but may involve intracellular water and electrolyte shifts.


Attachment of lipoprotein to murein (peptidoglycan) of Escherichia coli in the presence and absence of penicillin FL 1060.
In vivo studies on the attachment of lipoprotein to the murein (peptidoglycan) of Escherichia coli showed that it takes several generations of growth until the amount of lipoprotein on newly made murein is equilibrated. The technique used involves degradation of the sodium dodecyl sulfate-insoluble murein-lipoprotein complex (sacculus, rigid layer) with lysozyme and separation of the labeled products on paper. No lipoprotein was found on murein subunits incorporated during a pulse of [3H]diaminopimelate for 1 min in logarithmically growing cells at 37 C. Even after one doubling of the cell mass, only 4 to 8% of the labeled murein was isolated as bound to lipoprotein. With uniformly labeled murein, 30% remains bound to lipoprotein after lysozyme treatment, corresponding to three murein subunits. Therefore it can be concluded that during pulse labeling either no lipoprotein is incorporated into the newly synthesized murein or no murein subunits are inserted into existing murein around lipoprotein attachment sites. Longer pulse and pulse-chase experiments argue for the latter interpretation. It is therefore concluded that incorporation of murein subunits into the growing murein polymer is not at all a random process. Instead, quite large areas of murein, on which lipoprotein is situated, seem to be preserved. Under the influence of penicillin FL 1060 murein synthesis is 50% inhibited. The rate of lipoprotein attachment is less affected so that increasing amounts of lipoprotein become attached during spheroplast formation. By the time the stationary growth phase has been reached, the lipoprotein content of the murein has doubled. Diaminopimelate auxotrophic mutants require, in the presence of penicillin FL 1060, more diaminopimelate for full growth than in the absence of penicillin FL 1060. This finding and the fact that murein synthesis is always inhibited by 50% over a wide range of penicillin concentration (1 to 1,000 mug/ml) point to the inhibition of an enzymatic step of murein synthesis which can be partially bypassed by a second enzyme, less efficient but resistant to penicillin FL 1060.


Discovery of potent, nonsteroidal, and highly selective glucocorticoid receptor antagonists.
An approach to the computer-assisted, pharmacophore design of nonsteroidal templates for the glucocorticoid receptor (GR) that contained an element of pseudo-C2 symmetry was developed. The enatiomer of the initial design, 1Ra, and not the designed molecule, 1S, showed the desired ligand binding to the GR. The pseudo-C2 symmetry of the template allowed for rapid improvements in GR activity resulting in potent, selective, nonsteroidal GR antagonists, CP-394531 and CP-409069.


Being in a lived retreat--embodied meaning of alleviated suffering.
Meanings of alleviated suffering in persons living with life-threatening cancer are explored in this life-world phenomenologic study. In repeated conversations, 16 patients with cancer who were receiving palliative care shared their embodied experiences in personal narratives. When interpreting the narratives, the following meanings of experiencing alleviation of suffering were disclosed: an endurable body being independent and feeling at home, feelings of connectedness, taking a long view of the suffering, being lifted out of the suffering, and an inner peace. Movements that were found in alleviation were dampening the suffering, arousing a zest for life, and focusing on both the present and the patient's dignity. As an interpreted whole, alleviation of suffering was found to be an embodied experience of "being in a lived retreat." This is a symbolic place owned by the person and is experienced in either the company of others or solitude. This lived retreat can provide a feeling of being at home, creating peace, rest, confidence, and breathing space in the person's suffering. It means coping with the altered lived body and feeling dignified. This is a personal experience that is both intersubjectively created and dependent. The importance of openness and responsibility in palliative care is emphasized in the findings and the notion of control of suffering in palliative care is accordingly rejected.


Thalamocortical Mechanisms Regulating the Relationship between Transient Beta Events and Human Tactile Perception.
Transient neocortical events with high spectral power in the 15-29 Hz beta band are among the most reliable predictors of sensory perception. Prestimulus beta event rates in primary somatosensory cortex correlate with sensory suppression, most effectively 100-300 ms before stimulus onset. However, the neural mechanisms underlying this perceptual association are unknown. We combined human magnetoencephalography (MEG) measurements with biophysical neural modeling to test potential cellular and circuit mechanisms that underlie observed correlations between prestimulus beta events and tactile detection. Extending prior studies, we found that simulated bursts from higher-order, nonlemniscal thalamus were sufficient to drive beta event generation and to recruit slow supragranular inhibition acting on a 300 ms timescale to suppress sensory information. Further analysis showed that the same beta-generating mechanism can lead to facilitated perception for a brief period when beta events occur simultaneously with tactile stimulation before inhibition is recruited. These findings were supported by close agreement between model-derived predictions and empirical MEG data. The postevent suppressive mechanism explains an array of studies that associate beta with decreased processing, whereas the during-event facilitatory mechanism may demand a reinterpretation of the role of beta events in the context of coincident timing.


Animal Welfare Aspects in Planning and Conducting Experiments on Rodent Models of Subarachnoid Hemorrhage.
Subarachnoid hemorrhage is an acute life-threatening cerebrovascular disease with high socio-economic impact. The most frequent cause, the rupture of an intracerebral aneurysm, is accompanied by abrupt changes in intracerebral pressure, cerebral perfusion pressure and, consequently, cerebral blood flow. As aneurysms rupture spontaneously, monitoring of these parameters in patients is only possible with a time delay, upon hospitalization. To study alterations in cerebral perfusion immediately upon ictus, animal models are mandatory. This article addresses the points necessarily to be included in an animal project proposal according to EU directive 2010/63/EU for the protection of animals used for scientific purposes and herewith offers an insight into animal welfare aspects of using rodent models for the investigation of cerebral perfusion after subarachnoid hemorrhage. It compares surgeries, model characteristics, advantages, and drawbacks of the most-frequently used rodent models-the endovascular perforation model and the prechiasmatic and single or double cisterna magna injection model. The topics of discussing anesthesia, advice on peri- and postanesthetic handling of animals, assessing the severity of suffering the animals undergo during the procedure according to EU directive 2010/63/EU and weighing the use of these in vivo models for experimental research ethically are also presented. In conclusion, rodent models of subarachnoid hemorrhage display pathophysiological characteristics, including changes of cerebral perfusion similar to the clinical situation, rendering the models suited to study the sequelae of the bleeding. A current problem is low standardization of the models, wherefore reporting according to the ARRIVE guidelines is highly recommended. Animal welfare aspects of rodent models of subarachnoid hemorrhage. Rodent models for investigation of cerebral perfusion after subarachnoid hemorrhage are compared regarding surgeries and model characteristics, and 3R measures are suggested. Anesthesia is discussed, and advice given on peri- and postanesthetic handling. Severity of suffering according to 2010/63/EU is assessed and use of these in vivo models weighed ethically.


Anomalous muscles within the first dorsal extensor compartment of the wrist.
A 73-year-old woman presented with a 12-month history of a tender first dorsal extensor compartment of her right wrist along with swelling which extended proximally. Caring for her grandchildren exacerbated her pain, and rest relieved it. Over a 2-month period, two injections and splint immobilization failed to provide pain relief and swelling reduction. An ultrasound showed anomalous muscles within the first dorsal extensor compartment. Surgical release of the first compartment showed the abductor pollicis longus and extensor pollicis brevis tendons flanked by muscles within an inflamed sheath. Releasing the compartment resulted in complete pain relief. Anatomic variations within the first dorsal extensor compartment have been reported, but there has been no report on double anomalous muscles within the compartment. The details of the case, utility of ultrasound, and a brief review of the literature are described.


Molecular phylogeny of kinorhynchs.
We reconstructed kinorhynch phylogeny using maximum-likelihood and Bayesian analyses of nuclear 18S and 28S rRNA gene sequences from 30 species in 13 genera (18S) and 23 species in 12 genera (28S), representing eight families and both orders (Cyclorhagida and Homalorhagida) currently recognized in the phylum. We analyzed the two genes individually (18S and 28S datasets) and in combination (18S+28S dataset). We detected four main clades (I-IV). Clade I consisted of family Echinoderidae. Clade II contained representatives of Zelinkaderidae, Antygomonidae, Semnoderidae, Centroderes, and Condyloderes, the latter two currently classified in Centroderidae; within Clade II, Zelinkaderidae, Antygomonidae, and Semnoderidae comprised a clade with strong nodal support. Clade III contained only two species in Campyloderes, also currently classified in the Centroderidae, indicating polyphyly for this family. Clades I-III, containing all representatives of Cyclorhagida included in the analysis except for Dracoderes abei, formed a clade with high nodal support in the 28S and 18S+28S trees. Clade IV, resolved in the 18S and 18S+28S trees with high nodal support, contained only species in order Homalorhagida, with the exception of the cyclorhagid Dracoderes abei. Order Cyclorhagida as it currently stands is thus polyphyletic, and order Homalorhagida paraphyletic. Our results indicate that Dracoderidae has been misplaced in Cyclorhagida based on homoplasious characters. Our analyses did not resolve the relationships among Clades I-III within Cyclorhagida. Neither gene alone nor the combined dataset resolved all nodes in trees, indicating that additional markers will be needed to reconstruct kinorhynch phylogeny.


Years of potential life lost by children and adolescent victims of homicide, Recife, 1997.
This is a study of years of potential life lost (YPLL) by children and adolescents aged between 1 month and 19 years who were victims of homicide in Recife during 1997. It also draws a profile of the victims. A descriptive, cross-sectional study was made of death certificates of Recife residents, aged between 1 month and 19 years, occurring during 1997, to identify homicides and the three other most frequent causes of death in the age group, in order to make a profile of homicide victims. YPLL was calculated for this cause of death and the other three. Homicide was responsible for 36.6 per cent of the deaths, followed by pneumonia (9.4 per cent), vehicle accidents (6.3 per cent) and other accidents (6.0 per cent). Most of the murder victims were 15-19-year-old male students, but their level of schooling was unknown in 96.6 per cent of cases. Death was caused by firearms in 93.2 per cent of the cases. Homicides were responsible for 59.1 per cent of YPLL, followed by pneumonia, vehicle accidents and other accidents. The risk of losing years of potential life by homicide in the group studied was 27.20 in 1000. These figures show the magnitude of homicides as a cause of premature death and how they have become a public health problem.


Clinical translation of folate receptor-targeted therapeutics.
Folate receptor-α (FR-α) has been established as a membrane marker for ovarian cancer. In addition, it is frequently overexpressed in other major types of epithelial tumors. FR-α-based tumor-targeted therapy and drug carriers have been an active area of laboratory research for more than 20 years. Recently, there has been a great increase in the effort to finally translate this promising technology into the clinic and bring FR-targeted therapeutics into the market. Two FR-targeted therapeutic agents have moved into Phase III clinical trials, the monoclonal antibody farletuzumab and the low molecular weight vintafolide, combined with etarfolatide as a companion imaging agent, representing two alternative strategies for targeting the FR. Each of the two strategies has advantages and disadvantages. Identification of the best target patient population is likely critical to the ultimate success of FR-targeted agents in the clinic. A successful clinical strategy may require the integration between FR expression analysis and an optimal combination of FR-targeted therapy and standard chemotherapy. Advancement into Phase III trials and the ongoing clinical development of several additional folate conjugates are likely to usher in a new era of clinical translation and validation of FR-targeted imaging and therapeutic agents.


Association of weekly suicide rates with temperature anomalies in two different climate types.
Annual suicide deaths outnumber the total deaths from homicide and war combined. Suicide is a complex behavioral endpoint, and a simple cause-and-effect model seems highly unlikely, but relationships with weather could yield important insight into the biopsychosocial mechanisms involved in suicide deaths. This study has been designed to test for a relationship between air temperature and suicide frequency that is consistent enough to offer some predictive abilities. Weekly suicide death totals and anomalies from Toronto, Ontario, Canada (1986-2009) and Jackson, Mississippi, USA (1980-2006) are analyzed for relationships by using temperature anomaly data and a distributed lag nonlinear model. For both analysis methods, anomalously cool weeks show low probabilities of experiencing high-end suicide totals while warmer weeks are more likely to experience high-end suicide totals. This result is consistent for Toronto and Jackson. Weekly suicide totals demonstrate a sufficient association with temperature anomalies to allow some prediction of weeks with or without increased suicide frequency. While this finding alone is unlikely to have immediate clinical implications, these results are an important step toward clarifying the biopsychosocial mechanisms of suicidal behavior through a more nuanced understanding of the relationship between temperature and suicide.


Ethnographic edutainment for transformative medical education: Thailand.
Transformative learning is a most important issue in medical education. Ethnographic edutainment is a concept that consists of reward, competition, and motivation strategies, which are more effective in engaging with learners. First-year medical students (N = 321) were included in this study during the Doctor and Society course at Chulalongkorn University in 2011. Four preset learning objectives were set and participants assigned a term group project with clouding technologies. The deliverables and the attitude toward this method were evaluated. Nineteen of 20 (95%) groups achieved all objectives. Females rated higher scores for this activity than males (P < 0.001). Statistically significant differences were found between lecture-based sessions and field visit sessions as well as ethnographic edutainment activity sessions and other types (P < 0.01). The results were consistent in both male and female groups. Ethnographic edutainment can be well-accepted with higher satisfaction than some other types of teaching.


A life history theory of father absence and menarche: a meta-analysis.
Is the absence of biological fathers related to their daughters' earlier age at menarche? Drawing on evolutionary psychology and life history theory, prior research has suggested such a relationship (Belsky, Steinberg, and Draper, 1991; Draper and Harpending, 1982; Ellis, 2004). Although qualitative reviews have shown narrative support for this relationship (Allison and Hyde, 2013; Ellis, 2004; Kim, Smith, and Palermiti, 1997; Susman and Dorn, 2009), no quantitative review exists to provide empirical support for this relationship or to explain mixed results. Thus, we conducted a random-effects meta-analysis of correlations (Card, 2012) on father absence and daughter menarcheal age (k=33; N=70,403). The weighted mean correlation was .14, 95% CI [.09, .19], suggesting that father absence was significantly related to earlier menarche; effect sizes were heterogeneous. Egger's regression (Egger, Smith, Schneider, and Minder, 1997) showed no evidence of publication bias (file-drawer effect; r=.34, p=.052). Outcome measure differences (menarcheal age vs. menarcheal age embedded in a multi-item pubertal timing scale) did not moderate effect sizes. Study year effects (Schooler, 2011) were also non-significant. Our findings support one aspect of the life history model and provide groundwork for subsequent examination of other pathways in the model.


Sub-nanometer surface chemistry and orbital hybridization in lanthanum-doped ceria nano-catalysts revealed by 3D electron microscopy.
Surface chemical composition, electronic structure, and bonding characteristics determine catalytic activity but are not resolved for individual catalyst particles by conventional spectroscopy. In particular, the nano-scale three-dimensional distribution of aliovalent lanthanide dopants in ceria catalysts and their effect on the surface electronic structure remains unclear. Here, we reveal the surface segregation of dopant cations and oxygen vacancies and observe bonding changes in lanthanum-doped ceria catalyst particle aggregates with sub-nanometer precision using a new model-based spectroscopic tomography approach. These findings refine our understanding of the spatially varying electronic structure and bonding in ceria-based nanoparticle aggregates with aliovalent cation concentrations and identify new strategies for advancing high efficiency doped ceria nano-catalysts.


Seroprevalence of human T lymphtropic virus (HTLV) among tissue donors in Iranian tissue bank.
Iranian Tissue Bank prepares a wide range of human tissue homografts such as; heart valve, bone, skin, amniotic membrane and other tissues for different clinical applications. The purpose of this study was to determine the seroprevalence of HTLV in tissue donors. About 1,548 tissue donors were studied during a 5-years period by ELISA assays. HTLV(1,2)-antibodies were tested for all of donors with other tests upon American Association of Tissue Banks (AATB) standards. About 25 (1.61%) out of 1,548 tissue donors were HTLV positive that 17 donors were male and 8 were female (female/male ratio was approximately 47%). Regarding to the prevalence of HTLV among tissue donors and importance of cell and tissue safety and quality assurance, we recommend that all blood, cell and tissue banks should be involved both routine serological methods and other complementary tests such as polymerase chain reaction (PCR) for diagnosis of HTLV.


Moths passing in the night: Phenological and genomic divergences within a forest pest complex.
Temporal separation of reproductive timing can contribute to species diversification both through allochronic speciation and later reinforcement of species boundaries. Such phenological differences are an enigmatic component of evolutionary divergence between two major forest defoliator species of the spruce budworm complex: Choristoneura fumiferana and C. occidentalis. While these species interbreed freely in laboratory settings, natural hybridization rates have not been reliably quantified due to their indistinguishable morphology. To assess whether temporal isolation is contributing to reproductive isolation, we collected adult individuals throughout their expected zone of sympatry in western Canada at 10-day intervals over two successive years, assigning taxonomic identities using thousands of single nucleotide polymorphisms. We found unexpectedly broad sympatry between C. fumiferana and C. occidentalis biennis and substantial overlap of regional flight periods. However, flight period divergence was much more apparent on a location-by-location basis, highlighting the importance of considering spatial scale in these analyses. Phenological comparisons were further complicated by the biennial life cycle of C. o. biennis, the main subspecies of C. occidentalis in the region, and the occasional occurrence of the annually breeding subspecies C. o. occidentalis. Nonetheless, we demonstrate that biennialism is not a likely contributor to reproductive isolation within the species complex. Overall, interspecific F1 hybrids comprised 2.9% of sequenced individuals, confirming the genomic distinctiveness of C. fumiferana and C. occidentalis, while also showing incomplete reproductive isolation of lineages. Finally, we used F ST-based outlier and genotype-environment association analyses to identify several genomic regions under putative divergent selection. These regions were disproportionately located on the Z linkage region of C. fumiferana, and contained genes, particularly antifreeze proteins, that are likely to be associated with overwintering success and diapause. In addition to temporal isolation, we conclude that other mechanisms, including ecologically mediated selection, are contributing to evolutionary divergence within the spruce budworm species complex.


Perceiving a continuous visual world across voluntary eye blinks.
People blink their eyes every few seconds, but the changes in retinal illumination that accompany eyeblinks are hardly noticed. Furthermore, despite the loss of visual input, visual experience remains continuous across eyeblinks. Two hypotheses were investigated to account for these phenomena. The first proposes that perceptual information is maintained across a blink whereas the second proposes that perceptual information is not maintained but rather postblink perceptual experience is antedated to the beginning of the blink. Two experiments found no evidence for temporal antedating of a stimulus presented during a voluntary eyeblink. In a third experiment subjects judged the temporal duration of a stimulus that was interrupted by a voluntary eyeblink with that of a stimulus presented while the eyes were open. The duration of stimuli that were interrupted by eyeblinks was judged to be 117 ms shorter than that of stimuli presented while the eyes remained open, indicating that blink duration was not accounted for in the perception of stimulus duration. This suggests that perceptual experience is neither maintained nor antedated across eyeblinks, but rather is ignored, perhaps in response to the extraretinal signal that accompanies the eyeblink. (PsycINFO Database Record


Unusual Cause and Presentation of Collapsing Focal Segmental Glomerulosclerosis.
Collapsing focal segmental glomerulosclerosis (c-FSGS), a structural variant of focal segmental glomeruloslecrosis (FSGS), is considered to be the most aggressive FSGS form. Most patients present with severe nephrotic syndrome and often have rapidly progressing renal failure and progression to end-stage kidney disease. We are reporting a 28-year-old previously healthy woman, who was started on griseofulvin for onchomycosis; she subsequently developed acute renal failure with significant proteinuria. Exposure to the drug caused dramatic decline in the renal function. Renal biopsy was compatible with c-FSGS. To the best of our knowledge, this is the first case of biopsy-proven griseofulvin-associated c-FSGS. Our patient showed rapid improvement in renal function after discontinuation of griseofulvin. Universally, c-FSGS carries poor prognosis, but this case is unique because patient showed rapid improvement in renal function with a short duration after cessation of griseofulvin.


Physiological characteristics of Corynebacterium glutamicum as a cell factory under anaerobic conditions.
Corynebacterium glutamicum, a gram-positive and facultative anaerobic bacterium, is widely used for the industrial production of amino acids, such as L-glutamate and L-lysine. C. glutamicum grows and produces amino acids under aerobic conditions. When restricted under anaerobic conditions, it produces organic acids, such as L-lactate and succinate, through metabolic shift. With the increasing threat of global warming, these organic acids have drawn considerable attention as bio-based plastic monomers. In addition to the organic acids, the anaerobic bioprocess is also used to produce other value-added compounds, including isobutanol, ethanol, 3-methyl-1-butanol, 2,3-butanediol, L-alanine, and L-valine. Therefore, C. glutamicum is now a versatile cell factory for producing a wide variety of useful chemicals under both aerobic and anaerobic conditions. The growth and metabolism of the bacterium depend on the oxygen levels, which modulate the rearrangement of the carbon flux by reprogramming gene expression patterns and intracellular redox states. Anaerobic cell growth and L-lysine production as well as aerobic succinate production have been demonstrated by engineering the metabolic pathways or supplying a terminal electron acceptor instead of oxygen. In this review, we discuss the physiological and metabolic changes in C. glutamicum associated with its application as a cell factory under different oxygen states. Physiological switching in bacteria is initiated with the sensing of oxygen availability. While such a sensor has not been identified in C. glutamicum yet, the molecular mechanism for oxygen sensing in related bacteria is also discussed. KEY POINTS: • C. glutamicum produces a wide variety of useful compounds under anaerobic conditions. • C. glutamicum is a versatile cell factory under both aerobic and anaerobic conditions. • Metabolic fate can be overcome by engineering metabolic pathways.


Lifetime cumulative risk factors predict cardiovascular disease mortality in a 50-year follow-up study in Finland.
Systolic blood pressure, total cholesterol and smoking are known predictors of cardiovascular disease (CVD) mortality. Less is known about the effect of lifetime accumulation and changes of risk factors over time as predictors of CVD mortality, especially in very long follow-up studies. Data from the Finnish cohorts of the Seven Countries Study were used. The baseline examination was in 1959 and seven re-examinations were carried out at approximately 5-year intervals. Cohorts were followed up for mortality until the end of 2011. Time-dependent Cox models with regular time-updated risk factors, time-dependent averages of risk factors and latest changes in risk factors, using smoothing splines to discover nonlinear effects, were used to analyse the predictive effect of risk factors for CVD mortality. A model using cumulative risk factors, modelled as the individual-level averages of several risk factor measurements over time, predicted CVD mortality better than a model using the most recent measurement information. This difference seemed to be most prominent for systolic blood pressure. U-shaped effects of the original predictors can be explained by partitioning a risk factor effect between the recent level and the change trajectory. The change in body mass index predicted the risk although body mass index itself did not. The lifetime accumulation of risk factors and the observed changes in risk factor levels over time are strong predictors of CVD mortality. It is important to investigate different ways of using the longitudinal risk factor measurements to take full advantage of them.


Efficacy and Tolerability of Peritendinous Hyaluronic Acid in Patients with Supraspinatus Tendinopathy: a Multicenter, Randomized, Controlled Trial.
Physical therapy and peritendinous hyaluronic acid (HA) injections have both shown promising results in the treatment of shoulder tendinopathies. However, the superiority of treatment combining physical therapy and HA is unclear. Patients with ultrasound-confirmed supraspinatus tendinopathy were randomized to receive either physical therapy + subacromial HA injections or physical therapy only. Treatment efficacy was assessed using a Visual Analog Scale (VAS) for pain and an Activities of Daily Living (ADL) scale. Other measures were the number of rehabilitation sessions and days needed for recovery, the Tampa Scale for Kinesiophobia (TSK), and the physician and patient's perception of efficacy and tolerability. Patients were followed up for 90 days. Overall, VAS and ADL scores showed a progressive decrease during the follow-up (P < 0.01 at all visits for both groups), without significant differences between groups. The TSK score decreased significantly more in the HA group than in the control group (3.6 vs. 2.4; P < 0.001). Patients in the control group needed more rehabilitation sessions (28 vs. 22 in the HA group; P = 0.006) and more days for returning to their pre-injury activity (32 vs. 20 in the HA group; P = 0.013). Both patients and investigators perceived higher efficacy in the HA group than in the control group (P = 0.034). Both treatments were safe and well tolerated. Subacromial HA injections combined with physical therapy have high efficacy in the treatment of supraspinatus tendinopathy, leading to an earlier return to pre-injury activity and the need for fewer rehabilitation sessions, which may benefit both patients and the healthcare system.


Characterisation of Natural Fibres for Sustainable Discontinuous Fibre Composite Materials.
Growing environmental concerns and stringent waste-flow regulations make the development of sustainable composites a current industrial necessity. Natural fibre reinforcements are derived from renewable resources and are both cheap and biodegradable. When they are produced using eco-friendly, low hazard processes, then they can be considered as a sustainable source of fibrous reinforcement. Furthermore, their specific mechanical properties are comparable to commonly used, non-environmentally friendly glass-fibres. In this study, four types of abundant natural fibres (jute, kenaf, curaua, and flax) are investigated as naturally-derived constituents for high performance composites. Physical, thermal, and mechanical properties of the natural fibres are examined to evaluate their suitability as discontinuous reinforcements whilst also generating a database for material selection. Single fibre tensile and microbond tests were performed to obtain stiffness, strength, elongation, and interfacial shear strength of the fibres with an epoxy resin. Moreover, the critical fibre lengths of the natural fibres, which are important for defining the mechanical performances of discontinuous and short fibre composites, were calculated for the purpose of possible processing of highly aligned discontinuous fibres. This study is informative regarding the selection of the type and length of natural fibres for the subsequent production of discontinuous fibre composites.


On waveguide modeling of stiff piano strings.
Bensa et al. [J. Acoust. Soc. Am. 114, 1095-1107 (2003), Sec. IV] recently proposed a waveguide model for the transverse displacement of a stiff piano string. The study described here is an attempt to cast a complementary light on this topic, based on a common wave approach instead of a modal approach. A pair of weakly attenuated traveling waves and a pair of fast-decaying waves both satisfy the one-dimensional wave equation developed by Bensa et al. These solutions have to be carefully considered, however, for portions of string interacting with the hammer felt, the bridge, or the capo d'astro bar.


Ras1-induced hyphal development in Candida albicans requires the formin Bni1.
Formins are downstream effector proteins of Rho-type GTPases and are involved in the organization of the actin cytoskeleton and actin cable assembly at sites of polarized cell growth. Here we show using in vivo time-lapse microscopy that deletion of the Candida albicans formin homolog BNI1 results in polarity defects during yeast growth and hyphal stages. Deletion of the second C. albicans formin, BNR1, resulted in elongated yeast cells with cell separation defects but did not interfere with the ability of bnr1 cells to initiate and maintain polarized hyphal growth. Yeast bni1 cells were swollen, showed an increased random budding pattern, and had a severe defect in cytokinesis, with enlarged bud necks. Induction of hyphal development in bni1 cells resulted in germ tube formation but was halted at the step of polarity maintenance. Bni1-green fluorescent protein is found persistently at the hyphal tip and colocalizes with a structure resembling the Spitzenkörper of true filamentous fungi. Introduction of constitutively active ras1G13V in the bni1 strain or addition of cyclic AMP to the growth medium did not bypass bni1 hyphal growth defects. Similarly, these agents were not able to suppress hyphal growth defects in the wal1 mutant which is lacking the Wiskott-Aldrich syndrome protein (WASP) homolog. These results suggest that the maintenance of polarized hyphal growth in C. albicans requires coordinated regulation of two actin cytoskeletal pathways, including formin-mediated secretion and WASP-dependent endocytosis.


[Liver anatomy: echography and Doppler].
Ultrasonography is an excellent tool for the study of the anatomy of the human liver. This article shows, with the help of sonographic views along the long axis of portal and hepatic veins, and the different landmarks of the liver, how to delineate the eight segments of the liver. Doppler examination allows indentification of the portal veins and the hepatic arteries in the portal triad.


[Bronchoalveolar lavage and induced sputum in asthmatic and COPD patient].
Scientific studies of the material obtained during bronchial biopsy, bronchoalveolar lavage and sputum induction altered the view on the pathogenesis of asthma and COPD. In the result, both bronchial diseases are considered inflammatory. Eosinophils play the main role in the pathogenesis of asthma, whereas in COPD the most significant are neutrophils. Bronchial biopsy and bronchoalveolar lavage have been applied mainly in scientific studies, while sputum induction as a non-invasive method can be useful in everyday practice too. Increased level of eosinophils in sputum allows to forecast the efficiency of glucocorticosteroids in the therapy of asthma and COPD.


The history of photosynthetic thermoluminescence.
A fundamental discovery of photosynthetis research in the 1950s was the detection of thermally stimulated light emission from preilluminated photosynthetic material [Arnold W and Sherwood H (1957) Proc Natl Acad Sci USA 43: 105-114]. This phenomenon, called thermoluminescence (TL), is characteristic of a wide range of materials (minerals, semiconductors, inorganic and organic crystals, and complex biological systems), which share the ability of storing radiant energy in thermally stabilized trap states. The original discovery of TL in dried chloroplasts later proved to be a phenomenon common to all photosynthetic organisms: photosynthetic bacteria, cyanobacteria, algae and higher plants, which can be observed in isolated membrane particles, intact chloroplasts and unicellular organisms, and whole leaves. Following the initial observations considerable effort has been devoted to the identification and characterization of photosynthetic TL components. This work has firmly established the participation of various oxidation states of the water-oxidizing complex, the redox-active tyrosines, and the quinone electron acceptors of Photosystem II (PS II) in the generation of photosynthetic glow curves. Since TL characteristics are very sensitive to subtle changes in the redox properties of the involved electron transport components, the TL method has become a powerful tool in probing a wide range of PS II redox reactions and their modifications by environmental stress effects. Here, the main milestones of research in photosynthetic TL are covered until the present day.


[Effect of psychological pressure on muscle elasticity and the function of the autonomic nervous system].
The purpose of this study was to clarify the following: (1) effect on the elasticity of the musculus trapezius caused by psychological load, and (2) relationship between psychological load, muscle elasticity, and the autonomic nervous system (ANS) by frequency analysis of heart rate variability. The experiment was conducted on a group of 30 healthy volunteers, consisting of 16 males and 14 females with an average age of 31.2 years old. We investigated and compared the changes in muscle elasticity and ANS in the case of control (resting), phonating and mental calculation as psychological load. Psychological status and stress response were measured by using State-Trate Anxiety Inventory (STAI), Stress Checklist (SCL), and Stress Tolerance Checklist (STCL). As a result, the subjects experienced effective acute emotional stress during mental calculation, and muscle elasticity increased significantly. Heart rate (HR), low frequency (LF) component, and LF/HF increased significantly during mental calculations. The high frequency (HF) component tended to decrease during mental calculations. The rate of elevation of muscle elasticity and HR (difference between at rest and when calculating) was significantly related to STAI and STCL. STCL was significantly related to state of anxiety. The results of this study suggest that anxiety and stress tolerance affect muscle elasticity.


Adriamycin, bleomycin, vinblastine and DTIC in advanced diffuse lymphocytic poorly differentiated lymphoma.
From January 1975 to December 1979, 14 consecutive patients with advanced (stage III-IV) diffuse lymphocytic, poorly differentiated lymphoma (DLPD) were treated with adriamycin, bleomycin, vinblastine and DTIC (ABVD). Either maintenance combination chemotherapy with CVP or radiotherapy over bulky disease was added in the cases with complete response (CR). Fifty per cent of the patients achieved CR and 80% achieved objective responses. Among CRs, 100% were alive at 2 years, 70% of them without evidence of disease. Overall, 75% of the patients were alive at 2 years, 30% without evidence of disease. Toxicity was acceptable and no drug-related deaths occurred. ABVD is not the ideal combination for DLPD, but it should be taken into consideration in patients with advanced DLPD in which first line combination chemotherapy regimens are not successful.


Thermal ablation may improve outcomes in patients with colorectal liver metastasis: a case-control study.
Local thermal ablation may extend the scope of palliative therapy in patients with colorectal liver metastasis. We performed a retrospective, case-controlled study to compare patients with colorectal liver metastases that were treated with percutaneous radiofrequency (RF) or microwave (MW) thermal ablation, against the control group of chemotherapy alone. We described baseline demographics, ablation sessions, procedure duration and related complications. We compared outcomes of percutaneous thermal ablation versus chemotherapy alone (controls) in patients with colorectal liver metastasis. The control group assigned (non-ablated patients) had similar demographics and prior treatment profile when compared to ablated patients. Progression-free survival (PFS) and overall survival (OS) were estimated for the two groups. Twenty-eight cases with 57 baseline hepatic lesions (median age 68 years; male to female ratio 2:1) were evaluated and compared with 48 controls. A total of 55 sessions (52 RF, 3 MW) were performed among the cases, with minimal procedural time (median 8 min), zero mortality and no severe complications (3 cases of local hepatic hematoma not requiring hospitalization). Ablated patients had prolonged median PFS (19.4 months) and OS (27.5 months) when compared against controls (14.0 and 21.4 months, respectively). After adjusting for hepatic involvement, PFS estimates were comparable and OS was better for the ablated group. One and 2-year survival estimates were 0.96 and 0.79 for thermal ablation patients compared with 0.82 and 0.52 for controls (p=0.05 and p=0.07, respectively). Percutaneous thermal ablation may delay progression and death in colorectal cancer patients with metastatic liver disease.