[COMPREHENSIVE GERIATRIC ASSESSMENT SCALES].
The process of comprehensive geriatric assessment is one of the key elements of geriatric care management aimed at the population. it includes evaluating the clinical, functional, mental and social aspects of aging result and/or pathological processes that appear at this stage of the life cycle. For their achievement, as well as other tools, professionals have a large number of validated rating scales specifically designed in the assessment of the different areas or fields. Its use can be very useful, especially for the objectification of evaluation results. The future of research in this area goes through deepening the adequacy of the scales to the characteristics and needs of older people in each care level or place of care.


Turn-timing in signed conversations: coordinating stroke-to-stroke turn boundaries.
In spoken interactions, interlocutors carefully plan, and time their utterances, minimizing gaps and overlaps between consecutive turns. Cross-linguistic comparison has indicated that spoken languages vary only minimally in terms of turn-timing, and language acquisition research has shown pre-linguistic vocal turn-taking in the first half year of life. These observations suggest that the turn-taking system may provide a fundamental basis for our linguistic capacities. The question remains, however, to what extent our capacity for rapid turn-taking is determined by modality constraints. The avoidance of overlapping turns could be motivated by the difficulty of hearing and speaking at the same time. If so, turn-taking in sign might show greater toleration for overlap. Alternatively, signed conversations may show a similar distribution of turn-timing as spoken languages, thus avoiding both gaps and overlaps. To address this question we look at turn-timing in question-answer sequences in spontaneous conversations of Sign Language of the Netherlands. The findings indicate that although there is considerable overlap in two or more signers' articulators in conversation, when proper allowance is made for onset preparation, post-utterance retraction and the intentional holding of signs for response, turn-taking latencies in sign look remarkably like those reported for spoken language. This is consistent with the possibility that, at least with regard to responses to questions, speakers and signers follow similar time courses in planning and producing their utterances in on-going conversation. This suggests that turn-taking systems may well be a shared cognitive infrastructure underlying all modern human languages, both spoken and signed.


Major cost savings associated with biologic dose reduction in patients with inflammatory arthritis.
The purpose of this study was to explore whether patients with Inflammatory Arthritis (IA) (Rheumatoid Arthritis (RA), Psoriatic Arthritis (PsA) or Ankylosing Spondylitis (AS)) would remain in remission following a reduction in biologic dosing frequency and to calculate the cost savings associated with dose reduction. This prospective non-blinded non-randomised study commenced in 2010. Patients with Inflammatory Arthritis being treated with a biologic agent were screened for disease activity. A cohort of those in remission according to standardized disease activity indices (DAS28 < 2.6, BASDAI < 4) was offered a reduction in dosing frequency of two commonly used biologic therapies (etanercept 50 mg once per fortnight instead of weekly, adalimumab 40 mg once per month instead of fortnightly). Patients were assessed for disease activity at 3, 6, 12, 18 and 24 months following reduction in dosing frequency. Cost saving was calculated. 79 patients with inflammatory arthritis in remission were recruited. 57% had rheumatoid arthritis (n = 45), 13% psoriatic arthritis (n = 10) and 30% ankylosing spondylitis (n = 24). 57% (n = 45) were taking etanercept and 43% (n = 34) adalimumab. The percentage of patients in remission at 24 months was 56% (n = 44). This resulted in an actual saving to the state of approximately 600,000 euro over two years. This study demonstrates the reduction in biologic dosing frequency is feasible in Inflammatory Arthritis. There was a considerable cost saving at two years. The potential for major cost savings in biologic usage should be pursued further.


Asymmetrical division of Saccharomyces cerevisiae.
The unequal division model proposed for budding yeast (L. H. Hartwell and M. W. Unger, J. Cell Biol. 75:422-435, 1977) was tested by bud scar analyses of steady-state exponential batch cultures of Saccharomyces cerevisiae growing at 30 degrees C at 19 different rates, which were obtained by altering the carbon source. The analyses involved counting the number of bud scars, determining the presence or absence of buds on at least 1,000 cells, and independently measuring the doubling times (gamma) by cell number increase. A number of assumptions in the model were tested and found to be in good agreement with the model. Maximum likelihood estimates of daughter cycle time (D), parent cycle time (P), and the budded phase (B) were obtained, and we concluded that asymmetrical division occurred at all growth rates tested (gamma, 75 to 250 min). D, P, and B are all linearly related to gamma, and D, P, and gamma converge to equality (symmetrical division) at gamma = 65 min. Expressions for the genealogical age distribution for asymmetrically dividing yeast cells were derived. The fraction of daughter cells in steady-state populations is e-alpha P, and the fraction of parent cells of age n (where n is the number of buds that a cell has produced) is (e-alpha P)n-1(1-e-alpha P)2, where alpha = IN2/gamma; thus, the distribution changes with growth rate. The frequency of cells with different numbers of bud scars (i.e., different genealogical ages) was determined for all growth rates, and the observed distribution changed with the growth rate in the manner predicted. In this haploid strain new buds formed adjacent to the previous buds in a regular pattern, but at slower growth rates the pattern was more irregular. The median volume of the cells and the volume at start in the cell cycle both increased at faster growth rates. The implications of these findings for the control of the cell cycle are discussed.


Thymectomy in the management of myasthenia gravis.
There continues to be a debate regarding the effectiveness of thymectomy in the treatment of nonthymomatous myasthenia gravis (MG) and, when undertaken, which thymectomy technique is the procedure of choice. The debate persists primarily because of the lack of controlled prospective studies. Analysis has been complicated by the absence, until very recently, of accepted objective definitions of severity of the illness and response to therapy as well as variable patient selection, timing of surgery, type of surgery, and methods of analysis of results. Without resolution of these issues by properly controlled prospective studies, there can be no unequivocal determination of the effectiveness of thymectomy or valid comparison of the various thymectomy techniques. In this review, based on previous analyses, attempts will be made to clarify some of the controversial issues concerning thymectomy for nonthymomatous MG and make limited recommendations based on the best available evidence.


Crystal structures of TAFI elucidate the inactivation mechanism of activated TAFI: a novel mechanism for enzyme autoregulation.
Thrombin-activatable fibrinolysis inhibitor (TAFI) is a pro-metallocarboxypeptidase that can be proteolytically activated (TAFIa). TAFIa is unique among carboxypeptidases in that it spontaneously inactivates with a short half-life, a property that is crucial for its role in controlling blood clot lysis. We studied the intrinsic instability of TAFIa by solving crystal structures of TAFI, a TAFI inhibitor (GEMSA) complex and a quadruple TAFI mutant (70-fold more stable active enzyme). The crystal structures show that TAFIa stability is directly related to the dynamics of a 55-residue segment (residues 296-350) that includes residues of the active site wall. Dynamics of this flap are markedly reduced by the inhibitor GEMSA, a known stabilizer of TAFIa, and stabilizing mutations. Our data provide the structural basis for a model of TAFI auto-regulation: in zymogen TAFI the dynamic flap is stabilized by interactions with the activation peptide. Release of the activation peptide increases dynamic flap mobility and in time this leads to conformational changes that disrupt the catalytic site and expose a cryptic thrombin-cleavage site present at Arg302. This represents a novel mechanism of enzyme control that enables TAFI to regulate its activity in plasma in the absence of specific inhibitors.


[Sports injuries and NSAID].
Sports medicine physicians often treat painful athletes with non steroidal anti-inflammatory drugs (NSAID). However, there is a lack of high-quality evidence to guide them and the adverse effects of those medications have clinical relevance. Moreover, their potential negative consequences on long-term healing process are slowly growing. This article reviews some practical management guidelines with NSAID drawn to assist sports physicians in frequent sports-related injuries. We do not recommend their use in muscle injuries, bone fracture or stress fracture, neither in tendinopathies. In all the cases, if used, length of NSAID treatment should always be kept as short as possible, with considerations of the specific type of injury, level of dysfunction and pain.


A facile nanoparticle immunoassay for cancer biomarker discovery.
Gold nanoparticles (AuNPs) scatter light intensely at or near their surface plasmon wavelength region. Using AuNPs coupled with dynamic light scattering (DLS) detection, we developed a facile nanoparticle immunoassay for serum protein biomarker detection and analysis. A serum sample was first mixed with a citrate-protected AuNP solution. Proteins from the serum were adsorbed to the AuNPs to form a protein corona on the nanoparticle surface. An antibody solution was then added to the assay solution to analyze the target proteins of interest that are present in the protein corona. The protein corona formation and the subsequent binding of antibody to the target proteins in the protein corona were detected by DLS. Using this simple assay, we discovered multiple molecular aberrations associated with prostate cancer from both mice and human blood serum samples. From the mice serum study, we observed difference in the size of the protein corona and mouse IgG level between different mice groups (i.e., mice with aggressive or less aggressive prostate cancer, and normal healthy controls). Furthermore, it was found from both the mice model and the human serum sample study that the level of vascular endothelial growth factor (VEGF, a protein that is associated with tumor angiogenesis) adsorbed to the AuNPs is decreased in cancer samples compared to non-cancerous or less malignant cancer samples. The molecular aberrations observed from this study may become new biomarkers for prostate cancer detection. The nanoparticle immunoassay reported here can be used as a convenient and general tool to screen and analyze serum proteins and to discover new biomarkers associated with cancer and other human diseases.


Changes in the structure and mechanical properties of pulmonary arteries of rats exposed to cigarette smoke.
The effect of cigarette smoke on the structure and mechanical properties of pulmonary arteries was studied in 2- and 3-month smoke-exposed rats. The animals were exposed to cigarette smoke in a smoke-generating system 10 times per day with one cigarette each time. The smoke density and the puffing duration and frequency of the system were regulated in accordance with reference values measured from human smokers. The volume fractions of the cells, including smooth muscle cells and fibroblasts, and extracellular matrix components, including collagen, elastin, and remainder (components not specified in this study), of the pulmonary arteries of approximately 450 microns in external diameter (at zero pressure) were determined in smoke-exposed and control rats by using an electron microscopic method. It was found that the volume fractions of the fibroblasts, the collagenous bundles, and the elastic laminae of the pulmonary arteries were increased significantly, whereas those of the smooth muscle cells and the remainder were decreased significantly in both the 2- and 3-month smoke-exposed rats in comparison with those of the corresponding control rats. The mechanical properties of the pulmonary arteries were determined based on the in vitro dimensional measurement of the vessels at various inflation pressures and zero-stress state. An increase in the stiffness of the pulmonary arteries was found in both the 2- and 3-month smoke-exposed rats. We conclude that cigarette smoke can induce structural and mechanical remodeling in the pulmonary arteries of rats.


A Combination of Chemotherapy and Oncolytic Virotherapy Sensitizes Colorectal Adenocarcinoma to Immune Checkpoint Inhibitors in a cDC1-Dependent Manner.
Immune checkpoint therapy has shown great promise in the treatment of cancers with a high mutational burden, such as mismatch repair-deficient colorectal carcinoma (dMMR CRC). However, many patients fail to respond to immune checkpoint therapy. Using a mouse model of dMMR CRC, we demonstrated that tumors can be further sensitized to immune checkpoint therapy by using a combination of low-dose chemotherapy and oncolytic HSV-1. This combination induced the infiltration of CD8+ and CD4+ T cells into the tumor and the upregulation of gene signatures associated with the chemoattraction of myeloid cell subsets. When combined with immune checkpoint therapy, the combination promoted the infiltration of activated type 1 conventional dendritic cells (cDC1s) into the tumor. Furthermore, we found this combination strategy to be dependent on cDC1s, and its therapeutic efficacy to be abrogated in cDC1-deficient Batf3-/- mice. Thus, we demonstrated that the adjuvanticity of dMMR CRCs can be improved by combining low-dose chemotherapy and oncolytic HSV-1 in a cDC1-dependent manner.


Evaluation of InnoTyper® 21 in a sample of Rio de Janeiro population as an alternative forensic panel.
The use of bi-allelic markers such as retrotransposable element insertion polymorphisms or Innuls (for insertion/null) can overcome some limitations of short tandem repeat (STR) loci in typing forensic biological evidence. This study investigated the efficiency of the InnoTyper® 21 Innul markers in an urban admixed population sample in Rio de Janeiro (n = 40) and one highly compromised sample collected as evidence by the Rio de Janeiro police. No significant departures from Hardy-Weinberg equilibrium were detected after the Bonferroni correction (α' ≈ 0.05/20, p < 0.0025), and no significant linkage disequilibrium was observed between markers. Assuming loci independence, the cumulative random match probability (RMP) was 2.3 × 10-8. A lower mean Fis value was obtained for this sample population compared with those of three North American populations (African-American, Southwest Hispanic, US Caucasian). Principal component analysis with the three North American populations and one from 21 East Asian population showed that African Americans segregated as an independent group while US Caucasian, Southwest Hispanic, East Asian, and Rio de Janeiro populations are in a single large heterogeneous group. Also, a full Innuls profile was produced from an evidence sample, despite the DNA being highly degraded. In conclusion, this system is a useful complement to standard STR kits.


Using a quality improvement initiative to reduce acute kidney injury during on-pump coronary artery bypass grafting.
In response to a perceived high incidence of acute kidney injury following cardiopulmonary bypass at our institution, a quality improvement initiative consisting of a systematic change to a delivered oxygen (DO2) goal-directed perfusion practice was implemented. We sought to maintain DO2 > 270 mL/min/m2 to reduce the incidence of acute kidney injury. 'The study population included all patients receiving isolated, non-emergent, on-pump coronary artery bypass grafting from January 2015 through December 2018, excluding patients requiring preoperative hemodialysis. DO2 goal-directed perfusion was instituted in February 2017. Acute kidney injury was defined using Acute Kidney Injury Network criteria. The pre-goal-directed perfusion cohort included 257 patients, and the post-goal-directed perfusion cohort included 226 patients. The DO2 was significantly higher in the post-goal-directed perfusion group (p < 0.001). Postoperative change in serum creatinine and incidence of acute kidney injury were significantly lower in the post-goal-directed perfusion group (p < 0.001, p = 0.001, respectively). Estimation with probit and ordered probit models support these findings. This initiative confirms previous assertions that DO2 is a critical intraoperative parameter and should direct perfusion intervention accordingly.


A review of deep learning and radiomics approaches for pancreatic cancer diagnosis from medical imaging.
Early and accurate diagnosis of pancreatic cancer is crucial for improving patient outcomes, and artificial intelligence (AI) algorithms have the potential to play a vital role in computer-aided diagnosis of pancreatic cancer. In this review, we aim to provide the latest and relevant advances in AI, specifically deep learning (DL) and radiomics approaches, for pancreatic cancer diagnosis using cross-sectional imaging examinations such as computed tomography (CT) and magnetic resonance imaging (MRI). This review highlights the recent developments in DL techniques applied to medical imaging, including convolutional neural networks (CNNs), transformer-based models, and novel deep learning architectures that focus on multitype pancreatic lesions, multiorgan and multitumor segmentation, as well as incorporating auxiliary information. We also discuss advancements in radiomics, such as improved imaging feature extraction, optimized machine learning classifiers and integration with clinical data. Furthermore, we explore implementing AI-based clinical decision support systems for pancreatic cancer diagnosis using medical imaging in practical settings. Deep learning and radiomics with medical imaging have demonstrated strong potential to improve diagnostic accuracy of pancreatic cancer, facilitate personalized treatment planning, and identify prognostic and predictive biomarkers. However, challenges remain in translating research findings into clinical practice. More studies are required focusing on refining these methods, addressing significant limitations, and developing integrative approaches for data analysis to further advance the field of pancreatic cancer diagnosis.


Derivatives of a new heterocyclic system - pyrano[3,4-c][1,2,4]triazolo[4,3-a]pyridines: synthesis, docking analysis and neurotropic activity.
8-Hydrazino derivatives of pyrano[3,4-c]pyridines and derivatives of the new heterocyclic system 3-thioxopyrano[3,4-c][1,2,4]triazolo[4,3-a]pyridines on the basis of methanesulfonates of pyrano[3,4-c]pyridinium were synthesized by optimization of a previously used method. Derivatives of alkylsulfonyl pyrano[3,4-c][1,2,4]triazolo[4,3-a]pyridines were also synthesized. All compounds were evaluated for their neurotropic activity. Among all the compounds tested for anticonvulsant activity by pentylenetetrazole and maximal electric shock seizure (MES) tests, six compounds (5a, 5b, 5e, 5g, 5j, and 5p) appeared to be active. These compounds were also evaluated for their anxiolytic as well as antidepressant activities using "open field", "elevated plus maze" (EPM), and "forced swimming" tests, respectively. It should be mentioned that compounds tested by the "rotating rod" method did not affect neuromuscular coordination. The most active compound appeared to be 5g in all tests. Docking studies of the most active compounds were performed on the GABAA receptor, SERT and 5-HT1A receptor.


A binding mode hypothesis of tiagabine confirms liothyronine effect on γ-aminobutyric acid transporter 1 (GAT1).
Elevating GABA levels in the synaptic cleft by inhibiting its reuptake carrier GAT1 is an established approach for the treatment of CNS disorders like epilepsy. With the increasing availability of crystal structures of transmembrane transporters, structure-based approaches to elucidate the molecular basis of ligand-transporter interaction also become feasible. Experimental data guided docking of derivatives of the GAT1 inhibitor tiagabine into a protein homology model of GAT1 allowed derivation of a common binding mode for this class of inhibitors that is able to account for the distinct structure-activity relationship pattern of the data set. Translating essential binding features into a pharmacophore model followed by in silico screening of the DrugBank identified liothyronine as a drug potentially exerting a similar effect on GAT1. Experimental testing further confirmed the GAT1 inhibiting properties of this thyroid hormone.


Expression and in silico structural analysis of a rice (Oryza sativa) hemoglobin 5.
This work reports the analysis of an additional hemoglobin (hb) gene copy, hb5, in the genome of rice. The amino acid sequence of Hb5 differs from the previously determined rice Hbs 1-4 in missing 11 residues in helix E. Transcripts of hb5 were found to be ubiquitous in rice organs, and hormone- and stress-response promoters exist upstream of the rice hb5 gene. Furthermore, the modeled structure of Hb5 based on the known crystal structure of rice Hb1 is unusual in that the putative distal His is distant from the heme Fe. This observation suggests that Hb5 binds and releases O(2) easily and thus that it functions as an O(2)-carrier or in some aspects of the O(2) metabolism.


Larsen's syndrome: clinical and genetic aspects.
A case of the Larsen's syndrome in a family is described. The girl has joint dislocations, an unusual face and bone abnormalities. Larsen's syndrome in this case has a genetic recessive origin. Both dominant and recessive forms may exist. The heterogeneity of the syndrome is emphasized and the differential diagnosis has been cited. A divergent strabismus is reported as an additional clinical finding.


Monocyte/macrophage β2-AR as a target of antisympathetic excitation-induced atherosclerotic progression.
The aim of this study was to determine whether monocyte/macrophage β2-AR could act as the therapeutic target of antisympathetic excitation-induced atherosclerotic progression. Cultivated human THP-1 cells were divided into different groups and incubated with isoprenaline, metoprolol, propranolol or β2-AR blocker for 24 h, together with oxidized low-density lipoprotein (ox-LDL). Afterwards, each group was analyzed for C-C chemokine receptor type 2 (CCR2) expression, monocyte chemotactic protein 1 (MCP-1) release into medium and cell migration ability. In the isoprenaline group, CCR2 protein level was increased, as well as the secretion of MCP-1, and cell motility was enhanced, in a concentration-dependent manner. Propranolol and ICI 118,551 significantly reversed the stimulatory effect of isoprenaline on THP-1 cells induced by ox-LDL, but only high concentrations of metoprolol interfered significantly with the action of isoprenaline (P < 0.05). Isoprenaline or a β-AR blocker could mediate through β2-AR, affecting MCP-1 secretion, CCR2 protein expression and cell migration capacity of THP-1 cells. Therefore, monocyte-macrophage β2-AR may act as a target of antisympathetic excitation-induced atherosclerotic progression.


Establishment of monoclonal antibodies against a novel eosinophil-specific cell surface molecule, major facilitator super family domain containing 10.
Eosinophilic inflammation is the prominent feature of bronchial asthma, though the importance of eosinophils in the pathogenesis of this disease is controversial. We here established monoclonal antibodies against a newly identified cell surface molecule specifically expressed on mouse eosinophils. Eosinophils were highly purified from small intestine lamina propria and thymus as CD11c(+)Gr1(low)F4/80(+)B220(-) cells. Upon comparative microarray analysis for mRNA expressed in eosinophils and other leukocytes, major facilitator super family domain containing 10 (Mfsd10) was identified as a novel eosinophil-specific cell surface molecule. Hybridomas were established from spleen cells of rats immunized with Mfsd10-introduced Ba/F3 cells. One of three monoclonal antibodies against Mfsd10 displayed selective binding activity against eosinophils recovered in bronchoalveolar lavage fluid of ovalbumin-immunized and -challenged mice. Administration of this antibody in vivo induced a significant reduction of eosinophils recruited in the allergic lungs. Anti-Mfsd10 antibody is useful for investigating the pathophysiological roles of eosinophils with its selective binding and neutralizing activity for mouse eosinophils.


Structural and optical properties of wood and wood finishes studied using optical coherence tomography: application to an 18th century Italian violin.
Optical coherence tomography (OCT) is especially attractive for the study of cultural heritage artifacts because it is noninvasive and nondestructive. We have developed an original full-field time-domain OCT system dedicated to the investigation of varnished and painted artifacts: an interferometric Mirau objective allows one to perform the scan without moving the works of art. The axial and transverse high resolution (respectively, 1.5 and 1 microm) are well adapted to the detection of the investigated structures (pigment grains, wood fibers, etc.). The illumination spectrum is in the visible range (centered at 630 nm, 150 nm wide) to potentially allow us to perform spectroscopic OCT on pigment particles. The examination of wood samples coated with a traditional finish, demonstrates the ability of the system to detect particles, characterize layers thickness, and image the three-dimensional wood structures below the varnishes. OCT has finally been applied to study in situ the coated wood surface of an 18th century Italian violin and provides important information for its conservation treatment.


Development of PMA real-time PCR method to quantify viable cells of Pantoea agglomerans CPA-2, an antagonist to control the major postharvest diseases on oranges.
Dilution plating is the quantification method commonly used to estimate the population level of postharvest biocontrol agents, but this method does not permit a distinction among introduced and indigenous strains. Recently, molecular techniques based on DNA amplification such as quantitative real-time PCR (qPCR) have been successfully applied for their high strain-specific detection level. However, the ability of qPCR to distinguish viable and nonviable cells is limited. A promising strategy to avoid this issue relies on the use of nucleic acid intercalating dyes, such as propidium monoazide (PMA), as a sample pretreatment prior to the qPCR. The objective of this study was to optimize a protocol based on PMA pre-treatment samples combined with qPCR to distinguish and quantify viable cells of the biocontrol agent P. agglomerans CPA-2 applied as a postharvest treatment on orange. The efficiency of PMA-qPCR method under the established conditions (30μM PMA for 20min of incubation followed by 30min of LED light exposure) was evaluated on an orange matrix. Results showed no difference in CFU or cells counts of viable cells between PMA-qPCR and dilution plating. Samples of orange matrix inoculated with a mixture of viable/dead cells showed 5.59log10 CFU/ml by dilution plating, 8.25log10 cells/ml by qPCR, and 5.93log10 cells/ml by PMA-qPCR. Furthermore, samples inoculated with heat-killed cells were not detected by dilution plating and PMA-qPCR, while by qPCR was of 8.16log10 cells/ml. The difference in quantification cycles (Cq) among qPCR and PMA-qPCR was approximately 16cycles, which means a reduction of 65,536 fold of the dead cells detected. In conclusion, PMA-qPCR method is a suitable tool for quantify viable CPA-2 cells, which could be useful to estimate the ability of this antagonist to colonize the orange surface.


Nuclear receptors in nonalcoholic Fatty liver disease.
Nuclear receptors comprise a superfamily of ligand-activated transcription factors that are involved in important aspects of hepatic physiology and pathophysiology. There are about 48 nuclear receptors in the human. These nuclear receptors are regulators of many hepatic processes including hepatic lipid and glucose metabolism, bile acid homeostasis, drug detoxification, inflammation, regeneration, fibrosis, and tumor formation. Some of these receptors are sensitive to the levels of molecules that control lipid metabolism including fatty acids, oxysterols, and lipophilic molecules. These receptors direct such molecules to the transcriptional networks and may play roles in the pathogenesis and treatment of nonalcoholic fatty liver disease. Understanding the mechanisms underlying the involvement of nuclear receptors in the pathogenesis of nonalcoholic fatty liver disease may offer targets for the development of new treatments for this liver disease.


Secreted immunodominant Mycobacterium tuberculosis antigens are processed by the cytosolic pathway.
Exposure to Mycobacterium tuberculosis can result in lifelong but asymptomatic infection in most individuals. Although CD8(+) T cells are elicited at high frequencies over the course of infection in both humans and mice, how phagosomal M. tuberculosis Ags are processed and presented by MHC class I molecules is poorly understood. Broadly, both cytosolic and noncytosolic pathways have been described. We have previously characterized the presentation of three HLA-I epitopes from M. tuberculosis and shown that these Ags are processed in the cytosol, whereas others have demonstrated noncytosolic presentation of the 19-kDa lipoprotein as well as apoptotic bodies from M. tuberculosis-infected cells. In this paper, we now characterize the processing pathway in an additional six M. tuberculosis epitopes from four proteins in human dendritic cells. Addition of the endoplasmic reticulum-Golgi trafficking inhibitor, brefeldin A, resulted in complete abrogation of Ag processing consistent with cytosolic presentation. However, although addition of the proteasome inhibitor epoxomicin blocked the presentation of two epitopes, presentation of four epitopes was enhanced. To further examine the requirement for proteasomal processing of an epoxomicin-enhanced epitope, an in vitro proteasome digestion assay was established. We find that the proteasome does indeed generate the epitope and that epitope generation is enhanced in the presence of epoxomicin. To further confirm that both the epoxomicin-inhibited and epoxomicin-enhanced epitopes are processed cytosolically, we demonstrate that TAP transport and new protein synthesis are required for presentation. Taken together, these data demonstrate that immunodominant M. tuberculosis CD8(+) Ags are processed and presented using a cytosolic pathway.


Effect of the SV40 T antigen on the posttranscriptional regulation of the proliferating cell nuclear antigen and DNA polymerase-alpha genes.
tk-ts13 cells are G1-specific temperature-sensitive mutants of the cell cycle that arrest in G1 at the restrictive temperature. In these cells the mRNAs for early growth-regulated genes (for instance, c-myc) are inducible by serum at both permissive and restrictive temperatures. In contrast, the mRNAs for late growth-regulated genes [such as histones, proliferating cell nuclear antigen (PCNA), and DNA polymerase-alpha] are not detectable at the restrictive temperature, although they are normally induced by serum at the permissive temperature. Despite the absence of their mRNAs at the restrictive temperature, transcription rates for DNA polymerase-alpha, PCNA, and histone H3 are the same in serum-deprived cells and in cells that are serum stimulated at either the permissive or the restrictive temperature. Since the half-lives of the mRNAs are not substantially different at the two temperatures, the conclusion is that in tk-ts13 cells the mRNA levels of these late growth-regulated genes are regulated at a posttranscriptional level, presumably during hnRNA processing. When serum-deprived tk-ts13 cells carrying a stably integrated SV40 T antigen-coding gene (T-neo cells) are stimulated with serum, they are capable of one additional round of DNA replication at the restrictive temperature. At 20 h after stimulation of T-neo cells, the mRNAs for the late growth-regulated genes are detectable at the restrictive temperature in amounts not substantially different than those at the permissive temperature. Transcription rates in T-neo cells are increased for histone H3 (in comparison to tk-ts13 cells) but not for PCNA and DNA polymerase-alpha. The presence of the T antigen does not seem to seriously affect the half-lives of the mature mRNAs. The conclusion is that the presence of the SV40 T antigen in tk-ts13 cells promotes the appearance of mature mRNAs for DNA polymerase-alpha and PCNA. These experiments suggest that T antigen, in this instance, may intervene either directly or indirectly at a posttranscriptional level in the regulation of the steady state mRNA levels of certain cellular genes.


Inhibition of cisplatin-induced Acsl4-mediated ferroptosis alleviated ovarian injury.
Given that the severity of the chemotherapy-induced ovarian damage, effective fertility preservation is a necessary part of the treatment process. Ferroptosis is a regulated cell death triggered by excessive phospholipid peroxidation caused by iron and the role of ferroptosis in chemotherapy-induced ovarian damage remains unclear. In this study, we demonstrated that cisplatin treatment caused the accumulation of iron ions which induced ferroptosis in ovarian tissue. And our results show that ferrostatin-1 was able to suppress the ovarian injury and granulosa cell death caused by cisplatin (Cis) in vivo and in vitro. At the same time, we observed significant changes in the expression levels of Acyl-CoA synthetase long-chain family member 4 (Acsl4) and glutathione peroxidase 4 (GPX4). Similarly, Rosiglitazone, an inhibitor of Acsl4, administration alleviated the ovary damage of the mice undergoing chemotherapy. Further mechanistic investigation showed that cisplatin increased the expression level of specificity protein 1 (SP1), and SP1 could bind to the promoter of Acsl4 to increased Acsl4 transcription. Overall, ferroptosis plays an important role in Cis induced ovarian injury, and inhibition of ferroptosis protects ovarian tissues from damage caused by cisplatin, and for the first time, we have identified the potential of Fer-1 and Rosi to protect ovarian function in female mice undergoing chemotherapy.


Molecular mechanisms of cholangiocarcinoma cell inhibition by medicinal plants.
Cholangiocarcinoma (CCA) is one of the most common causes of cancer-associated mortality in Thailand. Certain phytochemicals have been demonstrated to modulate apoptotic signaling pathways, which may be targeted for the prevention and treatment of cancer. Therefore, the aim of the present study was to investigate the effect of specific medicinal plants on the inhibition of CCA cell proliferation, and to identify the molecular mechanisms underlying this. A WST-1 cell proliferation assay was performed using an RMCCA1 cell line, and apoptotic signaling pathways were also investigated using a PathScan Stress and Apoptosis Signaling Antibody Array Kit. The cell proliferation assay indicated that extracts from the Phyllanthus emblica fruit pulp (PEf), Phyllanthus emblica seed (PEs), Terminalia chebula fruit pulp (TCf), Terminalia chebula seed (TCs), Areca catechu seed (ACs), Curcuma longa (CL) and Moringa oleifera seed (MOs) exerted anti-proliferative activity in RMCCA1 cells. In addition, the PathScan assay revealed that certain pro-apoptotic molecules, including caspase-3, poly (ADP-ribose) polymerase, checkpoint kinase 2 and tumor protein 53, exhibited increased activity in RMCCA1 cells treated with the aforementioned selected plant extracts, with the exception of PEf. The mitogen-activated protein kinase (MAPK) pathways (including ERK1/2 and p38 MAPK) expression level was significantly increased in RMCCA1 cells pre-treated with extracts of PEs, TCf, CL and MOs. The activation of protein kinase B (Akt) was significantly demonstrated in RMCCA1 cells pre-treated with extracts of TCf, ACs and MOs. In summary, the present study demonstrated that extracts of PEs, TCf, TCs, ACs, CL and MOs exhibited anti-proliferative effects in CCA cells by inducing pro-apoptotic signals and modulating signal transduction molecules. Further studies in vivo are required to demonstrate the potential applications of specific plant extracts for the treatment of human cancer.


Factors that influence the scale up of new interventions in low-income settings: a qualitative case study of the introduction of chlorhexidine cleansing of the umbilical cord in Bangladesh.
There is a well-recognized need for empirical study of processes and factors that influence scale up of evidence-based interventions in low-income countries to address the 'know-do' gap. We undertook a qualitative case study of the scale up of chlorhexidine cleansing of the umbilical cord (CHX) in Bangladesh to identify and compare facilitators and barriers for the institutionalization and expansion stages of scale up. Data collection and analysis for this case study were informed by the Consolidated Framework for Implementation Research (CFIR) and the WHO/ExpandNet model of scale up. At the national level, we interviewed 20 stakeholders involved in CHX policy or implementation. At the district level, we conducted interviews with 31 facility-based healthcare providers in five districts and focus group discussions (FGDs) with eight community-based providers and eight programme managers. At the community level, we conducted 7 FGDs with 53 mothers who had a baby within the past year. Expanded interview notes were thematically coded and analysed following an adapted Framework approach. National stakeholders identified external policy and incentives, and the engagement of stakeholders in policy development through the National Technical Working Committee for Newborn Health, as key facilitators for policy and health systems changes. Stakeholders, providers and families perceived the intervention to be simple, safe and effective, and more consistent with family preferences than the prior policy of dry cord care. The major barriers that delayed or decreased the public health impact of the scale up of CHX in Bangladesh's public health system related to commodity production, procurement and distribution. Bangladesh's experience scaling up CHX suggests that scale up should involve early needs assessments and planning for institutionalizing new drugs and commodities into the supply chain. While the five CFIR domains were useful for categorizing barriers and facilitators, additional constructs are needed for common health systems barriers in low-income settings.


Trends in Overweight and Obesity in Czech Schoolchildren from 1998 to 2014.
Overweight and obesity in adolescents is associated with many health risks and considerable direct and indirect healthcare costs. The purpose of this study is to examine trends in the prevalence of overweight and obesity in 11-, 13- and 15-year-old adolescents in the Czech Republic from 1998 to 2014. Data from five self-reported survey rounds (1998, 2002, 2006, 2010, and 2014) of the Health Behaviour in School-aged Children Study (HBSC) were used to assess trends in overweight and obesity among Czech adolescents. The total sample consisted of 19,103 adolescents (51.2% girls). A logistic regression analysis was used to assess trends in different age and gender categories. From 1998 to 2014 a significant increase in the prevalence of overweight and obesity was observed among boys in all age categories (11 years old 22.2%1998- 28.3%2014; 13 years old 17.9%1998- 26.7%2014; 15 years old 9.8%1998- 20.8%2014) and among 15-year-old girls (6.0%1998- 10.9%2014). None of the age and gender categories showed an overall decrease over the 16-year period. In boys, the prevalence of overweight was significantly higher with steeper negative trends compared with girls. However, stabilization in overweight rates was observed between 2010 and 2014 in all age and gender groups. Nationally representative self-reported data show a significant increase in overweight (including obesity) prevalence among children from 1998 to 2014 in the Czech Republic. The results also suggest stabilization in overweight prevalence between 2010 and 2014. Continuing research is needed to determine future trends while interventions aimed at reducing overweight and obesity in children should be implemented on different levels of public policy.


Characterizing Strategy Use During the Performance of Hippocampal-Dependent Tasks.
Recalling the past, thinking about the future, and navigating in the world are linked with a brain structure called the hippocampus. Precisely, how the hippocampus enables these critical cognitive functions is still debated. The strategies people use to perform tasks associated with these functions have been under-studied, and yet, such information could augment our understanding of the associated cognitive processes and neural substrates. Here, we devised and deployed an in-depth protocol to examine the explicit strategies used by 217 participants to perform four naturalistic tasks widely acknowledged to be hippocampal-dependent, namely, those assessing scene imagination, autobiographical memory recall, future thinking, and spatial navigation. In addition, we also investigated strategy use for three laboratory-based memory tasks, one of which is held to be hippocampal-dependent - concrete verbal paired associates (VPA) - and two tasks, which are likely hippocampal-independent - abstract VPA and the dead or alive semantic memory test. We found that scene visual imagery was the dominant strategy not only when mentally imagining scenes, but also during autobiographical memory recall, when thinking about the future and during navigation. Moreover, scene visual imagery strategies were used most frequently during the concrete VPA task, whereas verbal strategies were most prevalent for the abstract VPA task and the dead or alive semantic memory task. The ubiquity of specifically scene visual imagery use across a range of tasks may attest to its, perhaps underappreciated, importance in facilitating cognition, while also aligning with perspectives that emphasize a key role for the hippocampus in constructing scene imagery.


Childhood family structure and complexity in partnership life courses.
This study investigated the associations between childhood living arrangements and complex adult partnership trajectories. The authors defined first union dissolution as the event initiating a complex partnership life course, and measured the level of complexity using a weighted cumulative index of subsequent partnership episodes. The analyses were based on a representative sample of the German population born in 1971-73 from the German Family Panel and used multivariate hurdle models to estimate the probability of experiencing the initiation of a complex partnership trajectory, as well as the level of complexity. Results showed that respondents who did not grow up with both biological parents (i.e. those who experienced an alternative family structure) had both a greater likelihood of experiencing the dissolution of their own first union, and followed more complex subsequent partnership trajectories. These associations varied across types of (alternative) family structures experienced during childhood and according to the level of parental partnership (in)stability. This study contributes to our understanding of contemporary partnership complexity and its precursors using a long term life course theoretical and methodological frame. We acknowledge that continuities and disruptions in the development of adult (complex) partnership trajectories can be linked to a growing diversity of family structure in childhood. Thereby, we expand knowledge on intergenerational interdependencies of family instability and complexity beyond the reproduction of the event of union dissolution.


An antibody targeting type III secretion system induces broad protection against Salmonella and Shigella infections.
Salmonella and Shigella bacteria are food- and waterborne pathogens that are responsible for enteric infections in humans and are still the major cause of morbidity and mortality in the emerging countries. The existence of multiple Salmonella and Shigella serotypes as well as the emergence of strains resistant to antibiotics requires the development of broadly protective therapies. Recently, the needle tip proteins of the type III secretion system of these bacteria were successfully utilized (SipD for Salmonella and IpaD for Shigella) as vaccine immunogens to provide good prophylactic cross-protection in murine models of infections. From these experiments, we have isolated a cross-protective monoclonal antibody directed against a conserved region of both proteins. Its conformational epitope determined by Deep Mutational Scanning is conserved among needle tip proteins of all pathogenic Shigella species and Salmonella serovars, and are well recognized by this antibody. Our study provides the first in vivo experimental evidence of the importance of this common region in the mechanism of virulence of Salmonella and Shigella and opens the way to the development of cross-protective therapeutic agents.


Patient perceptions of service quality in group versus solo practice clinics.
To compare patient perceptions of service quality at solo and group practices, and to examine the association of perceptions with 'potential patient loyalty' (PPL), the potential for seeking future service from the same clinic. A self-administered, cross-sectional survey of clinic outpatients, using an adapted SERVQUAL questionnaire translated into Chinese, with additional items on overall satisfaction and intent to return/recommend the clinic to others. Sampling and study subjects. Every third outpatient at all newly started group practices (four) and solo clinics (thirteen) in Taiwan in the preceding 4-7 months, including 150 and 50 patients from each group and solo practice, respectively, for a total of 1250 patients. Perceived service quality on five dimensions-tangibles, reliability, responsiveness, assurance, and empathy-and PPL. All constructs were measured on a five-point scale. After accounting for random effects of clinical and geographical location, group practice patients perceived significantly higher service quality on all dimensions relative to solo practice patients, after adjusting for age, gender, education, and illness type. All service quality dimensions except assurance were significantly positively associated with PPL after adjusting for age, gender, education, and illness type, and random effects at the clinical and geographical location levels. Patients perceive better service quality at group practices compared with solo practices on all dimensions. Patients' quality perceptions are significant predictors of PPL. The implications for physician practices both internationally and in Taiwan are discussed, as well as policy implications for the Taiwan government.


The use of chiral BINAM NHC-Rh(III) complexes in enantioselective hydrosilylation of 3-oxo-3-arylpropionic acid methyl or ethyl esters.
Axially chiral BINAM N-heterocyclic carbene (NHC)-Rh(III) complexes were applied in the enantioselective hydrosilylation of 3-oxo-3-arylpropionic acid methyl or ethyl esters. The reduction products 3-hydroxy-3-arylpropionic acid methyl or ethyl esters could be obtained in good yields with good to excellent enantioselectivities under mild conditions.


Survey of U.S. Residents and Their Usage of Electronic Cigarettes with Drugs Other Than Nicotine.
Electronic cigarettes (e-cigs), originally intended to be used as cigarette substitutes, have evolved into discreet devices for consuming drugs other than nicotine (DOTNs). Presented are the results of an exploratory survey in which information regarding demographics, e-cig device type, DOTN use, frequency and context of use was collected. The average reported age of respondents was 27.4 years of age (SD = 12.0), and respondents predominantly identified as male (73%). Vape pens (disposable or refillable) were the most reported device across all DOTN classes. Cannabinoids were the most reported class of DOTN used, for both lifetime and past 30-day use. Other DOTNs reported included herbal supplements, amphetamines, caffeine, kratom, vitamins, opiates, DMT, fentanyl, and ketamine. Combinations of DOTNs used in e-cigs and trends in poly-substance use were reported. The most commonly reported context was vaping alone, followed by with friends, at home, and at social events; less commonly reported contexts included when driving, at work, and at school. Results from this study are useful for developing future national surveys to consider a comprehensive substance use-focused strategy that includes vaping, building awareness of DOTN e-cig use, and highlighting public safety issues in driving impairment, crime scene investigations, and death investigations.


House physicians. Accountabilities and possibilities.
Current house physicians' practice, responsibilities, and earnings are reviewed. House physicians are licensed, ordinarily institutionally based, typically salaried physician employees of 1 or more hospitals or systems. Many are hourly workers, often foreign medical graduates or physicians in training, with little professional status and less visibility. Yet managed care sees a new, creative role for house physicians that makes them masters of quality and models of service. No longer dependent beings shielded by an institution's coverage, house physicians can emerge as efficient, educated champions of inpatient medicine. To produce hospital generalist physicians for the patient's good, physician availability, institutional financial incentives, and patient values must align.


Differential expression of islet glutaredoxin 1 and 5 with high reactive oxygen species production in a mouse model of diabesity.
The onset and progression of diabetes mellitus type 2 is highly contingent on the amount of functional beta-cell mass. An underlying cause of beta-cell decay in diabetes is oxidative stress, which markedly affects the insulin producing pancreatic cells due to their poor antioxidant defence capacity. Consequently, disturbances of cellular redox signaling have been implicated to play a major role in beta-cell loss in diabetes mellitus type 2. There is evidence suggesting that the glutaredoxin (Grx) system exerts a protective role for pancreatic islets, but the exact mechanisms have not yet been elucidated. In this study, a mouse model for diabetes mellitus type 2 was used to gain further insight into the significance of Grx for the islets of Langerhans in the diabetic metabolism. We have observed distinct differences in the expression levels of Grx in pancreatic islets between obese, diabetic db mice and lean, non-diabetic controls. This finding is the first report about a decrease of Grx expression levels in pancreatic islets of diabetic mice which was accompanied by declining insulin secretion, increase of reactive oxygen species (ROS) production level, and cell cycle alterations. These data demonstrate the essential role of the Grx system for the beta-cell during metabolic stress which may provide a new target for diabetes mellitus type 2 treatment.


CO-promoted formation of the alkali-oxygen bond on Ni(111).
High-resolution electron energy loss spectroscopy was used to study the coadsorption of alkali metals (Na, K) and oxygen on clean and CO-modified Ni(111) surfaces. We unambiguously show that on an alkali-precovered surface, the alkali-O bond was not formed upon O(2) exposure. On the contrary, the alkali-O bond was readily observed by exposing to O(2) the Ni(111) surface precovered with an alkali+CO phase. This enhanced oxidation rate of alkali metals in the presence of CO molecules was ascribed to the short-range CO-induced modification of the electronic charge of alkali-metal adatoms.


Aspirin in the Treatment of Cancer: Reductions in Metastatic Spread and in Mortality: A Systematic Review and Meta-Analyses of Published Studies.
Low-dose aspirin has been shown to reduce the incidence of cancer, but its role in the treatment of cancer is uncertain. We conducted a systematic search of the scientific literature on aspirin taken by patients following a diagnosis of cancer, together with appropriate meta-analyses. Searches were completed in Medline and Embase in December 2015 using a pre-defined search strategy. References and abstracts of all the selected papers were scanned and expert colleagues were contacted for additional studies. Two reviewers applied pre-determined eligibility criteria (cross-sectional, cohort and controlled studies, and aspirin taken after a diagnosis of cancer), assessed study quality and extracted data on cancer cause-specific deaths, overall mortality and incidence of metastases. Random effects meta-analyses and planned sub-group analyses were completed separately for observational and experimental studies. Heterogeneity and publication bias were assessed in sensitivity analyses and appropriate omissions made. Papers were examined for any reference to bleeding and authors of the papers were contacted and questioned. Five reports of randomised trials were identified, together with forty two observational studies: sixteen on colorectal cancer, ten on breast and ten on prostate cancer mortality. Pooling of eleven observational reports of the effect of aspirin on cause-specific mortality from colon cancer, after the omission of one report identified on the basis of sensitivity analyses, gave a hazard ratio (HR) of 0.76 (95% CI 0.66, 0.88) with reduced heterogeneity (P = 0.04). The cause specific mortality in five reports of patients with breast cancer showed significant heterogeneity (P<0.0005) but the omission of one outlying study reduced heterogeneity (P = 0.19) and led to an HR = 0.87 (95% CI 0.69, 1.09). Heterogeneity between nine studies of prostate cancer was significant, but again, the omission of one study led to acceptable homogeneity (P = 0.26) and an overall HR = 0.89 (95% CI 0.79-0.99). Six single studies of other cancers suggested reductions in cause specific mortality by aspirin, and in five the effect is statistically significant. There were no significant differences between the pooled HRs for the three main cancers and after the omission of three reports already identified in sensitivity analyses heterogeneity was removed and revealed an overall HR of 0.83 (95% CI 0.76-0.90). A mutation of PIK3CA was present in about 20% of patients, and appeared to explain most of the reduction in colon cancer mortality by aspirin. Data were not adequate to examine the importance of this or any other marker in the effect of aspirin in the other cancers. On bleeding attributable to aspirin two reports stated that there had been no side effect or bleeding attributable to aspirin. Authors on the other reports were written to and 21 replied stating that no data on bleeding were available. The study highlights the need for randomised trials of aspirin treatment in a variety of cancers. While these are awaited there is an urgent need for evidence from observational studies of aspirin and the less common cancers, and for more evidence of the relevance of possible bio-markers of the aspirin effect on a wide variety of cancers. In the meantime it is urged that patients in whom a cancer is diagnosed should be given details of this research, together with its limitations, to enable each to make an informed decision as to whether or not to take low-dose aspirin. CRD42015014145.


Effects of Puerarin on Clinical Parameters, Vascular Endothelial Function, and Inflammatory Factors in Patients with Coronary Artery Disease.
BACKGROUND The aim of this study was to investigate the effects of puerarin on vascular endothelial function and inflammatory factors in coronary artery disease (CAD) patients with stable angina pectoris (SAP). MATERIAL AND METHODS To evaluate the effects of angina pectoris, the differences of scores of the Seattle angina questionnaire (SAQ), vascular endothelial function [endothelial progenitor cells (EPCs), nitric oxide (NO) and endothelin 1 (ET-1)], and inflammatory factors [tumor necrosis factor a (TNF-α), hypersensitive C-reactive protein (hs-CRP), interleukin-6 (IL-6)] in 2 groups were assessed before and after treatment. RESULTS Regarding the curative effect of angina pectoris, the total effective rate of the treatment group was significantly superior to that of the control group (89% vs. 65%, P<0.05). The duration of angina pectoris, the number of abnormal leads, the improvement of the ST segment depression of electrocardiogram, and the scores of SAQ life quality indexes in the treatment group were better than those of the control group (P<0.05). In the 2 groups, EPCs and NO were both elevated, while ET-1 was decreased, and the improvements of the treatment group were superior to those of the control group (P<0.05). After treatment, the average levels of serum TNF-α, hs-CRP and IL-6 in the 2 groups were all decreased, which the treatment group showed a much sharper decrease than in the control group (P<0.05). CONCLUSIONS Puerarin effectively improves clinical symptoms and vascular endothelial function and reduces the levels of inflammatory factors in patients with CAD.


Dosimetric effect of internal metallic ports in temporary tissue expanders on postmastectomy radiation therapy: a Monte Carlo study.
To investigate the dosimetric effect of the internal metallic port (IMP) in a tissue expander (TE) on the dose distribution of postmastectomy radiation therapy (PMRT). A total of 10 patients who have received PMRT with a TE were selected retrospectively. For each patient, the dose distributions of treatment plans with a 10 MV photon beam were calculated using the Monte Carlo (MC) method with CT images. The dose distributions without the TE were also calculated by designating the mass densities of the TE including the IMP as those of tissue. From the MC calculations, the dose-volumetric parameters were calculated and analyzed for several structures: the planning target volume (PTV) including the TE, the PTV excluding the TE (PTVreal), the TE alone, heart, and lungs. For the PTV and PTVreal, dose-volumetric parameters did not appear to depend on the IMP. Within the TE volume, the maximum dose and D 1% were higher with the IMP than without the IMP (62.8 ± 1.4 Gy versus 57.9 ± 1.3 Gy with p < 0.001 and 58.6 ± 1.6 Gy versus 57.0 ± 1.2 Gy with p = 0.035). The values of V 100% and V 95% were lower with the IMP than without the IMP (77.9% ± 7.6% versus 87.2% ± 5.3% with p = 0.008 and 89.5% ± 5.6% versus 94.6% ± 2.9% with p = 0.027). The IMP did not affect dose-volumetric parameters of heart and lungs. Dosimetric changes due to the IMP occurred mainly within the TE, and not in the target volume, heart, and lungs.


The value of Gallium67 scanning in the evaluation of head and neck malignancy.
Gallium (67Ga) citrate is a scanning agent that has been shown to have a differential uptake in a variety of malignancies. Investigation of the usefulness of 67Ga scanning patients with proven squamous cell carcinoma of the head and neck region is now in progress. These patients have a 67Ga total body scan as part of the pre-treatment evaluation. The accuracy of the procedure is then judged by correlation with clinical and surgical findings. The results in 25 patients show that a clearly positive uptake occurs in 60 percent in the region of the primary. Uptake in metastatic disease in lymph nodes is much less, occurring in 6 of 18 sides of the neck. In one case, where clinical examination was considered to be negative, the gallium scan was positive and subsequently proven to be correct by histological examination of the surgical specimen. The various difficulties encountered in interpreting gallium scans in the head and neck region are described. It is felt that by improved patient selection and special techniques the yield of positive cases can be improved and unsuspected extension of malignancy demonstrated.


Long-term efficacy of fractionated conformal radiotherapy for the management of primary optic nerve sheath meningioma.
Fractionated conformal radiotherapy (FCRT) is now used to treat vision-threatening optic nerve sheath meningioma (ONSM), but long-term efficacy and safety data are lacking; the purpose of this study was to assess these key data. This is a retrospective chart review with prospective follow-up of adult patients treated with FCRT for primary ONSM at four academic medical centres between 1995 and 2007 with ≥10 years of follow-up after treatment. 16 patients were identified with a mean post-treatment follow-up of 14.6 years (range: 10.5-20.7 years). The mean age at symptom onset was 47.6 years (range: 36-60 years). FCRT was performed at a mean of 2.3 years after symptom onset (range: 0.2-14.0 years). At last follow-up, visual acuity had improved or stabilised in 14 of the 16 (88%) patients, and 11 (69%) had retained or achieved ≥20/40. The mean deviation on automated perimetry remained stable (-14.5 dB pretreatment vs -12.2 dB at last follow-up; p=0.68, n=10). Two (11%) patients had persistent pain, proptosis or diplopia, compared with six (38%) pretreatment (p=0.11). Two (13%) patients developed radiation retinopathy more than 6 months after completion of therapy, one (50%) of whom had worse visual acuity compared with pretreatment. No patient developed tumour involvement or radiation damage in the fellow eye. FCRT stabilises or improves visual function in patients with primary ONSM and is associated with a low risk of significant ocular sequelae. This treatment should be considered instead of surgery in patients with primary ONSM who require intervention due to loss of visual sensory and/or ocular motor function.


Estimating population effects of vaccination using large, routinely collected data.
Vaccination in populations can have several kinds of effects. Establishing that vaccination produces population-level effects beyond the direct effects in the vaccinated individuals can have important consequences for public health policy. Formal methods have been developed for study designs and analysis that can estimate the different effects of vaccination. However, implementing field studies to evaluate the different effects of vaccination can be expensive, of limited generalizability, or unethical. It would be advantageous to use routinely collected data to estimate the different effects of vaccination. We consider how different types of data are needed to estimate different effects of vaccination. The examples include rotavirus vaccination of young children, influenza vaccination of elderly adults, and a targeted influenza vaccination campaign in schools. Directions for future research are discussed. Copyright © 2017 John Wiley & Sons, Ltd.


Health risks of the clean-shave chiskop haircut.
The clean-shave haircut known locally as the chiskop is rare among females but popular with black South African men, who are also predisposed to folliculitis keloidalis nuchae (FKN) (keloids on the back of the head). During a previous study, participants described an unexpected symptom of haircut-associated bleeding. As this is not a widely recognised entity, we conducted the present study at an HIV clinic servicing the same population, with the objective of comparing the prevalences of haircut-associated bleeding and FKN in 390 HIV-positive subjects with published data for Langa (Western Cape, South Africa). The results for HIV-positive participants were similar to the population data, but in both groups the prevalence of haircut-associated bleeding (24.5% v. 32%; p=0.17) was much higher than that of FKN (10.2% v. 10.5%), suggesting that the hairstyle increases the risk of bleeding even in people with healthy scalps without folliculitis. This study does not (and was not intended to) prove a higher HIV prevalence in chiskop wearers or in FKN sufferers, but it confirms a history of haircut-associated bleeding in at least a quarter of our male study participants. The risk of transmission of blood-borne infection via haircuts is likely to be low, but requires formal quantification. Public education on adequate sterilisation of barber equipment between haircuts and promotion of individual hair-clipper ownership for chiskop clients should not be delayed. Depilatory creams formulated for African hair offer a non-mechanical means of achieving clean-shave hairstyles.


Effect of virgin coconut oil enriched diet on the antioxidant status and paraoxonase 1 activity in ameliorating the oxidative stress in rats - a comparative study.
Virgin coconut oil (VCO) extracted by wet processing is popular among the scientific field and society nowadays. The present study was carried out to examine the comparative effect of VCO with copra oil (CO), olive oil (OO) and sunflower oil (SFO) on endogenous antioxidant status and paraoxonase 1 activity in ameliorating the oxidative stress in rats. Male Sprague-Dawley rats were fed different oils at 8% level for 45 days along with the synthetic diet. Results revealed that dietary VCO improved the antioxidant status compared to other three oil fed groups (P < 0.05), which is evident from the increased activities of catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase in tissues. Concentration of reduced glutathione was also found to be increased significantly in liver (532.97 mM per 100 g liver), heart (15.77 mM per 100 g heart) and kidney (1.58 mM per 100 g kidney) of VCO fed rats compared to those fed with CO, OO and SFO (P < 0.05). In addition, the activity of paraoxonase 1 was significantly increased in VCO fed rats compared to other oil fed groups (P < 0.05). Furthermore, VCO administration prevented the oxidative stress, which is indicated by the decreased formation of lipid peroxidation and protein oxidation products like malondialdehyde, hydroperoxides, conjugated dienes and protein carbonyls in serum and tissues compared to other oil fed rats (P < 0.05). Wet processing of VCO retains higher amounts of biologically active unsaponifiable components like polyphenols (84 mg per 100 g oil) and tocopherols (33.12 μg per 100 g oil) etc. compared to other oils (P < 0.05). From these observations, it is concluded that VCO has a beneficial role in improving antioxidant status and hence preventing lipid and protein oxidation.


Baseline prediction of combination therapy outcome in hepatitis C virus 1b infected patients by discriminant analysis using viral and host factors.
Current treatment of chronic hepatitis C virus (HCV) infection has limited efficacy -especially among genotype 1 infected patients-, is costly, and involves severe side effects. Thus, predicting non-response is of major interest for both patient wellbeing and health care expense. At present, treatment cannot be individualized on the basis of any baseline predictor of response. We aimed to identify pre-treatment clinical and virological parameters associated with treatment failure, as well as to assess whether therapy outcome could be predicted at baseline. Forty-three HCV subtype 1b (HCV-1b) chronically infected patients treated with pegylated-interferon alpha plus ribavirin were retrospectively studied (21 responders and 22 non-responders). Host (gender, age, weight, transaminase levels, fibrosis stage, and source of infection) and viral-related factors (viral load, and genetic variability in the E1-E2 and Core regions) were assessed. Logistic regression and discriminant analyses were used to develop predictive models. A "leave-one-out" cross-validation method was used to assess the reliability of the discriminant models. Lower alanine transaminase levels (ALT, p=0.009), a higher number of quasispecies variants in the E1-E2 region (number of haplotypes, nHap_E1-E2) (p=0.003), and the absence of both amino acid arginine at position 70 and leucine at position 91 in the Core region (p=0.039) were significantly associated with treatment failure. Therapy outcome was most accurately predicted by discriminant analysis (90.5% sensitivity and 95.5% specificity, 85.7% sensitivity and 81.8% specificity after cross-validation); the most significant variables included in the predictive model were the Core amino acid pattern, the nHap_E1-E2, and gamma-glutamyl transferase and ALT levels. Discriminant analysis has been shown as a useful tool to predict treatment outcome using baseline HCV genetic variability and host characteristics. The discriminant models obtained in this study led to accurate predictions in our population of Spanish HCV-1b treatment naïve patients.


[The 'dreams' of Cesare Augusto Levi: a pre-Freud interpretation].
On 25th February, 1887 Cesare Augusto Levi, a poet and archaeologist born in Venice in 1856, held a conference on dreams at the "Ateneo di Venezia". The conference deals with the nature of dreams, with the unconscious, with hypnosis and magnetism. Levi advocates a socially oriented version of psychiatry and he may be considered as a forerunner of Freud's theories.


Prediction from low birth weight to female adolescent depression: a test of competing hypotheses.
Low birth weight (LBW) predicts later-onset hypertension and diabetes mellitus. Its role as a predictor of depression is unclear. To examine whether LBW predicts depression in male and female children and adolescents and to compare the following 2 hypotheses: Low birth weight is one among several perinatal, childhood, and adolescent risk factors for depression (biopsychosocial hypothesis). Low birth weight is a marker for poor intrauterine conditions that provoke adjustments in fetal development, with long-term consequences for stress response (fetal programming hypothesis). A representative population-based sample from an 11-county area in western North Carolina was assessed annually for psychiatric disorders between the ages of 9 and 16 years. We tested the prediction from LBW and depression in models that included LBW only, LBW plus other prenatal and perinatal adversities, LBW plus significant perinatal and childhood adversities, and LBW plus significant perinatal and childhood adversities and adolescent correlates. Academic research. There were 1420 participants, of whom 49% were female. Main Outcome Measure Cumulative prevalence of DSM-IV depressive disorder at 1 assessment or more during childhood (age range, 9-12 years) and during adolescence (age range, 13-16 years). The cumulative prevalence of depression among adolescent girls with LBW was 38.1% (95% confidence interval [CI], 16.3%-66.0%) compared with 8.4% (95% CI, 5.2%-13.3%) among adolescent girls with normal birth weight. Rates among children and adolescent boys did not exceed 4.9%. In adolescence, there was a significant interaction between LBW and sex (odds ratio, 0.2 [95% CI, 0.1-0.5]; P<.001). Low birth weight predicted female adolescent depression after controlling for other perinatal, childhood, and adolescent adversities. Girls with LBW and normal birth weight with no adversities had no adolescent depression, but each additional adversity increased the risk of in girls with LBW more than in girls with normal birth weight. Low birth weight did not predict other psychiatric disorders in either sex. Low birth weight predicts depression in adolescent girls but not boys. Data support fetal programming over the biopsychosocial hypothesis, suggesting vulnerability to adversities in girls with LBW after puberty.


Examining associations between childhood asthma and traffic flow using a geographic information system.
Using geographic information systems (GIS) and routinely collected data, we explored whether childhood residence near busy roads was associated with asthma in a low-income population in San Diego County, California. We examined the locations of residences of 5,996 children [less than/equal to] 14 years of age who were diagnosed with asthma in 1993 and compared them to a random control series of nonrespiratory diagnoses (n = 2,284). Locations of the children's residences were linked to traffic count data at streets within 550 ft. We also examined the number of medical care visits in 1993 for children with asthma to determine if the number of visits was related to traffic flow. Analysis of the distribution of cases and controls by quintiles and by the 90th, 95th, and 99th percentiles of traffic flow at the highest traffic street, nearest street, and total of all streets within a 550-ft buffer region did not show any significantly elevated odds ratios. However, among cases, those residing near high traffic flows (measured at the nearest street) were more likely than those residing near lower traffic flows to have two or more medical care visits for asthma than to have only one visit for asthma during the year. The results of this exploratory study suggest that higher traffic flows may be related to an increase in repeated medical visits for asthmatic children. Repeated exposure to particulate matter and other air pollutants from traffic exhaust may aggravate asthmatic symptoms in individuals already diagnosed with asthma.


Clinical application value of impulse oscillometry in geriatric patients with COPD.
The diagnosis and assessment of COPD rely mainly on the use of spirometry, which is an effort-dependent test and requires good patient cooperation. Impulse oscillometry (IOS) is a non-volitional method that requires less effort and cooperation and presents advantages for geriatric patients. However, the clinical application value of IOS in geriatric patients with COPD remains unclear. The aim of this study was to investigate the clinical application value of IOS in geriatric patients with COPD. A total of 234 subjects were retrospectively enrolled in this study, including 133 patients with COPD and 101 healthy volunteers. All the participants underwent IOS and spirometry examination. The data were collected and analyzed in the overall group, the geriatric group (aged ≥65 years), and the advanced elderly group (aged ≥80 years). 1) In COPD patients, a significant increase in respiratory impedance (Z5), resonant frequency (Fres), and respiratory resistance (R5, R20, R5-R20) and a decrease in respiratory reactance (X5) were observed in the overall group, the geriatric group, and the advanced elderly group compared with the healthy control subjects. 2) The IOS parameters correlated well with spirometry in COPD. In particular, R5-R20 showed the best correlation with forced expiratory volume in 1 second (FEV1) in the different age groups. 3) Fres and R5-R20 had the best diagnostic efficiency for COPD. The area under the curve (AUC) values for Fres, expressed by the receiver operating characteristic (ROC) curve, were 0.905, 0.909, and 0.914, for the different age groups, respectively. 4) The optimal cutoff values for Fres to diagnose airflow obstruction from ROC curves was 17.715 in the COPD patients. Its sensitivity and specificity were 0.789 and 0.931, respectively, and the cutoff values were similar in geriatric and advanced elderly patients. IOS demonstrated good relevance compared with spirometry for geriatric patients with COPD. IOS may serve as an alternative method for spirometry in elderly subjects for the evaluation of the state of COPD.


An Irish breast cancer survivorship study: are we meeting our patients' needs?
Irish breast cancer survivor's needs have not been studied. Physical, psychological, social and spiritual concerns were investigated. Patient satisfaction with hospital discharge, GP follow-up, and the benefit of a discharge pack was investigated. A cohort of patients from the South East Cancer Centre was identified. localized breast cancer, completion of adjuvant therapy, GP-led follow-up in the last 5 years. An anonymous questionnaire was developed, and ethical approval obtained. Subgroup analyses for age and time since diagnosis and discharge were completed. 80 patients were identified. 44 patients (55%) completed the questionnaire, 5 (6%) were excluded. Commonest concerns included: fatigue (51%), fear of recurrence (69%) and second cancers concerns (69%) 23 (59%) and 25 patients (64%) were satisfied with discharge and GP follow-up respectively. 27 patients (67%) reported benefit from a discharge pack. Irish breast cancer survivors had concerns, and were satisfied with GP follow-up.


Alterations in energy expenditure in Roux-en-Y gastric bypass rats persist at thermoneutrality.
The compensatory decrease in energy expenditure (EE) in response to body weight loss is attenuated by Roux-en-Y gastric bypass (RYGB) surgery in rats. The thermoneutral zone (TNZ) is at higher temperatures in rodents than in humans. Consequently, rodents may be under moderate cold stress if EE is measured at room temperature, leading to increased EE due to adaptive thermogenesis. We speculated that the reported alterations in EE of RYGB rats at room temperature are caused by higher adaptive thermogenesis and are therefore not present at thermoneutrality. Male Wistar rats were randomized for RYGB or sham surgery. Some sham rats were body weight matched (BWM) to the RYGB rats by food restriction, the others received ad libitum access to food (AL). EE, body temperature, physical activity and food intake were measured at ambient temperatures between 22 and 32 °C to determine the TNZ. Adaptive thermogenesis requires β3-adrenergic receptor-mediated uncoupling protein-1 (UCP-1) expression in brown adipose tissue (BAT). The in vivo thermogenic capacity of BAT was determined by administering the β3-adrenergic agonist CL316,243, and UCP-1 protein expression was measured at room temperature. The TNZ was between 28 and 30 °C for AL and RYGB and between 30 and 32 °C for BWM rats, respectively. In contrast to AL and BWM rats, EE was not significantly higher at room temperature than at thermoneutrality in RYGB rats, reflecting a lack of adaptive thermogenesis. Consistently, both the thermogenic capacity of BAT and UCP-1 expression were decreased in RYGB compared with AL rats at room temperature. Our data confirm that the decrease in EE after body weight loss is attenuated by RYGB surgery and show that this effect persists at thermoneutrality. Contrary to our hypothesis, we found that adaptive thermogenesis at room temperature is reduced in RYGB rats.


Preparation of 131I-asialo-alpha1-acid glycoprotein.
Alpha1-Acid glycoprotein (orosomucoid) was prepared from a byproduct of the ethanol plasma fractionation by means of ion-exchange procedures. Immunoelectrophoresis suggested a high degree of purity; the purified protein contained 13.5% sialic acid and 17.8% hexose. The alpha1-acid glycoprotein was modified by removal of sialic acid with neuraminidase (EC 126.96.36.199) followed by iodination with 131I. The purpose of the preparation, its potential use as a pharmacon for liver function studies in nuclear medicine is the subject of further study.


Cold blockade of axonal transport activates premitotic activity of Schwann cells and wallerian degeneration.
Between 3 and 4 days after transection of cat sciatic nerve, Schwann cell-associated premitotic activity spreads anterogradely along degenerating distal nerve stumps at a rate of approximately 200 mm/day. We investigated whether fast anterograde axonal transport contributes to the initiation of this component of Wallerian degeneration. Axonal transport was blocked in intact and transected cat sciatic nerves by focally chilling a proximal segment to temperatures below 11 degrees C for 24 hr. Incorporation of [3H]thymidine (a marker of premitotic DNA synthesis) was then measured 3 and 4 days posttransection in cold blocked- and control-degenerating nerves. Effects of cold block prior to and concomitant with nerve transection were studied. Results failed to support the hypothesis that Schwann-cell premitotic activity after axotomy is associated with entry into the axon of mitogenic substances and their anterograde fast transport along the distal stump. Instead, data suggested that progressive anterograde failure of fast anterograde transport distal to transection serves to effect the Schwann-cell premitotic response to axotomy.


Comparison of effects of dietary T-2 toxin on growth, immunogenic organs, antibody formation, and pathologic changes in turkeys and chickens.
The effect of T-2 toxin (trichothecene mycotoxin) consumption on Broad-Breasted White turkey poults and White Leghorn chicks was studied. Groups of ten 8-day-old poults were fed rations containing T-2 at 10 ppm, 2ppm, or 0 ppm (controls) for a period of 4 weeks; a 4th group (inanition control) was fed control rations equal to the amount consumed by the group fed rations containing T-2 at 10 ppm during the previous 24 hours. A similar experimental design was used to study the effect of the toxin on 1-day-old chicks. The thymus glands of the poults given the feed containing 10 ppm were markedly decreased in size compared with thymus glands from poults in the control group, 0.182 vs 0.331 (percentage of body weight). There was no significant (P less than or equal to 0.05) decrease in thymus gland size in poults given 2 ppm or in the inanition controls. Dietary treatment did not appear to affect the size of the bursa or spleen of the poults. Histopathologic examination of thymus glands from poults given 10 ppm of T-2 revealed a depletion of cortical lymphocytes. Chicks appeared less sensitive to T-2 toxin than did the poults. There was no effect by any dietary treatment on the size of the thymus gland, bursa, or spleen of chicks. Reductions were noticed in feed efficiency and weight gain. There was no effect of T-2 toxin on agglutinating antibody formation to Pasteurella multocida bacterin.


Both naturally occurring insertions of transposable elements and intermediate frequency polymorphisms at the achaete-scute complex are associated with variation in bristle number in Drosophila melanogaster.
A restriction enzyme survey of a 110-kb region including the achaete scute complex (ASC) examined 14 polymorphic molecular markers in a sample of 56 naturally occurring chromosomes. Large insertions as a class were associated with a reduction in both sternopleural and abdominal bristle number, supporting deleterious mutation-selection equilibrium models for the maintenance of quantitative genetic variation. Two polymorphic sites were independently associated with variation in bristle number measured in two genetic backgrounds as assessed by a permutation test. A 6-bp deletion near sc alpha is associated with sternopleural bristle number variation in both sexes and a 3.4-kb insertion between sc beta and sc gamma is associated with abdominal bristle number variation in females. Under an additive genetic model, the small deletion polymorphism near sc alpha accounts for 25% of the total X chromosome genetic variation in sternopleural bristle number, and the 3.4 kb insertion accounts for 22% of the total X chromosome variation in female abdominal bristle number. The observation of common polymorphisms associated with variation in bristle number is more parsimoniously explained by models that incorporate balancing selection or assume variants affecting bristle number are neutral, than mutation-selection equilibrium models.


Hazard identification, dose-response and environmental characteristics of stachybotryotoxins and other health-related products from Stachybotrys.
An extensive growth of Stachybotrys in water-damaged buildings is of great public health concern. It is inconclusive whether Stachybotrys is responsible for the reported health effects on the occupants in these contaminated environments. However, based on the veterinary, occupational and laboratory toxicity studies, it is reasonable to project that Stachybotrys can cause adverse health responses once the toxic level of the corresponding agents reached the target systems. In order to assess the risk to occupants in contaminated buildings, it is essential to outline and collect information for risk assessment. This review paper presents the current information in the format of hazard identification, dose-response and environmental characteristics and aims to discuss existing information with researchers and risk assessors and help to conduct risk characterization under different indoor conditions.


[Brown fat tissue in humans].
Brown adipose tissue (BAT) is universally present in mammals. Thermal production in such tissue is physiologically important for maintaining temperature homeostasis and regulation of body mass in small-size homoiotherms. At present it is clearly established that unlike other large mammals, brown adipose in man and primates is retained throughout the whole postnatal othogenesis. Therefore, BAT appears as a possible effector of pharmacogenetic protection from human excessive adiposis. Systematic reserach of various functioning aspects of this unique organ of mammals were started abroad as early as 1960-es, and are actively developing at present. Domestic research of energy circulation physiology and of thermoregulation developed mostly outside the brown adipose tissue. Therefore, the principal objective of this publication is to draw attention of experimental and clinical researches to an intriguing aspect of the issue of energy circulation in humans--the issue of brown adipose functioning.


Pharmacokinetics and safety of solifenacin succinate in healthy young men.
The pharmacokinetic profile of solifenacin succinate (YM905; Vesicare), a new once-daily bladder-selective muscarinic receptor antagonist, was examined in 2 controlled trials of healthy young men. A single-dose study evaluated 5-, 10-, 20-, 40-, 60-, 80-, and 100-mg doses. A multidose study evaluated 5-, 10-, 20-, and 30-mg doses. In the single-dose study, mean time to maximal concentration and elimination half-life ranged from 3.3 to 4.8 and from 40.2 to 57.6 hours, respectively; in the multidose study, the corresponding ranges were 2.9 to 5.8 and 45.0 to 64.8. Plasma concentration and area under the curve increased linearly with single doses in both trials. At steady state, a less regular increase was seen, with higher values in the 20-mg group than in the 30-mg group. All doses in the single-dose study were well tolerated. At steady state, only the 30-mg dose was not well tolerated. The most commonly reported adverse events were dry mouth, blurred vision, and headache. Solifenacin 5 and 10 mg, either as single doses or at steady state, had minimal effect on salivary flow, visual nearpoint, and the incidence of adverse events. Solifenacin was well tolerated up to single doses of 100 mg and after multiple doses of 20 mg. Its pharmacokinetic profile makes it suitable for qd administration.


Improving care after hip fracture: the fracture? Think osteoporosis (FTOP) program.
Hip fractures are a common and serious consequence of osteoporosis, and hip fracture patients are at high risk for recurrence. Appropriate pharmacotherapy reduces this risk and is associated with reduced mortality after hip fracture, but a care gap exists for fracture prevention in these patients. This evaluation determined rates of osteoporosis treatment and bone mineral density (BMD) testing in hip fracture patients following discharge from a rehabilitation unit. A prospective cohort study of hip fracture patients aged ≥ 50 on an inpatient rehabilitation unit in 2008 and 2011. Patients were seen by a nurse specialist, and encouraged to see their family physician for further assessment and treatment. Physicians were sent a letter indicating the need to follow up with their patient. Patients were contacted following discharge from hospital to determine treatment rates. Of 310 eligible hip fracture patients admitted to the rehabilitation unit in the years studied, 207 patients were reached post-discharge and provided data. Of patients who were not previously taking osteoporosis medication, 59% of patients from the 2008 cohort, and 42% of patients from the 2011 cohort had osteoporosis treatment initiated by six months following discharge. By 2 months following discharge, 46% of patients in the 2008 cohort had a new BMD performed or scheduled, while this was true for 14% of patients from the 2011 cohort. 35% of patients in 2011 had not seen their family physician by 2 months following discharge. Rates for osteoporosis treatment and BMD testing were higher than those reported in the literature for patients not enrolled in case manager programs. BMD testing declined from 2008 to 2011. Lower treatment rates may be due to concerns regarding reports of possible association between bisphosphonate use and atypical fractures. Improving rates of patient follow-up with family physicians will be important for increasing hip fracture treatment rates after discharge.


Herbal anti-inflammatory agents for skin disease.
Herbs have been used in clinical medicine for thousands of years. However, it is only in recent times that we have been able to employ scientific methods to prove the efficacy of many of these herbs and to give us a better understanding of their mechanisms of action. This article will focus on the use of herbs in various dermatological conditions characterized by inflammation and pruritus. Topical preparations of many of these herbs are more commonplace in Europe. However, their availability is increasing in the US. As this is occurring we are witnessing a growing marriage between alternative and traditional medicines.


[Painless apoplectiform paralysis of the brachial plexus].
A 40 year-old glass-blower suddenly experienced a painless weakness of his left shoulder and arm, more severe in C5 and C6 territories. The disorders regressed. Il was suspected that this brachial plexus neuropathy was of ischemic origin. However the absence of pain was surprising.


Terms of Engagement: Transfer of Biological Materials for Research in Australia.
The shift from basic science to potentially more lucrative applied science and commercialisation has had a profound impact on sharing biological materials for research purposes. Free exchanges of ideas and research materials have become cloaked in contractual obligations, driven by commercialisation and impact policies, particularly through material transfer agreements (MTAs). There has been no analysis of the terms included in MTAs routinely used by Australian universities and research institutes for the transfer of biological materials for research. This study analyses terms from 45 MTAs used by Australian universities and research organisations as well as common standard agreements. Our findings suggest that drafters need to refocus MTA terms to the purpose behind which materials are exchanged. Terms need to be directed primarily towards compatibility with the research effort rather than the remote possibility of future commercial and translational opportunities. This refocusing should simplify MTA terms, expediting materials transfer and supporting research.


The controversy over radiation safety. A historical overview.
The hazards of ionizing radiation have aroused concern since a short time after the discovery of x-rays and natural radioactivity in the 1890s. Misuse of x-rays and radium prompted efforts to encourage radiation safety and to set limits on exposure, culminating in the first recommended "tolerance doses" in 1934. After World War II, the problems of radiation protection became more complex because of the growing number of people subjected to radiation injury and the creation of radioactive elements that had never existed before the achievement of atomic fission. Judging the hazards of radiation became a matter of spirited controversy. Major public debates over the dangers of radioactive fallout from atmospheric bomb testing in the 1950s and early 1960s and the risks of nuclear power generation in later periods focused attention on the uncertainties about the consequences of exposure to low-level radiation and the difficulties of resolving them.


[Bio-IGRT - biological image-guided radiotherapy].
Image-guided radiotherapy (IGRT) represents a novel method to precisely deliver radiation to tumours while sparing surrounding normal tissues. Integration of biological imaging using PET or MRI appears to be a promising concept to improve radiotherapy (Bio-IGRT). For this it is essential that biological imaging provides radiobiologically relevant information. Preclinical and clinical investigations into validation of PET tracers and MR methods in the context of curative radiotherapy and of concepts for biology-based escalation of radiation dose as well as other therapeutic interventions are an important task for further cancer research.


On the lack of ATP-induced midpoint potential shift for cytochrome b-566 in plant mitochondria.
Recently proposed mechanisms of site II energy transduction that assign a key role to cytochrome b-566 are based on the finding that the apparent midpoint potential of b-566 in animal mitochondria increases by more than 250 mV upon addition of ATP [Chance et al. (1970) Proc. Nat. Acad. Sci. USA 66, 1175-1182]. However, since it has never been shown that the redox mediators used in the midpoint potential measurements equilibrate directly with b-566, the observed midpoint potential shift could merely reflect reversed electron transport. In mung bean mitochondria, the apparent midpoint potential of b-566 is known to be unaffected by addition of ATP [Dutton and Storey (1971) Plant Physiol. 47, 282-288]. In the present work, mung bean b-566 is shown to undergo an ATP-induced reduction similar to that observed for b-566 in animal mitochondria. However, in mung bean mitochondria the reduction is found to be rapidly relaxed by addition of redox mediator (phenazine methosulfate, PMS) and concomitantly PMS causes a marked, antimycinsensitive stimulation of ATPase activity. These results suggest that the ATP-induced reduction in mung bean mitochondria is due to reversed electron transport and that PMS can effectively short-circuit reversed electron transport in this system, bringing it close to equilibrium. Moreover, since mung bean and animal b-566 are identical in all other respects tested, the results support the idea that the apparent midpoint potential shift in animal mitochondria is also merely due to reversed electron transport, and that the mediators are now not effective enough to bring the system to equilibrium.


Replication of linkage of familial combined hyperlipidemia to chromosome 1q with additional heterogeneous effect of apolipoprotein A-I/C-III/A-IV locus. The NHLBI Family Heart Study.
Familial combined hyperlipidemia (FCHL), the most common familial dyslipidemia, is implicated in up to 20% of cases of premature coronary heart disease. Although underlying mutations for FCHL have yet to be identified, several candidate genes/regions have been identified. A positive linkage to chromosome 1q markers has been reported, with the highest lod score of 5.93 occurring at a location between D1S104 and D1S1677. Using the same diagnostic criteria, the Family Heart Study (FHS) has defined 71 FCHL families, comprising 170 cases, for a total of 137 possible affected sibling pairs. The FCHL criteria require elevation in serum low density lipoprotein cholesterol and triglyceride levels within the family, with at least 2 affected first-degree relatives. Markers D1S104 and D1S1677 were typed, and significant allele sharing was found in FCHL sibships (multipoint lod score with use of the model from the Finnish study was 2.52, and multipoint nonparametric score was 2.48; P=0.007), replicating linkage in this chromosome 1 region. In addition, previously reported linkage of FCHL to apolipoprotein A-I/C-III/A-IV has been investigated in FHS families. FHS results revealed positive but nonsignificant allele sharing among FCHL sibships with apolipoprotein A-I/C-III/A-IV by use of marker D11S4127 (nonparametric linkage score 1.11, P=0.13). Two-locus analyses of D1S104 and D11S4127 suggested possible heterogeneity rather than epistasis, with a maximum 2-locus lod score of 3.05. A nonparametric 2-locus analysis revealed significant improvement in the 2-locus versus single-locus scores. Finally, no linkage was found with markers near the lipoprotein lipase gene region.


Open vs. closed sphincterotomy for chronic anal fissure: long-term results.
This study was undertaken to compare the healing rate and long-term effects on continence of open and closed lateral internal sphincterotomy. Charts of 864 patients with chronic anal fissure who underwent internal sphincterotomy as a single procedure over five years by a group of 12 colorectal surgeons were reviewed. Open internal sphincterotomy (OIS) was performed in 521 patients, whereas 343 had closed internal sphincterotomy (CIS). There was no difference in sex or age between the groups. A questionnaire inquiring about clinical outcome, changes in continence, and degree of satisfaction with the procedure was mailed to all patients. A total of 549 (63.5 percent) patients, 324 (62.2 percent) with OIS and 225 (65.6 percent) with CIS, returned their questionnaires. Average follow-up was three (range, 1-6) years. Differences in persistence of symptoms (3.4 OIS vs. 5.3 percent CIS), recurrence of the fissure (10.9 vs. 11.7 percent CIS), and need for reoperation (3.4 percent OIS vs. 4 percent CIS) were statistically not significant. However, statistically significant differences were seen in the percentage of patients with permanent postoperative difficulty controlling gas (30.3 vs. 23.6 percent; P 0.062), soiling underclothing (26.7 vs. 16.1 percent; P < 0.001), and accidental bowel movements (11.8 vs. 3.1 percent; P < 0.001) between those who underwent OIS and those who had CIS. Although 90 percent of patients reported general overall satisfaction, more patients undergoing CIS (64.4 percent) than OIS (49.7 percent) were very satisfied with the results of the procedure. Lateral internal sphincterotomy is highly effective in treatment of chronic anal fissure but is associated with significant permanent alterations in continence. CIS is preferable to OIS because it effects a similar rate of cure with less impairment of control.