Working memory and long-term memory for faces: Evidence from fMRI and global amnesia for involvement of the medial temporal lobes.
Behavioral studies with amnesic patients and imaging studies with healthy adults have suggested that medial temporal lobe (MTL) structures known to be essential for long-term declarative memory (LTM) may also be involved in the maintenance of information in working memory (WM). To examine whether MTL structures are involved in WM maintenance for faces, and the nature of that involvement, WM and LTM for faces were examined in normal participants via functional magnetic resonance imaging (fMRI) and in amnesic patients behaviorally. In Experiment 1, participants were scanned while performing a WM task in which they determined if two novel faces, presented 7 s apart, were the same or different. Later, participants' LTM for the faces they saw during the WM task was measured in an unexpected recognition test. During WM maintenance, the hippocampus was activated bilaterally, and there was greater activation during maintenance for faces that were later remembered than faces later forgotten. A conjunction analysis revealed overlap in hippocampal activations across WM maintenance and LTM contrasts, which suggested that the same regions were recruited for WM maintenance and LTM encoding. In Experiment 2, amnesic and control participants were tested on similar WM and LTM tasks. Amnesic patients, as a group, had intact performance with a 1-s maintenance period, but were impaired after a 7-s WM maintenance period and on the LTM task. Thus, parallel neuroimaging and lesion designs suggest that the same hippocampal processes support WM maintenance, for intervals as short as 7 s, and LTM for faces.


[Tuberculous spondylitis with a psoas abscess in a young man without an immigrant background].
Tuberculosis is a common disease in Africa, Asia, and South America. In Denmark the incidence is 10/100,000 and highest in HIV positive patients, alcoholics, and some immigrant groups. We describe a young Dane, who was referred to the department of rheumatology for back pain. It turned out to be tuberculosis spondylitis with a major psoas abscess.


Dedifferentiated Low-Grade Osteosarcoma, Outcome with or Without Chemotherapy: A Systematic Review.
The treatment of low-grade osteosarcomas is surgical resection with wide margins. In instances of dedifferentiation, a therapeutic paradigm similar to that of conventional high-grade osteosarcoma has not been adequately evaluated in these neoplasms. The main objective of this review was to define whether the addition of chemotherapy to surgical treatment has an impact on the survival of patients with dedifferentiated low-grade osteosarcomas. Secondary objectives were to observe the degree of histological response to neoadjuvant chemotherapy and to describe the percentage of de novo dedifferentiation. A systematic search of articles including dedifferentiated low-grade osteosarcomas, published between 1980 and 2022 was carried out in the PubMed, Cochrane and Scielo databases. A qualitative synthesis of the results was performed. Twenty-three articles comprising 117 patients were included. The survival of patients treated with surgery alone and surgery with chemotherapy was not statistically significant between the two groups. A good histological response was seen in 20% of specimens treated with neoadjuvant chemotherapy. De novo dedifferentiation was seen in approximately a fifth of low-grade osteosarcomas. The evidence available suggests that the addition of chemotherapy does not have an impact on the survival of patients with low-grade dedifferentiated osteosarcomas.


Identification of two novel PNPLA1 mutations in Turkish families with autosomal recessive congenital ichthyosis.
Dökmeci-Emre S, Taşkıran ZE, Yüzbaşıoğlu A, Önal G, Akarsu AN, Karaduman A, Özgüç M. Identification of two novel PNPLA1 mutations in Turkish families with autosomal recessive congenital ichthyosis. Turk J Pediatr 2017; 59: 475-482. Autosomal recessive congenital ichthyosis (ARCI) is a group of inherited keratinization disorders that are characterized by abnormal epidermal keratinization. ARCI patients generally represent serious symptoms including collodion baby phenotype accompanied by dehydration, heat loss, electrolytic imbalance, and sepsis. ARCI shows high degree of clinical and genetic heterogeneity. To date, nine genes were shown to be responsible for ARCI phenotype. One of these genes, patatin-like phospholipase domain containing protein-1 (PNPLA1) was suggested to be involved in the synthesis of ω-O-acylceramides related to epidermal cornified lipid envelope organization. In addition to previously reported PNPLA1 mutations, we report two novel PNPLA1 mutations including one novel missense mutation c.335C > A (p.Ser112Tyr) and one novel deletion mutation c.733_735delTAC (p.Tyr245del) in Turkish ARCI patients from unrelated consanguineous families. We also report previously reported missense mutation c.514G > A (p.Asp172Asn) in Turkish ARCI patients. Novel PNPLA1 mutations were shown to be located in the catalytic patatin domain of PNPLA1 gene. Identification of novel mutations in PNPLA1 gene expands the mutational spectrum in the causative gene. Increase in the total number of cases has high diagnostic value in terms of genotype-phenotype correlation in ARCI patients.


Some public attitudes about health and the environment.
Public opinion is formed both by long-term developments and--at the other extreme--by single unanticipated events. This suggests that readers of opinion survey findings should note field interviewing dates and further determine what the news media have been reporting about relevant developments and events. Personal health and the cost of health care are high on the public's agenda; this is an important backdrop to a review of public attitudes and priorities related to health and the environment. What about the environment? Americans increasingly believe that we are not spending enough on environmental protection and improvement. The public thinks of environmentalists in a favorable light, and a very sizeable minority believe they have too little influence--the same number who feel it's "about right." Our surveys have shown that the more people perceive an environmental threat to their safety, well-being and health, the more they will want regulation or industry action to meet the threat. High on the public's anxiety list are hazardous wastes (especially their disposal) and the transport and use of toxic materials in manufacturing and processing, industrial accidents involving the release of pollutants, the leakage of chemical waste into the soil, and the pollution of water and air from industrial sources. Our data support the assumption that for the foreseeable future these and certain other ecological dangers will be seen as serious by large majorities of Americans. For example, even the safety of drinking water has slowly become more questionable in the public's mind.(ABSTRACT TRUNCATED AT 250 WORDS)


Alpha 2-adrenoceptor mechanisms in guinea-pig trachea.
In the presence of propranolol tracheal strips from guinea-pigs were markedly contracted by norepinephrine and clonidine but only slightly by phenylephrine. The contractile responses to clonidine and norepinephrine were inhibited by yohimbine but not by prazosin. The specific binding of [3H]p-aminoclonidine to the microsomal fractions from guinea-pig tracheal muscle was much greater than that of [125I]BE2254. These results indicate that alpha 2-adrenoceptors are the predominant subtype of alpha-adrenoceptor in the guinea-pig trachea. The response to norepinephrine was abolished by cyclooxygenase inhibitors, suggesting the release of excitatory prostaglandins by norepinephrine. These results raise the possibility that norepinephrine interacts with alpha 2-adrenoceptors and releases prostaglandins to contract tracheal muscle.


Long noncoding RNA BMPR1B-AS1 facilitates endometrial cancer cell proliferation and metastasis by sponging miR-7-2-3p to modulate the DCLK1/Akt/NF-κB pathway.
Endometrial carcinoma (EC) originates from the endometrium and is one of the most common tumors in female patients, and its incidence has continued to increase in recent decades. LncRNAs are involved in the pathogenesis and metastasis of a variety of malignant tumors, which indicates that lncRNAs can be used as tumor diagnostic markers and potential therapeutic targets. In this study, we analyzed the RNA transcripts of EC cells from The Cancer Genome Atlas (TCGA) and first reported a novel lncRNA, BMPR1B-AS1, that was more highly expressed in endometrial cancer tissues than in adjacent tissues, and BMPR1B-AS1 could promote endometrial cancer cell proliferation and metastasis. Bioinformatics prediction and experimental results both suggested that BMPR1B-AS1 could modulate the malignant behaviors of endometrial cancer cell lines by sponging miR-7-2-3p to modulate DCLK1, and a DCLK1 inhibitor blocked the activation of the PI3K/Akt/NF-κB signaling pathway. Collectively, this study suggests that the BMPR1B-AS1/miR-7-2-3p/DCLK1 axis contributes to the proliferation and metastasis of endometrial cancer cells via the PI3K/Akt/NF-κB pathway.


Free energy landscape for the translocation of polymer through an interacting pore.
Free energy landscapes for polymer chain translocating through an interacting pore are calculated by using exact enumeration method. A potential barrier exists at weak attractive or repulsive polymer-pore interaction and it changes to a potential well with the increase in the attraction. The result reveals that there is a free translocation point where polymer is free of energy barrier. Using the free energy landscape, the translocation time tau for polymer worming through the pore and the migration time tau(m) for polymer migrating from cis side to trans side are calculated with the Fokker-Plank equation. It shows that a moderate attractive polymer-pore interaction accelerates the migration of polymer from cis side to trans side.


Somatic mutation variant analysis in rural, resectable non-small cell lung carcinoma patients.
Rural non-small cell lung cancer (NSCLC) patients do worse, largely related to lack of access to care. In this study, the mutational characteristics and potential for targeted therapy in rural, resectable NSCLC patients using whole exome sequencing (WES) were analyzed. WES was performed on tumor-adjacent normal pairs from rural patients undergoing resection for NSCLC. Sequencing alignment, variant-calling, annotation, and tumor mutational burden (TMB) calculations were performed using standard methods. cBioportal and OncoKB were used for comparisons of mutational frequencies and actionable targets. Thirty-four NSCLC patients underwent WES after surgical resection. The gene most frequently containing somatic variants was TP53. The median number of somatic variants was 188 (Range 11-1056), and median TMB was 3.30 (0.33-18.56) nonsynonymous mutations per Mb. Tumor stage and survival were not associated with number of variants, TMB or TP53 mutational status. Significant concordance among the most common mutations when cross-referenced to cBioportal (R = 0.78, p < 0.0001) was observed. 24% of patients had variants in actionable genes based on OncoKB annotation. In summary, we demonstrate baseline mutational frequency and establish foundations for targeted adjuvant trials in rural NSCLC patients with specific differences. Future studies must ensure to include rural patients to improve NSCLC patient outcomes.


The multifaceted role of the vasculature in endochondral fracture repair.
Fracture healing is critically dependent upon an adequate vascular supply. The normal rate for fracture delayed or non-union is estimated to be between 10 and 15%, and annual fracture numbers are approximately 15 million cases per year. However, when there is decreased vascular perfusion to the fracture, incidence of impaired healing rises dramatically to 46%. Reduction in the blood supply to the fracture can be the result of traumatic injuries that physically disrupt the vasculature and damage supportive soft tissue, the result of anatomical location (i.e., distal tibia), or attributed to physiological conditions such as age, diabetes, or smoking. The role of the vasculature during repair is multifaceted and changes during the course of healing. In this article, we review recent insights into the role of the vasculature during fracture repair. Taken together these data highlight the need for an updated model for endochondral repair to facilitate improved therapeutic approaches to promote bone healing.


Bacterial peritonitis and beta-2 microglobulin (B2M) production by peritoneal macrophages (PM0) in CAPD patients.
To evaluate the role of bacterial peritonitis in peritoneal macrophage (PMO) Beta-2 Microglobulin (B2M) production and its relationship with PMO Interleukin-1 (IL-1) and Leukotriene B4 (LTB4) release we analyzed in 20 CAPD patients (10 with peritonitis): 1. in vivo plasma and peritoneal dialysis effluent (PDE) B2M, IL-1 and LTB4 levels; 2. in vitro B2M, IL-1 and LTB4 release by PMO. Values were compared with those seen in the plasma or with peripheral blood monocytes of 30 hemodialysis (HD) patients (10 treated with Cuprophan-CU-, 10 with Polyacrylonitrile - PAN, and 10 with Cellulose Acetate - CA). Results showed that in CAPD patients with bacterial peritonitis B2M, IL-1 and LTB4 concentrations in the PDE were significantly higher than those seen in CAPD patients without peritonitis or in the plasma of HD patients treated with PAN or CA, but were similar to those seen in HD patients treated with CU. At the same time, in vitro, PMO from CAPD patients with bacterial peritonitis produced more B2M, IL-1 and LTB4 than did PMO from CAPD patients without peritonitis or peripheral blood monocytes from HD patients treated with PAN or CA. We conclude that in CAPD patients bacterial peritonitis is able to induce PMO B2M production, probably via a cytokine-mediated process, which may be analogous to what occurs with peripheral blood monocytes of HD patients treated with CU.


Mitophagy-mediated molecular subtypes depict the hallmarks of the tumour metabolism and guide precision chemotherapy in pancreatic adenocarcinoma.
Background: Mitophagy is closely related to cancer initiation and progression. However, heterogeneity with reference to mitophagy remains unexplored in pancreatic adenocarcinoma (PAAD). Materials and methods: We used Reactome database to download the mitophagy-related, glycolysis-related and cholesterol biosynthesis-related signaling pathways. Unsupervised clustering using the "ConsensusClusterPlus" R package was performed to identify molecular subtypes related to mitophagy and metabolism. Prognosis-related mitophagy regulators were identified by univariate Cox regression analysis. Receiver operating characteristics (ROC) and Kaplan-Meier (K-M) survival analyses were used to assess the diagnostic and prognostic role of the hub genes and prognosis risk model. Weighted gene co-expression network analysis (WGCNA) was utilized for screening the mitophagy subtype-related hub genes. Metascape was utilized to carry out functional enrichment analysis. The "glmnet" R package was utilised for LASSO, and the "e1071" R package was utilised for SVM. Chemotherapeutic drug sensitivity was estimated using the R package "pRRophetic" and Genomics of Drug Sensitivity in Cancer (GDSC) database. The nomogram was established by the "rms" R package. Results: Three distinct mitophagy subtypes (low, high and intermediate) of PAAD were identified based on the landscape of mitophagy regulators. The high mitophagy subtype had the worst prognosis, highest mRNA expression-based stemness index scores and most hypoxic environment compared to the other subtypes. Additionally, glycolysis and cholesterol biosynthesis were significantly elevated. Three mitophagy subtype-specific gene signatures (CAST, CCDC6, and ERLIN1) were extracted using WGCNA and machine learning. Moreover, PAAD tumours were insensitive to Erlotinib, Sunitinib and Imatinib in the high mitophagy subtype and high CAST, CCDC6, and ERLIN1 expressed subtypes. Furthermore, CAST, CCDC6, and ERLIN1 affected immune cell infiltration (M1 and CD8Tcm), resulting in the altered prognosis of patients with PAAD. A nomogram was constructed to screen patients with the low mitophagy subtype, which showed a higher sensitivity to chemotherapeutic agents. Conclusion: Based on various bioinformatics tools and databases, the PAAD heterogeneity regarding mitophagy was systematically examined. Three different PAAD subtypes having different outcomes, metabolism patterns and chemosensitivity were observed. Moreover, three novel biomarkers that are closely associated with mitophagy and have the potential to guide individualised treatment regimens in PAAD were obtained.


Genetically Modified (GM) Crop Use 1996-2020: Environmental Impacts Associated with Pesticide Use CHANGE.
This paper assesses the environmental impacts associated with changes in pesticide use with GM crops at a global level. The main technologies impacting on pesticide use have been crops modified to be tolerant to specific herbicides so as to facilitate improved weed control and crops resistant to a range of crop insect pests that otherwise damage crops or typically require the application of insecticides to control them. Over the 24 year period examined to 2020, the widespread use of GM insect resistant and herbicide tolerant seed technology has reduced pesticide application by 748.6 million kg (-7.2%) of active ingredient and, as a result, decreased the environmental impact associated with insecticide and herbicide use on these crops (as measured by the indicator, the Environmental Impact Quotient (EIQ)) by a larger 17.3% between 1996 and 2020. The technology that has delivered the largest change in pesticide use has been insect resistant cotton, where a 339 million kg of active ingredient saving has occurred and the associated environmental impact (as measured by the EIQ indicator) has fallen by about a third.


Use of rheolytic thrombectomy in treatment of acute massive pulmonary embolism.
The 6-F Xpeedior (AngioJet; Possis Medical, Minneapolis, MN) rheolytic thrombectomy catheter (RTC) uses high velocity saline jets for thrombus aspiration, maceration, and evacuation, through the Bernoulli principle. The purpose of this study was to evaluate the efficacy of thrombus removal using the RTC in patients with acute massive pulmonary embolism (PE). Seventeen patients (mean age, 51.7 + 16.6 years; range, 30-86 years; 9 men, 8 women) with massive PE initially diagnosed by computed tomography (CT) or VQ scan and confirmed by pulmonary angiography were treated with the RTC. All patients had acute onset of PE symptoms and all presented with hemodynamic compromise and dyspnea. Ten of 17 patients had enough residual thrombus to warrant adjuvant catheter directed thrombolytic infusion with reteplase. Six patients had contraindications to thrombolytic therapy. One patient presented with renal cell carcinoma and tumor embolus as suspected cause of PE. Angiographic and clinical outcomes during the hospital stay were evaluated. The RTC was successfully delivered and operated via a 0.035-inch guide wire in all attempted cases. Treatment resulted in immediate angiographic improvement and initial relief of PE symptoms (improvement in dyspnea and oxygen saturation) in 16 of 17 patients. One patient developed heart block during the procedure, and further treatment with the RTC was discontinued. Bradycardia occurred in one patient (managed with lidocaine). After thrombectomy, 10 patients received adjunctive reteplase thrombolysis for treatment of residual thrombus, and 12 received inferior vena cava (IVC) filters. In the patient with renal cell carcinoma, histopathologic analysis of the evacuated material confirmed tumor origin of the embolism. There were two deaths, both within 24 hours of treatment and secondary to PE. One death occurred in a patient who had only minimal thrombus removal after treatment with the RTC and no thrombolysis. The remaining 15 patients showed continued improvement in PE symptoms and were eventually discharged from the hospital with mean length of stay 10.3 + 6.5 days (range, 5-30 days). Rheolytic thrombectomy can be performed effectively in patients with massive PE. However, a large portion of the patients in this study underwent adjuvant overnight thrombolytic infusion. Further evaluation in a larger cohort of patients is warranted to assess whether this treatment may offer an alternative or complement to thrombolysis or surgical thrombectomy.


[Distinctive morphofunctional features of the bill and hyoid apparatus of turacos (Aves, Musophagidae): relations with frugivory].
The present study points to morpho-anatomical features that allow vegetarian but mainly frugivorous turacos to fill at best their specific feeding requirements. Mechanisms are analysed which the bird can use to detach a fruit and avoid it rolls out of the bill. It is also examined how vegetable items can be processed particularly when they have to be cut, and what can facilitate their ingestion particularly when they are fruits that have to be swallowed entirely and are large and/or have dry or fibrous skin or flesh. The skeletal and muscular anatomy of the bill and hyoid apparatus is described in details and illustrated. The particularly short and stout bill coupled with a relatively simple system of aponevroses of the adductors reflects a trade-off between two important jaw functional requirements: huge efforts for clamping, and a wide opening for plucking, processing and swallowing relatively large fruit. The clearly oblique orientation of the modified outer adductor seems an adaptation to the detachment of fruits. The os uncinatum, particularly developed in this bird family, is interpreted as maintaining transversal stability, particularly when jaws act as a pair of scissors. Most food items being processed near the base of the bill, mechanisms have been developed which contribute to overcome the risk of breakage at the level of the prokinetic hinge because of a vertically oriented force there.


magu is required for germline stem cell self-renewal through BMP signaling in the Drosophila testis.
Understanding how stem cells are maintained in their microenvironment (the niche) is vital for their application in regenerative medicine. Studies of Drosophila male germline stem cells (GSCs) have served as a paradigm in niche-stem cell biology. It is known that the BMP and JAK-STAT pathways are necessary for the maintenance of GSCs in the testis (Kawase et al., 2004; Kiger et al., 2001; Schulz et al., 2004; Shivdasani and Ingham, 2003; Tulina and Matunis, 2001). However, our recent work strongly suggests that BMP signaling is the primary pathway leading to GSC self-renewal (Leatherman and DiNardo, 2010). Here we show that magu controls GSC maintenance by modulating the BMP pathway. We found that magu was specifically expressed from hub cells, and accumulated at the testis tip. Testes from magu mutants exhibited a reduced number of GSCs, yet maintained a normal population of somatic stem cells and hub cells. Additionally, BMP pathway activity was reduced, whereas JAK-STAT activation was retained in mutant testes. Finally, GSC loss caused by the magu mutation could be suppressed by overactivating the BMP pathway in the germline.


Changes in the quality of meat (Longissimus thoracis et lumborum) from Kamieniec lambs during long-term freezer storage.
The aim of this study was to determine changes in the quality of lamb meat (Longissimus thoracis et lumborum), which was vacuum-packaged and freezer-stored (-26°C) for 6 and 12 months. The experiment was performed on 12 male lambs of the Kamieniec Longwool breed, raised to 106 days of age. In comparison with fresh meat, thawed meat was characterized by lower ash content, higher pH, greater natural drip loss and cooking loss, and lower scores for taste intensity. Vacuum packaging and low-temperature storage protected lamb meat against oxidative changes, and alleviated the adverse effects of oxidation on the color, aroma and taste of meat. It can be concluded that freezer storage (-26°C) of vacuum-packaged meat can help meet consumer demand for lamb meat products in periods when fresh meat is unavailable. However, it should be noted that long-term frozen storage induces undesirable changes in meat quality, including a decrease in water-holding capacity and taste intensity.


IL-10 Family Cytokines IL-10 and IL-22: from Basic Science to Clinical Translation.
Cytokines are among the most important effector and messenger molecules in the immune system. They profoundly participate in immune responses during infection and inflammation, protecting against or contributing to diseases such as allergy, autoimmunity, and cancer. Manipulating cytokine pathways, therefore, is one of the most effective strategies to treat various diseases. IL-10 family cytokines exert essential functions to maintain tissue homeostasis during infection and inflammation through restriction of excessive inflammatory responses, upregulation of innate immunity, and promotion of tissue repairing mechanisms. Their important functions in diseases are supported by data from many preclinical models, human genetic studies, and clinical interventions. Despite significant efforts, however, there is still no clinically approved therapy through manipulating IL-10 family cytokines. Here, we summarize the recent progress in understanding the biology of this family of cytokines, suggesting more specific strategies to maneuver these cytokines for the effective treatment of inflammatory diseases and cancers.


Effect of inspiratory muscle training (IMT) on aerobic capacity, respiratory muscle strength and rate of perceived exertion in paraplegics.
Objectives: The purpose is to study the effect of inspiratory muscle training on aerobic capacity, respiratory muscle strength and rate of perceived exertion in paraplegics.Study Design: Randomized controlled trial.Settings: Rehabilitation department in Indian Spinal Injuries Centre, New Delhi.Participants: A sample of 30 paraplegics (T1-T12) were randomly allocated into two groups: inspiratory muscle training (IMT) group and control group.Interventions: The IMT group received inspiratory muscle training for 15 minutes 5 times a week for 4 weeks whereas the control group was given breathing exercises.Outcome measures: Maximal inspiratory pressure(MIP), maximal expiratory pressure (MEP), modified Borg's scale (MBS), 12 minute wheelchair aerobic test (12MWAT), multistage fitness test (MSFT), and 6 minutes push test (6MPT).Results: Out of 30 participants, 27 completed the study. The results show that after four weeks of IMT training, there were significant improvements in mean change scores of IMT group as compared to control group. Participants in IMT group performed better on 12MWAT (P = 0.001), MSFT (P = 0.001) and 6MPT (P = 0.001). Improvements in MIP scores (P = 0.001), MEP scores (P = 0.001) and MBS scores (P = 0.004) were also seen in IMT group.Conclusion: Both groups showed significant improvements, however inspiratory muscle training was seen to be more effective than deep breathing exercises for improving aerobic capacity, respiratory muscle strength and rate of perceived exertion in paraplegics.


Chemodiversity of Cirsium fruits: Antiproliferative lignans, neolignans and sesquineolignans as chemotaxonomic markers.
While analyzing the fruit composition of nine European Cirsium species representing three sections (i.e., Cephalonoplos, Chamaeleon and Eriolepis), four lignans, three neolignans and three sesquineolignans were determined and used as chemotaxonomic markers. Among them, desmethyl balanophonin and desmethyl picrasmalignan were determined for the first time in the plant kingdom, as the main metabolites of the Chamaeleon section. Prebalanophonin and prepicrasmalignan, identified so far exclusively in C. eriophorum, were also confirmed in C. boujartii and C. vulgare, highlighting the chemotaxonomic significance of these compounds in the Eriolepis section. The antiproliferative assay of the compounds isolated from their optimum sources, confirmed a dose-dependent inhibitory effect of the structures bearing the 4',7-epoxy moiety (balanophonin, picrasmalignan, desmethyl balanophonin, desmethyl picrasmalignan) against SW480 colon cancer cells, while those bearing the 4',7-dihydroxy motif (prebalanophonin, prepicrasmalignan) were inactive.


Discriminant learning through multiple principal angles for visual recognition.
Canonical correlation has been prevalent for multiset-based pairwise subspace analysis. As an extension, discriminant canonical correlations (DCCs) have been developed for classification purpose by learning a global subspace based on Fisher discriminant modeling of pairwise subspaces. However, the discriminative power of DCCs is not optimal as it only measures the "local" canonical correlations within subspace pairs, which lacks the "global" measurement among all the subspaces. In this paper, we propose a multiset discriminant canonical correlation method, i.e., multiple principal angle (MPA). It jointly considers both "local" and "global" canonical correlations by iteratively learning multiple subspaces (one for each set) as well as a global discriminative subspace, on which the angle among multiple subspaces of the same class is minimized while that of different classes is maximized. The proposed computational solution is guaranteed to be convergent with much faster converging speed than DCC. Extensive experiments on pattern recognition applications demonstrate the superior performance of MPA compared to existing subspace learning methods.


MitraClip for High-Risk Patients with Significant Mitral Insufficiency: Shall We Unreservedly Recommend It?
MitraClip (Abbott Inc.) is propagated as a palliative option for high-risk patients with mitral insufficiency considered not qualifying for surgical repair. A proportion of patients requires consecutive surgery because of technical failure or inappropriate clinical improvement. Furthermore, surgical reconstruction is impossible in almost all patients after MitraClip implantation. Consequently, these patients receive replacement although primary repair may have been possible. The outcome of those patients compared with patients receiving primary mitral valve replacement (MVR) or mitral valve repair (MVP) was analyzed. A total of 23 patients were retrospectively analyzed after MVR following MitraClip. Overall, 46 patients with corresponding demographic data and risk profile receiving primary MVR (23 patients) or MVP (23 patients) were retrieved for matched pair analysis. Mean age was 70 years in all groups, log European system for cardiac operative risk evaluation (EuroSCORE) was 22.47% ± 16.30 in MVR after MitraClip (MC), 22.34% ± 16.23 in MVP, and 22.33% ± 16.14 in MVR group. Preoperative left ventricular ejection fraction (LVEF) was 44%, and postoperative LVEF was 48% in all groups. The 30-day mortality was 21.7% in the MitraClip group whereas it was 4.3% in the MVR and 13.0% in the MVP group. The 1-year survival was 56.5% in the MitraClip group while it was 95.6% in the MVR group and 82.6% in the MVP group (Wilcoxon test: p = 0.007; chi-square test: p = 0.001 MitraClip vs. MVR; p = 0.054 MitraClip vs. MVP). Patients requiring surgical MVR after the previous MitraClip fared worse than matched cohorts receiving primary MVR or MVP. Indication for MitraClip should, therefore, be made very cautiously given the excellent results gained with primary surgery.


[Treatment of fractures of the mandible: a new type of external fixator].
The use of external fixators in the treatment of complex mandibular fractures is described, as are the advantages offered by the technique which permits accurate, controlled reduction of the bone fragment without immobilising the temporomandibular joint.


Unveiling microbial life in the new deep-sea hypersaline Lake Thetis. Part II: a metagenomic study.
So far only little is known about the microbial ecology of Mediterranean deep-sea hypersaline anoxic lakes (DHALs). These brine lakes were formed by evaporite dissolution/brine seeps and are important model environments to provide insights into possible metabolisms and distributions of microorganisms on the early Earth. Our study on the Lake Thetis, a new thalassohaline DHAL located South-East of the Medriff Corridor, has revealed microbial communities of contrasting compositions with a high number of novel prokaryotic candidate divisions. The major finding of our present work is co-occurrence of at least three autotrophic carbon dioxide fixation pathways in the brine-seawater interface that are likely fuelled by an active ramified sulphur cycle. Genes for the reductive acetyl-CoA and reductive TCA pathways were also found in the brine suggesting that these pathways are operational even at extremely elevated salinities and that autotrophy is more important in hypersaline environments than previously assumed. Surprisingly, genes coding for RuBisCo were found in the highly reduced brine. Three types of sulphide oxidation pathways were found in the interface. The first involves a multienzyme Sox complex catalysing the complete oxidation of reduced sulphur compounds to sulphate, the second type recruits SQR sulphide:quinone reductase for oxidation of sulphide to elemental sulphur, which, in the presence of sulphide, could further be reduced by polysulphide reductases in the third pathway. The presence of the latter two allows a maximal energy yield from the oxidation of sulphide and at the same time prevents the acidification and the accumulation of S(0) deposits. Amino acid composition analysis of deduced proteins revealed a significant overrepresentation of acidic residues in the brine compared with the interface. This trait is typical for halophilic organisms as an adaptation to the brine's extreme hypersalinity. This work presents the first metagenomic survey of the microbial communities of the recently discovered Lake Thetis whose brine constitutes one of saltiest water bodies ever reported.


Does endorsement of the disease concept of alcoholism predict humanitarian attitudes to alcoholics?
It has been widely assumed that the disease concept of alcoholism is a powerful vehicle for the promotion of humanitarian attitudes to alcoholics. However, Crawford and Heather have argued that individual differences in attitudes to alcoholics are liable to be a reflection of broader attitudes to deviancy rather than a function of endorsement/rejection of a disease conception. This argument was subjected to empirical scrutiny by means of a questionnaire distributed to 200 members of the public. The questionnaire (1) measured attitudes to four deviant groups--alcoholics, drug addicts, compulsive gamblers, and juvenile delinquents--and (2) recorded whether respondents endorsed or rejected a disease conception of these deviant conditions. Attitudes to the non-alcoholic deviant groups were better predictors of humanitarian attitudes to alcoholics than was endorsement of a disease conception of alcoholism.


Combinatorial quantification of distinct neural projections from retrograde tracing.
Comprehensive quantification of neuronal architectures underlying anatomical brain connectivity remains challenging. We introduce a method to identify the distinct axonal projection patterns from a source to a set of target regions and the count of neurons with each pattern. For a source region projecting to n targets, there are 2n - 1 theoretically possible projection types, although only a subset of these types typically exists. By injecting uniquely labeled retrograde tracers in k regions (k < n), one can experimentally count the cells expressing different combinations of colors in the source region1,2. Such an experiment can be performed for n choose k combinations. The counts of cells with different color combinations from all experiments provide constraints for a system of equations that include 2n - 1 unknown variables, each corresponding to the count of neurons for a projection pattern. Evolutionary algorithms prove to be effective at solving the resultant system of equations, thus allowing the determination of the counts of neurons with each of the possible projection patterns. Numerical analysis of simulated 4 choose 3 retrograde injection experiments using surrogate data demonstrates reliable and precise count estimates for all projection neuron types. We illustrate the experimental application of this framework by quantifying the projections of mouse primary motor cortex to four prominent targets: the primary and secondary somatosensory and motor cortices.


Effect of thalidomide in different tumors in rodents.
This study investigated the effects of chronic administration of thalidomide on three different neoplasms of ectodermic origin in rodents: 1) chemically induced tumors of the nervous system of rats by transplacental exposure to ethylnitrosourea; 2) transplanted RPMI-1846 melanoma in hamsters and 3) transplanted C6 glioblastoma in rats. No effects were seen on thalidomide-treated rats on the frequency- and time of tumor development induced by ethylnitrosourea. In contrast, a reduction in tumoral growth and mitotic-index was obtained in animals treated with thalidomide in transplanted tumors, melanoma and glioblastoma, when compared with controls (P < 0.001 and 0.025, respectively). These results suggest that, although thalidomide is not a cytotoxic drug for neoplastic cells, it might partially inhibit the tumoral growth through any of its pharmacological actions; by blockage of cell-surface adhesion receptors induction of DNA oxidation, or inhibition of angiogenesis. Further investigations on the use of thalidomide perhaps associated to cytotoxic drugs, for treatment of ectodermic neoplasms seem guaranteed.


In vivo and in vitro anti-inflammatory activity of Cryptostegia grandiflora Roxb. ex R. Br. leaves.
Despite Cryptostegia grandiflora Roxb. ex R. Br. (Apocynaceae) leaves are widely used in folk Caribbean Colombian medicine for their anti-inflammatory effects, there are no studies that support this traditional use. Therefore, this work aimed to evaluate the effect of the total extract and primary fractions obtained from Cryptostegia grandiflora leaves, using in vivo and in vitro models of inflammation, and further get new insights on the mechanisms involved in this activity. Ethanolic extract of Cryptostegia grandiflora leaves, and its corresponding ether and dichloromethane fractions, significantly reduced inflammation and myeloperoxidase activity (MPO) in ear tissue of mice treated with 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Histological analysis revealed a reduction of edema and leukocyte infiltration. Complementarily, we demonstrated that extract and fractions reduced nitric oxide (NO•) and prostaglandin E2 (PGE2) production in LPS-stimulated RAW 264.7 macrophages, as well as scavenging activity on DPPH and ABTS radicals. Our results demonstrated for the first time the anti-inflammatory activity of Cryptostegia grandiflora leaves, supporting its traditional use. This activity was related to inhibition of MPO activity, and PGE2 and NO• production. These mechanisms and its antioxidant activity could contribute, at least in part, to the anti-inflammatory effect showed by this plant.


Human LPP gene is fused to MLL in a secondary acute leukemia with a t(3;11) (q28;q23).
The mixed lineage leukemia, MLL, gene is frequently rearranged in patients with secondary leukemia following treatment with DNA topoisomerase II inhibitors. By FISH and Southern blot analyses we identified a rearrangement in the MLL gene due to a novel t(3;11)(q28;q23) chromosomal translocation in a patient who developed AML-M5 3 years after treatment for a follicular lymphoma. Through inverse PCR, the LPP (lipoma preferred partner) gene on 3q28 was identified as the MLL fusion partner. LPP contains substantial identity to the focal adhesion protein, zyxin, and is frequently fused to HMGIC in lipomas. The breakpoint occurred in intron 8 of MLL and LPP. Two in-frame MLL-LPP transcripts, which fuse MLL exon 8 to LPP exon 9, were detected by RT-PCR, although the smaller of these contained a deletion of 120 bp from the MLL sequence. The predicted MLL-LPP fusion protein includes the A/T hook motifs and methyltransferase domain of MLL joined to the two last LIM domains of LPP. A reciprocal LPP-MLL transcript, predicted to include the proline-rich and leucine zipper motifs, and the first LIM domain of LPP were also detected by RT-PCR. In summary, LPP is a newly identified MLL fusion partner in secondary leukemia resulting from topoisomerase inhibitors. The MLL-LPP and LPP-MLL predicted proteins contain many of the features present in other MLL rearrangements.


Romantic relationships and psychological distress among adolescents: Moderating role of friendship closeness.
The formation of romantic relationships and friendships in adolescence is a defining milestone in the progression toward social maturity. Thus, examining adolescents' friendship and romantic experiences serves a vital role in understanding their psychological adjustment. The main purposes of the current study were to examine (a) whether romantic involvement, romantic security, and friendship closeness were independently predictive of late adolescents' depression and loneliness, and (b) whether friendship closeness would moderate the negative effects of adolescents' lower degrees of romantic involvement and romantic security on depression and loneliness. Data came from 12th grade adolescents (N = 110, 53 females) as well as their parents and a same-sex best friend. Adolescents reported on their romantic involvement, romantic security, and psychological distress. Parent reports of adolescents' depressive symptoms and friend reports of friendship closeness were also included. Higher degrees of romantic involvement and friendship closeness were related to lower degrees of loneliness. Higher degrees of romantic security were related to lower degrees of depression and loneliness. The effect of romantic involvement on depression and loneliness was moderated by friendship closeness. Also, the effect of romantic security on loneliness was moderated by friendship closeness. Future research should focus on the interactive roles that friendships and romantic relationships play in the emergence of psychopathology during adolescence.


[Swimming-induced pulmonary oedema].
Swimming-induced pulmonary oedema (SIPE) is a rare condition, where hemodynamic changes associated with immersion in water and swimming induces pulmonary oedema. Here, we report a case with a 57-year old very fit female triathlete experiencing critical lung edema during low intensity open water swimming. We speculate, that SIPE in this particular patient was caused by a combination of factors: 1) Stress-induced diastolic dysfunction, 2) tendency to vasoconstriction upon stress and 3) possibly paroxysmal atrial fibrillation induced by increased atrial pressure during the event.


Determination of tissue optical properties in PDT treated Head & Neck patients.
Determination of optical properties (absorption (μa) and scattering (μs') coefficients) in human tissue is important when it comes to accurate calculation of fluence rate in and around tissue area. ALA application to the tissue induces production of protoporphyrin IX when activated by red light. Changes in the tissue optical properties can send information such as treatment outcome and tissue drug concentration. Patients in this study were treated with PDT for head and neck mucosal dysplasia. They were enrolled in a phase I study of escalating light doses and oral ALA with 60mg/kg. Red light at 630nm was administered to the tumor from a laser. The light dose was escalated from 50-200J/cm2 with a measured fluence rate at tissue surface of 100mW/cm2. We developed a light detection device for the purpose of determining optical properties in vivo using the semi-infinite method. The light detection device consists of two parallel, placed 5mm apart. In one of the catheters a 2 mm long linear diffusing light source is placed while in the second catheter, a calibrated isotropic detector is placed. The detector is scanned along the length of the light source containing catheter. Scans are done with the device placed on the treatment area (tumor) and on the normal tissue. Optical properties were measured in-vivo before and after PDT delivery for both normal tissue and tumor.


Theoretical in-Solution Conformational/Tautomeric Analyses for Chain Systems with Conjugated Double Bonds Involving Nitrogen(s).
Conformational/tautomeric transformations for X=CH-CH=Y structures (X = CH2, O, NH and Y = NH) have been studied in the gas phase, in dichloromethane and in aqueous solutions. The paper is a continuation of a former study where s-cis/s-trans conformational equilibria were predicted for analogues. The s-trans conformation is preferred for the present molecules in the gas phase on the basis of its lowest internal free energy as calculated at the B97D/aug-cc-pvqz and CCSD(T)CBS (coupled-cluster singles and doubles with non-iterative triples extrapolated to the complete basis set) levels. Transition state barriers are of 29-36 kJ/mol for rotations about the central C-C bonds. In solution, an s-trans form is still favored on the basis of its considerably lower internal free energy compared with the s-cis forms as calculated by IEF-PCM (integral-equation formalism of the polarizable continuum dielectric solvent model) at the theoretical levels indicated. A tetrahydrate model in the supermolecule/continuum approach helped explore the 2solute-solvent hydrogen bond pattern. The calculated transition state barrier for rotation about the C-C bond decreased to 27 kJ/mol for the tetrahydrate. Considering explicit solvent models, relative solvation free energies were calculated by means of the free energy perturbation method through Monte Carlo simulations. These calculated values differ remarkably from those by the PCM approach in aqueous solution, nonetheless the same prevalent conformation was predicted by the two methods. Aqueous solution structure-characteristics were determined by Monte Carlo. Equilibration of conformers/tautomers through water-assisted double proton-relay is discussed. This mechanism is not viable, however, in non-protic solvents where the calculated potential of mean force curve does not predict remarkable solute dimerization and subsequent favorable orientation.


Demonstration of Mycobacterium leprae specific antigens in leprosy lesions using monoclonal antibodies.
Cryostat sections of dermal lesions from 13 untreated patients of leprosy were studied by indirect immunoperoxidase using monoclonal antibodies (MLO4 & MLO6), defining M. leprae specific antigens. The lymphocytes and macrophages in both the tuberculoid and lepromatous granulomas showed membranous staining with the above antibodies. M. leprae organisms in the lepromatous granulomas and the cells in the section of lymph nodes of patients with tuberculosis, or sections of normal skin or psoriatic lesions did not show any staining with these antibodies. These observations suggest that M. leprae specific antigens are present and expressed on the cells infiltrating the granulomas of leprosy lesions.


Hydrocapacitor for Harvesting and Storing Energy from Water Movement.
Based on porous carbon nanotube/polyaniline composite (CNT/PANI) and poly(vinyl alcohol) gel, we fabricated centimeter-sized hydrocapacitors with dual functions of energy conversion and storage with an efficient low-cost method. Owning to excellent hydrophily and large specific capacitance of CNT/PANI, the hydrocapacitors can easily convert energy from water movement induced by capillarity, gravity, or air pressure difference into electricity and store the generated electricity. Especially, sandwich-like hydrocapacitors outputted large current of 1.65 mA through an external load of 100 Ω, and hydrocapacitors showed good extendibility by connecting in series. To explain the mechanism of hydrocapacitors in this work, a possible model based on capillarity and traditional streaming potential was proposed and discussed. Hydrocapacitors here also provide a reference for future integration of nanogenerators and energy storage parts.


The Role of Professional Journals and Societies in the Future of a Field: A Reflection on the Partnership Between the American Journal of Epidemiology and the Society for Epidemiologic Research.
On this, the 100th anniversary of Johns Hopkins Bloomberg School of Public Health, we take the opportunity to reflect on the ties between the School, the American Journal of Epidemiology, and the Society for Epidemiologic Research. We discuss briefly the intersection of the School, the Journal, and the Society throughout their histories, with the aim of providing some insight into how the Journal and the Society have contributed to the evolution of the field. In so doing, we articulate the challenges that the Journal and the Society jointly face today, with an eye to finding opportunities in these challenges that can be helpful in coming decades.


Plasma Transthyretin as A Biomarker of Sarcopenia in Elderly Subjects.
Skeletal muscle (SM) mass, the chief component of the structural compartment belonging to lean body mass (LBM), undergoes sarcopenia with increasing age. Decreased SM in elderly persons is a naturally occurring process that may be accelerated by acute or chronic nutritional deficiencies and/or inflammatory disorders, declining processes associated with harmful complications. A recently published position paper by European experts has provided an overall survey on the definition and diagnosis of sarcopenia in elderly persons. The present review describes the additional contributory role played by the noninvasive transthyretin (TTR) micromethod. The body mass index (BMI) formula is currently used in clinical studies as a criterion of good health to detect, prevent, and follow up on the downward trend of muscle mass. The recent upsurge of sarcopenic obesity with its multiple subclasses has led to a confused stratification of SM and fat stores, prompting workers to eliminate BMI from screening programs. As a result, investigators are now focusing on indices of protein status that participate in SM growth, maturation, and catabolism that might serve to identify sarcopenia trajectories. Plasma TTR is clearly superior to all other hepatic biomarkers, showing the same evolutionary patterns as those displayed in health and disease by both visceral and structural LBM compartments. As a result, this TTR parameter maintains positive correlations with muscle mass downsizing in elderly persons. The liver synthesis of TTR is downregulated in protein-depleted states and suppressed in cytokine-induced inflammatory disorders. TTR integrates the centrally-mediated regulatory mechanisms governing the balance between protein accretion and protein breakdown, emerging as the ultimate indicator of LBM resources. This review proposes the adoption of a gray zone defined by cut-off values ranging from 200 mg/L to 100 mg/L between which TTR plasma values may fluctuate and predict either the best or the worst outcome. The best outcome occurs when appropriate dietary, medicinal and surgical decisions are undertaken, resuming TTR synthesis which manifests rising trends towards pre-stress levels. The worst occurs when all therapeutic means fail to succeed, leading inevitably to complete exhaustion of LBM and SM metabolic resources with an ensuing fatal outcome. Some patients may remain unresponsive in the middle of the gray area, combining steady clinical states with persistent stagnant TTR values. Using the serial measurement of plasma TTR values, these last patients should be treated with the most aggressive and appropriate therapeutic strategies to ensure the best outcome.


Mean field approach for describing thin film morphology.
A mean field approach is employed for determining the kinetics of two main quantities for film morphology, namely the number of islands and the film perimeter. These two quantities have been computed for both coalescence and impingement growth regimes. For each case the growth of two- and three-dimensional islands has been considered. In addition, the effect of the spatial correlation among nuclei has been taken into account on the grounds of the hard core interaction. Analytic formulae have been derived for each case.


Role of the SulB (FtsZ) protein in division inhibition during the SOS response in Escherichia coli: FtsZ stabilizes the inhibitor SulA in maxicells.
Induction of the SOS response in Escherichia coli by DNA-damaging treatments results in the synthesis of the SulA polypeptide, and this is sufficient to cause the resulting inhibition of cell division. Mutations at either sulA (sfiA) or sulB (sfiB) suppress this division inhibition. The SulB protein is identical to FtsZ, a protein required for normal division in E. coli. In the presence of FtsZ, the half-life of SulA synthesized in maxicells is approximately 12 min. In contrast, in the absence of FtsZ or in the presence of a mutant form of FtsZ (SulB114) that prevents division inhibition in vivo, SulA is extremely unstable with a half-life of only 3 min. Both FtsZ and SulA are isolated with the inner membrane of E. coli maxicells in the presence of MgCl2. We propose that the SulA inhibitor interacts directly with FtsZ in vivo to block the essential division function of this protein.


Transduction of a functional domain of the AT1 receptor in neurons by HIV-Tat PTD.
Despite advances in transgenic and gene transfer technologies, in vivo structure-function studies of the angiotensin II type I receptor (AT1R) have revealed limited information on the diverse actions of angiotensin II. Our objective in the present study was to determine if protein transduction technology with the use of the HIV-Tat protein transduction domain could fill this gap. Recombinant HIV-Tat protein transduction domain fused to EGFP and to the third intracellular loop of the AT1R was expressed. Incubation of hypothalamus and brainstem neurons with this peptide indicated an efficient transport of the protein to most of the cells. This transduction was accompanied by an increase in neuronal firing rate, an effect similar to that observed with angiotensin II stimulation of the neuronal AT1R. The characteristics of the chronotropic effects of recombinant third intracellular loop and its synthetic counterpart were similar and comparable to the effects of angiotensin II on these neurons. In addition, in the presence of the protein kinase C inhibitor calphostin C, the peptide failed to increase firing rate. These observations demonstrated that transduction of neurons with the third intracellular loop of the AT1R produces chronotropic effects similar to those induced by angiotensin II. The data suggests that protein transduction technology could be useful for in vivo AT1R domain transduction.


Photodegradation of bisphenol A in Fe(III)-oxalate complexes solution.
The aqueous photodegradation of bisphenol A (BPA) in the presence of Fe(III)-oxalate complexes (Fe(III)-Ox), which are common compositions of natural water, was investigated in this study. BPA underwent rapid indirect photolysis in Fe(III)-Ox solution under simulated solar irradiation, proceeding pseudo-first-order kinetics. The photolysis rate increased with decreasing pH or initial BPA level and increasing Fe(III)/oxalate concentration ratio. Hydroxyl radicals (*OH), which were generated from the photochemical processes of Fe(III)-Ox complexes and contributed to the photooxidation of BPA, were determined by molecular probe and electron spin resonance (ESR) methods with the steady-state concentration of 2.56 x 10(-14) mol/L. Superoxide anion radical (O2*-) was considered as the precursor of *OH and qualitatively determined by adding nitro blue tetrazolium as well as ESR experiments. Based on the structural analysis of the intermediate photoproducts of BPA in Fe(III)-Ox complexes solution, the possible degradation pathways of BPA were proposed, involving *OH addition, alkyl scission and alky oxidation. The results indicate that the photochemical reactivity of Fe(III) may affect the environmental fate of BPA in natural water significantly.


Healthy Eating and Barriers Related to Social Class. The case of vegetable and fish consumption in Norway.
The article examines the constraints on healthy eating by exploring whether barriers such as taste, competence, time, price, quality and limited selection reduce consumption of vegetables and fish among Norwegians. In order to understand the socio-economic gradient of healthy diets, the study examines how these barriers are related to specific class positions. Regular consumption of both fish and vegetables are recommended by health authorities, and they are broadly perceived as healthy foods by Norwegians. Nevertheless, more than half of the population consumes vegetables less frequently than daily, and the average consumption of fish is far below the recommended two to three dinner portions of fish on a weekly basis. Informed by Bourdieu's theories of social class, this article argues for two overarching barriers related to food consumption, food knowledge and perceived food quality by consumers, and it finds that barriers are tied to scarcity of cultural, economic and social capital. A survey of 2000 respondents subjected to multiple linear regression analysis and factor analysis (PCA) provides the evidence for this study.


A priori assumptions about characters as a cause of incongruence between molecular and morphological hypotheses of primate interrelationships.
When molecules and morphology produce incongruent hypotheses of primate interrelationships, the data are typically viewed as incompatible, and molecular hypotheses are often considered to be better indicators of phylogenetic history. However, it has been demonstrated that the choice of which taxa to include in cladistic analysis as well as assumptions about character weighting, character state transformation order, and outgroup choice all influence hypotheses of relationships and may positively influence tree topology, so that relationships between extant taxa are consistent with those found using molecular data. Thus, the source of incongruence between morphological and molecular trees may lie not in the morphological data themselves but in assumptions surrounding the ways characters evolve and their impact on cladistic analysis. In this study, we investigate the role that assumptions about character polarity and transformation order play in creating incongruence between primate phylogenies based on morphological data and those supported by multiple lines of molecular data. By releasing constraints imposed on published morphological analyses of primates from disparate clades and subjecting those data to parsimony analysis, we test the hypothesis that incongruence between morphology and molecules results from inherent flaws in morphological data. To quantify the difference between incongruent trees, we introduce a new method called branch slide distance (BSD). BSD mitigates many of the limitations attributed to other tree comparison methods, thus allowing for a more accurate measure of topological similarity. We find that releasing a priori constraints on character behavior often produces trees that are consistent with molecular trees. Case studies are presented that illustrate how congruence between molecules and unconstrained morphological data may provide insight into issues of polarity, transformation order, homology, and homoplasy.


Enzymatic cis-Decalin Formation in Natural Product Biosynthesis.
Stereoselective synthesis of cis-decalin structures using [4 + 2] cycloaddition is challenging. We explored the biosynthetic pathway of the fungal natural product fischerin (1) to identify a new pericyclase FinI that can catalyze such a reaction. The cocrystal structure of FinI, a predicted O-methyltransferase, with the product and SAM provides insight into cis-decalin formation in nature.


Identification and nucleotide sequence of the promoter region of the Bacillus subtilis gluconate operon.
The nucleotide sequence (742 bp) of the promoter region of the Bacillus subtilis gluconate (gnt) operon is presented. Nuclease Sl mapping revealed the start point of the transcription and suggested that the expression of this operon is probably regulated at the transcriptional level. The sequences of the -35 and -10 regions suggested that RNA polymerase possessing sigma-43 may recognize this structure. The 223 bp fragment containing 100 bp upstream from the transcription start site actually exhibited a promoter activity when cloned in a promoter probe vector of pPL603B. This promoter activity was highly derepressed and although still under catabolite repression. The fragment on a high copy plasmid could titrate a regulator of the gnt operon so that the expression of the operon on the host chromosome also became derepressed.


Alcohol exacerbates the association between partner-related issues regarding condom use and condomless anal receptive sex among young Black men who have sex with men.
This study determined associations between a three-item measure of partner-related issues regarding condom use (PRI-CU) and recent condomless anal sex among a sample of young Black men who have sex with men (MSM). Of 172 men indicating an absence of PRI-CU, 10.5% reported recent condomless anal receptive sex (CARS). In contrast, of 122 men indicating recent PRI-CU, 23.8% reported CARS (P = 0.002). Drunkenness during sex exacerbated this association; however, being high during sex conferred a protective value against the association between PRI-CU and CARS. Alcohol use during sex may magnify the potential for PRI-CU to result in CARS among MSM. Conversely, marijuana use may have the opposite effect.


Metabolic mechanisms of stress hyperglycemia.
Stress hyperglycemia has gained the attention of virtually every physician who encounters critically ill patients, with the emergence of clinical data supporting tight glycemic control and intensive insulinization for optimal outcome. In order to effectively manage stress hyperglycemia, newer theories of critical illness and the interactions of the brain, neuroendocrine axis, and immune system need to be explored. Nonlinear physiologic processes, glucose allostasis, immune-neuroendocrine axis activation, and molecular mechanisms of insulin receptor signal transduction contribute to a novel model of stress hyperglycemia. In chronic critical illness, allostatic overload leads to a plurality of organ-system derangements and eventually death. Intervention not only involves insulinization according to neurofuzzy logic but also targeting more proximate events with cognitive/behavioral therapy and hypothalamic releasing factors.


[Relationship between heart rate variability and serum levels of thyroid hormones, cortisol and prognosis in patients with systemic inflammatory response syndrome].
To explore the relationship of autonomic nerve system regulation function in patients with systemic inflammatory response syndrome (SIRS) to hypothalamo-pituitary-adrenal axis and to find useful markers to predict the prognosis of patients with SIRS. Acute physiology and chronic health evaluation II (APACHE II) and multiple organ dysfunction syndrome (MODS) scores were obtained and heart rate variability (HRV) was analyzed with both time-domain and frequency-domain methods. The serum levels of thyroid hormone and cortisol (COR) were measured by radio-immunoassay. (1) The patients with SIRS showed significantly higher APACHE II scores and MODS scores but lower HRV when compared with the non-SIRS patients and control group (P<0.05 or P<0.01). In addition, in the SIRS group, the non-survivors were found to have statistically higher APACHE II and MODS scores as well as lower HRV than the survivors (all P<0.01). (2) Multiple regression analysis revealed that there was a negative correlation between the outcome of the patients and standard differentiation of NN interval (SDNN), and there was a positive correlation between the outcome of the patients and APACHE II and MODS scores (P<0.01 and P<0.05). The correction rates of prediction in good or bad outcome were 81.1% and 74.5%, respectively. SDNN<or=55 ms may be the prognostic threshold value, and the sensitivity, specification, positive and negative prediction values were 76.2%, 76.7%, 90.4% and 52.6% respectively. (3) The patients with SIRS showed lower thyroid hormone levels of triiodothyronine(T3), tetraiodothyronine(T4), thyroid stimulating hormone(TSH), and higher concentration of COR compared with the non-SIRS patients and healthy controls, and they were correlated with the prognosis of the patients (P<0.05 or P<0.01). (4) In the SIRS group there were positive correlations between concentrations of T3, TSH and HRV, and opposite results were also obtained between the HRV and the concentration of COR, showing negative correlation (P<0.05 or P<0.01). (5) In the death group, there were positive correlations between concentrations of T3, T4, TSH and HRV (P<0.01 or P<0.05). Also in this group, there were positive correlations between MODS scores and COR, but negative correlation between COR and SDNN (P<0.05 or P<0.01). Evidently the neuroendocrine system exerts significant influences on the severity of disease, function of organs and prognosis. SDNN, concentration of COR, APACHE II and MODS scores were the useful indexes to evaluate the prognosis of the patients with SIRS.


Inhibition of CK2 activity by TGF-beta1 promotes IkappaB-alpha protein stabilization and apoptosis of immortalized hepatocytes.
Nuclear factor kappaB (NF-kappaB) is an antiapoptotic factor involved in development, regeneration, and neoplastic progression of the liver. Previously, we have shown that stabilization of inhibitor kappaB (IkappaB)-alpha protein following treatment of hepatocytes with transforming growth factor (TGF)-beta1 promoted NF-kappaB repression, which then permitted induction of AP-1/SMAD-mediated liver cell death. Because basal IkappaB-alpha protein turnover is regulated by protein kinase CK2, here we have elucidated the regulation of CK2 kinase activity and its role in control of NF-kappaB levels following treatment with TGF-beta1. We show that both messenger RNA (mRNA) and protein levels of the CK2alpha catalytic subunit are down-regulated following TGF-beta1 stimulation in murine hepatocyte cells. The ensuing inhibition of CK2 kinase activity promotes stabilization of IkappaB protein, which is followed by the shutoff of constitutive NF-kappaB activity and induction of apoptosis. Ectopic expression of CK2alpha inhibits TGF-beta1-induced apoptosis through sustained activation of NF-kappaB. Conversely, expression of a kinase-dead mutant of CK2alpha potentiates TGF-beta1 cell killing. Importantly, we show that hepatocellular carcinomas (HCCs) derived from TGF-beta1 transgenic mice and human HCC cell lines display enhanced CK2 IkappaB kinase activity that contributes in part to an elevated NF-kappaB activity in vivo. In conclusion, inhibition of CK2 expression levels by TGF-beta1 is crucial for the induction of apoptosis of hepatocytes. Circumvention of this process by up-regulation of CK2 activity in transformed cells may contribute to the promotion of TGF-beta1-induced liver carcinogenesis.


The Shear Stress Determination in Tubular Specimens under Torsion in the Elastic-Plastic Strain Range from the Perspective of Fatigue Analysis.
The comparison of shear stress determination methods in tubular specimens under torsion is presented in this paper. Four methods were analyzed: purely elastic solutions, purely plastic solutions, the midsection approach, and the Chaboche nonlinear kinematic hardening model. Using experimental data from self-designed and conducted fatigue experiments, an interesting insight on this problem was obtained that is not often tackled in the literature. It was shown that there are differences in determined shear stress values, and their level depends on a few factors. The midsection approach and purely plastic solution gave values of surface shear stress very close to the values obtained using the Chaboche nonlinear kinematic hardening model for high strain levels. The purely elastic solution gave proper results for the low strain ranges, close to the cyclic yield limit. Since none of the methods can be trusted in the full range of loading, an important conclusion from these analyses regards the formulated ranges of their applicability. It was also shown that the calculated values of shear stress and plastic and elastic strain energy density determined on this basis have a strong impact on fatigue life predictions. Finally, the influence of predicted values of shear stresses on the interpretation of cyclic hardening phenomena was also presented.


Construction of hierarchical nanostructured TiO2/Bi2MoO6 heterojunction for improved visible light photocatalysis.
In this study, Bi2MoO6 hollow microspheres were modified by depositing TiO2 nanoparticles through a simple hydrothermal method. The prepared TiO2/Bi2MoO6 photocatalysts were characterized by scanning and transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy and UV-vis diffuse reflectance spectroscopy. The photocatalytic performance of the heterostructured catalysts was evaluated by degradation of methylene blue (MB) under visible-light irradiation (lambda>420 nm). The photocatalysts based on nanostructured Bi2MoO6 and TiO2 exhibit much higher photocatalytic activity than the single-phase Bi2MoO6 or TiO2 and the mechanical mixture of Bi2MoO6 and TiO2 for degradation of MB under the same conditions. The results reported in this study provide insight into constructing other heterostructured photocatalysts.


A Hop Extract Lifenol® Improves Postmenopausal Overweight, Osteoporosis, and Hot Flash in Ovariectomized Rats.
In order to assess the effectiveness of a hop extract (HE) for postmenopausal symptoms, the effects of Lifenol on ovariectomy-induced osteoporosis, hyperlipidemia, body weight increase, and hot flash were investigated in rats. Female Sprague-Dawley rats were ovariectomized and subjected to a daily scheduled exercise training (15 min at 15 m/min) or treated with HE (30 or 100 mg/kg, oral) or 17β-estradiol (100 μg/kg, intraperitoneal) for 12 weeks. Body and visceral fat weights, serum lipid profiles, osteoporotic parameters in serum, and femoral bones were analyzed. Separately, forced running-induced dermal and rectal temperatures and blood flow velocity were measured in ovariectomized rats. Ovariectomy increased blood lipids including triglycerides, total cholesterol, and low-density lipoproteins, leading to visceral fat accumulation and overweight. Estrogen depletion caused osteoporosis, displaying decreased femoral bone weight, bone mineral density and content, and blood phosphorus level. The disturbances in lipid metabolism and bone resorption were recovered by treatment with HE in a dose-dependent manner. In addition, HE treatment shortened the duration of forced running-induced alterations in skin and rectal temperatures by reducing blood flow velocity. The results indicate that HE attenuated overweight, osteoporosis, and hot flash in estrogen-deficient animals by regulating blood lipid profile and fat accumulation, blood estrogen and bone resorption factors, and dermal blood flow.


Activation of specific cortical regions by apomorphine: an [15O]H2O PET study in humans.
The purpose of this study was to investigate the functional effects of apomorphine, a non-selective dopamine agonist, on regional neuronal activity using regional cerebral blood flow, measured using [15O]H2O and positron emission tomography (PET), as an index. Eight normal volunteers were scanned twice before and twice after receiving 10 micrograms/kg subcutaneous apomorphine. Apomorphine produced the expected side-effects and endocrine response. Analysis of the PET scans revealed that apomorphine increased regional cerebral blood flow (rCBF), presumably reflecting a change in neuronal activity, in the anterior cingulate, ventral motor cortex and the dorsolateral prefrontal cortex along with a decrease in rCBF in the retrosplenial cingulate region. These regions form a functional network of brain regions modulated by the dopaminergic system.


Microwave Parboiling: Reduction in Process Time, Browning of Rice and Residual Phosphorus Content in the Waste Water.
The conventional prolonged parboiling process results in high operation cost and grain darkening, which may limit consumption. Moreover, residue generation by rice industries is another challenge. The objective of this study was to evaluate the use of microwave irradiation during soaking and gelatinization stages of parboiling rice. Processing time, colorimetric profile, broken and nongelatinized grains, sucrose and glucose content, free 5-hydroxymethyl-2-furfural, and residual phosphorus were evaluated. As the soaking and gelatinization times during microwave treatments increased, the colorimetric parameters increased; however, the values were lower than those with the conventional process. Regardless of soaking time, a decrease in broken and nongelatinized grains was obtained by using the lowest steaming time (5 min). Additionally, lower residual phosphorus content was found in soaking water (10 and 20 min) when using microwave irradiation. Under favorable conditions, a reduction in the levels of broken and nongelatinized grains, residual phosphorus, and color changes was observed, indicating that microwave irradiation may be more beneficial than conventional parboiling. PRACTICAL APPLICATION: Parboiling requires a high volume of water and soaking time, which leads to high costs, underutilization of infrastructures, and high residue in the water after processing. The rapid parboiling process involves the use of microwaves during the soaking and gelatinization stages. The main advantages of the microwave parboiling process include reduced processing time, ranging from 83% to 95%, higher gelatinization, greater yield, reduced darkening, and reduced residual phosphorus in the effluents by 60%. This report can aid industries in streamlining their processes, thereby providing a high-quality, lower cost, and environmentally safe product.


[Prophylactic requirements for sanitary and epidemiological surveillance in dentistry].
The paper outlines the requirements for sanitary-and-epidemiological surveillance to prevent dental diseases. The investigations pose tasks to medical prevention centers to solve the problems in tooth prophylaxis, such as organizational-and-methodological, sanitary-and-educational, health-improving, and others. The sanitary-and-hygienic requirements for therapeutic-and-prophylactic dental facilities are defined. A procedure for keeping a management protocol for the prevention of tooth diseases is described.


The effect of choline and cystine on the utilisation of methionine for protein accretion, remethylation and trans-sulfuration in juvenile shrimp Penaeus monodon.
This 35-d feeding experiment examined in juvenile shrimp Penaeus monodon (3·3 g initial body weight) the effects of methionine (Met), choline and cystine on protein accretion and the activity of two key enzymes of remethylation (betaine-homocysteine methyltransferase; BHMT) and trans-sulfuration (cystathionine β-synthase; CBS). The interaction between Met and choline was tested using semi-purified diets either adequate or limiting (30 or 50 %) in total sulphur amino acid (SAA) content with a constant cystine:Met ratio. The diets contained either basal or excess choline (3 v. 7 g/kg feed). Cystine was added to two other 30 and 50 % Met-limiting diets to adjust the SAA supply to that of the control diet in order to evaluate the interaction between Met and cystine. As expected, N accretion was significantly lower with the SAA-limiting diets but increased back to control levels by the extra choline or cystine, demonstrating their sparing effect on Met utilisation for protein accretion. We show, for the first time, the activities of BHMT and CBS in shrimp hepatopancreas. Only BHMT responded to the SAA deficiencies, whereas the extra choline and cystine did not stimulate remethylation or down-regulate trans-sulfuration. Our data also suggest the capacity of P. monodon to synthesise taurine, being significantly affected by the cystine level in the 30 % SAA-limiting diets. Further research is warranted to better understand the metabolic regulation of taurine synthesis in shrimp and of the observed Met-sparing effects.


Dopamine transporter binding in the rat striatum is increased by gestational, perinatal, and adolescent exposure to heptachlor.
Heptachlor is a persistent cyclodiene pesticide that affects GABAergic function. Recent reports indicate that heptachlor exposure also alters dopamine transporter (DAT) expression and function in adult mice. The aim of this study was to determine whether gestational, perinatal, and/or adolescent heptachlor exposure in rats altered dopamine-receptor and DAT binding. Adolescent exposure to dieldrin was included to evaluate the generality of the findings. Sprague-Dawley rats received doses (po) ranging from 0 to 8.4 mg/kg/day of heptachlor, or dieldrin, 3 mg/kg/day, during different developmental periods. There were dose-related decreases in maternal weight gain and pup survival, as well as delayed righting reflex, at heptachlor doses > or =3 mg/kg/day. There were no changes in striatal dopamine receptor-D1 ([(3)H]SCH-23390) and -D2 ([(3)H]spiperone) binding in preweanling pups exposed perinatally to heptachlor, and no differences in the response of adult rats to the motor activity-increasing effects of d-amphetamine. However, there were significant (27-64%) increases in striatal DAT binding of [(3)H]mazindol in preweanling rats exposed only gestationally. In rats exposed perinatally and/or during adolescence, there were also increases (34-65%) in striatal DAT binding at postnatal days (PND) 22, 43, and 128. Adolescent exposure to dieldrin also increased DAT binding. In other rats exposed perinatally and throughout adolescence, even the lowest dose of heptachlor 0.3 mg/kg/d increased DAT binding on PND 130. The DAT affinity for mazindol was unchanged in heptachlor-exposed striata. In vitro binding studies indicated that heptachlor (> or =10 microM) displaced mazindol binding. Thus, gestational, perinatal, and/or adolescent exposure to heptachlor produced an increase in DAT binding as early as PND 10, and this change persisted into adulthood.


[Use of plasmakinetics vessel sealing vs suture material in abdominal total hysterectomy].
To compare the safety and efficacy of the use of bipolar plasmakinetic vessel sealing versus standard technique when performing total abdominal hysterectomy for benign disease. Controlled randomized trial involving 94 women who underwent total abdominal hysterectomy. Fourty seven procedures were performed using bipolar plasmakinetics vessel sealing and the remaining 47 with the standard suture technique. The primary outcomes were improvement in terms of blood loss, procedure time, hospital length of stay, and overall cost of the procedure. Statistical methodology considered significant p < 0.05. Mean operational time was shorter with bipolar vessel sealing duration of 82 minutes (range 78-85) versus 99 minutes (range 93-104) with standard technique; (p < 0.001). Days in hospital for the bipolar vessel sealing group was 2.06 days (range 2-2.1), versus 3.2 days (range 2.9-3.4), (p < 0.001), estimated blood loss of 209 mL (range 182-235) as compared to the standard group with 330 mL(range 297-362) (p < 0.003), there was a significant difference in terms of overall cost with bipolar vessel sealing as compared to the standard technique (p < 0.001).The incidence of perioperative complications was similar. Women who underwent the procedure with bipolar plasmakinetics vessel sealing showed a significant reduction in blood loss, operative time, length of stay, and also a decrease in the final cost of the procedure.


Autonomy in practice.
When the nurse practitioner (NP) role was first described in the early 1960s it was clear that important dimensions had been added to the role of the nurse. One of these dimensions was the increased professional autonomy. As the NP role continued to evolve, autonomy became a characterizing feature of the role. the purpose of this paper is to present basic assumptions concerning automony and its relationship to the definition of profession; to examine the implications of autonomy to the individual NP, to the nursing profession, and to the health care system; and to offer a model for considering professional autonomy in relation to the NP role.


Electrophysiological indexes of encoding and behavioral indexes of recall: examining relations and developmental change late in the first year of life.
Long-term memory undergoes pronounced development in the latter part of the 1st year. This research combines electrophysiological (event-related potential [ERP]) and behavioral (deferred imitation) measures of encoding and recall, respectively, in an examination of age-related changes in and relations between encoding and recall during this time. In a short-term longitudinal study, infants were exposed to different multistep sequences at 9 and at 10 months. In both phases, they were tested for immediate recognition of the events via ERPs (as an index of encoding), and for recall of them 1 month later. At both ages, infants encoded the events; encoding was more robust at 10 months than at 9 months. After the 1-month delay, infants failed to recall the events experienced at 9 months, but evidenced recall of the events experienced at 10 months. In spite of developmental differences in encoding and recall over this period, indexes of encoding at 9 months were correlated with measures of recall of events experienced at 10 months and tested 1 month later.


[Intestinal permeability in Crohn's disease and effects of elemental dietary therapy].
Enteral intake of non-metabolic monosacharide and disaccharide, followed by measurement of the urinary excretion ratio of the two, is a method used to investigate intestinal permeability. L/R ratio (lactulose/1-rhamnose urinary excretion ratio) is considered an indicator of permeability of the small intestine. An increased L/R ratio is caused by mucosal disorders of the small intestine. The L/R ratio in all patients (n = 92) with Crohn's disease was 0.079 +/- 0.081 (mean +/- S.D.), which was significantly higher than the value in normal controls (0.027 +/- 0.009, n = 20, p < 0.05). In 39 patients with Crohn's disease, we assessed intestinal permeability before after treatment with an elemental diet, and during remission. The L/R ratio was 0.120 +/- 0.092, before treatment and 0.065 +/- 0.097 after treatment (p < 0.05), showing increased intestinal permeability before elemental dietary treatment. During remission, the L/R ratio was 0.035 +/- 0.028; this did not differ significantly from the value obtained after treatment. We conclude that intestinal permeability is useful for investigating disease activity in patients with Crohn's disease.


Human critical power-oxygen uptake relationship at different pedalling frequencies.
Critical power (CP) is lower at faster rather than slower pedalling frequencies and traditionally reported in watts (W). Faster pedalling frequencies also engender a greater metabolic rate (VO2) at low work rates, but with progressive increases in power output, the initial difference in VO2 between fast and slower pedalling frequencies is reduced. We tested the hypothesis that CP represents a unique metabolic rate for any given individual which would be similar at different pedalling frequencies. Eleven collegiate athletes (five cross-country runners, END; six sprinters, SPR), aged 18-23 years, performed exhaustive rides at either 60 or 100 r.p.m. on separate days for the determination of the pedal rate-specific CP. The VO2 at CP (CP-VO2) was determined from an 8 min ride at the CP for each pedal frequency. The group mean CP was significantly lower at 100 r.p.m. (189 +/- 50 W) compared to 60 r.p.m. (207 +/- 53 W, P < 0.05). However, the group mean CP-VO2 values at 60 (2.53 +/- 0.60 l min(-1)) and 100 r.p.m. (2.58 +/- 0.53 l min(-1)) were not significantly different. Critical power was significantly higher in the END athletes (242 +/- 50 W at 60 r.p.m.; 221 +/- 56 W at 100 r.p.m.) compared to SPR athletes at both pedal frequencies (177 +/- 38 W at 60 r.p.m.; 162 +/- 27 W at 100 r.p.m., P < 0.05), but the CP-VO2 was not (P > 0.05). However, when the CP-VO2 was scaled to body weight, the END athletes had a significantly greater CP-VO2 (41.3 +/- 4.1 ml min(-1) kg(-1) at 60 r.p.m.; 40.8 +/- 5.5 ml min(-1) kg(-1) at 100 r.p.m.) compared to the SPR athletes at both pedal frequencies (27.7 +/- 4.6 ml min(-1) kg(-1) at 60 r.p.m.; 29.4 +/- 2.8 ml min(-1) kg(-1) at 100 r.p.m., P < 0.05). We conclude that CP represents a specific metabolic rate (VO2) which can be achieved at different combinations of power outputs and pedalling frequencies.


Altered accumulation of a membrane protein unique to a membrane-deoxyribonucleic acid complex in a dna initiation mutant of Bacillus subtilis.
Membrane-deoxyribonucleic acid complexes (M-bands) have been isolated from Bacillus subtilis by their affinity for crystals of Mg2+-Sarkosyl. The membrane proteins of these complexes were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Comparison of the membrane protein composition of M-band and unfractionated membrane revealed three protein components of 125,000 (mac-1), 57,000 (mac-2), and 42,000 (mac-3) daltons unique to M-band membrane. Growth of a temperature-sensitive dna initiation mutant at the restrictive temperature resulted in an accumulation in the membrane of mac-2. This accumulation did not begin, however, until cell growth had nearly ceased, some 3 to 4 h after the cessation of deoxyribonucleic acid synthesis. Upon return of the mutant to the permissive temperature, mac-2 did not begin to return to normal levels until after the first round of deoxyribonucleic acid synthesis. A protein of 30,000 daltons, common to both M-band and whole membrane, was found to disappear from the membrane when the mutant was grown at the restrictive temperature. This disappearance is the result of increased degradation or removal from the membrane followed by a decreased rate of synthesis or insertion.


A conserved RAS/mitogen-activated protein kinase pathway regulates DNA damage-induced cell death postirradiation in Radelegans.
Although the epidermal growth factor receptor (EGFR) signaling pathway is overactive in more than half of human cancers and mediates resistance to cytotoxic therapy, the molecular mechanisms of EGFR pathway-mediated resistance have remained elusive in cancer research. This difficulty partly stems from the lack of tissue models enabling clear separation of the many forms of cell death that the downstream signaling pathways of EGFR affect. We have created a model in Caenorhabditis elegans of radiation-induced reproductive cell death ("Radelegans") in isolation of all other forms of cell death. We have employed Radelegans to genetically define the role of the EGFR signaling pathway in protection from reproductive cell death, the primary form of tumor stem or clonogen cell death postirradiation. We have found that the RAS/mitogen-activated protein kinase (MAPK) downstream signal transduction pathway of EGFR is critical for protection from reproductive cell death in Radelegans. In addition, we have shown that RAS/MAPK pathway signaling is genetically linear with the DNA damage response pathway and acts downstream of the DNA damage checkpoint in the radioresponse, implicating this pathway in DNA repair post-cytotoxic therapy. These findings support the hypothesis that enhanced repair is a mechanism of RAS/MAPK pathway-mediated resistance to cytotoxic therapy through its interaction with the DNA damage response pathway postirradiation. We postulate that these findings also help explain why current treatment strategies, based on the presumption that tumors have ineffective repair compared with normal tissues, are ineffective in EGFR/RAS/MAPK pathway-mediated tumors. Radelegans is a platform to further define the genetic basis of the radiation response in tissues.


Expression of Amyloid Precursor Protein, Caveolin-1, Alpha-, Beta-, and Gamma-Secretases in Penumbra Cells after Photothrombotic Stroke and Evaluation of Neuroprotective Effect of Secretase and Caveolin-1 Inhibitors.
Our studies reveal changes in the expression of the main participants in the processing of amyloid precursor protein (APP) in neurons and astrocytes after photothrombotic stroke (PTS). Here we show the increase in the level of N- and C-terminal fragments of APP in the cytoplasm of ischemic penumbra cells at 24 h after PTS and their co-immunoprecipitation with caveolin-1. The ADAM10 α-secretase level decreased in the rat brain cortex on the first day after PTS. Levels of γ-secretase complex proteins presenilin-1 and nicastrin were increased in astrocytes, but not in neurons, in the penumbra after PTS. Inhibitory analysis showed that these changes lead to neuronal death and activation of astrocytes in the early recovery period after PTS. The caveolin-1 inhibitor daidzein shifted APP processing towards Aβ synthesis, which caused astroglial activation. γ-secretase inhibitor DAPT down-regulated glial fibrillary acidic protein (GFAP) in astrocytes, prevented mouse cerebral cortex cells from PTS-induced apoptosis, and reduced the infarction volume. Thus, new generation γ-secretase inhibitors may be considered as potential agents for the treatment of stroke.


Derivatives of 4-methyl-1,2,3-benzoxathiazine 2,2-dioxide as selective inhibitors of human carbonic anhydrases IX and XII over the cytosolic isoforms I and II.
A series of 4-methyl-1,2,3-benzoxathiazine-2,2-dioxides with various substituents in 5, 6 or 7 positions was obtained from corresponding 2'-hydroxyacetophenones in their reaction with sulphamoyl chloride. 6- and 7-aryl substituted 4-methyl-1,2,3-benzoxathiazine-2,2-dioxides were obtained from aryl substituted 2'-hydroxyacetophenonesprepared from 4- or 5-bromo-2'-hydroxyacetophenones via two-step protocol. 4-Methyl-1,2,3-benzoxathiazine-2,2-dioxides were investigated as inhibitors of four human (h) carbonic anhydrase (hCA, EC 18.104.22.168) isoforms, off-target cytosolic hCA I and II, and target transmembrane, tumour-associated hCA IX and XII. Twenty derivatives of 4-methyl-1,2,3-benzoxathiazine 2,2-dioxide were obtained. With one exception (compound2a), they mostly act as nanomolar inhibitors of target hCA IX and XII. Basically, all screened compounds express none or low inhibitory properties towards off-target hCA I. hCA II is inhibited in micromolar range. Overwhelming majority of 4-methyl-1,2,3-benzoxathiazine 2,2-dioxides express excellent selectivity towards CA IX/XII over hCA I as well as very good selectivity towards CA IX/XII over hCA II.


Ultrasound modalities and quantification: developments of multiparametric ultrasonography, a new modality to detect, localize and target prostatic tumors.
An imaging tool providing reliable prostate cancer (PCa) detection and localization is necessary to improve the diagnostic pathway with imaging targeted biopsies. This review presents the latest developments in existing and novel ultrasound modalities for the detection and localization of PCa. The ultrasound modalities that were very promising on introduction (HistoScanning and Doppler) have shown a wane in performance when tested in larger patient populations. In the meantime, novel ultrasound modalities have emerged in the field of PCa detection. Modalities, such as shear wave elastography (SWE) and contrast-enhanced ultrasound (CEUS) show very promising results. SWE produces an absolute elasticity measure and removes the need for manual compression of the tissue. The former allows comparison between scans and patients, the latter reduces the interoperator variability. Quantification of CEUS enables easily interpretable and accurate imaging of the microvascular changes associated with clinically significant prostate tumors. The novel ultrasound modalities of SWE and CEUS imaging open the door for taking targeted biopsies based on the detection and localization of PCa by these novel modalities. This potentially improves PCa detection wherein significantly reducing the number of biopsy cores.


Introduction to Curriculum Development and Medical Education Scholarship for Resident Trainees: A Webinar Series.
A common career aspiration among residents is to become a clinician-educator, though standard postgraduate training may not prepare trainees for the academic and scholarly requirements of this career. To address this need, we designed and implemented an asynchronous, interactive webinar series detailing a systematic approach to medical education research and scholarship. The series was piloted as part of a new track at the University of Chicago for residents interested in additional training and completing an educational learning project in medical education. We aimed to use this series to introduce relevant frameworks in curriculum development, program evaluation, and learning theory. Materials associated with this publication include six webinars and corresponding summary reference handouts, discussion assignments, and answer keys. Additional materials include a faculty course director packet and sample feedback for discussion assignments. Each webinar is an 8- to 20-minute narrated presentation with goals and objectives, an overview of each session's content, and example vignettes. Residents viewed presentations and completed a two-part discussion assignment for each webinar, which included reflection on the educational material and vignettes, faculty feedback on this reflection, and application of webinar material and faculty feedback to their own experiences in medical education. All residents in the pilot completed the webinars and assignments. Residents' reactions to the webinar series have been positive, and residents have commented that self-paced learning with directed faculty feedback is a desirable instructional method for this material. This series is well suited to introduce fundamental concepts in medical education scholarship and inspire self-directed study for motivated learners.


Pseudomonas taeanensis sp. nov., isolated from a crude oil-contaminated seashore.
A novel Gram-negative, aerobic, motile, short rod-shaped bacterium, designated MS-3(T), was isolated from a crude oil-contaminated seashore in Taean, Korea. Strain MS-3(T) grew at 4-30 °C, at pH 6.0-9.5 and with 0-5 % NaCl and was oxidase- and catalase-positive. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain MS-3(T) was most similar to Pseudomonas marincola KMM 3042(T) (97.9 % 16S rRNA gene sequence similarity), P. cuatrocienegasensis 1N(T) (97.8 %), P. borbori R-20821(T) (97.3 %) and P. lundensis ATCC 49968(T) (97.1 %). Relatively low levels of DNA-DNA relatedness were found between strain MS-3(T) and P. cuatrocienegasensis LMG 24676(T) (57.2 %), P. borbori LMG 23199(T) (39.7 %), P. marincola KMM 3042(T) (32.2 %) and P. lundensis KACC 10832(T) (32.1 %), which support the classification of strain MS-3(T) within a novel species of the genus Pseudomonas. The G+C content of the genomic DNA of strain MS-3(T) was 57.6 mol% and the major isoprenoid quinone was Q-9. Strain MS-3(T) contained summed feature 3 (iso-C(15 : 0) 2-OH and/or C(16 : 1)ω7c; 38.0 %), C(16 : 0) (24.4 %), C(18 : 1)ω7c (12.8 %), C(12 : 0) (9.6 %) and C(10 : 0) 3-OH (4.9 %) as the major cellular fatty acids. On the basis of the phenotypic, genotypic and phylogenetic data, strain MS-3(T) represents a novel species of the genus Pseudomonas, for which the name Pseudomonas taeanensis sp. nov. is proposed. The type strain is MS-3(T) (=KCTC 22612(T) =KACC 14032(T) =JCM 16046(T) =NBRL 105641(T)).


Angular benzoperylenetetracarboxylic bisimides.
Benzoperylene derivatives with two angularly attached dicarboxylic imide rings, which were prepared by the Diels-Alder-reaction, exhibit strong fluorescence and their free peri positions allow either control of the UV/Vis spectra through their substituents or form anchor positions for the attachment of functional units. The angular chromophore 3 may be used both for fluorescent labeling such as for primary amines or enzymes or as building blocks for more complex assemblies where they may act as energy donors for FRET or electron acceptors in PET such as for photovoltaic solar cells.


[Epidemiology of various types of vascular epilepsy in adults].
From studies of the incidence of epilepsy, figures of between 40 and 70 per 100,000 inhabitants are obtained whilst in studies of prevalence, 5 to 7 cases per 1,000 are found. Cerebrovascular disease is the commonest cause of epileptic crises in the developed world, being more frequent in patients aged over 60, who make up 50% of all cases. Depending on the moment of presentation of crises in relation to the cerebrovascular disease, these may be classified as herald crises or precursors of vascular epilepsy, early crises if they occur during the first week and late crises if they occur after. Whilst early crises are usually due to metabolic or cytotoxic factors, the late crises occur in true vascular epilepsy. When these patients are assessed it is also important to consider increased hospital mortality in those with early crises and possible deterioration of neurological deficit as sequelae following late epileptic crises.