An immunoblot assay reveals that bacteriophage T4 thymidylate synthase and dihydrofolate reductase are not virion proteins.
Numerous reports describe the phage T4 enzymes thymidylate synthase and dihydrofolate reductase as structural components of the baseplate. However, Y. Wang and C. K. Mathews (J. Virol. 63:4736-4743, 1989) reported that antisera against the respective recombinant enzymes failed to neutralize phage infectivity, in contrast to previous results. Moreover, a deletion mutant lacking the genes for these two enzymes adsorbed normally to host cells. Since these findings tended to undermine the idea of the two enzymes as structural proteins, we developed a quantitative immunoblot assay to resolve the issue directly. Our results show that both enzymes are present only as minor contaminants (< 0.05 copy per phage) and as such cannot be bona fide structural proteins.


MicroRNA-146a and microRNA-146b expression and anti-inflammatory function in human airway smooth muscle.
MicroRNA (miR)-146a and miR-146b are negative regulators of inflammatory gene expression in lung fibroblasts, epithelial cells, monocytes, and endothelial cells. The abundance of cyclooxygenase-2 (COX-2) and IL-1β is negatively regulated by the miR-146 family, suggesting miR-146a and/or miR-146b might modulate inflammatory mediator expression in airway smooth muscle thereby contributing to pathogenesis of asthma. To test this idea we compared miR-146a and miR-146b expression in human airway smooth muscle cells (hASMCs) from nonasthmatic and asthmatic subjects treated with cytomix (IL-1β, TNF-α, and IFNγ) and examined the miRNAs' effects on COX-2 and IL-1β expression. We found that cytomix treatment elevated miR-146a and miR-146b abundance. Induction with cytomix was greater than induction with individual cytokines, and asthmatic cells exhibited higher levels of miR-146a expression following cytomix treatment than nonasthmatic cells. Transfection of miR-146a or miR-146b mimics reduced COX-2 and IL-1β expression. A miR-146a inhibitor increased COX-2 and IL-1β expression, but a miR-146b inhibitor was ineffective. Repression of COX-2 and IL-1β expression by miR-146a correlated with reduced abundance of the RNA-binding protein human antigen R. These results demonstrate that miR-146a and miR-146b expression is inducible in hASMCs by proinflammatory cytokines and that miR-146a expression is greater in asthmatic cells. Both miR-146a and miR-146b can negatively regulate COX-2 and IL-1β expression at pharmacological levels, but loss-of-function studies showed that only miR-146a is an endogenous negative regulator in hASMCs. The results suggest miR-146 mimics may be an attractive candidate for further preclinical studies as an anti-inflammatory treatment of asthma.


Deletion mapping on the long arm of chromosome 7 in splenic lymphoma with villous lymphocytes.
Splenic lymphoma with villous lymphocytes (SLVL) is a low-grade lymphoproliferative disorder characterized by splenomegaly and circulating villous lymphocytes in the peripheral blood. It is considered to be the leukemic form of splenic marginal zone lymphoma (SMZL). The genetic basis of this lymphoma type remains unknown. Conventional cytogenetic studies have identified frequent structural abnormalities of chromosome 7, in the form of translocations, mainly unbalanced, and 7q deletions. In this current study, we undertook deletion mapping of the long arm of chromosome 7 in a series of cases with SLVL. Metaphase fluorescence in situ hybridization (FISH) was used in the first instance, followed by a study of loss of heterozygosity (LOH). The common area of deletion identified by FISH spanned from the YAC clone HSC7E1289 (mapping to 7q32.1) to in between YACs HSC7E195 and HSC7E648 (7q32-3). By application of 50 microsatellite markers mapping to the FISH-CDR and to areas of deletion reported in other studies, four distinct hotspot loci were identified, with abnormalities present in 29-55% cases. In three of them, both LOH and biallelic deletions were found. The LOH in the majority of patients was noncontiguous. The presence of a high incidence of abnormalities in the established hotspot areas and in particular the finding of biallelic deletions is indicative of the existence of genes important for the pathogenesis of SLVL in these areas.


Effect of chronic lithium treatment on rat pineal rhythms: N-acetyltransferase, N-acetylserotonin and melatonin.
Chronic lithium treatment in rats suppressed the peak activity of pineal N-acetyltransferase as well as the maximal concentrations of pineal N-acetylserotonin and melatonin which occur during the dark phase of the light/dark cycle. These changes were not related to changes in the precursor indoles tryptophan, 5-hydroxytryptophan and serotonin, which were unaltered by lithium treatment. The change in N-acetyltransferase activity appears in part to be due to a decreased Vmax of the enzyme, as assessed using tryptamine as the substrate. Lithium also suppressed pineal activity during the light phase of the diurnal lighting cycle as indicated by a markedly reduced cyclic AMP response to L-isoproterenol. In addition, lithium treatment elicited a 1- to 3-hr delay in peak pineal N-acetyltransferase activity. These effects may result from a lithium-induced desensitization of pineal beta adrenergic receptors, from a direct effect of the ion on the suprachiasmatic nucleus and/or from an action on a site distal to this hypothalamus nucleus.


A review of the epidemiology and surveillance of viral zoonotic encephalitis and the impact on human health in Australia.
Human encephalitis in Australia causes substantial mortality and morbidity, with frequent severe neurological sequelae and long-term cognitive impairment. This review discusses a number of highly pathogenic zoonotic viruses which have recently emerged in Australia, including Hendra virus and Australian bat lyssavirus which present with an encephalitic syndrome in humans. Encephalitis surveillance currently focuses on animals at sentinel sites and animal disease or definitive diagnosis of notifiable conditions that may present with encephalitis. This is inadequate for detecting newly emerged viral encephalatides. Hospital-based sentinel surveillance may aid in identifying increases in known pathogens or emergence of new pathogens that require a prompt public health response.


Acquired STAT4 deficiency as a consequence of cancer chemotherapy.
Signal Transducer and Activator of Transcription 4 (STAT4) is a transcription factor that is activated by IL-12 signaling and promotes Th1-cell differentiation and IFN-γ production. Defective IFN-γ production because of STAT4 mRNA and protein deficiency occurs after autologous stem cell transplantation for lymphoma. In the present study, we investigated the mechanisms of STAT4 deficiency in lymphoma patients. The tumor-bearing state is not responsible, because STAT4 levels were not significantly different in PBMCs obtained from healthy control subjects compared with those from lymphoma patients before treatment. STAT4 protein levels were significantly decreased in PBMCs and T cells obtained from lymphoma patients after standard-dose chemotherapy. Furthermore, treatment of control PBMC cultures or a natural killer cell line with chemotherapy drugs in vitro also resulted in reduced STAT4 protein and diminished, IL-12-induced IFN-γ production. Translation of STAT4 protein was not impaired in chemotherapy-treated cells, whereas the STAT4 protein half-life was significantly reduced. Chemotherapy drugs promoted the ubiquitination and proteasomal degradation of STAT4. Treatment with the proteasome inhibitor bortezomib reversed chemotherapy-induced STAT4 deficiency and defective IFN-γ production. We conclude that acquired STAT4 deficiency in lymphoma patients is a consequence of treatment with chemotherapy, results that have important implications for the design of optimal immunotherapy for lymphoma.


Gray Mold Caused by Botryotinia fuckeliana on Edible Pods of Pea in Brazil.
Gray mold on edible pods of snow pea (Pisum sativum Lam. [Fabaceae]) was observed in greenhouse-cultivated pea (cvs. Luana Gigante and Gigante Flor Roxa) in the city of Pelotas (Rio Grande do Sul, Brazil) in September and October 2012. The incidence of diseased pods was high (∼25% of immature pods) after up to 3 cloudy and rainy days that hindered the ventilation inside the greenhouse resulting in high relative humidity. Infection occurred first on senescing petals adhered to the forming pods, leading to pod abortion or rotting that began at the contact site with the infected petal. The first symptoms on pods included water soaked tissue that quickly turned light brown and progressed to necrosis. Conidia and conidiophores produced on profuse gray mycelium could be easily seen on infected tissue 2 to 3 days after the appearance of symptoms. Conidiophores were smooth-walled, 400 μm to over 1.5 mm long, hyaline to pale brown, and branched in their upper part; each branch ended with a hemispherical or spherical swelling, 5 to 9 μm in diameter with minute sterigmata. Macroconidia were globose, ellipsoidal, smooth, hyaline to pale brown, usually with protuberant hila, 7 to 15 × 5 to 9 μm. Microconidia were not observed. On potato dextrose agar (PDA), colonies were fast-growing, white, low, covering entire 10 cm petri plates in 4 to 5 days when they turned gray to brownish-gray. Conidiophores and conidia were often formed in sectors. Shield-like, elliptical, lenticular to irregular, black, 1.5 to 6.0 × 1.0 to 4.0 mm sclerotia developed in 10-day-old colonies incubated at room temperature. Genomic DNA was extracted from conidia, conidiophores, and mycelium and used to amplify both the internal transcribed spacer (ITS) (ITS1-5.8s-ITS2) region and the β-tubulin gene using the ITS1/4 and Bt2a/b primers, respectively (1,4). The ITS (541 bp) and β-tubulin (467 bp) sequences were deposited in GenBank under accessions KC683713 and KC683712, respectively. BLASTn searches revealed similarity of 100% (EF207415) and 99% (FQ790278) with Botryotinia fuckeliana (De Bary) Whetzel for the ITS and β- tubulin sequences, respectively. Based on morphological characteristics and sequence analysis, the pathogen causing pod rot of peas was identified as B. fuckeliana. To fulfill Koch's postulates, 10 unwounded pods of P. sativum 'Luana Gigante' were inoculated by depositing PDA plugs (5 mm) colonized with fungal mycelium on their surface. Non-inoculated and mock-inoculated pods with sterile PDA plugs served as control. Inoculated and control pods were incubated inside a clear plastic box (11 × 11 × 3.5 cm) and over moistened filter paper under 12-h photoperiod at 25 ± 1°C. A surrounding water-soaked halo was visible only on pods inoculated with the fungus 48 h after inoculation (hai). Intense sporulation and necrosis were visible 96 hai. Botrytis spp. was previously detected, through standard blotter test, on seeds of P. sativum in Brazil, but without pathogenicity test nor its transmission through seeds (2,3). To our knowledge, this is the first report of B. fuckeliana causing epidemics on pea pods in Brazil. The high incidence of the disease in a protected environment has the potential to cause significant economic impact due to its damage to the pods, rendering them unmarketable. References: (1) N. L. Glass and G. Donaldson. Appl. Environ. Microbiol. 61:1323, 1995. (2) M. A. S. Mendes et al. Fungos em Plantas no Brasil. Embrapa-Cenargen, Brasília, 1998. (3) W. M. Nascimento and S. M. Cícero. Rev. Bras. Sementes 13:5, 1991. (4) T. J. White et al. PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego, 1990.


Transdermal scopolamine for prevention of motion sickness : clinical pharmacokinetics and therapeutic applications.
A transdermal therapeutic system for scopolamine (TTS-S) was developed to counter the adverse effects and short duration of action that has restricted the usefulness of scopolamine when administered orally or parenterally. The plaster contains a reservoir of 1.5 mg of scopolamine programmed to deliver 0.5 mg over a 3-day period. A priming dose (140 microg) is incorporated into the adhesive layer to saturate certain binding sites within the skin and to accelerate the achievement of steady-state blood levels. The remainder is released at a constant rate of approximately 5 microg/hour. The protective plasma concentration of scopolamine is estimated to be 50 pg/mL. TTS-S attains that concentration after 6 hours; a steady state of about 100 pg/mL is achieved 8-12 hours after application. Yet 20-30% of subjects failed to attain the estimated protective concentration, and plasma concentrations measured in subjects who failed to respond to TTS-S were lower than in responders. These findings may explain some of the treatment failures. Overall, the product appears to be the approximate functional equivalent of a 72-hour slow intravenous infusion. A combination of transdermal and oral scopolamine (0.3 or 0.6 mg) was effective and well tolerated in producing desired plasma concentrations 1-hour post-treatment. TTS-S has proved to be significantly superior to placebo in reducing the incidence and severity of motion sickness by 60-80%. It was more effective than oral meclizine or cinnarizine, similar to oral scopolamine 0.6 mg or promethazine plus ephedrine, and the same as or superior to dimenhydrinate. The addition of ephedrine or the use of two patches did not improve its efficacy, but rather increased the rate of adverse effects. TTS-S was most effective against motion sickness 8-12 hours after application. Despite previous evidence to the contrary, a recent bioavailability study demonstrated similar intraindividual absorption and sustained clinical efficacy with long-term use of the drug. The adverse effects produced by TTS-S, although less frequent, are qualitatively typical of those reported for the oral and parenteral formulations of this agent. Dry mouth occurs in about 50-60% of subjects, drowsiness in up to 20%, and allergic contact dermatitis in 10%. Transient impairment of ocular accommodation has also been observed, in some cases possibly the result of finger-to-eye contamination. Low-dose pyridostigmine was found effective in preventing cycloplegia but not mydriasis. Adverse CNS effects, including toxic psychosis (mainly in elderly and paediatric patients), have been reported only occasionally, as have difficulty in urinating, headache, rashes and erythema. Adverse effects were not correlated with plasma scopolamine concentrations. TTS-S produced only about half the incidence of drowsiness caused by oral dimenhydrinate or cinnarizine, and a level of adverse effects similar to that found with oral meclizine. Performance is not affected by short-term use. Prolonged or repeated application may cause some impairment of memory storage for new information. However, sea studies revealed significantly less reports of a decrement in performance or drowsiness due to prevention of sea sickness. The recommended dosage is a single TTS-S patch applied to the postauricular area at least 6-8 hours before the anti-motion sickness effect is required. For faster protection, the patch may be applied 1 hour before the journey in combination with oral scopolamine (0.3 or 0.6 mg). After 72 hours, the patch should be removed and a new one applied behind the opposite ear. Its place in therapy is mainly on long journeys (6-12 hours or longer), to avoid repeated oral doses, or when oral therapy is ineffective or intolerable.


Kinetochores accelerate centrosome separation to ensure faithful chromosome segregation.
At the onset of mitosis, cells need to break down their nuclear envelope, form a bipolar spindle and attach the chromosomes to microtubules via kinetochores. Previous studies have shown that spindle bipolarization can occur either before or after nuclear envelope breakdown. In the latter case, early kinetochore-microtubule attachments generate pushing forces that accelerate centrosome separation. However, until now, the physiological relevance of this prometaphase kinetochore pushing force was unknown. We investigated the depletion phenotype of the kinetochore protein CENP-L, which we find to be essential for the stability of kinetochore microtubules, for a homogenous poleward microtubule flux rate and for the kinetochore pushing force. Loss of this force in prometaphase not only delays centrosome separation by 5-6 minutes, it also causes massive chromosome alignment and segregation defects due to the formation of syntelic and merotelic kinetochore-microtubule attachments. By contrast, CENP-L depletion has no impact on mitotic progression in cells that have already separated their centrosomes at nuclear envelope breakdown. We propose that the kinetochore pushing force is an essential safety mechanism that favors amphitelic attachments by ensuring that spindle bipolarization occurs before the formation of the majority of kinetochore-microtubule attachments.


Antimicrobial susceptibility of Neisseria gonorrhoeae isolates in Vientiane, Lao PDR.
The aim of this study was to determine the antimicrobial susceptibility of Neisseria gonorrhoeae isolates in the Lao People's Democratic Republic (Laos). A total of 165 gonococcal isolates (1.3%) were obtained from 12 281 genital samples routinely submitted to a diagnostic laboratory in Vientiane, Laos, between 2011 and 2015. Susceptibility to five antibiotics was determined by the standard disk diffusion method for 158 of the isolates. Rates of resistance to penicillin (by β-lactamase production), tetracycline and ciprofloxacin were 89.9%, 99.4% and 84.8%, respectively. All isolates were susceptible to ceftriaxone and spectinomycin. The situation in Laos is similar to that in neighbouring countries; this fortunately means that the latest Lao national guidelines for treating gonorrhoea should still be effective.


Two-site time-resolved immunofluorometric assay of human insulin.
We describe a two-site "sandwich"-type time-resolved immunofluorometric assay for human insulin, based on use of two monoclonal antibodies with different specificities. The first antibody is immobilized on the surface of microtiter plate strip wells, the other is labeled with Eu3+. Serum samples can be assayed with one incubation step; two incubation steps are required when plasma samples are assayed. After the immunoreactions are complete, the bound fraction of Eu3+-label is quantified by dissociating it in a fluorescence-enhancement solution and measuring its fluorescence with a fluorometer with time-resolution. The sensitivity of the assay is 0.24 micro-int. units/mL. The standard curve is linear from 0.24 to 2400 micro-int. units/mL.


Evidence against proteoglycan mediated collagen fibril load transmission and dynamic viscoelasticity in tendon.
The glycosaminoglycan (GAG) dermatan sulfate and chondroitin sulfate side-chains of small leucine-rich proteoglycans have been increasingly posited to act as molecular cross links between adjacent collagen fibrils and to directly contribute to tendon elasticity. GAGs have also been implicated in tendon viscoelasticity, supposedly affecting frictional loss during elongation or fluid flow through the extra cellular matrix. The current study sought to systematically test these theories of tendon structure-function by investigating the mechanical repercussions of enzymatic depletion of GAG complexes by chondroitinase ABC in a reproducible tendon structure-function model (rat tail tendon fascicles). The extent of GAG removal (at least 93%) was verified by relevant spectrophotometric assays and transmission electron microscopy. Dynamic viscoelastic tensile tests on GAG depleted rat tail tendon fascicle were not mechanically different from controls in storage modulus (elastic behavior) over a wide range of strain-rates (0.05, 0.5, and 5% change in length per second) in either the linear or nonlinear regions of the material curve. Loss modulus (viscoelastic behavior) was only affected in the nonlinear region at the highest strain-rate, and even this effect was marginal (19% increased loss modulus, p=0.035). Thus glycosaminoglycan chains of small leucine-rich proteoglycans do not appear to mediate dynamic elastic behavior nor do they appear to regulate the dynamic viscoelastic properties in rat tail tendon fascicles.


Escherichia coli recA gene product inactivates phage lambda repressor.
Phage lambda repressor is inactivated and cleaved into two detectable fragments during incubation with purified Escherichia coli recA gene protein in vitro, in a reaction that requires ATP. This reaction reproduces the recA-dependent inactivation of repressor that occurs in vivo during induction of the SOS functions. The proteolytic activity may reside in the recA protein itself and may be a fundamental activity of it.


Outcome measurement in dysphagia: not so hard to swallow.
This article reports on the use of a new tool from the Australian Therapy Outcome Measures (AusTOMs) set--the Swallowing scale. The scale is one of six, designed to measure outcomes of clients attending speech pathology practices in Australia. The tool was used for six months in clinical practices across 14 healthcare sites in Victoria, Australia (including six acute hospitals, six rehabilitation services, one specialist pediatric hospital, and one specialist cancer institute). This article provides preliminary descriptive data and analyses of outcomes from swallowing therapy, along with discussion of the strengths and weaknesses of this tool. Potential clinical applications are suggested.


Comparison of the Effectiveness of Probiotic, Chlorhexidine-based Mouthwashes, and Oil Pulling Therapy on Plaque Accumulation and Gingival Inflammation in 10- to 12-year-old Schoolchildren: A Randomized Controlled Trial.
The use of a mouthwash augments mechanical removal of plaque by brushing and flossing and helps maintain oral health through its antiplaque and antibacterial chemical properties. To evaluate the effectiveness of a probiotic mouthwash, sesame oil pulling therapy, and chlorhexidine-based mouth-wash on plaque accumulation and gingival inflammation in schoolchildren aged 10 to 12 years. The randomized controlled trial included 45 healthy schoolchildren aged 10 to 12 years and studying in Government High School, Tiruchengode, Tamil Nadu, India. The participants were randomly divided into three groups, I, II, and III, with 15 children in each group as follows: group I: probiotic mouthwash; group II: chlorhexidine mouthwash; and group III: sesame oil. Baseline scores of plaque index (PI) and modified gingival index (GI) were recorded followed by a full mouth oral prophylaxis. The designated mouth rinses were distributed to the respective groups and they were instructed to rinse once daily. Their parents supervised the children during the use of mouthwash. On the 15th and 30th day, the children were subjected to the same clinical measurements. Children's acceptance of their plaque control method was assessed using a modified facial image scale. Intragroup comparisons for both the GI and PI scores were statistically significant (p ≤ 0.001) in all the three groups. Difference in the GI scores between the 15th and 30th day was statistically significant for chlorhexidine group alone (p = 0.024). Intergroup comparisons between the three groups were not statistically significant. Probiotic mouthwash, chlorhexidine mouthwash, and sesame oil were equally effective in reducing plaque and in improving the gingival status of children. The difference between the gingival scores on the 15th and 30th day was statistically significant in the chlorhexidine group.How to cite this article: Kandaswamy SK, Sharath A, Priya PRG. Comparison of the Effectiveness of Probiotic, Chlorhexidine-based Mouthwashes, and Oil Pulling Therapy on Plaque Accumulation and Gingival Inflammation in 10- to 12-year-old Schoolchildren: A Randomized Controlled Trial. Int J Clin Pediatr Dent 2018;11(2):66-70.


The pH sensibility of actin-bundling LIM proteins is governed by the acidic properties of their C-terminal domain.
Actin-bundling Arabidopsis LIM proteins are subdivided into two subfamilies differing in their pH sensitivity. Widely-expressed WLIMs are active under low and high physiologically-relevant pH conditions, whereas pollen-enriched PLIMs are inactivated by pH values above 6.8. By a domain swapping approach we identified the C-terminal (Ct) domain of PLIMs as the domain responsible for pH responsiveness. Remarkably, this domain conferred pH sensitivity to LIM proteins, when provided "in trans" (i.e., as a single, independent, peptide), indicating that it operates through the interaction with another domain. An acidic 6xc-Myc peptide functionally mimicked the Ct domain of PLIMs and efficiently inhibited LIM actin bundling activity under high pH conditions. Together, our data suggest a model where PLIMs are regulated by an intermolecular interaction between their acidic Ct domain and another, yet unidentified, domain.


Impact of neuromuscular electrical stimulation on functional capacity of patients with chronic kidney disease on hemodialysis.
Literature shows that patients undergoing hemodialysis present poor physical conditioning and low tolerance to exercise. They may also suffer from respiratory dysfunctions. The purpose of this study was to evaluate the effects of neuromuscular electrical stimulation on pulmonary function and functional capacity of patients with chronic kidney disease on hemodialysis. Forty adult patients with chronic kidney disease on hemodialysis were prospectively studied and randomized into two groups (control n = 20 and treatment n = 20). The treatment group underwent bilateral femoral quadriceps muscles electrical stimulation for 30 minutes during hemodialysis, three times per week, for two months. The patients were evaluated by pulmonary function test, maximum respiratory pressures, maximum one-repetition test, and six-minute walk test (6MWT), before and after the treatment protocol. The treatment group presented increased maximum inspiratory (MIP) (p = 0.02) and expiratory pressures (MEP) (p < 0.0001), muscular strength in maximum one-repetition test (p < 0.001), and distance covered in the 6MWT (p = 0.03), and decreased systolic blood pressure (p < 0.001) and respiratory frequency (p < 0.001) when compared with the control group. Electrical neuromuscular stimulation had a positive impact on pulmonary function and functional capacity, leading to better physical performance in patients on hemodialysis.


The association of primary biliary cirrhosis and systemic sclerosis is not accounted for by cross reactivity between mitochondrial and centromere antigens.
A proportion of patients with primary biliary cirrhosis (PBC) develop the CREST variant of systemic sclerosis (SSc) and in these individuals antimitochondrial antibodies (AMA) and anticentromere antibodies (ACA) coexist. Immunological cross-reactivity between mitochondrial and centromere-associated antigens might account for the clinical and serological overlap between these conditions. Therefore, antibodies were affinity purified from the 70 kD polypeptide corresponding to the E2 component of the pyruvate dehydrogenase complex (PDHC) and from CENP-C, a 140 kD centromere-associated protein, to examine this possibility. Although the purified antibodies reacted with their corresponding antigens, no evidence of shared determinants between the 70 kD protein and CENP-C could be detected whether the antibodies were prepared from monospecific sera or from sera containing both AMA and ACA. Therefore, AMA and ACA present discrete autoantibody populations which may coexist in the same patient and may influence the clinical picture but have both structural and immunologically independent antigenic targets.


Methods for characterizing differences in longitudinal glomerular filtration rate changes between children with glomerular chronic kidney disease and those with nonglomerular chronic kidney disease.
The rate of decline of glomerular filtration rate (GFR) in children with chronic kidney disease (CKD) can vary, even among those with similar diagnoses. Classic regression methods applied to the log-transformed GFR (i.e., lognormal) quantify only rigid shifts in a given outcome. The generalized gamma distribution offers an alternative approach for characterizing the heterogeneity of effect of an exposure on a positive, continuous outcome. Using directly measured GFR longitudinally assessed between 2005 and 2010 in 529 children enrolled in the Chronic Kidney Disease in Children Study, the authors characterized the effect of glomerular CKD versus nonglomerular CKD diagnoses on the outcome, measured as the annualized GFR ratio. Relative percentiles were used to characterize the heterogeneity of effect of CKD diagnosis across the distribution of the outcome. The rigid shift assumed by the classic mixed models failed to capture the fact that the greatest difference between the glomerular and nonglomerular diagnosis' annualized GFR ratios was in children who exhibited the fastest GFR declines. Although this difference was enhanced in children with an initial GFR level of 45 mL/minute/1.73 m(2) or less, the effect of diagnosis on outcome was not significantly modified by level. Generalized gamma models captured heterogeneity of effect more richly and provided a better fit to the data than did conventional lognormal models.


The multidrug resistance mechanisms and their interactions with the radiopharmaceutical probes used for an in vivo detection.
The resistance of human malignancy to multiple chemotherapeutic agents ts remains a major obstacle in cancer therapy. This resistance phenomenon is called "multiple" because when cells are resistant they fail to respond to any of a wide range of anticancer agents. This leads to a complete ineffectiveness of any treatment and has dramatic consequences for the patients. This chemoresistance can be intrinsic--when tumour cells do not respond initially to the treatment--or acquired--when resistance appear during the therapy. Our understanding of the mechanisms responsible of the drug resistance has increased over the past few years. The tumour resistance is able to develop several strategies to inactivate the chemotherapeutic agents such as activation of the detoxification process, and overexpression of efflux pump proteins. The phenotype resistance of the cell is mainly characterised by an increased expression of membrane transport proteins such as the P-glycoprotein and the Multidrug Resistance Protein--MRPI--that act as real efflux pump to anticancer agent and contribute to physiological alterations i.e. intracellular pH and plasma membrane potentials. The detoxification procedure is also implicated with the Glutathione S transferase enzymes and the major anti oxidant of the cells the glutathione (GSH). More recently a newly reported transporter called "Breast Resistance Cancer Protein" has appeared. The role of all these transporters and the link with the detoxification systems in the clinical outcome of cancer chemotherapy is the subject of intense research. Particularly, one way of interest concerned in vivo investigations with radiolabelled compounds used in nuclear medicine. The understanding of how the radiolabelled compounds could interact with the phenotype resistance of the cells had a key role for further exploration of molecular imaging of the MDR phenotype.


[The effect of hypoxic hypoxia on the activity of glycolysis enzymes in rat erythrocytes].
The oxygen-binding properties of hemoglobin, concentration of 2,3-diphosphoglycerate, activity of carbohydrate metabolism enzymes and kinetics of rat erythrocyte hemolysis have been studied at high altitudes. The hemoglobin affinity to oxygen, glycolysis enzyme activity and erythrocyte membrane resistance are established to increase at the initial period of adaptation. The activation of the pentose-phosphate pathway of the glucose, transformation and inhibition of the glycolytic process in these cells are observed on the 10th day.


Circulating Folate and Vitamin B12 and Risk of Prostate Cancer: A Collaborative Analysis of Individual Participant Data from Six Cohorts Including 6875 Cases and 8104 Controls.
Folate and vitamin B12 are essential for maintaining DNA integrity and may influence prostate cancer (PCa) risk, but the association with clinically relevant, advanced stage, and high-grade disease is unclear. To investigate the associations between circulating folate and vitamin B12 concentrations and risk of PCa overall and by disease stage and grade. A study was performed with a nested case-control design based on individual participant data from six cohort studies including 6875 cases and 8104 controls; blood collection from 1981 to 2008, and an average follow-up of 8.9 yr (standard deviation 7.3). Odds ratios (ORs) of incident PCa by study-specific fifths of circulating folate and vitamin B12 were calculated using multivariable adjusted conditional logistic regression. Incident PCa and subtype by stage and grade. Higher folate and vitamin B12 concentrations were associated with a small increase in risk of PCa (ORs for the top vs bottom fifths were 1.13 [95% confidence interval (CI), 1.02-1.26], ptrend=0.018, for folate and 1.12 [95% CI, 1.01-1.25], ptrend=0.017, for vitamin B12), with no evidence of heterogeneity between studies. The association with folate varied by tumour grade (pheterogeneity<0.001); higher folate concentration was associated with an elevated risk of high-grade disease (OR for the top vs bottom fifth: 2.30 [95% CI, 1.28-4.12]; ptrend=0.001), with no association for low-grade disease. There was no evidence of heterogeneity in the association of folate with risk by stage or of vitamin B12 with risk by stage or grade of disease (pheterogeneity>0.05). Use of single blood-sample measurements of folate and B12 concentrations is a limitation. The association between higher folate concentration and risk of high-grade disease, not evident for low-grade disease, suggests a possible role for folate in the progression of clinically relevant PCa and warrants further investigation. Folate, a vitamin obtained from foods and supplements, is important for maintaining cell health. In this study, however, men with higher blood folate levels were at greater risk of high-grade (more aggressive) prostate cancer compared with men with lower folate levels. Further research is needed to investigate the possible role of folate in the progression of this disease.


4-Aminobutyrate (GABA) transporters from the amine-polyamine-choline superfamily: substrate specificity and ligand recognition profile of the 4-aminobutyrate permease from Bacillus subtilis.
A previous study [Ferson, Wray and Fisher (1996) Mol. Microbiol. 22, 693-701] has shown that transposon-mediated disruption of a protein 47% identical to the Escherichia coli GABA (4-aminobutyrate) transporter abolishes the ability of nitrogen-limited culture conditions to induce expression of a GABA transport activity in Bacillus subtilis. Here it is demonstrated directly that the B. subtilis GABA permease (gabP) gene can complement the transport defect in the gabP-negative E. coli strain. Unexpectedly, the ligand-recognition profile of the B. subtilis GabP was found to differ substantially from that of the highly homologous E. coli GabP. Unlike the E. coli GabP, the B. subtilis GabP: (i) exhibits approx. equal preference for the 3-carbon (beta-alanine, Km=9.6 microM) and the 4-carbon (GABA, Km=37 microM) amino acids, and (ii) resists inhibition by bulky, conformationally constrained compounds (e.g. nipecotic acid, guvacine), which are active against GABA transporters from brain. The present study shows additionally that the B. subtilis GabP can translocate several open-chain GABA analogues (3-aminobutyrate, 3-aminopropanoate, cis-4-aminobutenoate) across the membrane via counterflow against [3H]GABA. Thus, consistent with the idea that the ligand-recognition domain of the B. subtilis GabP is less spacious than that of the close homologue from E. coli, the former exhibits more stringent requirements than the latter for substrate recognition and translocation. These distinct functional characteristics of the E. coli and B. subtilis GABA transporters provide a basis by which to identify ligand-recognition domains within the amine-polyamine-choline transporter superfamily.


"Green informed consent" in the classroom, clinic, and consultation room.
The carbon emissions of global health care activities make up 4-5% of total world emissions, placing it on par with the food sector. Carbon emissions are particularly relevant for health care because of climate change health hazards. Doctors and health care professionals must connect their health care delivery with carbon emissions and minimize resource use when possible as a part of their obligation to do no harm. Given that reducing carbon is a global ethical priority, the informed consent process in health care delivery must change. I argue that the expanded role of bioethicists in this climate crisis is to promote and support "green informed consent:" the sharing of climate information with patients, offering options for lower-carbon health care, and accepting the patient's right to decline treatments which are deemed too carbon intensive for their values.


Endothelial cells secrete a novel collagen type in vitro independently of prolyl hydroxylation.
Endothelial cells from bovine aorta, vena cava, and cornea secrete a novel collagen in vitro (Sage et al., 1980). Endothelial collagen (EC), which is sensitive to pepsin and to several neutral proteases, exhibited an additional unusual property in its mode of secretion. In the absence of added sodium ascorbate, EC was secreted by both aortic and corneal endothelial cells at levels which were very similar to those observed in cultures supplemented with this vitamin. In contrast, the secretion of type III procollagen, which normally constitutes 75-80% of collagenous protein in the culture medium, was significantly decreased in ascorbate-deficient cultures. Incubation of aortic endothelial cells with alpha, alpha'-dipyridyl, an inhibitor of prolyl and lysyl hydroxylases, reduced the extent of prolyl hydroxylation in total culture medium protein by 98% but also did not affect the secretion of EC. The secretion of EC by endothelial cells appears to be independent of a requirement for prolyl hydroxylation. This property differs markedly from the secretory characteristics of the interstitial procollagens and more closely resembles that described for type IV (basement membrane) procollagen.


Redox activity and structural transition of heptyl viologen adlayers on Cu(100).
The redox behaviour and potential-dependent adsorption structure of heptyl viologen (1,1'-diheptyl-4,4'-bipyridinium dichloride, DHV(2+)) on a Cu(100) electrode was investigated in a chloride-containing electrolyte solution by cyclic voltammetry (CV) and in situ electrochemical scanning tunneling microscopy (EC-STM). The dicationic DHV molecules generate a few pairs of current waves in CV measurements which are ascribed to two typical one-electron transfer steps. STM images obtained in a KCl-containing electrolyte solution disclose a well-ordered c(2x2) chloride adlayer on a Cu(100) electrode surface. After injecting DHV(2+) molecules into the KCl electrolyte solution, a highly ordered 2D "dot-array" structure in STM images emerges on the c(2x2)-Cl modified Cu(100) electrode surface. DHV(2+) molecules spontaneously arrange themselves with their molecular planes facing the electrode surface and their long molecular axis parallel to the step edge. Such adsorption structure can be described by mirror domains and rotational domains which stably exist between 200 mV and -100 mV. One-electron reduction of the dications DHV(2+) around -150 mV causes a phase transition from a 'dot-array' assembly to a stripe pattern formed by DHV(*+) radical monocations in STM images which has a bilayer structure. With a further decrease of the applied electrode potential, the structure of the DHV(*+) adlayer undergoes a change from a loose stripe phase to a more compact stripe phase, a subsequent decay of the compact structure, and finally the formation of a new dimer phase. A further electron transfer reaction at -400 mV causes the formation of an amorphous phase on the chloride free electrode surface. In a reverse anodic sweep, the reproduction of the ordered DHV(*+) stacking phase occurs again on top of the chloride lattice.


Tissue-specific regulation of two functional malic enzyme mRNAs by triiodothyronine.
Rat liver malic enzyme (ME) synthesis is known to be regulated by 3,5,3'-triiodo-L-thyronine (T3). Hybridization of 32P-labeled ME cDNA with RNA extracted from normal and T3-induced livers (15 or 50 micrograms/100 g body weight for 10 days) showed an increase in the ME mRNA concentration by approximately 11-fold in T3-treated rats. ME activity and ME mass were stimulated to the same degree as ME mRNA. Northern blot analysis of either total or poly(A+) RNA revealed two distinct ME mRNAs (21 and 27 S) which were equally induced by T3 treatment. Both mRNAs were shown by in vitro translation assay to program the synthesis of the same immunoprecipitable protein corresponding to full-sized ME. From all the above, we concluded that both messages code for active enzyme. ME activity and ME mRNA were also detected in nonhepatic tissues for which different responses to T3 induction were observed without direct correlation with their respective content of T3 nuclear receptor. Increases in ME activity and level of hybridizable ME mRNA were seen 48 h after a single administration of T3 (200 micrograms/100 g body weight) in liver, kidney, and heart (10.3- and 15.5-, 1.7- and 2.6-, and 1.72- and 3.4-fold above basal values, respectively). Lower levels of induction could already be detected after 24 h, liver being the most stimulated tissue. ME was not affected in brain, lung, testis, and spleen. Northern blot analysis showed that both ME mRNAs are present in all tissues tested, although in different relative proportions.(ABSTRACT TRUNCATED AT 250 WORDS)


Hyposialylated α1-acid glycoprotein inhibits phagocytosis of feline neutrophils.
Feline α1-acid glycoprotein (fAGP) modifies both its serum concentration and its glycan moiety during diseases. fAGP is hyposialylated in cats with feline infectious peritonitis (FIP), but not in clinically healthy cats or in cats with other diseases. This study was aimed to determine whether hyposialylated fAGP influences phagocytosis. A flow cytometric method based on ingestion of fluoresceinated bacteria and adapted to feline blood was used to assess phagocytosis of leukocytes incubated with 'non-pathological' fAGP (purified from sera with normal concentrations of AGP) and 'pathological' fAGP (purified from sera with >1.5mg/mL hyposialylated AGP). The flow cytometric method provided repeatable results for neutrophils (coefficients of variations, CVs <15%) but not for monocytes (CVs>20%) which had also a high individual variability. Compared with saline solution and with non-pathological fAGP, pathological fAGP significantly decreased phagocytosis in neutrophils and monocytes. This study demonstrated that hyposialylated fAGP down-regulates the phagocytic activity of feline neutrophils.


Simultaneous surgical treatment of ruptured abdominal aortic aneurysm and acute carotid occlusive disease.
Combined rupture of abdominal aortic aneurysm and acute thrombosis of internal carotid artery is extremely rare but fatal combination resulting in high mortality rate. Presented case, shows successfully performed simultaneous surgery of ruptured abdominal aortic aneurysm and acute cerebrovascular insult caused by thrombosis of carotid artery in 81 year-old male. Post operative course was uneventfull. At 24 months follow up patient was in good condition, with full neurological recovery. Simultaneous surgical treatment of acute occlusive carotid disease and ruptured abdominal aortic aneurysm (RAAA) seems to be the only life saving procedure for this rare, but very complicated condition. To our knowledge, this is the first reported successful simultaneous surgical treatment of RAAA and acute thrombosis of internal carotid artery.


Empagliflozin mitigates type 2 diabetes-associated peripheral neuropathy: a glucose-independent effect through AMPK signaling.
Diabetic peripheral neuropathy (DPN) represents a severe microvascular condition that dramatically affects diabetic patients despite adequate glycemic control, resulting in high morbidity. Thus, recently, anti-diabetic drugs that possess glucose-independent mechanisms attracted attention. This work aims to explore the potentiality of the selective sodium-glucose cotransporter-2 inhibitor, empagliflozin (EMPA), to ameliorate streptozotocin-induced DPN in rats with insight into its precise signaling mechanism. Rats were allocated into four groups, where control animals received vehicle daily for 2 weeks. In the remaining groups, DPN was elicited by single intraperitoneal injections of freshly prepared streptozotocin and nicotinamide (52.5 and 50 mg/kg, respectively). Then EMPA (3 mg/kg/p.o.) was given to two groups either alone or accompanied with the AMPK inhibitor dorsomorphin (0.2 mg/kg/i.p.). Despite the non-significant anti-hyperglycemic effect, EMPA improved sciatic nerve histopathological alterations, scoring, myelination, nerve fibers' count, and nerve conduction velocity. Moreover, EMPA alleviated responses to different nociceptive stimuli along with improved motor coordination. EMPA modulated ATP/AMP ratio, upregulated p-AMPK while reducing p-p38 MAPK expression, p-ERK1/2 and consequently p-NF-κB p65 as well as its downstream mediators (TNF-α and IL-1β), besides enhancing SOD activity and lowering MDA content. Moreover, EMPA downregulated mTOR and stimulated ULK1 as well as beclin-1. Likewise, EMPA reduced miR-21 that enhanced RECK, reducing MMP-2 and -9 contents. EMPA's beneficial effects were almost abolished by dorsomorphin administration. In conclusion, EMPA displayed a protective effect against DPN independently from its anti-hyperglycemic effect, probably via modulating the AMPK pathway to modulate oxidative and inflammatory burden, extracellular matrix remodeling, and autophagy.


Tumorigenic poxviruses: genomic organization of malignant rabbit virus, a recombinant between Shope fibroma virus and myxoma virus.
The genome of malignant rabbit virus (MRV), a newly discovered tumorigenic poxvirus of rabbits, has been analyzed using cloned DNA probes from Shope fibroma virus (SFV) and myxoma virus. Under high stringency conditions for Southern blotting such that SFV probes do not cross-hybridize with myxoma virus DNA, it is demonstrated that greater than 90% of the MRV genome has been derived from myxoma virus, and that approximately 10 kb of SFV-derived sequences have substituted for a similar amount of myxoma sequences. Mapping of the MRV genome indicates that the SFV sequences are present in two regions of the genome, one in each copy of the MRV terminal inverted repeat sequence. Furthermore, fine mapping studies of the integration sites for SFV into the myxoma background show that these SFV sequences are not symmetrical with respect to the left and right genomic termini. At the left end, 4 kb of SFV-derived DNA maps between 6 and 10 kb from the terminus, while at the right end about 5.5 kb of SFV sequences are found to extend at least 1 kb further toward the unique internal sequences. Based on this asymmetrical bipartite distribution of SFV sequences in MRV, a two-stage model to rationalize the origin of MRV is proposed. This model postulates an initial recombination event similar to gene conversion between myxoma and SFV at the right terminus of myxoma, followed by an incomplete transposition of only part of these SFV sequences to the left terminus.


[Infantile metachromatic leukodystrophy in twins].
The authors report two cases of infantile metachromatic leucodystrophy in monozygotic female twins, born from a second cousin marriage (f = 1/32). The zygosity was determined by means of obstetrics and genetics marker findings.


Safety of fenbendazole use in cattle.
Fenbendazole (Panacur: Hoechst) has a low degree of toxicity, teratogenicity and adverse effects on the reproductive tract, and a high degree of safety in experimental animals. Acute, subacute and long-term toxicity trials in cattle given fenbendazole at dosages of up to 2 g/kg revealed no adverse effects. Studies of teratogenicity, effects on fertility, compatibility with other drugs, and safety for animal handlers had similarly negative results.


The hypoxia-inducible factor-responsive proteins semaphorin 4D and vascular endothelial growth factor promote tumor growth and angiogenesis in oral squamous cell carcinoma.
Growth and metastasis of solid tumors requires induction of angiogenesis to ensure the delivery of oxygen, nutrients and growth factors to rapidly dividing transformed cells. Through either mutations, hypoxia generated by cytoreductive therapies, or when a malignancy outgrows its blood supply, tumor cells undergo a change from an avascular to a neovascular phenotype, a transition mediated by the hypoxia-inducible factor (HIF) family of transcriptional regulators. Vascular endothelial growth factor (VEGF) is one example of a gene whose transcription is stimulated by HIF. VEGF plays a crucial role in promoting tumor growth and survival by stimulating new blood vessel growth in response to such stresses as chemotherapy or radiotherapy-induced hypoxia, and it therefore has become a tempting target for neutralizing antibodies in the treatment of advanced neoplasms. Emerging evidence has shown that the semaphorins, proteins originally associated with control of axonal growth and immunity, are regulated by changes in oxygen tension as well and may play a role in tumor-induced angiogenesis. Through the use of RNA interference, in vitro and in vivo angiogenesis assays and tumor xenograft experiments, we demonstrate that expression of semaphorin 4D (SEMA4D), which is under the control of the HIF-family of transcription factors, cooperates with VEGF to promote tumor growth and vascularity in oral squamous cell carcinoma (OSCC). We use blocking antibodies to show that targeting SEMA4D function along with VEGF could represent a novel anti-angiogenic therapeutic strategy for the treatment of OSCC and other solid tumors.


Defining haplotype blocks and tag single-nucleotide polymorphisms in the human genome.
Recent studies suggest that the genome is organized into blocks of haplotypes, and efforts to create a genome-wide haplotype map of single-nucleotide polymorphisms (SNPs) are already underway. Haplotype blocks are defined algorithmically and to date several algorithms have been proposed. However, little is known about their relative performance in real data or about the impact of allele frequencies and parameter choices on the detection of haplotype blocks and the markers that tag them. Here we present a formal comparison of two major algorithms, a linkage disequilibrium (LD)-based method and a dynamic programming algorithm (DPA), in three chromosomal regions differing in gene content and recombination rate. The two methods produced strikingly different results. DPA identified fewer and larger haplotype blocks as well as a smaller set of tag SNPs than the LD method. For both methods, the results were strongly dependent on the allele frequency. Decreasing the minor allele frequency led to an up to 3.7-fold increase in the number of haplotype blocks and tag SNPs. Definition of haploytpe blocks and tag SNPs was also sensitive to parameter changes, but the results could not be reconciled simply by parameter adjustment. These results show that two major methods for detecting haplotype blocks and tag SNPs can produce different results in the same data and that these results are sensitive to marker allele frequencies and parameter choices. More information is needed to guide the choice of method, marker allele frequencies, and parameters in the development of a haplotype map.


Robotic thymectomy in patients with myasthenia gravis: neurological and surgical outcomes.
Thymectomy is frequently used in the treatment of myasthenia gravis (MG). But indication, timing or surgical approach remain controversial. This study reports our experiences with robotic thymectomy and surgical and neurological outcomes in a large cohort of patients with MG. We retrospectively analysed the outcome of 125 patients with MG who underwent a robotic thymectomy using the da Vinci Surgical System (Intuitive Surgical, Inc., Sunnyvale, CA, USA) between 2004 and 2012. The Myasthenia Gravis Foundation of America (MGFA) Classification was used to determine preoperative and postintervention status. Ninety-five women and 30 men underwent a robotic thymectomy. One hundred patients had a neurological follow-up of more than 12 months. Preoperative most severe MGFA classification was Stage I in 11 patients (8.8%), Stage IIA in 18 patients (14.4%), Stage IIB in 18 patients (14.4%), Stage IIIA in 7 patients (5.6%), Stage IIIB in 29 patients (23.2%), Stage IVA in 10 patients (8.0%), Stage IVB in 29 patients (23.2%) and Stage V in 3 patients (2.4%). Median surgical procedure time was 123 min (range 45-353 min). There were no major perioperative complications or deaths. The median postoperative hospital stay was 3 days (range 2-24 days). Histological analysis showed thymic remnant tissue in 41 patients (32.8%), follicular hyperplasia in 52 patients (41.6%), thymoma in 31 patients (24%), lipoma in 1 patient (0.8%) and a cyst in 1 patient (0.8%). Patients with thymic remnant tissue were significantly more preoperative steroid users compared with the follicular hyperplasia group (P = 0.02). With a median follow-up of 33 months (range 12-104 months), 77% of the patients showed neurological improvement. Three-year probability remission rate [complete stable remission (CSR) and pharmacological remission] is 28.2%. Patients who were not treated with prednisolone preoperatively showed a significant higher CSR than patients who did take prednisolone (P = 0.014). No significant difference was observed regarding timing of surgery (P = 0.37). Robotic thymectomy in patients with MG is safe and feasible. A neurological benefit and decreased use of steroids can be obtained in the majority of patients. No significant difference in neurological outcome was observed as the result of timing of robot thymectomy after the onset of MG.


Distribution of shortest path lengths in a class of node duplication network models.
We present analytical results for the distribution of shortest path lengths (DSPL) in a network growth model which evolves by node duplication (ND). The model captures essential properties of the structure and growth dynamics of social networks, acquaintance networks, and scientific citation networks, where duplication mechanisms play a major role. Starting from an initial seed network, at each time step a random node, referred to as a mother node, is selected for duplication. Its daughter node is added to the network, forming a link to the mother node, and with probability p to each one of its neighbors. The degree distribution of the resulting network turns out to follow a power-law distribution, thus the ND network is a scale-free network. To calculate the DSPL we derive a master equation for the time evolution of the probability P_{t}(L=ℓ), ℓ=1,2,⋯, where L is the distance between a pair of nodes and t is the time. Finding an exact analytical solution of the master equation, we obtain a closed form expression for P_{t}(L=ℓ). The mean distance 〈L〉_{t} and the diameter Δ_{t} are found to scale like lnt, namely, the ND network is a small-world network. The variance of the DSPL is also found to scale like lnt. Interestingly, the mean distance and the diameter exhibit properties of a small-world network, rather than the ultrasmall-world network behavior observed in other scale-free networks, in which 〈L〉_{t}∼lnlnt.


Vancomycin-resistant enterococcal bacteremia pharmacotherapy.
To review the literature on the pharmacotherapy of bloodstream infections (BSI) caused by vancomycin-resistant enterococci (VRE). A MEDLINE literature search was performed for the period 1946 to May 2014 using the search terms Enterococcus, enterococci, vancomycin-resistant, VRE, bacteremia, and bloodstream infection. References were also identified from selected review articles. English-language case series, cohort studies, and meta-analyses assessing the options in the pharmacotherapy of VRE BSIs in adult patients were evaluated. Studies were identified that utilized linezolid, quinupristin/dalfopristin (Q/D), and daptomycin. In all, 8 comparative retrospective cohort studies, 2 meta-analyses of daptomycin and linezolid, and 3 retrospective comparisons of linezolid and Q/D were included for review. Mortality associated with VRE BSIs was high across studies, and the ability to determine differences in outcomes between agents was confounded by the complex nature of the patients included. Two meta-analyses comparing daptomycin with linezolid for VRE BSIs found modest advantages for linezolid, but these conclusions may be hampered by heterogeneity within the included studies. VRE BSIs remain a difficult-to-treat clinical situation. Differences in toxicity between the agents used to treat it are clear, but therapeutic differences are more difficult to discern. Meta-analyses suggest that a moderate advantage for linezolid over daptomycin may exist, but problems with the nature of studies that they included make definitive conclusions difficult.


Ultrastructural analysis of olfactory ensheathing cells derived from olfactory bulb and nerve of neonatal and juvenile rats.
Olfactory nerve derived and olfactory bulb derived olfactory ensheathing cells (OECs) have the ability to promote axonal regeneration and remyelination, both of which are essential in a successful cell transplant. Thus, morphological identification of OECs is a key aspect to develop an applicable cell therapy for injuries to the nervous system. However, there is no clear definition regarding which developmental stage or anatomical origin of OECs is more adequate for neural repair. In the present study, an ultrastructural comparison was made between OECs recovered from primary cultures of olfactory nerve and bulb in two developmental stages. The most notorious difference between cells obtained from olfactory nerve and bulb was the presence of indented nuclei in bulb derived OECs, suggesting a greater ability for possible chemotaxis. In neonatal OECs abundant mitochondria, lipid vacuoles, and smooth endoplasmic reticulum were detected, suggesting an active lipid metabolism, probably involved in synthesis of myelin. Our results suggest that neonatal OECs obtained from olfactory bulb have microscopic properties that could make them more suitable for neural repair.


Effect of exogenous immunogenic RNA on the antibody synthesis in rat transplantable lymphosarcoma cells.
Cytoplasmic and nuclear RNA were isolated from sheep red cells immunized rat and mouse spleens. Rat spleen nuclear RNA was fractionated in the following steps: 1. thermal fractionation according to Georgiev, 2. hydroxylapatite chromatography of thermal fraction, 3. agar gel electrophoresis of saline hydroxylapatite fractions. The effect of all these fractions on hemolysin synthesis in rat transplantable lymphosarcoma cells was studied. It was shown that the total cytoplasmic RNA of rat and mouse spleen and some nuclear RNA fractions of rat spleen are able to induce hemolysin synthesis. The antibody synthesis induced in vitro by addition of rat spleen RNA can be proved in about 10-12 cell generations at subsequent transplantations of the tumor. The 4S nuclear RNA, as well as high molecular RNA are apt to induce antibody synthesis. The mechanism of 4S RNA action can not be the same as that of mRNA. Concluding our experimental data and those available in the literature we assume that there are two different mechanisms of immunogenic exogenous RNA activity in transfer of the biological information in immunogenesis: that of mRNA information transfer and that of deblockation of corresponding genes in recipient cells.


[Myocardium damage in experimental anemia and its prevention with the antioxidant ionol].
Rats with hemolytic (phenylhydrazine) anemia were shown to develop simultaneously with hypertrophy of the myocardium marked damages of cardiomyocytes of the type of I-III degree contractures, myocytolysis, vacuolation, fatty infiltration, small focal necrosis as well as a peculiar form of damages defined as "central lumpy degeneration". An inhibitor of lipid peroxidation, antioxidant ionol, decreases the extent of myocardial hypertrophy and the intensity of the above morphological changes in cardiomyocytes. This indicates a significant role of lipid peroxidation in myocardial damage in hemolytic anemia and the importance of research on the use of antioxidants in combined treatment of cardial disorders in patients with anemia.


Pulmonary artery atherosclerosis: correlation with systemic atherosclerosis and hypertensive pulmonary vascular disease.
Atherosclerosis of the pulmonary arteries is a common autopsy finding and is associated with a variety of clinical conditions. To delineate the morphologic changes associated with pulmonary artery atherosclerosis, autopsies of 337 consecutive adults (greater than 15 years of age) were studied. For each, 35 features were studied, including age, coronary vascular disease, cardiac chamber hypertrophy and dilation, pulmonary artery and aortic atherosclerosis, and pulmonary thromboemboli and emphysema. These were compared using correlation coefficients and forward and backward stepwise regression procedures for selected variables. Pulmonary artery atherosclerosis correlated significantly with age, right ventricular dilation and hypertrophy, pulmonary emphysema, and aortic atherosclerosis. Regional evaluations of systemic and pulmonary atherosclerosis showed highly significant internal correlations. In the ligamentum arteriosum, the intensity of atherosclerosis over the aortic insertion correlated with the severity of a similar atheroma at the pulmonary artery insertion. With the multiple-regression procedure, pulmonary artery atherosclerosis was a significant predictor of aortic atherosclerosis, right ventricular hypertrophy, and pulmonary embolization. Our study shows that pulmonary embolization. Our study shows that pulmonary embolization. Our study shows that pulmonary artery atherosclerosis is accelerated in patients with atherosclerosis of the systemic arteries and the pathologic lesions associated with hypertensive pulmonary vascular disease.


[Nutrition and periodontal disease].
It is difficult ro assess the role of nutrition in the etiology and progression of periodontal disease because many other factors besides the local effect of plaque affect periodontal tissue metabolism. It is clear that nutrition can affect host response to bacterial plaque and it is also apparent that there may be a need for the intake of greater amounts of certain nutrients (such as ascorbic acid, iron etc.). Inadequate nutrient intake or deficiency is significant because of the number of interactions that occur during the assimilation of foods and the effects of stress and medication. Periodontal health cannot be achieved unless nutrient deficiency is corrected along with the other phases of treatment.


Isolation and characterization of pig enamelins.
Enamel proteins were extracted from pig developing enamel by sequential extraction procedures. Two proteins identified as enamelins by slab-gel electrophoresis (Mr 67,000 and 63,000) were separated from amelogenins by gel sieving and ion-exchange chromatography. Their enamelin characteristic was confirmed by hydroxyapatite-binding studies and amino acid analysis. Degradation of extracted enamel proteins was also studied in vitro. The larger of the two enamelins appeared to be resistant to degradation by endogenous enamel proteinases. Hydroxyapatite showed strong binding with the enamelins, but did not prevent the degradation of the Mr-63,000 enamelin. These results indicate that at least one high-Mr enamelin in pig developing enamel is a source of enamelin breakdown products.


Nrf2 Activation by SK-119 Attenuates Oxidative Stress, UVB, and LPS-Induced Damage.
The Nrf2 signaling pathway plays a pivotal role in neutralizing excess reactive oxygen species formation and therefore enhancing the endogenous cellular protection mechanism. Thus, activating this pathway may provide therapeutic options against oxidative stress-related disorders. We have recently applied a computer-aided drug design approach to the design and synthesis of novel Nrf2 enhancers. The current study was aimed at investigating the potential beneficial impact of (E)-5-oxo-1-(4-((2,4,6-trihydroxybenzylidene)amino)phenyl)pyrrolidine-3-carboxylic acid (SK-119) in skin oxidative damage models. SK-119, tested initially in PC-12 cells, attenuated oxidative stress-induced cytotoxicity concomitantly with Nrf2 activation. The potential impact of this compound was evaluated in skin-based disease models both in vitro (HaCaT cells) and ex vivo (human skin organ culture). The data clearly showed the marked anti-inflammatory and photoprotection properties of the compound; SK-119-treated cells or tissues displayed a reduction in cytokine secretion induced by lipopolysaccharides (LPS) in a manner comparable with dexamethasone. In addition, topical application of SK-119 was able to block UVB-induced oxidative stress and attenuated caspase-mediated apoptosis, DNA adduct formation, and the concomitant cellular damage. These results indicate that SK-119 is an Nrf2 activator that can be used as a prototype molecule for the development of novel treatments of dermatological disorders related to oxidative stress.


Medication management concerns of ethnic minority family caregivers of people living with dementia.
This qualitative study explored the medication management experiences of Australian ethnic minority family caregivers of people living with dementia. From the perspective of this group of caregivers, medication management was a source of stress resulting from the progressive loss of ability of care recipients to manage their own medications; the complexity of the medication regime and the caregiver's lack of trust of the care recipient to safely and effectively manage medications. Caregivers used various strategies to manage medications and avoid conflict with care recipients including being watchful and involving other family members in medication management tasks. Family caregivers indicated that a lack of information and access to support to inform their medication management role added to their stress, which was exacerbated in some cases by limited English proficiency. Supportive factors noted by caregivers included a well-established relationship with a community pharmacist, involvement of a geriatrician, family support and caregiver support group participation.


Simple regional strain pattern analysis to predict response to cardiac resynchronization therapy: rationale, initial results, and advantages.
A classical strain pattern of early contraction in one wall and prestretching of the opposing wall followed by late contraction has previously been associated with left bundle branch block (LBBB) activation and short-term response to cardiac resynchronization therapy (CRT). Aims of this study were to establish the long-term predictive value of an LBBB-related strain pattern and to identify changes in contraction patterns during short-term and long-term CRT. Sixty-seven patients with standard CRT criteria were prospectively enrolled between early 2009 and late 2010. Echocardiography including regional strain analysis by 2-dimensional speckle tracking was performed 1 week before implantation, at day 1, and 6 months after. Response was defined as a decrease in left ventricular end-systolic volume ≥ 15%. The predictive ability of a classical pattern was compared with time-to-peak measurements from velocity and deformation analysis. Forty-three patients (65%) were classified as responders. The presence of a classical pattern showed 91% specificity and 95% sensitivity for response and performed significantly better than time-to-peak parameters in prediction of response to CRT (P < .001, all). In responders, CRT acutely increased septal longitudinal peak systolic strain (-8.7% ± 3.6% to -11.1% ± 3%, P < .001) but not in nonresponders. The classical pattern is highly predictive of response to CRT and superior to time-to-peak methods. Patients who obtain long-term reverse remodeling are characterized by short-term reversal of the classical strain pattern. These findings emphasize the value of recognizing potentially reversible strain patterns in selection of CRT candidates.


Stander Use in Spinal Muscular Atrophy: Results From a Large Natural History Database.
The purpose of this study was to describe stander use in a natural history cohort of drug therapy-naïve children with spinal muscular atrophy (SMA) who are not walking and identify factors associated with consistent stander use. Data from 397 children with SMA types 1 and 2 characterized the prevalence and frequency of stander use. Predictors of consistent stander use explored were SMA type, survival motor neuron 2 gene (SMN2) copy number, respiratory support, and motor performance. Prevalence of consistent stander use was 13% in type 1 and 68% in type 2. SMA type, SMN2 copy number, respiratory support, and head rotation control each predicted consistent stander use. Findings characterize stander use in children with SMA who are not walking, address important safety considerations, identify factors that may inform physical therapists' clinical decision-making related to standing program prescription, and provide guidance for future prospective studies.


[Radiological and clinical aspects of diaphragmatic injuries (author's transl)].
In experience of generally increasing frequency of diaphragmatic injuries, nowadays mostly caused by blunt body traumata in traffic accidents, a review is made about diagnostic and morphologic aspects outlining syndromal relations of 70 cases treated from 1950 until 1980 in the Department of Surgery of the Bonn University. Diaphragmatic tears following indirect (closed) trauma are surely more often associated with a transposition of abdominal organs (73%) than those secondary to direct (penetrating) wounds with an amount to 23%. In typical associated injuries like multiple rib fractures (29%, in relation to blunt injuries even 42%) and pelvic fractures (24% resp. 35%) diaphragmatic damage has to be investigated for if there is any doubtful abdominal or cardiorespiratory symptom. Especially in less symptomatic intervals roentgenographic methods come to use predominantly.


Tropical butterflies use thermal buffering and thermal tolerance as alternative strategies to cope with temperature increase.
Climate change poses a severe threat to many taxa, with increased mean temperatures and frequency of extreme weather events predicted. Insects can respond to high temperatures using behaviour, such as angling their wings away from the sun or seeking cool local microclimates to thermoregulate or through physiological tolerance. In a butterfly community in Panama, we compared the ability of adult butterflies from 54 species to control their body temperature across a range of air temperatures (thermal buffering ability), as well as assessing the critical thermal maxima for a subset of 24 species. Thermal buffering ability and tolerance were influenced by family, wing length, and wing colour, with Pieridae, and butterflies that are large or darker in colour having the strongest thermal buffering ability, but Hesperiidae, small, and darker butterflies tolerating the highest temperatures. We identified an interaction between thermal buffering ability and physiological tolerance, where species with stronger thermal buffering abilities had lower thermal tolerance, and vice versa. This interaction implies that species with more stable body temperatures in the field may be more vulnerable to increases in ambient temperatures, for example heat waves associated with ongoing climate change. Our study demonstrates that tropical species employ diverse thermoregulatory strategies, which is also reflected in their sensitivity to temperature extremes.


Nursing Student's Satisfaction With Virtual Learning During COVID-19 Pandemic in India.
The COVID-19 pandemic significantly impacted the world in 2020. Every country adopted quarantine measures to prevent the transmission of the coronavirus infection. These measures resulted in dramatic changes in the daily lives of most people. In the academic world, students faced a shift from the traditional classroom-based teaching to virtual distance learning platforms. This shift in nursing education posed challenges both to the instructors and students as they were not fully prepared for this transition. The study assessed the nursing students' satisfaction with the virtual learning experience during the COVID-19 pandemic in selected nursing colleges in India. The study was conducted in four nursing colleges in India. A total of 1,166 Diploma, Post Basic BSc (N), BSN, and MSN nursing students participated in the study. Ethical approval was obtained from all the nursing colleges included in the study. The Google Forms satisfaction survey included student, teacher, course, technology, environmental, and practical dimensions. The response rate was 86.31% (n = 1,166). The overall satisfaction with virtual theory and practical classes has a mean and SD score of 67.14 + 11 and 16.21 + 3.46, respectively. The results showed that overall 51% of the students had good satisfaction with virtual theory classes while 48% had moderate satisfaction. In terms of overall satisfaction with virtual practical classes, approximately 39% had good satisfaction, 58% had moderate satisfaction and nearly 3% had poor satisfaction. In addition, the students expressed that they had good satisfaction with Teacher dimension (64.3%), Student dimension (63%), and Course dimension (57.2%). On the contrary, they expressed poor satisfaction in the Technical dimension (11.3%) and Environmental dimension (5.6%). The results showed that the courses, the place of attending class, and health issues were significantly associated with the student's level of satisfaction with virtual learning. Although the majority of the students rated their satisfaction level as being "good" in virtual theory classes and "moderate" in virtual practical learning, most of them were dissatisfied with the Technical and Environmental dimensions of virtual learning. This results calls for blended learning strategies to be designed to enhance better learning outcomes and, to ensure deepened level of satisfaction with virtual learning activities.


MiR-199a-3p Overexpression Suppressed Cell Proliferation and Sensitized Chronic Myeloid Leukaemia Cells to Imatinib by Inhibiting mTOR Signalling.
Chronic myeloid leukaemia (CML) is a myeloproliferative neoplasm characterized by constitutive activity of the tyrosine kinase BCR-ABL1. Drug resistance remains one of the major challenges in CML therapy. MicroRNA (miR)-199a-3p plays an important role in many tumours but has rarely been investigated in CML. We aimed to analyse the role and mechanism of miR-199a-3p in regulating imatinib resistance in CML. The expression of miR-199a-3p and mammalian target of rapamycin (mTOR) in the serum of CML patients and CML cells was examined by quantitative real-time polymerase chain reaction. The levels of apoptosis-related proteins were determined using western blot. The relative cell survival rate and cell proliferation were determined using a CCK-8 assay and a bromodeoxyuridine (BrdU) assay, respectively. Cell cycle and apoptosis were analysed using flow cytometry. Moreover, a dual-luciferase reporter assay was performed to verify the correlation between miR-199a-3p and mTOR. MiR-199a-3p was downregulated in the serum of CML patients and in CML cells, while mTOR was upregulated. Both miR-199a-3p overexpression and mTOR silencing inhibited CML cell proliferation, promoted CML cell apoptosis, and sensitized these cells to imatinib. mTOR silencing reversed the promoting effect of miR-199a-3p inhibition on the proliferation of CML cells and the inhibitory effects on cell apoptosis and sensitivity to imatinib. MiR-199a-3p directly targeted mTOR. MiR-199a-3p suppressed cell propagation, facilitated apoptosis of CML cells, and sensitized CML cells to imatinib by downregulating mTOR signalling.


Studies on sex-organ development. Changes in the oestrogenic response of the chick Müllerian duct as measured by chromatin template and ribonucleic acid initiation capacity.
Assays of transcription in vitro, with Escherichia coli RNA polymerase or wheat-germ RNA polymerase II, were used to characterize chromatin templates isolated from the left Müllerian duct of the chick embryo during normal development, and during development in the presence of diethylstilboestrol. Control Müllerian-duct template capacity with E. coli RNA polymerase decreased from 6.42% on day 10 to 4.34% by day 15 of development. Similar results were found with wheat-germ RNA polymerase II. In the presence of rifampicin and heparin, the prokaryotic enzyme transcribed a number-average RNA chain of 670 nucleotide residues, at an average rate of 110 nucleotide residues/min, from Müllerian-duct chromatin of all developmental stages. From day 10 to day 15 there was a 44% decrease in the number of initiation sites for E. coli RNA polymerase on Müllerian-duct chromatin. A 47% decline was observed when these chromatins were transcribed with excess RNA polymerase II in the presence of rifamycin Af/013. Signs of increasing responsiveness to oestrogen developed between days 10 and 16. Embryos exposed to maximally responsive doses of diethylstilboestrol for 2 days showed increases in Müllerian-duct chromatin template capacity, RNA-chain initiation sites, wet weight, protein and RNA. The changes seen in the oviduct of the 1-week-old chick injected for 2 days with diethylstilboestrol were defined as 100% responses. By comparison, the Müllerian duct, after exposure to diethylstilboestrol from day 10 to day 12, from day 13 to day 15 or from day 16 to day 18, showed a 15%, 39% and 72% template response respectively, and a 42%, 56% and 85% initiation-site change respectively. A similar developmental trend was observed in all parameters. It is concluded that oestrogenic responsiveness in the developing Müllerian duct increases from day 10 to nearly maximal values by day 16 of development, and that this transition is paralleled by a progressive restriction of genomic activity.


Tyrosine Kinase Inhibitors for Renal Cell Carcinoma: A Bibliometric Analysis via CiteSpace from 2000 to 2022.
The aim of the study was to identify the cooperation of authors, countries, institutions and explore the hot spots regarding research of tyrosine kinase inhibitors (TKIs) for renal cell carcinoma (RCC) treatment in the past 22 years. Relevant original and review articles were obtained from the Web of Science Core Collection from 2000 to 2022. CiteSpace software was used to perform the visualization of scientific productivity and emerging trends. Network maps were generated to evaluate the collaborations between different authors, countries, institutions, and keywords. A total of 4,951 articles related to TKI for RCC treatment were identified. We observed a gradual increase in the number of publications from 2000 to 2022. The USA dominated the field in all countries, and Mem Sloan Kettering Cancer Centre (USA) had more extensive cooperating relationships with other institutions. Motzer RJ and Escudier B were two of the authority scholars in this specific field with the most publications and co-citations. Journal of Clinical Oncology had the most citations of all the journals. A total of 10 major clusters were explored based on the reference co-citation analysis. From 2000 to 2022, the research hot spots have undergone two dramatic shifts during 2006 and 2019, respectively, relevant topics were TKI and TKI combined with immune checkpoint inhibitors (CPIs). At present, the research hot spots focus on CPI and targeted therapies. Bibliometric analysis is allowing researchers to recognize the current research status by providing a comprehensive overview of the development of scientific literature related to TKI for RCC treatment, and information for further research be demonstrated as well.


The trophic effect of nerve growth factor in primary cultures of rat hippocampal neurons is associated to an anti-inflammatory and immunosuppressive transcriptional program.
Nerve growth factor, the prototype of a family of neurotrophins, elicits differentiation and survival of peripheral and central neuronal cells. Although its neural mechanisms have been studied extensively, relatively little is known about the transcriptional regulation governing its effects. We have previously observed that in primary cultures of rat hippocampal neurons treatment with nerve growth factor for 72 hr increases neurite outgrowth and cell survival. To obtain a comprehensive view of the underlying transcriptional program, we performed whole-genome expression analysis by microarray technology. We identified 541 differentially expressed genes and characterized dysregulated pathways related to innate immunity: the complement system and neuro-inflammatory signaling. The exploitation of such genes and pathways may help interfering with the intracellular mechanisms involved in neuronal survival and guide novel therapeutic strategies for neurodegenerative diseases.


[Recurrent parotitis in childhood (report of 102 cases)].
This article presents 102 cases of recurrent parotitis in childhood with studies of clinical findings, sialographic manifestations, dynamic functions of the parotid gland examined with radionuclide, laboratory findings and follow-up studies of 28 cases including sialography. The following conclusions are reached: 1. The etiology is retrograde infection induced by mumps virus and upper respiratory infection which lower the resistance of the child. Familial abnormalities are potential factors. Incomplete immune function of the children is also a factor related to pathogenesis of this disease, and following growth and development of the immune system this disease will undergo remission. 2. This disease involves both parotid gland generally. 3. Sialographic manifestations will disappear following subsidence of clinical symptoms, but it may take years. 4. If the disease has not been cured in childhood, it may continue to adult and then healing will take place. Relationship with Sjögren's syndrome has not been revealed.


Physical Activity Design Guidelines for School Architecture.
Increasing children's physical activity at school is a national focus in the U.S. to address childhood obesity. While research has demonstrated associations between aspects of school environments and students' physical activity, the literature currently lacks a synthesis of evidence to serve as a practical, spatially-organized resource for school designers and decision-makers, as well as to point to pertinent research opportunities. This paper describes the development of a new practical tool: Physical Activity Design Guidelines for School Architecture. Its aims are to provide architects and designers, as well as school planners, educators, and public health professionals, with strategies for making K-12 school environments conducive to healthy physical activity, and to engage scientists in transdisciplinary perspectives toward improved knowledge of the school environment's impact. We used a qualitative review process to develop evidence-based and theory-driven school design guidelines that promote increased physical activity among students. The design guidelines include specific strategies in 10 school design domains. Implementation of the guidelines is expected to enable students to adopt healthier physical activity behaviors. The tool bridges a translational gap between research and environmental design practice, and may contribute to setting new industry and education standards.


That mr. Alzheimer… you never know what he's up to, but what about me? A discourse analysis of how Swedish spouse caregivers can make their subject positions understandable and meaningful.
The spouses of people suffering from dementia are commonly first-in-line caregivers. This can have a considerable effect on their own lives, health and marriages. Several studies have focused on spouses' experiences, but very few have focused in any depth on their descriptions of themselves as subjects. Therefore, the aim of this study is to describe how spouse caregivers can express themselves when living with and caring for their partners with dementia. The study has a qualitative approach with a discourse analysis design and uses analytical tools such as rhetoric, subject positions and categorization. The results reveal three subject positions: as an actor, as a parent and as a survivor. The results show that as spouses struggle with external and internal clashes as subjects, they therefore need to develop coping strategies. They also experience pronounced loneliness and a risk to their own health. There is thus a need to support these spouses as individuals in their differing and changing needs.


Tibetan sound meditation for cognitive dysfunction: results of a randomized controlled pilot trial.
Although chemotherapy-induced cognitive impairment is common among breast cancer patients, evidence for effective interventions addressing cognitive deficits is limited. This randomized controlled trial examined the feasibility and preliminary efficacy of a Tibetan Sound Meditation (TSM) program to improve cognitive function and quality of life in breast cancer patients. Forty-seven breast cancer patients (mean age 56.3 years), who were staged I-III at diagnosis, 6-60 months post-chemotherapy, and reported cognitive impairment at study entry were recruited. Participants were randomized to either two weekly TSM sessions for 6 weeks or a wait list control group. Neuropsychological assessments were completed at baseline and 1 month post-treatment. Self-report measures of cognitive function (Functional Assessment of Cancer Therapy (FACT)-Cog), quality of life (SF-36), depressive symptoms (Center for Epidemiologic Studies Depression Scale), sleep disturbance (Pittsburgh Sleep Quality Index), fatigue (Brief Fatigue Inventory), and spirituality (FACT-Sp) were completed at baseline, the end of treatment, and 1 month later. Relative to the control group, women in the TSM group performed better on the verbal memory test (Rey Auditory Verbal Learning Test trial 1) (p = 0.06) and the short-term memory and processing speed task (Digit Symbol) (p = 0.09) and reported improved cognitive function (p = 0.06), cognitive abilities (p = 0.08), mental health (p = 0.04), and spirituality (p = 0.05) at the end of treatment but not 1 month later. This randomized controlled trial revealed that TSM program appears to be a feasible and acceptable intervention and may be associated with short-term improvements in objective and subjective cognitive function as well as mental health and spirituality in breast cancer patients.


Enhanced electrocatalytic hydrogen evolution by molybdenum disulfide nanodots anchored on MXene under alkaline conditions.
Efficient hydrogen production through electrocatalysis represents a promising path for the future clean energy. Molybdenum disulfide (MoS2) is a good substitute for platinum-based catalysts, due to its low cost and high activity. However, the limited active sites and low electrical conductivity of MoS2 hinder its large-scale industrial application under alkaline conditions. Herein, we constructed MoS2 nanodots anchored on an MXene/nickel foam (MoS2 NDs/MXene/NF) heterostructure by a cascade polymerization synthesis and in situ vulcanization. The prepared heterostructure displays an ultralow overpotential of 94 mV at a current density of 10 mA cm-2 with a Tafel slope of only 59 mV dec-1 in alkaline (1 M KOH) hydrogen evolution reaction (HER), and is better than conventional MoS2 electrocatalysts reported so far. Fine structural analysis indicates that MoS2 NDs are dispersed uniformly on the surface of the heterostructure with consistent orientation, leading to the improvement of MoS2 conductivity with more paths for electron transfer. Moreover, the orientation of the synthesized MoS2 NDs was verified to expose the more (002) crystal plane, which exhibits higher activity than other planes. Our results demonstrate that MoS2 NDs with heterostructure design and preferential growth can serve as high-efficiency noble-metal free electrocatalysts for the HER in alkaline solution.


[Prevalence of HIV, HTLV, and hepatitis B and C viruses in blood donors in France, 1992-1996].
The prevalence of HIV, HTLV, HBV and HCV infections has been calculated by age and sex of blood donors and not, as generally done, according to the number of donations. This study has been conducted on the basis of two surveys. The first one collected information about the sex and age of the seropositive donors. A second survey, begun in 1992, collected information about the demographic characteristics of blood donors. This population has a higher male to female sex ratio (1:2 versus 1:0) and is younger than the general population. Thus, the prevalence of these viral infections has been determined according to sex, age and type of donors (first-time or repeat) from 1992 to 1996 and the trends have been analysed. The main results are the following: a decreasing prevalence of HIV in first-time donors from 1992 to 1996, more marked in men than in women and in the 18-29 year age group than in the other age groups; a slighter decrease in prevalence of HBV and HCV in first-time donors from 1992 to 1996 with no difference in this decrease between sex and age groups. HBs Ag prevalence in first-time donors was twice as high in men than in women and was highest in donors aged from 40 to 49 years in both sexes. Prevalence of antibodies to HCV in first-time donors was comparable in both sexes but varied greatly with age. In men, a peak was observed in the 30-39 age group and in women, the highest prevalence was seen in the 50-65 age group.


Mucin genes (MUC2, MUC4, MUC5AC, and MUC6) detection in normal and pathological endometrial tissues.
Changes in the composition and physical properties of the mucous gel covering the endometrial surface are detected during the menstrual cycle and in pathological conditions. The aim of this study is to analyze the expression patterns of the 11p15 secreted mucins, MUC2, MUC5AC, and MUC6, and the membrane-bound mucin MUC4 in proliferative and secretory normal endometrium, simple and complex hyperplasia, and endometrial adenocarcinoma. A total of 98 samples, 19 of normal endometrium (11 proliferative and 8 secretor), 44 of endometrial hyperplasia (23 simple, 21 complex), and 35 of endometrial endometrioid adenocarcinomas were analyzed by immunohistochemical techniques using specific antimucin antibodies. In the endometrial proliferative glandular epithelium, only MUC4 is detected (36.3% cases). During the secretory phase, increased levels of MUC2 are found (37.5%), whereas MUC4 is less detected (12.5%). In simple hyperplasia, higher levels of mucins are expressed in the endometrial glands: MUC2 is detected in 8.7%, MUC4 in 43.4%, and MUC5AC and MUC6 in 13% of the samples, whereas in complex hyperplasia, decreased levels of mucin expression are found: MUC2 and MUC5AC are not detected, and MUC4 (28.5%) and MUC6 (20.4%) are positive. In endometrial adenocarcinoma, MUC4 is highly detected (77.1%) and increased levels of MUC5AC and MUC6 are found (61.7% and 48.5%), whereas MUC2 is poorly detected (8.5%). These findings suggest that during endometrial neoplasic transformation, increased levels of MUC4, MUC5AC, and MUC6 are detected, whereas MUC2 is only significantly detected in the secretory endometrium.


Featured Article: Interpersonal Stressors and Resources as Predictors of Adolescent Adjustment Following Traumatic Brain Injury.
The present study sought to examine adolescents' perceptions of their interpersonal stressors and resources across parent, sibling, friend, and school relationships, and the longitudinal associations with self-reported adjustment after traumatic brain injury (TBI) over a 12-month period. We examined the main effects of stressors and resources on internalizing and externalizing symptoms in 152 adolescents who had sustained complicated mild-to-severe TBI. We also investigated the conjoint effects of stressors and resources and the moderating effects of TBI severity with stressors and resources on outcomes. High stressors consistently predicted worse adjustment. High resources were generally only associated with fewer internalizing symptoms. Main effects were qualified by interactions between school stressors and resources in predicting externalizing symptoms and between friend stressors and resources in predicting internalizing and externalizing symptoms. For school stressors, the effects of resources on externalizing symptoms functioned as a buffer. In comparison, the buffering effects of friend resources on internalizing and externalizing symptoms disappeared at moderate-to-high levels of friend stress. Moderating effects of TBI severity were also observed, such that as family resources increased, only adolescents with complicated mild-to-moderate TBI, but not those with severe TBI, experienced decreases in internalizing and eternalizing symptoms. Interpersonal stressors and social support have important implications for adolescent adjustment after TBI. Adolescents with low levels of school resources, with high levels of friend stress, and who sustain severe TBI are at greatest risk for difficulties with adjustment.


Sequence-specific recognition of the HIV-1 long terminal repeat by distamycin: a DNAase I footprinting study.
Pharmacological modulation of the interaction between transcription factors and target DNA sequences of cellular and viral genes could have important effects in the experimental therapy of a large variety of human pathologies. For instance, alteration of the DNA/protein interaction might be among the molecular mechanisms of action of DNA-binding drugs, leading to an inhibition of the expression of genes involved in the control of in vitro and in vivo growth of neoplastic cells and virus DNA replication. Natural oligopeptides, such as distamycin, are powerful inhibitors of the interaction between nuclear factors and target DNA sequences and, therefore, have been proposed as compounds retaining antibiotic, antineoplastic and antiviral properties. In this study we performed DNAase I footprinting analysis using a PCR product mimicking a region of the long terminal repeat (LTR) of the human immunodeficiency type 1 (HIV-1) retrovirus. The data obtained suggest that distamycin binds to different regions of the HIV-1 LTR depending on the DNA sequence. Electrophoretic mobility shift assays using both crude nuclear extracts from the Jurkat T-lymphoid cell line and the recombinant proteins transcription factor IID and Sp1 suggest that distamycin differentially inhibits the interaction of these two proteins with their specific DNA target sequences, in good agreement with the results obtained by DNAase I footprinting analysis.


Transformation of Beauveria bassiana to produce EGFP in Tenebrio molitor for use as animal feed additives.
Efforts are underway to develop more effective and safer animal feed additives. Entomopathogenic fungi can be considered practical expression platforms of functional genes within insects which have been used as animal feed additives. In this work, as a model, the enhanced green fluorescent protein (egfp) gene was expressed in yellow mealworms, Tenebrio molitor by highly infective Beauveria bassiana ERL1170. Among seven test isolates, ERL1170 treatment showed 57.1% and 98.3% mortality of mealworms 2 and 5 days after infection, respectively. The fungal transformation vector, pABeG containing the egfp gene, was inserted into the genomic DNA of ERL1170 using the restriction enzyme-mediated integration method. This resulted in the generation of the transformant, Bb-egfp#3, which showed the highest level of fluorescence. Bb-egfp#3-treated mealworms gradually turned dark brown, and in 7-days mealworm sections showed a strong fluorescence. This did not occur in the wild-type strain. This work suggests that further valuable proteins can be efficiently produced in this mealworm-based fungal expression platform, thereby increasing the value of mealworms in the animal feed additive industry.


Role of tissue trace elements in liver cancers and non-cancerous liver parenchyma.
The role of trace elements in liver fibrosis, carcinogenesis and progression of hepatocellular carcinoma (HCC) has not yet been clarified. The aim of this study is to analyze the characteristics of trace elements in liver cancers and non-cancerous liver and to discuss their role in hepatic fibrosis, hepatocarcinogenesis and progression of HCC. The amount of zinc (Zn), iron (Fe), and copper (Cu) in 20 HCCs, 2 cholangiocellular carcinomas (CCC), 7 metastatic liver cancers (Meta) and their non-tumorous liver parenchyma were measured using an atomic absorption spectrophotometer. The amounts of Zn and Fe in non-tumorous liver parenchyma were reduced by liver fibrosis, and the amounts were lower in HCC tissue compared to non-tumorous liver parenchyma. The amounts of Zn and Cu were higher in HCC than the amounts found in CCC and Meta. The amount of Zn in HCC tissue decreased, but the amount of Fe increased in tumors more than 4cm in diameter. These results suggest that the decrease in the amount of Zn and Fe found in non-tumorous liver parenchyma correlates with liver fibrosis leading to cirrhosis and hepatocarcinogenesis. Also that decreases in Zn and increases of Fe in HCC tissue correlates with HCC tumor progression.