A new ambulatory classification and funding model for radiation oncology: non-admitted patients in Victorian hospitals.
The Victorian Department of Human Services has developed a classification and funding model for non-admitted radiation oncology patients. Agencies were previously funded on an historical cost input basis. For 1996-97, payments were made according to the new Non-admitted Radiation Oncology Classification System and include four key components. Fixed grants are based on Weighted Radiation Therapy Services targets for megavoltage courses, planning procedures (dosimetry and simulation) and consultations. The additional throughput pool covers additional Weighted Radiation Therapy Services once targets are reached, with access conditional on the utilisation of a minimum number of megavoltage fields by each hospital. Block grants cover specialised treatments, such as brachytherapy, allied health payments and other support services. Compensation grants were available to bring payments up to the level of the previous year. There is potential to provide incentives to promote best practice in Australia through linking appropriate practice to funding models. Key Australian and international developments should be monitored, including economic evaluation studies, classification and funding models, and the deliberations of the American College of Radiology, the American Society for Therapeutic Radiology and Oncology, the Trans-Tasman Radiation Oncology Group and the Council of Oncology Societies of Australia. National impact on clinical practice guidelines in Australia can be achieved through the Quality of Care and Health Outcomes Committee of the National Health and Medical Research Council.


The frataxin homologue Fra plays a key role in intracellular iron channeling in Bacillus subtilis.
Frataxin homologues are important iron chaperones in eukarya and prokarya. Using a native proteomics approach we were able to identify the structural frataxin homologue Fra (formerly YdhG) of Bacillus subtilis and to quantify its native iron-binding stoichiometry. Using recombinant proteins we could show in vitro that Fra is able to transfer iron onto the B. subtilis SUF system for iron-sulfur cluster biosynthesis. In a four-constituents reconstitution system (including SufU, SufS, Fra and CitB) we observed a Fra-dependent formation of a [4 Fe-4 S] cluster on SufU that could be efficiently transferred onto the target apo-aconitase (CitB). A Δfra deletion mutant showed a severe growth phenotype associated with a broadly disturbed iron homeostasis; this indicates that Fra is a central component of intracellular iron channeling in B. subtilis.


Variation in the diet and feeding morphology of polyphenic Lepomis macrochirus.
Bluegill Lepomis macrochirus showed variation in their diet and trophic morphology based on habitat. Pelagic L. macrochirus feed almost exclusively on cladocerans; littoral L. macrochirus feed on a variety of benthic invertebrates, molluscs, cladocerans and insects. Fish from the littoral habitat had wider pharyngeal jaws, which probably allowed them to crush gastropods and process benthic invertebrates.


Immunology in Africa.
Africa is a continent with a large burden of both infectious and non-communicable diseases. If we are to move forward as a continent, we need to equip our growing cadre of exceptional young scientists with the skills needed to tackle the diseases endemic to this continent. For this, immunology is among the key disciplines. Africans should be empowered to study and understand the diseases that affect them, and to perform their cutting-edge research in their country of origin. This requires a multifaceted approach, with buy-in from funders, overseas partners and perhaps, most important of all, African governments themselves.


Quantification of Duloxetine in the Bacterial Culture and Medium to Study Drug-gut Microbiome Interactions.
Expanding our understanding of drug-gut bacteria interactions requires high-throughput drug measurements in complex bacterial cultures. Quantification of drugs in the cultures, media, and cell pellets is prone to strong matrix effects. We have developed a liquid chromatography-high resolution mass spectrometry (LC-HRMS) method for quantifying duloxetine from high-throughput gut-drug interaction experiments. The method is partially validated for its reproducibility, sensitivity, and accuracy, which makes it suitable for largescale drug screens. We extensively used this method to study biotransformation and bioaccumulation of duloxetine and other drugs in several species of gut bacteria.


High-grade arteriovenous malformations and their management.
The aim of this study was to compare operatively and non-operatively managed high-grade arteriovenous malformations (AVMs) and to identify risk factors for surgical morbidity. Three hundred and ninety-one consecutively enrolled patients with AVMs were graded using the Spetzler Martin grading scheme. Forty-six of these patients had grade 4 or 5 AVMs. Twenty-nine patients underwent surgery and 17 were conservatively managed. During an average of 33 months follow-up the non-operative group experienced a decline in function in 27% of cases followed. These deteriorations were due to haemorrhage, progressive neurological deficits and seizures. In the surgical group completing treatment there was a mortality and morbidity impacting on self-care of 15%. In those without deep perforating arterial supply the morbidity was 10% and with deep perforating arterial supply or deep meningeal recruitment there was a combined morbidity and mortality of 44%. This difference in outcome was statistically significant (P<0.01). We conclude that high-grade AVMs have a high operative morbidity. However, these lesions often have a poor natural history and with careful selection (based on the presence or absence of deep perforating arterial supply) a group can be selected that benefits from surgery. Grade 4 and 5 AVMs with supply from lenticulostriate, choroidal, thalamic deep perforating arteries or deep meningeal recruitment may be best treated conservatively or possibly by multimodality treatment utilising radiotherapy and embolisation combined with surgery.


Isolation and Analysis of Plasma-Derived Exosomes in Patients With Glioma.
Gliomas including glioblastoma (GBM) are the most common primary malignant brain tumors. Glioma extracellular vesicles (EVs) including exosomes have biological effects (e.g., immunosuppression) and contain tumor-specific cargo that could facilitate liquid biopsies. We aimed to develop a simple, reproducible technique to isolate plasma exosomes in glioma patients. Glioma patients' and normal donors' plasma exosomes underwent brief centrifugation to remove cells/debris followed by serial density gradient ultracentrifugation (DGU). EV size/concentration was determined by nanoparticle tracking. Protein cargo was screened by array, western blot, and ELISA. Nanoscale flow cytometry analysis quantified exosome and microvesicle populations pre- and post-DGU. One-step DGU efficiently isolates exosomes for nanoparticle tracking. Wild type isocitrate dehydrogenase glioma patients' (i.e., more aggressive tumors) plasma exosomes are smaller but higher concentration than normal donors. A second DGU efficiently concentrates exosomes for subsequent cargo analysis but results in vesicle aggregation that skews nanoparticle tracking. Cytokines and co-stimulatory molecules are readily detected but appeared globally reduced in GBM patients' exosomes. Surprisingly, immunosuppressive programmed death-ligand 1 (PD-L1) is present in both patients' and normal donors' exosomes. Nanoscale flow cytometry confirms efficient exosome (<100 nm) isolation post-DGU but also demonstrates increase in microvesicles (>100 nm) in GBM patients' plasma pre-DGU. Serial DGU efficiently isolates plasma exosomes with distinct differences between GBM patients and normal donors, suggesting utility for non-invasive biomarker assessment. Initial results suggest global immunosuppression rather than increased circulating tumor-derived immunosuppressive exosomes, though further assessment is needed. Increased glioma patients' plasma microvesicles suggest these may also be a key source for biomarkers.


First Report of Brown Culm Streak of Phyllostachys praecox Caused by Arthrinium arundinis in Nanjing, China.
Early spring shoot bamboo (Phyllostachys praecox) is profitable for the production of bamboo shoots and is widely cultivated in Jiangsu and Zhejiang provinces in China. In recent years, a new disease named brown culm streak has commonly occurred in bamboo plantations. During initial stages, small yellow or sandy beige spots (1 to 2 mm diameter) develop on the culm. Spots expand and develop into fine brown streaks (10 to 15 × 1 to 2 mm), and the quantity of spots increases greatly at the mid-stage of the disease. The streaks continue to expand (10 to 30 × 2 to 3 mm) and may coalesce into brown patches that cover 70% of the culm surface in late stages of disease. Color of the internal bamboo cavity gradually changes from white to brown without an alcoholic odor, and plants eventually die. Diseased tissues (1 × 1.5 cm) were taken from the edges of brown streaks, surface disinfected in 0.1% HgCl2 for 3 min, rinsed in distilled water three times, and incubated on potato dextrose agar (PDA) at 25°C. Based on colony and conidial morphology, six different fungi (ZBY01, ZBY02, ZBY03, ZBY04, ZBY05, and ZBY06) were isolated. A suspension of hyphal fragments (106 pieces/ml) of each of the fungi was used to inoculate plants in the field. Healthy bamboo culms were stabbed with alcohol-sterilized needles after surface disinfection and wounds of each bamboo were inoculated with 3 ml hypha fragment suspensions by paintbrush, then covered with a piece of sterile plastic film. A control treatment was inoculated with sterile water. Each treatment had two replicates. Twenty days after inoculation, only fungus ZBY01 caused similar symptoms with the diseased bamboo in the field and was re-isolated from necrotic tissue of inoculated plants, thus fulfilling Koch's postulates. Mycelium of fungus ZBY01 covered entire PDA plates (90 mm diameter) after incubating for 6 days at 25°C and was white, flat, and floccose with moderate aerial mycelium. Mycelium consisted of smooth, hyaline, branched, septate hyphae, 2 to 3 μm diameter. Conidiophores were erect, septate, pale brown, smooth, and reduced to conidiogenous cells. Conidiogenous cells were pale brown, smooth, ampulliform, 6 to 9 μm long; the apical neck was 1 to 3 μm long, basal part 5 to 6 μm long. Conidia were 1-celled, dark brown to black, smooth, lenticular, 5 to 7 μm in diameter, 2 to 4 μm wide, lemon-shaped in side view, and spherical from top view with an equatorial ring. Based on morphological characteristics, it was identified as Arthrinium arundinis (Corda) Dyko & B. Sutton (1). The internal transcribed spacer (ITS) region from the isolate ZBY01 was amplified with PCR using ITS1-ITS4 primer pairs and the amplicon sequenced. Size of the sequenced region was 540 bp and had 99% identity with A. arundinis, which was in accord with morphological identification. The sequence was deposited in Gen Bank under accession number KF850624. To our knowledge, brown culm streak of P. praecox is a new disease of bamboo that has not been reported in other countries; however, A. arundinis has been reported as a pathogen on barley in Fairfield, Montana. Reference: (1) P. W. Crous and J. Z. Groenewald. A phylogenetic re-evaluation of Arthrinium. IMA Fungus. 4:133, 2013.


Estimation of in situ mating systems in wild sorghum (Sorghum bicolor (L.) Moench) in Ethiopia using SSR-based progeny array data: implications for the spread of crop genes into the wild.
Because transgenic sorghum (Sorghum bicolor L.) is being developed for Africa, we investigated the potential for transgenes to spread to conspecific wild/weedy sorghum populations in Ethiopia, which is considered the centre of origin of cultivated sorghum. In the current study, the extent of outcrossing, and uniparental and biparental inbreeding were investigated in seven wild/weedy sorghum populations collected at elevations ranging from 631 to 1709 m. Based on allele frequency data of 1120 progenies and 140 maternal plants from five polymorphic microsatellite markers, outcrossing rates were estimated using standard procedures. The average multilocus outcrossing rate was 0.51, with a range of 0.31-0.65 among populations, and the family outcrossing rate was in the extreme range of 0 to 100%. The highest outcrossing (t(m) = 0.65) was recorded in a weedy population that was intermixed with an improved crop variety in Abuare (Wello region). It was also observed that the inbreeding coefficient of the progenies (F(p)) tend to be more than the inbreeding coefficient of both their maternal parents (F(m)) and the level of inbreeding expected at equilibrium (F(eq)), which is a characteristic of predominantly outbreeding species. Biparental inbreeding was evident in all populations and averaged 0.24 (range = 0.10-0.33). The high outcrossing rates of wild/weedy sorghum populations in Ethiopia indicate a high potential for crop genes (including transgenes) to spread within the wild pool. Therefore, effective risk management strategies may be needed if the introgression of transgenes or other crop genes from improved cultivars into wild or weedy populations is deemed to be undesirable.


Vestibulo-ocular reflex abnormality in Vogt-Koyanagi-Harada syndrome.
The eye movements of 15 patients with Vogt-Koyanagi-Harada (VKH) syndrome were analysed. Transient dizziness occurred in 60% of the patients. Eight patients (53%) exhibited horizontal jerk nystagmus that was completely inhibited by visual fixation. Eight cases (53%) exhibited the elevation of vestibulo-ocular reflex (VOR) gain in darkness. Six of the patients with nystagmus had defective smooth pursuit movements with reduced gain on the side ipsilateral to the nystagmus. Saccadic and optokinetic eye movements were intact, and visual vestibular interaction was also normal. Impaired eye movements in VKH syndrome may be caused by asymmetry of the vestibular function secondary to the labyrinthine inflammation.


The effect of dihydropyrazines on lipopolysaccharide-stimulated human hepatoma HepG2 cells via regulating the TLR4-MyD88-mediated NF-κB signaling pathway.
Dihydropyrazines (DHPs), including 3-hydro-2,2,5,6-tetramethylpyrazine (DHP-3), are glycation products that are spontaneously generated in vivo and ingested via food. DHPs generate various radicals and reactive oxygen species (ROS), which can induce the expression of several antioxidant genes in HepG2 cells. However, detailed information on DHP-response pathways remains elusive. To address this issue, we investigated the effects of DHP-3 on the nuclear factor-κB (NF-κB) pathway, a ROS-sensitive signaling pathway. In lipopolysaccharide-stimulated (LPS-stimulated) HepG2 cells, DHP-3 decreased phosphorylation levels of inhibitor of NF-κB (IκB) and NF-κB p65, and nuclear translocation of NF-κB p65. In addition, DHP-3 reduced the expression of Toll-like receptor 4 (TLR4) and the adaptor protein myeloid differentiation primary response gene 88 (MyD88). Moreover, DHP-3 suppressed the mRNA expression of tumor necrosis factor-alpha (TNFα), and interleukin-1 beta (IL-1β). Taken together, these results suggest that DHP-3 acts as a negative regulator of the TLR4-MyD88-mediated NF-κB signaling pathway.


[Mucinous adenocarcinoma of the prostate. A case report and analysis of the literature].
An 80-year-old man, who had been treated for colon cancer 25 years ago, presented with gross hematuria. Rectal examination revealed a soft nodule in the right lobe. The serum prostatic specific antigen (PSA) was elevated to 5.2 ng/ml, while prostatic acid phosphate (PAP) was normal. Transrectal ultrasound revealed a hypoechoic mass in peripheral zone of the prostate and dilated seminal vesicle. A needle biopsy of the prostate showed mucinous adenocarcinoma. Under the diagnosis of prostatic tumor with seminal vesicle involvement, radical prostatectomy was performed. Histological findings showed organ confined cancer, of which most was composed of extracellular mucin lakes. Immunohistochemical study revealed the tumor cells positive for PSA and PAP. Mucinous adenocarcinoma of the prostate has been known to be clinically different from non-mucinous adenocarcinoma, in that the former is insensitive to hormonal therapy, is rarely associated with elevated PAP and rarely metastasize to the bone. But our analysis of the literatures is Japan showed no significant difference clinically between mucinous and non mucinous prostatic adenocarcinoma. However mucinous adenocarcinoma with signet ring cell rarely responds to hormonal therapy, which should not be classified to true mucinous adenocarcinoma in the current criteria. True mucinous adenocarcinoma could be a variant of prostatic adenocarcinoma, which is peripheral origin and should be treated like non-mucinous adenocarcinoma.


Sensory impairments and autism: a re-examination of causal modelling.
Sensory impairments are widely reported in autism, but remain largely unexplained by existing models. This article examines Kanner's causal reasoning and identifies unsupported assumptions implicit in later empirical work. Our analysis supports a heterogeneous causal model for autistic characteristics. We propose that the development of a standardised framework for analysing autistic characteristics would facilitate the identification of sub-groups and the location of biological markers for genetic variation. We also support a neuroconstructivist model proposing that peripheral sensory abnormalities disrupt compilation of complex skills; impact on synaptogenesis, synaptic pruning and myelination; and subsequently manifest themselves as autistic behaviours. This model explains some of the structural and functional brain abnormalities and many of the perceptual, cognitive and attentional features found in autism.


Ecopipam as a pharmacologic treatment of stuttering.
Stuttering, also known as childhood-onset fluency disorder, is a chronic neurodevelopmental disorder that affects 1% of the population and can greatly impact an individual's social, occupational, and academic functioning. Prior research has shown dopamine D2 antagonists are effective in reducing the severity of stuttering symptoms, but these compounds can be associated with metabolic and movement disorder adverse effects. Ecopipam is an investigational medication that acts as a selective dopamine D1 receptor antagonist. This mechanism should reduce the likelihood of metabolic and movement disorder adverse effects of D2 antagonists. This open-label pilot study investigated ecopipam in the treatment of adults who stutter. The results showed that a majority of participants demonstrated improvement in their stuttering. The medication was well tolerated. These positive, preliminary findings suggest that a doubleblind, randomized controlled clinical trial to examine the efficacy of ecopipam in the treatment of stuttering is warranted.


Heat stress, the follicle, and its enclosed oocyte: mechanisms and potential strategies to improve fertility in dairy cows.
Reduced reproductive performance of lactating cows during the summer is associated with decreased thermoregulatory competence due to intensive genetic selection for high milk production. This review examines the immediate and delayed effects of heat stress on follicular function and describes some potential strategies for their alleviation. It focuses on how heat stress affects the follicle and its enclosed oocyte, suggesting that perturbations in the follicular microenvironment, to which the oocytes are exposed for long periods of development, reduce their developmental competence. Among the potential alterations are reduction in gonadotropin secretion, alteration in follicular growth, attenuation of dominance, and disruption of steroidogenesis. Evaporative cooling methods are the most common strategy used to alleviate the effect of heat stress; however, there is a compelling need to find additional ways to improve fertility during the summer and autumn. Hormonal treatment to enhance removal of the impaired follicles by synchronization of follicular waves with GnRH and PGF2 alpha is suggested. An alternative method is stimulation of follicular growth by a brief treatment with bST or FSH. Other strategies, such as timed AI and embryo transfer, have been recently used, making the optimization of embryo cryopreservation procedures highly relevant. Protection of the ovarian pool of oocytes from thermal stress via nutritional manipulations or administration of antioxidants or other survival factors should also be considered. A better understanding of the underlying mechanisms by which heat stress impairs fertility may lead to the development of additional approaches to alleviate these effects.


Chicken Ig-like receptor B2, a member of a multigene family, is mainly expressed on B lymphocytes, recruits both Src homology 2 domain containing protein tyrosine phosphatase (SHP)-1 and SHP-2, and inhibits proliferation.
Ig-like inhibitory receptors have been the focus of intensive research particularly in mouse and human. We report the cloning and characterization of three novel inhibitory chicken Ig-like receptors (CHIR) that display a two Ig-domain extracellular structure, a transmembrane region lacking charged residues and a cytoplasmic domain containing two ITIM. The localization of all receptors to a small genomic region and the hybridization pattern indicated that they belong to a multigene family. The genomic structure of the extracellular domain with two exons encoding the signal peptide and single exons for each Ig domain resembled that of all human leukocyte Ig-like receptors and killer cell Ig-like receptors, whereas the exons encoding the C terminus displayed a structure closely resembling killer cell Ig-like receptor genes. A mAb generated against one receptor designated CHIR-B2 reacted with all B cells and a small T cell subset, but not with monocytes, thrombocytes, or various leukocyte-derived cell lines. The mAb immunoprecipitated a 46-kDa protein from bursal cells and transfected cells. The Src homology 2 domain containing protein tyrosine phosphatase (SHP)-2 bound to CHIR-B2 even in unstimulated cells, whereas pervanadate treatment induced the tyrosine phosphorylation and recruitment of several CHIR-B2-associated proteins including SHP-1 and increased levels of SHP-2. Moreover, mAb cross-linking of CHIR-B2 reduced the proliferation of a stable transfected cell line. Together, we have identified a multigene family containing multiple CHIR including one receptor designated CHIR-B2 that is mainly expressed on B lymphocytes and inhibits cellular proliferation by recruitment of SHP-1 and SHP-2.


A community of curious souls: an analysis of commenting behavior on TED talks videos.
The TED (Technology, Entertainment, Design) Talks website hosts video recordings of various experts, celebrities, academics, and others who discuss their topics of expertise. Funded by advertising and members but provided free online, TED Talks have been viewed over a billion times and are a science communication phenomenon. Although the organization has been derided for its populist slant and emphasis on entertainment value, no previous research has assessed audience reactions in order to determine the degree to which presenter characteristics and platform affect the reception of a video. This article addresses this issue via a content analysis of comments left on both the TED website and the YouTube platform (on which TED Talks videos are also posted). It was found that commenters were more likely to discuss the characteristics of a presenter on YouTube, whereas commenters tended to engage with the talk content on the TED website. In addition, people tended to be more emotional when the speaker was a woman (by leaving comments that were either positive or negative). The results can inform future efforts to popularize science amongst the public, as well as to provide insights for those looking to disseminate information via Internet videos.


Innovations in Rwanda's health system: looking to the future.
Rwanda is making substantial progress towards improvement of health and is working towards achievement of the Millennium Development Goals, which is a challenging task because the country has had genocide in 1994, has few natural resources, is landlocked, and has high population growth. Like many impoverished sub-Saharan countries, Rwanda's health system has had an uncoordinated plethora of donors, shortage of health staff, inequity of access, and poor quality of care in health facilities. This report describes three health system developments introduced by the Rwandan government that are improving these barriers to care-ie, the coordination of donors and external aid with government policy, and monitoring the effectiveness of aid; a country-wide independent community health insurance scheme; and the introduction of a performance-based pay initiative. If these innovations are successful, they might be of interest to other sub-Saharan countries. However, Rwanda still does not have sufficient financial resources for health and will need additional external aid for some time to attain the Millennium Development Goals.


[Paroxysmal nocturnal hemoglobinuria. Diagnosis aided by a monoclonal antibody directed against the decay accelerating factor glycoprotein].
The laboratory diagnosis of paroxysmal nocturnal haemoglobinuria (also called Marchiafava-Micheli disease) is based on the sensitivity of the patient's red cells to complement-induced lysis. In view of the clonal expression of the disease, haemolysis tests are difficult to interpret when the abnormal red cell population is small. The sensitivity of abnormal red cells to haemolysis is due to the absence of proteins attached to the cell membrane by a phosphatidyl-inositol link, which intervene in the regulation of the complement-induced lysis mechanism. Using a monoclonal antibody directed against one of these proteins, the decay accelerating factor (DAF, protein CD 55), makes it possible to diagnose paroxysmal nocturnal haemoglobinuria. DAF expression on patients' blood cells was measured by quantitative agglutination and by indirect flow cytometry. The agglutination test using polybren is a fast detection method, but it may be uninterpretable, notably in cases with positive antiglobulin (Coombs') test. In contrast, DAF expression measured by indirect flow cytometry correlates perfectly with measurement of red cell sensitivity by haemolysis tests. Using the monoclonal antibody by indirect flow cytometry is the method of choice to confirm the diagnosis of paroxysmal nocturnal haemoglobinuria and to measure the proportions of normal and abnormal red cells in case of haematological disorder.


[Pros and cons of preservatives in eyedrops. Questionnaire for practitioners and experimental studies with reference to the requirements of the German Pharmacopoeia of August 1978].
The first part of this paper deals with the regulations in the DAB 8/78 stating that eye-drops are to be preserved. A questionnaire prepared by the German Association of Ophthalmologists is analyzed. The four questions put to 353 ophthalmologists and answered by 350 of these concern the need for unpreserved eye-drops because of the danger of allergization; the expiry date once the bottle has been opened; infections due to eye-drops without preservatives; and the need for eye-drops made up by pharmacists. The second part deals with studies on the pH-values of lacrimal fluid in cases of normal and decreased lacrimation, as well as with the bactericidal action of the normal tear fluid containing lysozyme and lactotransferrine and various eye-drops containing preservatives. The authors conclude that the general addition of preservatives to eye-drops, especially to those containing antiphlogistic and astringent substances, is unnecessary. Concerning the expiry date on the bottle, it is suggested that the period of use be extended to three months, thus helping to cut costs.


Temporal sequence of major biochemical events during blood bank storage of packed red blood cells.
We used sensitive spectroscopic techniques to measure changes in Band 3 oligomeric state during storage of packed red blood cells (RBC); these changes were compared to metabolic changes, RBC morphology, cholesterol and membrane protein loss, phospholipid reorganisation of the RBC membrane, and peroxidation of membrane lipid. The aim of the study was to temporally sequence major biochemical events occurring during cold storage, in order to determine which changes may underlie the structural defects in stored RBC. Fifteen RBC units were collected from normal volunteers and stored under standard blood bank conditions; both metabolic changes and lipid parameters were measured by multiple novel assays including a new mass spectrometric measurement of isoprostane (lipid peroxidation) and flow cytometric assessment of CD47 expression. Band 3 oligomeric state was assessed by time-resolved phosphorescence anisotropy, and RBC morphology by microscopy of glutaraldehyde-fixed RBC. Extracellular pH decreased and extracellular potassium increased rapidly during cold storage. Band 3 on the RBC membrane aggregated into large oligomers early in the storage period and coincident with changes in RBC morphology. Membrane lipid changes, including loss of unesterified cholesterol, lipid peroxidation and expression of CD47, also changed early during the storage period. In contrast loss of acetylcholinesterase activity and haemolysis of RBC occurred late during storage. Our results demonstrate that changes in the macromolecular organisation of membrane proteins on the RBC occur early in storage and suggest that lipid peroxidation and/or oxidative damage to the membrane are responsible for irreversible morphological changes and loss of function during red cell storage.


Combat and Operational Stress Control.
Combat and Operational Stress (COS) includes all the physiological and emotional stresses encountered as a direct result of the dangers and mission demands of combat. Combat and Operational Stress Control (COSC) in the US. Army may be defined as programs developed and actions taken by military leadership to prevent, identify, and manage adverse Combat and Operational Stress Reactions (COSR) in units. This program optimizes mission performance, conserves the fighting strength, and prevents or minimizes adverse effects of COSR on Soldiers and their physical, psychological, intellectual, and social health. Its goal is to return Soldiers to duty expeditiously. COSC activities include routine screening of individuals when recruited; continued surveillance throughout military service, especially before, during, and after deployment; and continual assessment and consultation with medical and other personnel from garrison to the battlefield.


Transplacental transfer of zidovudine in the near-term pregnant baboon.
Approximately one third of infants born to human immunodeficiency virus type 1 seropositive mothers have evidence of infection or of acquired immunodeficiency syndrome by the age of 18 months. One fifth of infected infants also have died by age 18 months. This prevalence, combined with the demonstration that zidovudine (formerly azidothymidine) can decrease mortality and the frequency of opportunistic infections in patients with acquired immunodeficiency syndrome or acquired immunodeficiency syndrome--related complex, may lead to increasing use of azidothymidine in pregnancy despite a paucity of information regarding its pharmacokinetics. To further investigate the distribution of azidothymidine and its inactive metabolite 5'-glucuronide azidothymidine in the mother, fetus, and amniotic fluid, 12 near-term pregnant baboons were given oral azidothymidine (21 mg/kg/day in four divided doses every 6 hours, equivalent to the usual nonpregnant human dose of 1500 mg/day). Specimens of maternal blood, fetal arterial blood obtained by percutaneous umbilical cord blood sampling, and amniotic fluid were obtained after from one to 17 doses of azidothymidine. Azidothymidine levels were measured by radioimmunoassay with the INCSTAR commercial radioimmunoassay kit and using Escherichia coli beta-glucuronidase for determination of 5'-glucuronide azidothymidine levels. Paired analyses revealed significant concentration gradients between amniotic fluid, fetal serum, and maternal serum for both azidothymidine (p less than 0.019) and 5'-glucuronide azidothymidine (p less than 0.002). The amniotic fluid 5'-glucuronide azidothymidine level increased with increasing doses of azidothymidine despite the fact that the maternal azidothymidine and 5'-glucuronide azidothymidine concentrations were unchanged. This accumulation of amniotic fluid 5'-glucuronide azidothymidine may provide a functional drug reservoir and contribute to the higher fetal concentrations of the medication and its metabolite. Alternatively, the higher fetal levels may represent slower clearance in the fetus than in the mother. Further studies appear warranted with respect to possible adverse fetal effects, especially bone marrow suppression with prolonged and chronic exposure to azidothymidine.


An initial investigation of associations between dopamine-linked genetic variation and smoking motives in African Americans.
Nicotine dependence (ND) is a heterogeneous phenotype with complex genetic influences that may vary across ethnicities. The use of intermediate phenotypes may clarify genetic influences and reveal specific etiological pathways. Prior work in European Americans has found that the four Primary Dependence Motives (PDM) subscales (Automaticity, Craving, Loss of Control, and Tolerance) of the Wisconsin Inventory of Smoking Motives represent core features of nicotine dependence and are promising intermediate phenotypes for understanding genetic pathways to ND. However, no studies have examined PDM as an intermediate phenotype in African American smokers, an ethnic population that displays unique patterns of smoking and genetic variation. In the current study, 268 African American daily smokers completed a phenotypic assessment and provided a sample of DNA. Associations among haplotypes in the NCAM1-TTC12-ANKK1-DRD2 gene cluster, a dopamine-related gene region associated with ND, PDM intermediate phenotypes, and ND were examined. Dopamine-related genetic variation in the DBH and COMT genes was also considered on an exploratory basis. Mediational analysis was used to test the indirect pathway from genetic variation to smoking motives to nicotine dependence. NCAM1-TTC12-ANKK1-DRD2 region variation was significantly associated with the Automaticity subscale and, further, Automaticity significantly mediated associations among NCAM1-TTC12-ANKK1-DRD2 cluster variants and ND. DBH was also significantly associated with Automaticity, Craving, and Tolerance; Automaticity and Tolerance also served as mediators of the DBH-ND relationship. These results suggest that PDM, Automaticity in particular, may be a viable intermediate phenotype for understanding dopamine-related genetic influences on ND in African American smokers. Findings support a model in which putatively dopaminergic variants exert influence on ND through an effect on patterns of automatic routinized smoking.


Increased neurogenesis in the dentate gyrus after transient global ischemia in gerbils.
Neurogenesis in the dentate gyrus of adult rodents is regulated by NMDA receptors, adrenal steroids, environmental stimuli, and seizures. To determine whether ischemia affects neurogenesis, newly divided cells in the dentate gyrus were examined after transient global ischemia in adult gerbils. 5-Bromo-2'-deoxyuridine-5'-monophosphate (BrdU) immunohistochemistry demonstrated a 12-fold increase in cell birth in the dentate subgranular zone 1-2 weeks after 10 min bilateral common carotid artery occlusions. Two minutes of ischemia did not significantly increase BrdU incorporation. Confocal microscopy demonstrated that BrdU immunoreactive cells in the granule cell layer colocalized with neuron-specific markers for neuronal nuclear antigen, microtubule-associated protein-2, and calbindin D28k, indicating that the newly divided cells migrated from the subgranular zone into the granule cell layer and matured into neurons. Newborn cells with a neuronal phenotype were first seen 26 d after ischemia, survived for at least 7 months, were located only in the granule cell layer, and comprised approximately 60% of BrdU-labeled cells in the granule cell layer 6 weeks after ischemia. The increased neurogenesis was not attributable to entorhinal cortical lesions, because no cell loss was detected in this region. Ischemic preconditioning for 2 min, which protects CA1 neurons against subsequent ischemic damage, did not prevent increased neurogenesis in the granule cell layer after a subsequent severe ischemic challenge. Thus, ischemia-induced dentate neurogenesis is not attributable to CA1 neuronal loss. Enhanced neurogenesis in the dentate gyrus may be a compensatory adaptive response to ischemia-associated injury and could promote functional recovery after ischemic hippocampal injury.


The use of patient symptoms to screen for serious back problems.
Even when a patient is referred by a physician, the physical therapist must remain alert to the possibility that the patient may require medical care outside the realm of physical therapy. Physical therapists must be able to screen low back pain patients to identify those who have serious low back problems which require additional diagnostic evaluation and treatment by a physician. It is important for physical therapists to know which symptoms and signs or combination of symptoms and signs best indicate the likelihood of a serious problem. The purpose of this study was to test the sensitivity and specificity of low back pain symptoms in distinguishing individuals with a benign low back problem from those requiring surgical or medical intervention. Demographic and clinical data were collected retrospectively from a standardized low back pain questionnaire located in the medical records of 174 low back pain patients. Patients were classified as having a benign low back problem (N = 41) or a serious low back problem (N = 133) based on surgical findings or long term follow-up. Some individual symptoms had high specificity, but none had high sensitivity. To improve sensitivity while attempting to maintain moderate specificity, a number of symptoms were considered in parallel. The highest combination of sensitivity (.87) and specificity (.50) was obtained by combining in parallel the symptoms of unable to sleep, awakened and unable to fall back to sleep, medication required to sleep, and pain worsened by walking.


Effects of hemodialysis on plasma oxylipins.
Chronic kidney disease (CKD) is an important risk factor for cardiovascular and all-cause mortality. Survival rates among end-stage renal disease (ESRD) hemodialysis patients are poor and most deaths are related to cardiovascular disease. Oxylipins constitute a family of oxygenated natural products, formed from fatty acid by pathways involving at least one step of dioxygen-dependent oxidation. They are derived from polyunsaturated fatty acids (PUFAs) by cyclooxygenase (COX) enzymes, by lipoxygenases (LOX) enzymes, or by cytochrome P450 epoxygenase. Oxylipins have physiological significance and some could be of regulatory importance. The effects of decreased renal function and dialysis treatment on oxylipin metabolism are unknown. We studied 15 healthy persons and 15 CKD patients undergoing regular hemodialysis treatments and measured oxylipins (HPLC-MS lipidomics) derived from cytochrome P450 (CYP) monooxygenase and lipoxygenase (LOX)/CYP ω/(ω-1)-hydroxylase pathways in circulating blood. We found that all four subclasses of CYP epoxy metabolites were increased after the dialysis treatment. Rather than resulting from altered soluble epoxide hydrolase (sEH) activity, the oxylipins were released and accumulated in the circulation. Furthermore, hemodialysis did not change the majority of LOX/CYP ω/(ω-1)-hydroxylase metabolites. Our data support the idea that oxylipin profiles discriminate ESRD patients from normal controls and are influenced by renal replacement therapies.


A quantitative and qualitative description of electromyographic linear envelopes for synergy analysis.
The muscular synergy patterns of human locomotion can be described by the phasic activity of electromyographic linear envelopes (LE) and the interphasic spatio-temporal relations. To represent the phasic activity, the LE is modeled as the summation of Gaussian pulses of various lengths. The parameters of interest are the temporal features: time, duration, and amplitude of the phases of activity. A maximum likelihood approach to the parameter estimation for a mixture of normal distributions is adopted for extracting the temporal features. Based on the derived temporal features, a set of relational descriptors can be defined to describe the spatio-temporal relations between the multichannel phasic activities. The strength of this approach is not only that the phasic activity of LE can be quantitatively represented accurately, but also that the resulting synergy patterns can be easily interpreted by observers.


Qualitative analysis of facilitators and barriers to centre- and home-based exercise training in breast cancer patients - a Swiss tertiary centre experience.
Exercise is an effective therapy for breast cancer patients to reduce fatigue and to improve health-related quality of life and physical function. Yet breast cancer patients often do not meet the recommended physical activity guidelines. To better understand why recommendations are not met and to improve long-term physical activity maintenance, this study aimed at identifying facilitators and barriers of breast cancer survivors to supervised, centre-based exercise within a cardio-oncological rehabilitation programme and to unsupervised, home-based exercise both during and after the completion of the programme, as well as strategies used to manage these barriers. Breast cancer patients who had previously completed a structured centre-based exercise programme at a Swiss tertiary centre were recruited by mailed invitation letter. Semi-structured telephone interviews were conducted with consenting patients and subsequent thematic analysis was performed to identify common themes. Of the 37 eligible breast cancer patients, 19 patients (51%, mean age 48.9 ± 9.7 years) responded to our invitation. Baseline characteristics did not differ from the total eligible population. General facilitators for exercise were anticipated and experienced benefits on physical and mental health and enjoyment of exercise. Facilitators specific for supervised centre-based exercise were social support, accountability and the provision of structured exercise by the programme. Centre-based exercise barriers included physical, psychological and environmental barriers, whereby psychological barriers were reported predominantly in the context of home-based exercise. Strategies to manage these barriers were diverse and included the adaptation of training circumstances, behaviour change strategies and strategies to deal with side effects. This first study on facilitators of and barriers to exercise in breast cancer patients in Switzerland identified more barriers, particularly psychological barriers, for unsupervised home-based exercise than for supervised centre-based exercise. These findings support the importance of providing structured supervised exercise programmes for breast cancer patients and suggest that a special focus should be directed at the transition from supervised to self-organized exercise in order to enhance and maintain long-term exercise participation.


The effects of long- and short-term maternal caffeine ingestion on human fetal breathing and body movements in term gestations.
The possible effects of long- and short-term maternal ingestion of caffeine during normal human pregnancy on the breathing and body movements of third-trimester fetuses were studied in 14 patients, selected by a dietary questionnaire, and divided into two equal groups: high consumers (greater than 500 mg/day) (group 1) and low consumers (less than 250 mg/day) (group 2). All mothers followed a standard study protocol and underwent overnight fasting; studies began with a 30-minute control period, followed by oral administration of 200 mg caffeine, and a 180-minute subsequent observation period with continued maternal fasting. Blood samples for glucose and caffeine were obtained every 30 minutes and continuous recording of fetal breathing and body movements were entered on a microcomputer for off-line analysis. The two groups were similar for all obstetric outcome features. Plasma glucose levels were similar and constant in both groups whereas caffeine levels increased significantly at 60 minutes after administration; mean plasma caffeine levels were significantly higher in group 1 than in group 2 at all intervals. Fetal breathing rates and body movement incidences were similar in both groups before and after caffeine administration. Fetal breathing movement incidence decreased significantly in group 2 but was sustained at baseline levels in group 1 throughout the study. High long-term ingestion of caffeine during pregnancy is associated with higher maternal plasma caffeine levels and fetal breathing activity when compared with low caffeine ingestion. Short-term administration of 200 mg caffeine does not appear to have a significant physiologic impact on these activities.


Hyperelastic Nanocellulose-Reinforced Hydrogel of High Water Content for Ophthalmic Applications.
A nanocellulose-reinforced poly(vinyl alcohol) hydrogel material of exceptionally high water content for ophthalmic applications is presented (>90 wt %), which also features a hitherto unprecedented combination of optical, mechanical, viscoelastic, oxygen permeability, and biocompatibility properties. The hydrogel combines the desired softness with remarkable strain-dependent mechanical strength and thereby demonstrates hyperelastic, rubber-like mechanical properties. The observed unusual mechanical behavior is due to both high water content and the combination of relatively stiff cellulose nanowhiskers entangled in a soft polymer matrix of poly(vinyl alcohol) (PVA), thus mimicking the structural characteristics of the cornea's main constituents, i.e., water and collagen.


Distinct SoxB1 networks are required for naïve and primed pluripotency.
Deletion of Sox2 from mouse embryonic stem cells (ESCs) causes trophectodermal differentiation. While this can be prevented by enforced expression of the related SOXB1 proteins, SOX1 or SOX3, the roles of SOXB1 proteins in epiblast stem cell (EpiSC) pluripotency are unknown. Here, we show that Sox2 can be deleted from EpiSCs with impunity. This is due to a shift in the balance of SoxB1 expression in EpiSCs, which have decreased Sox2 and increased Sox3 compared to ESCs. Consistent with functional redundancy, Sox3 can also be deleted from EpiSCs without eliminating self-renewal. However, deletion of both Sox2 and Sox3 prevents self-renewal. The overall SOXB1 levels in ESCs affect differentiation choices: neural differentiation of Sox2 heterozygous ESCs is compromised, while increased SOXB1 levels divert the ESC to EpiSC transition towards neural differentiation. Therefore, optimal SOXB1 levels are critical for each pluripotent state and for cell fate decisions during exit from naïve pluripotency.


Strain-specific joint invasion and colonization by Lyme disease spirochetes is promoted by outer surface protein C.
Lyme disease, caused by Borrelia burgdorferi, B. afzelii and B. garinii, is a chronic, multi-systemic infection and the spectrum of tissues affected can vary with the Lyme disease strain. For example, whereas B. garinii infection is associated with neurologic manifestations, B. burgdorferi infection is associated with arthritis. The basis for tissue tropism is poorly understood, but has been long hypothesized to involve strain-specific interactions with host components in the target tissue. OspC (outer surface protein C) is a highly variable outer surface protein required for infectivity, and sequence differences in OspC are associated with variation in tissue invasiveness, but whether OspC directly influences tropism is unknown. We found that OspC binds to the extracellular matrix (ECM) components fibronectin and/or dermatan sulfate in an OspC variant-dependent manner. Murine infection by isogenic B. burgdorferi strains differing only in their ospC coding region revealed that two OspC variants capable of binding dermatan sulfate promoted colonization of all tissues tested, including joints. However, an isogenic strain producing OspC from B. garinii strain PBr, which binds fibronectin but not dermatan sulfate, colonized the skin, heart and bladder, but not joints. Moreover, a strain producing an OspC altered to recognize neither fibronectin nor dermatan sulfate displayed dramatically reduced levels of tissue colonization that were indistinguishable from a strain entirely deficient in OspC. Finally, intravital microscopy revealed that this OspC mutant, in contrast to a strain producing wild type OspC, was defective in promoting joint invasion by B. burgdorferi in living mice. We conclude that OspC functions as an ECM-binding adhesin that is required for joint invasion, and that variation in OspC sequence contributes to strain-specific differences in tissue tropism displayed among Lyme disease spirochetes.


Cannabinol inhibits oxytosis/ferroptosis by directly targeting mitochondria independently of cannabinoid receptors.
The oxytosis/ferroptosis regulated cell death pathway recapitulates many features of mitochondrial dysfunction associated with the aging brain and has emerged as a potential key mediator of neurodegeneration. It has thus been proposed that the oxytosis/ferroptosis pathway can be used to identify novel drug candidates for the treatment of age-associated neurodegenerative diseases that act by preserving mitochondrial function. Previously, we identified cannabinol (CBN) as a potent neuroprotector. Here, we demonstrate that not only does CBN protect nerve cells from oxytosis/ferroptosis in a manner that is dependent on mitochondria and it does so independently of cannabinoid receptors. Specifically, CBN directly targets mitochondria and preserves key mitochondrial functions including redox regulation, calcium uptake, membrane potential, bioenergetics, biogenesis, and modulation of fusion/fission dynamics that are disrupted following induction of oxytosis/ferroptosis. These protective effects of CBN are at least partly mediated by the promotion of endogenous antioxidant defenses and the activation of AMP-activated protein kinase (AMPK) signaling. Together, our data highlight the potential of mitochondrially-targeted compounds such as CBN as novel oxytotic/ferroptotic inhibitors to rescue mitochondrial dysfunction as well as opportunities for the discovery and development of future neurotherapeutics.


Creutzfeldt-Jakob Disease Mimicking Neurosyphilis: A Complex Presentation, Histopathological Findings, and Special Precautions for Autopsy.
Creutzfeldt-Jakob disease (CJD) is a complex and rapidly fatal prion infection of the central nervous system with characteristic clinical and pathological findings. Herein, we present the case of an 80-year-old man with a 2-month history of rapid cognitive decline and ataxic gait. He was found to have a positive rapid plasma reagin and fluorescent treponemal antibody absorption (FTA-ABS) upon clinical testing and was presumed to have neurosyphilis. His neurological status precipitously declined during his hospitalization and he died. A complete autopsy was performed, which revealed diffuse spongiform change throughout the cerebrum. Brain tissue was sent to the National Prion Disease Surveillance Center, where immunostaining for prion protein (3F4) showed granular deposits, confirming the diagnosis of CJD. There have been rare cases reported in which CJD was clinically suspected but neurosyphilis was confirmed at autopsy. To our knowledge, this is the first case to be published in which the clinical findings strongly favored neurosyphilis, but spongiform encephalopathy was identified at autopsy. We review the clinical, radiographic, electrophysiological, laboratory, and histopathological features of both diseases and discuss the overlapping findings and inherent diagnostic difficulties. We also review the recommended protocols for safely handling suspected prion-infected autopsy tissue. A heightened awareness of the features of CJD and other prion diseases is needed among forensic pathologists, neuropathologists, and general autopsy pathologists to understand how to safely handle the tissue to get definite diagnoses for the decedent's family members and clinical care team.


Language and theory of mind: a study of deaf children.
Theory-of-mind (ToM) abilities were studied in 176 deaf children aged 3 years 11 months to 8 years 3 months who use either American Sign Language (ASL) or oral English, with hearing parents or deaf parents. A battery of tasks tapping understanding of false belief and knowledge state and language skills, ASL or English, was given to each child. There was a significant delay on ToM tasks in deaf children of hearing parents, who typically demonstrate language delays, regardless of whether they used spoken English or ASL. In contrast, deaf children from deaf families performed identically to same-aged hearing controls (N=42). Both vocabulary and understanding syntactic complements were significant independent predictors of success on verbal and low-verbal ToM tasks.


Synthesis and biological evaluation of pyrophosphate mimics of thiamine pyrophosphate based on a triazole scaffold.
Novel triazole-based pyrophosphate analogues of thiamine pyrophosphate (TPP) have been synthesised and tested for inhibition of pyruvate decarboxylase (PDC) from Zymomonas mobilis. The thiazolium ring of thiamine was replaced by a triazole in an efficient two-step procedure. Pyrophosphorylation then gave extremely potent triazole inhibitors with K(I) values down to 20 pM, compared to a K(D) value of 0.35 microM for TPP. This triazole scaffold was used for further investigation and six analogues containing mimics of the pyrophosphate group were synthesised and tested for inhibition of PDC. Several effective analogues were found with K(I) values down to around 1 nM.


Effects of pre-experience of social exclusion on hypothalamus-pituitary-adrenal axis and catecholaminergic responsiveness to public speaking stress.
Being socially excluded is associated with a variety of psychological changes and with an increased risk of disease. Today, the immediate physiological consequences of being socially excluded are not well understood. In two recent studies employing a standardized exclusion paradigm (Cyberball) we found social exclusion in this virtual game did not alter cortisol secretion directly. However, exclusion pre-experience suppresses the normal cortisol response to public speaking stress in women. The present study aims to replicate our previous finding and further elucidate it by analyzing for the first time whether this alteration of cortisol-responsiveness is associated to ACTH and whether the catecholaminergic system is affected as well. Women were randomly assigned to Cyberball-induced exclusion (SE, n = 22) or inclusion (SI, n = 21), respectively. Immediately afterwards they were subjected to public speaking stress. Salivary cortisol, plasma ACTH, catecholamines and estradiol were assessed as were psychological distress and mood. Cyberball exclusion led to a highly significant immediate increase in negative affect in excluded women. After public speaking negative affect in included women increased as well and groups no longer differed. We replicate our previous finding of cortisol non-responsiveness to public speaking stress after exclusion pre-experience and find this effect to be significantly correlated with ACTH alterations. No such effects are observed for catecholamines. We replicated our previous study result of a suppressed cortisol stress response after a short exclusion experience via Cyberball, thereby underlining the profound effects of social exclusion on a subsequent cortisol stress response. This further demonstrates that these alterations are associated with ACTH. Lack of effects on catecholamines is discussed in view of the tend-and-befriend hypothesis but also from a methodological perspective.


[Rare combination of acromegaly, syringomyelia and Chiari I malformation].
Chiari I Malformation (CM) is a congenital pathology of rombencephalon development characterized by disparity of brain structures and bony compartment in posterior fossa. The incidence of Chiari I malformation ranges from 3.3 to 8.2 in 100 000. In 80% of cases CM is combined with syringomyelia. Combination of CM and pituitary adenoma (PA) is rare condition with just a few cases described in literature. Current article represents a case of successful treatment of patient with CM and PA combination and a 5-year follow-up.


Quantification of contamination levels and particular risk of Salmonella spp. in pigs in slaughterhouses in Chiang Mai and Lamphun provinces, Thailand.
Salmonella spp. is one of the important foodborne pathogens, and the slaughtering process is recognized as a potential point of contamination and the spread of the pathogens. The three objectives of this study are first, to quantify the contamination levels of Salmonella spp. in pig skins and carcasses, second, to evaluate the outcomes from different pig supply sources and different practices at three critical steps (scalding, splitting, and washing) for Salmonella spp. contamination, and third, to assess risk of Salmonella spp. contamination in pork products after slaughtering level. The study was performed in three representative slaughterhouses in Chiang Mai and Lamphun provinces, Thailand. Investigation conducted from May 2013 through October 2013 found the overall prevalence and contamination levels mean to be 11.85% and 0.34 MPN/cm2, respectively. There was no statistically significant in Salmonella spp. prevalence and contamination levels detected with different patterns at the slaughterhouses which were supplied pigs from either co-operative or integrated farms. Factors found to reduce Salmonella spp. loads on carcasses included good practices, e.g., regular changing of water in the scalding tank after each batch and the use of chlorine in the washing step. Risk of Salmonella spp. contamination of pork products at the final stage of slaughtering was nearly 10%. Good practices and proper hygiene measures should be applied to minimize the risk of Salmonella spp. exposure in the slaughtering line, which can reduce the contamination pressure downstream at retail shops as well as for end consumers.


[The peptide modulation of immune reactions].
A dose-dependent immunomodulating effect of synthetic low-molecular weight peptides was found in CBA mice. Talcin and its analogue, rigin, tripeptide SKE, substance P and its analogue, and vasopressin were shown to produce an immunostimulating effect, whereas vasopressin tetrapeptide, arginyl-asparagine, and tripeptide SKD showed an immunosuppressive effect. The immunomodulatory effect of the peptides tested was associated with the presence of amino acids such as arginine, lysine, tyrosine, glutamic acid in their chemical structure. These amino acids are essential in the mechanisms of immune responses.


Ketone bodies metabolism during ischemic and reperfusion brain injuries following bilateral occlusion of common carotid arteries in rats.
To evaluate the in vivo alterations on ketone bodies metabolism after cerebral ischemia/reperfusion through an experimental model of brain ischemia induced by simple occlusion of common carotid arteries (CCAs) in Wistar rats. Forty-eight male Wistar rats were randomly distributed on two groups (S - Sham; T - Test) and further redistributed into four times sets of study. After bilateral occlusion of CCAs for 30 min, the animals of group T were allowed reperfusion for 0, 5, 10 and 15 min. Samples of cerebral tissue and systemic arterial blood were collected and the metabolites acetoacetate (ACT) and beta-hydroxybutyrate (BHB) were determined. Cerebral ACT and BHB levels increased significantly in Group T after 30 min of carotid occlusion (time 0). The highest brain ketone bodies (ACT+BHB) concentration was verified at 5 min of reperfusion, decreasing after 10 min of recirculation. Systemic ketone bodies levels increased similarly between test and sham groups. Group S demonstrated a significant increase in cerebral and systemic ACT and BHB concentrations mainly after 40-45 min of study. The partial transient acute global brain ischemia induced by the bilateral carotid occlusion in Wistar rats triggered ketogenesis probably due to a central stimulation of catecholamine secretion. There was an increased cerebral uptake of ketone bodies following brain ischemia, reaffirming these metabolites as alternative energy substrates under conditions of cerebral metabolic stress as well as its potential role on neuroprotection. The greatest changes in ketone bodies metabolism were verified at initial minutes of recirculation as a result of the reperfusion injury phenomenon.


Properties of fructose-1,6-bisphosphate aldolase from Escherichia coli: an NMR analysis.
A class II Zn(2+)-dependent fructose-1,6-bisphosphate (FBP)- aldolase was purified from an overproducer strain of Escherichia coli and characterized by standard biochemical techniques and 13C NMR spectroscopy. The principal finding of these studies was identification, by 13C NMR spectroscopy, of an enzyme-bound reaction intermediate, the enediol(ate) form of dihydroxyacetone phosphate (DHAP). Formation of this intermediate requires the presence of Zn2+ and is pH dependent, with increasing amounts of this tautomer appearing at alkaline pH's. This pH dependence closely parallels the pH activity profile of the enzyme, suggesting an involvement of the enediol-DHAP form in the reaction pathway. In addition to these results the following observations were made on this enzyme: (a) E. coli FBP aldolase binds and utilizes only the carbonyl forms of FBP and DHAP; (b) the function of Zn2+ in this metalloaldolase appears to be polarization of the C = O bond of DHAP; (c) activity of this enzyme is unaffected by glycolytic intermediates or nucleotide phosphates such as ATP. Although these studies provide some information about the catalytic mechanism of E. coli FBP aldolase, they do not provide an explanation for the apparent regulation of this enzyme reported in previous in vivo NMR studies. While the possibility that the enzyme is allosterically regulated cannot be excluded at this time, an interesting possibility suggested by this and other studies is that in E. coli glycolytic substrates may be channeled through a multienzyme complex.


[Structural and functional state of the erythrocyte membrane in experimental carcinogenesis].
Structural and functional state of erythrocyte surface membrane was studied in C3H and C57B1/6 mice as well as in Wistar rats after 20-methylcholanthrene administration. It is shown that mice genetically susceptible to tumor growth as compared with mice resistant to carcinogenesis are characterized by an increased level of spinous erythrocytes (echinocytosis), higher membrane microviscosity and a tendency to increase polarity of their membrane lipid bilayer in the region of hydrophobic spine sound localization. The growth of chemically induced sarcomas was also accompanied by echinocytosis but with opposite changes in microviscosity and polarity of the erythrocyte membrane lipid bilayer. It is supposed that spinous erythrocyte transformation induced by different causes is based on different physicochemical factors.


Molecular mechanisms of the sedation and analgesia induced by xylazine on Wistar rats and PC12 cell.
In veterinary clinics, xylazine is commonly used as a sedative, analgesic agent that produces muscle relaxation. In this study, we aimed to explore the mechanism of action of xylazine both in vivo and in vitro. After determing the optimal dose of xylazine, 35 male Wistar rats were divided into seven groups (n=5 per group), including a control group (saline) and xylazine administration groups. Then, at six time points after xylazine administration indicators were evaluated for changes. Moreover, PC12 cells were co-cultured with xylazine, and extracellular regulated protein kinase (ERK) siRNA and protein kinase A (PKA) siRNA were transfected into cells to identify changes of relevant indicators. Our data showed that xylazine influenced the level of adenosine triphosphate (ATP) ase and cyclic adenosine monophosphate (cAMP), and regulated the expression of GluR1, ERK, PKA, cAMP-response element binding protein (CREB), and brain derived neurotrophic factor (BDNF) in the nervous system. However, xylazine did not significantly affect the expression of GluR2 and protein kinase C (PKC). Together, these results indicated that xylazine might exert sedation and analgesia by regulating the PKA/ERK/CREB signaling pathway.


The variable metabolic response to dietary isoflavones in humans.
The aim of this study was to better understand the metabolic fate of dietary estrogenic isoflavones in humans. Twelve volunteers were challenged with soya flour and urinary levels of the isoflavones daidzein (Da), genistein (Gen), and glycitein (Gly), and the isoflavonoid metabolites equol (Eq) and O-desmethylangolensin (O-Dma) determined by GC and GC-MS. Prior to challenge, Da, Gen, and Gly were present in the urine of all participants at low levels and Eq and O-Dma were present in 9/12 and 10/12 participants, respectively. Urinary levels of all five diphenols were increased in each individual on the day following challenge, returning to approximately prechallenge levels on the second or third day post-challenge. Mean post-challenge peak levels of the five diphenols compared with pre-challenge levels were Da (4x), Gen (8x), Gly (5x), Eq (45x), and O-Dma (66x). However, there was considerable individual variation in this metabolic response with peak levels of Eq showing the highest variation (1527x). An inverse relationship between Eq and O-Dma excretion was also found post-challenge suggesting individual variability in the preferred metabolic pathways of dietary isoflavones.


Use of emergency medical services for suspected acute cardiac ischemia among demographic and clinical patient subgroups: the REACT trial. Rapid Early Action for Coronary Treatment.
Barriers to the use of emergency medical services (EMS) and patient delay in seeking care can limit the receipt or effectiveness of reperfusion therapies and the availability of prehospital emergency cardiac care. The Rapid Early Action for Coronary Treatment (REACT) trial was designed to determine the impact of a community intervention on use of EMS among demographic and clinical subgroups of patients with suspected acute cardiac ischemia. A randomized controlled community trial was conducted in 20 pair-matched communities in the United States. One community from each pair received an 18-month, multicomponent community education program. Data were collected at 44 participating hospitals during a four-month baseline period and throughout the 18-month trial, using medical record abstracts to collect information on mode of transport to the hospital and other sociodemographic and clinical variables. Eligible patients were persons aged > or = 30 years presenting with chest pain or discomfort to emergency departments (EDs) who were admitted and discharged with a cardiac-related diagnoses (ICD 410-414, 427-429, 440, 786.9). The net change in the odds of EMS use was an increase of 34% in intervention compared with control communities [adjusted odds ratio (OR) 1.34, 95% CI 1.07-1.67]. We observed greater increases in the odds of EMS use among patients who had chronic or other cardiac diagnoses (adjusted OR 1.53, 95% CI 1.18-1.99, and adjusted OR 1.52, 95% CI 1.17-1.97, respectively) than in those diagnosed as having acute ischemia (adjusted OR 1.14, 95% CI 0.91-1.44). We observed greater increases in odds of EMS ulse in those who were retired (adjusted OR 1.62, 95% CI 1.29-2.04) or had systolic blood pressure (SBP) at or below 160 mm Hg upon presentation to the ED (adjusted OR 1.55, 95% CI 1.26-1.91 for SBP 100-160 mm Hg; 1.61, 95% CI 0.88-2.97 for SBP <100 mm Hg). The REACT trial demonstrated a significant impact on the use of EMS among patients admitted to the hospital for suspected acute myocardial infarction, with greater increases among patients with chronic or other cardiac ICD-9 discharge diagnoses, those presenting with lower SBP, and retired persons.


Sublingual/Buccal buprenorphine and dental problems: a pharmacovigilance study.
The association between dental problems and sublingual/buccal buprenorphine is unclear. We conducted an analysis of dental adverse drug reactions reported with sublingual/buccal buprenorphine in VigiBase®, the pharmacovigilance database of the World Health Organization. We performed disproportionality analyses to compare the reporting rates of dental problems with sublingual/buccal buprenorphine, compared to other buprenorphine formulations and methadone. Significant signals were considered if the lower boundary of the 95% confidence interval of the Reporting Odds Ratio (ROR) was > 1; cases were ≥ 3 and p-value <0.05. We conducted sensitivity analyses by calculating the ROR according to the reporter's qualification and the reporting continent (United States of America and Europe). We included 30,769 reports with all buprenorphine forms. We found 20 cases of dental problems with sublingual/buccal buprenorphine. Sublingual/buccal buprenorphine was associated with an overreporting of dental problems compared to other buprenorphine formulations (ROR = 15.10; 95% CI [7.50-30.39]; p < 0.005) and compared to methadone (ROR = 6.02; 95% CI [3.21-11.30]; p < 0.005). Overreporting of dental problems was consistent in sensitivity analyses, except in Europe compared with other buprenorphine formulations and with methadone. Sublingual/buccal buprenorphine might increase the risk of reporting dental problems. However, these results do not modify the benefits of sublingual/buccal buprenorphine in the treatment of opioid use disorders.


Evidence for a role of glycoprotein IIb-IIIa, distinct from its ability to support aggregation, in platelet activation by ionophores in the presence of extracellular divalent cations.
Ionophore A23187-induced 14C-serotonin secretion and thromboxane B2(TxB2) formation were found to be absent in citrated platelet-rich plasma (PRP) from thrombasthenic subjects and in normal PRP treated with glycoprotein (GP) IIb-IIIa complex-specific monoclonal antibodies. Both responses were restored to normal levels when 5 mmol/L EDTA was present, indicating that their absence was not caused by the absence of aggregation per se. In gel-filtered platelets (GFP) incubated with various additions, the blockade or absence of GPIIb-IIIa resulted in reduced A23187-induced secretion and TxB2 formation in media containing 1 mmol/L Ca2+ with or without fibrinogen and 1 mmol/L Mg2+ plus fibrinogen, but not when Ca, Mg-free buffer alone, 1 mmol/L EDTA, or fibrinogen alone were present. In contrast, no such dependence or GPIIb-IIIa was seen in GFP stimulated with thrombin or phorbol myristate acetate in the presence of 1 mmol/L Ca2+, 1 mmol/L EDTA, or buffer alone. The inhibition of ionophore-induced responses seen in both normal GFP treated with antibodies and thrombasthenic GFP was not associated with any significant alteration of the ionophore-mediated [Ca2+]i increase, as measured in both aequorin-loaded GFP stimulated with A23187 and fura-2-loaded GFP stimulated with ionomycin. Incubation of normal GFP with either the monoclonal antibodies or the ligand binding site peptide RGDS in the presence of 1 mmol/L Ca2+ caused virtually complete inhibition of A23187-induced aggregation, measured as the loss of single platelets, but RGDS, in contrast to the antibodies, did not inhibit secretion or TxB2 formation. We conclude that platelet activation induced by ionophores in the presence, but not in the absence, of extracellular divalent cations involves a GPIIb-IIIa-dependent process that most likely involves a property of the ligand-occupied form of the complex distinct from its ability to support aggregation. This could represent another example of an aggregation-independent activity of the receptor-occupied state of the GPIIb-IIIa complex in signal transduction.


Sialic acid glycoproteins inhibit in vitro and in vivo replication of rotaviruses.
We investigated the interactions of rotaviruses with glycoproteins and cells that support rotaviral replication. We found that a wide range of naturally occurring glycoproteins, including ovalbumins and ovomucoids from chicken and turkey eggs, and mucin derived from bovine submaxillary glands, inhibit the replication of rotaviruses in MA-104 cells. Our studies further indicated that the glycoproteins bind directly to rotaviruses and that virus-glycoprotein binding is dependent largely upon interactions with sialic acid oligosaccharides. We found that accessible sialic acid oligosaccharides are required for efficient rotavirus infection of MA-104 cells, thus demonstrating that sialic acid oligosaccharides play an important role in the interactions of rotaviruses with both glycoproteins and cells that support rotaviral replication. Bovine submaxillary mucin and chicken ovoinhibitor can also prevent the shedding of rotavirus antigen and the development of rotavirus gastroenteritis in a mouse model of rotavirus infection. Our findings document that a range of glycoproteins inhibit the in vivo and in vitro replication of rotaviruses and suggest that the alteration in the quantity or chemical composition of intestinal glycoproteins is a potential means for the modulation of enteric infections.


Volume expansive pressure (VEP) driven non-trivial topological phase transition in LiMgBi.
Topological Insulators (TI) exhibit robust spin-locked dissipationless Fermion transport along the surface states. In the current study, we use first-principles calculations to investigate a Topological Phase Transition (TPT) in a Half-Heusler (HH) compound LiMgBi driven by a Volume Expansive Pressure (VEP) which is attributed to the presence of, intrinsic voids, thermal perturbations and/or due to a phenomena known as cavity nuclei. We find that, the dynamically stable face-centred cubic (FCC) structure of LiMgBi (which belongs to the F4[combining macron]3m[216] space group), undergoes TPT beyond a critical VEP (at 4.0%). The continuous application of VEP from 0.0% to 8.0% results in a phase transition from a, band insulator to a Dirac semi-metal nature. Qualitatively, the Dirac cone formation and band inversion along the high symmetry point Γ in the Brillouin Zone (BZ) are analysed in terms of Electronic Band Structure (EBS) and Projected Local Density of States (LDOS). The TPT is further characterised by the [Doublestruck Z]2 invariant, (ν0, ν1ν2ν3) ≡ (1, 0 0 0) along the (0001) surface which indicates quantitatively that, HH LiMgBi is a strong TI. We hence propose, HH LiMgBi (known for its piezoelectric, thermo-electric and semi-conducting applications) as a strong TI with potential multi-purpose application in the field of electronics, spintronics and quantum computation.


Time course of attentional bias to painful facial expressions and the moderating role of attentional control: an eye-tracking study.
This study investigated the time course of attention to pain and examined the moderating effect of attentional control in the relationship between pain catastrophizing and attentional bias in chronic pain patients. A total of 28 patients with chronic pain and 29 pain-free individuals observed pictures of pain, happy and neutral facial expressions while their gaze behaviour was recorded. Pain intensity and duration, anxiety, depression, stress, attentional control and pain catastrophizing were assessed by questionnaires. In all subjects, the pattern of attention for pain faces was characterized by initial vigilance, followed by avoidance. No significant difference was found between the two groups in terms of orientation towards the stimuli, the duration of first fixation, the average duration of fixation or number of fixations on the pain stimuli. Attentional control moderated the relationship between catastrophizing and overall dwell time for happy faces in pain patients, indicating that those with high attentional control and high catastrophizing focused more on happy faces, whereas the reverse was true for those with low attentional control. This study supported the vigilance-avoidance pattern of attention to painful facial expressions and a moderation effect of attentional control in the association between pain catastrophizing and attentional bias to happy faces among pain patients.


The association between adverse childhood events and cluster C personality disorders: A meta-analysis.
Studies suggest that adverse childhood events (ACEs) may contribute to the onset and development of cluster C personality disorders. However, the association between ACEs and these disorders remains unclear in terms of consistency across studies and effect magnitude, as well as generalizability within cluster C. The current meta-analysis aimed to examine the associations between ACEs and cluster C personality disorders based on the available literature. Systematic searches were conducted in PubMed, Scopus, Web of Science and PsychInfo. Forty-eight eligible studies were included in the analyses, and pooled effect sizes were estimated both at the level of cluster C and at the level of each specific disorder. Moderation and meta-regression analyses were also conducted. ACEs were consistently associated with overall cluster C, as well as each of the specific disorders in this cluster. Sources of heterogeneity included type of instrument used to assess ACEs (questionnaires > interviews) and type of instrument used to assess the personality disorders (clinical interviews > questionnaires, as well as their combination with interview). The associations between ACEs and all cluster C personality disorders decreased with age. ACEs are consistently associated with all cluster C personality disorders. Future work could approach the mechanisms underlying this association, preferably using longitudinal designs and considering the potential sources of effect variability identified in the present study.


A biomagnetic system for in vivo cancer imaging.
An array of highly sensitive biomagnetic sensors of the superconducting quantum interference detector (SQUID) type can identify disease in vivo by detecting and imaging microscopic amounts of nanoparticles. We describe in detail procedures and parameters necessary for implementation of in vivo detection through the use of antibody-labelled magnetic nanoparticles as well as methods of determining magnetic nanoparticle properties. We discuss the weak field magnetic sensor SQUID system, the method of generating the magnetic polarization pulse to align the magnetic moments of the nanoparticles, and the measurement techniques to measure their magnetic remanence fields following this pulsed field. We compare these results to theoretical calculations and predict optimal properties of nanoparticles for in vivo detection.


Alcohol's involvement in recurrent child abuse and neglect cases.
This paper examined whether or not: (a) care-giver 'alcohol abuse' is associated with recurrent child maltreatment; (b) other 'risk factors' affect this relationship; and (c) which of alcohol abuse or other drug abuse plays a stronger role. It also examined (d) how children and families where alcohol-related child abuse was identified were managed by child protection services (CPS) in Victoria, Australia. Using anonymized data from Victorian CPS, repeat cases were examined involving 29 455 children identified between 2001 and 2005. Carer alcohol abuse, other drug abuse, mental ill-health, carer experience of abuse as a child, child age and gender, family type, socio-economic variables and level of child protection service intervention as recorded in the CPS electronic database were examined as risk factors for recurrence, using bivariate and multivariate techniques. Almost one-quarter of children in CPS experienced a recurrent incident of child maltreatment in a 5-year period. Where carer alcohol abuse was identified children were significantly more likely to experience multiple incidents compared with children where this was not identified (P < 0.001), as were children where other family risk factors (including markers of socio-economic disadvantage) were identified. The majority of children whose carers were identified with alcohol abuse experienced either repeat incidents or interventions (84%), although almost three-quarters of these children were managed without resort to the most serious outcome, involving court orders. Alcohol and drug abuse in carers are important risk-factors for recurrent child maltreatment after accounting for other known risk factors; the increased risk appears to be similar between alcohol and drug abuse.


[Occurrence of weevils (Insecta: Coleoptera) in pet food traded in the Metropolitan Region of Recife, Pernambuco State, Brazil].
With the purpose of verifying the occurrence of insect pests in dog food commercialized in the Metropolitan Region of Recife, samples from 15 different pet stores were submitted to the extraction of insects in a Berlese-Tullgren apparatus. Tribolium castaneum (Herbst) (Tenebrionidae) (55.2%) was the most frequent specie followed by Oryzaephilus surinamensis (L.) (Cucujidae) (31.3%), Rhyzopertha dominica (Fabricius) (Bostrichidae) (8.9%) and Lasioderma serricorne (Fabricius) (Anobiidae) (4.7%), all from Coleoptera. Recife showed the highest rate of infestation (53.6%), followed by Olinda (34.4%) and Jaboatão dos Guararapes (12.0%). The infestation by coleopters in the region occurs with high frequency and may represent a threat mainly in commercialized products in bulk.


Mutations of connexin43 in fetuses with congenital heart malformations.
Gap junction channels formed by connexin43 (Cx43) protein are important in cardiac morphogenesis, and Cx43 gene is thought to be associated with congenital heart malformation (CHM). This study was undertaken to detect the mutations of Cx43 in fetuses with CHM. Cx43 extron DNA was amplified by PCR from 16 fetuses with a variety of CHM. The PCR products were analyzed by SSCP and DNA sequencing. Thirty children who had no CHM were selected as controls. Eight homozygous mutations of Cx43 were observed in a fetus with double outlet right ventricule (DORV), five of the 8 mutations were missense mutations including Arg239Trp, Ser251Thr, Ala253Pro, Pro283Leu and Thr290Asn, and the remaining 3 were silent polymorphisms including Gly252Gly, Pro256Pro and Thr275Thr. No mutations were found in other fetuses and the control group. Mutations of Cx43 may be associated with congenital conotruncal anomalies. PCR-SSCP is an effective method for screening the mutations of Cx43.


[Severe Lower Extremity Infections Treated with Hip Disarticulation - Case Series].
Hip disarticulation is a major ablative procedure with serious risks as well as consequences for the patient, performed rarely for a lower extremity infection. According to literature, the mortality rate in these procedures reaches up to 60%. Unfavourable prognostic factors are emergency surgeries without adequate preparation of the patient and surgeries indicated for an ischemic terrain infection. The authors present four cases of hip disarticulation for severe lower extremity infection. In one patient, the procedure was performed urgently for necrotising fasciitis in the lower extremity extending up to the groin area, in the other three patients for non-healing femoral stump infection following the lower extremity amputation for vascular causes, of which two cases got complicated by the presence of TKA. Two of the patients treated surgically for stump infection died two months after the surgery due to respiratory complications. The two surviving patients underwent the last check one year following the surgery, they are both capable of independent locomotion with two underarm crutches and use the prosthesis only rarely. In the discussion, the factors influencing the mortality rate of the procedure, the principles of surgical and antimicrobial therapy, and the use of the negative-pressure wound therapy are analysed. The underlying principles of the care for patients with severe infections of the musculoskeletal system are infection focus debridement with the removal of foreign material, antibiotic (anti-infective) therapy targeted based on the cultivation results, wound management aimed to prevent contamination with nosocomial strains, and multidisciplinary cooperation - orthopaedist/surgeon, infectious disease physician, intensive care specialist, nutrition and rehabilitation specialist, nursing and prosthetic care providers. Key words: hip disarticulation, infection, necrotizing fasciitis.


New Physical Deposition Approach for Low Cost Inorganic Hole Transport Layer in Normal Architecture of Durable Perovskite Solar Cells.
In this work we reported sputter deposited NiOx/Ni double layer as an HTM/contact couple in normal architecture of perovskite solar cell. A perovskite solar cell that is durable for more than 60 days was achieved, with increasing efficiency from 1.3% to 7.28% within 6 days. Moreover, low temperature direct deposition of NiOx layer on perovskite layer was introduced as a potential hole transport material for an efficient cost-effective solar cell applicable for various morphologies of perovskite layers, even for perovskite layers containing pinholes, which is a notable challenge in perovskite solar cells. The angular deposition of NiOx layers by dc reactive magnetron sputtering showed uniform and crack-free coverage of the perovskite layer with no negative impact on perovskite structure that is suitable for nickel back contact layer, surface shielding against moisture, and mechanical damages. Replacing the expensive complex materials in previous perovskite solar cells with low cost available materials introduces cost-effective scalable perovskite solar cells.


[Scavenging effect of re-du-qing on free radicals].
The general Shwartzman reactions of rabbits were induced by intravenously injecting endotoxin twice with 24 hours interval. The lipid peroxides (LPO) in sera and liver homogenates of rabbits in normal saline group (12.26 +/- 0.84 n mol MDA/ml, 1.86 +/- 0.43 n mol MDA/mg protein respectively) were significantly higher than those of rabbits in normal control group (7.93 +/- 2.90, 1.31 +/- 0.22, both P less than 0.01), and LPO in sera and liver homogenates of rabbits in Re-Du-Qing group (6.55 +/- 2.97, 1.19 +/- 0.12) were evidently lower than those of rabbits in normal saline group (P less than 0.01), accessed to the LPO level of rabbits in normal control group. In in vitro experiment, LPO of mitochondria in Re-Du-Qing group (1.50 +/- 0.43 n mol MDA/mg protein) dramatically decreased, compared with that of endotoxin group (2.39 +/- 0.69, P less than 0.05) and of control group (2.23 +/- 0.75, P less than 0.05). The findings of both in vivo and in vitro experiments showed that Re-Du-Qing possesses scavenging effect on free radicals. In view of the detoxification mechanism of Re-Du-Qing, in addition to inhibiting bacteria and degrading. endotoxin, the scavenging effect of Re-Du-Qing on free radicals are also included.


Can Electrochemical Measurements Be Used To Predict X-ray Photoelectron Spectroscopic Data? The Case of Ferrocenyl-β-Diketonato Complexes of Manganese(III).
In order to better understand intramolecular communication between molecular fragments, a series of ferrocene-functionalized β-diketonato manganese(III) complexes, [Mn(FcCOCHCOR)3] with R = CF3, 1, CH3, 2, Ph = C6H5, 3, and Fc = FeII(η5-C5H4)(η5-C5H5), 4, the mixed ligand β-diketonato complex [Mn(FcCOCHCOFc)2(FcCOCHCOCH3)], 5, as well as the acac complex [Mn(CH3COCHCOCH3)3], 6, were subjected to an electrochemical and X-ray photoelectron spectroscopy (XPS) study. The ferrocenyl (FeII) and MnIII redox potentials, E°', and photoelectron lines were sufficiently resolved in each complex to demonstrate a linear correlation between E°' and group electronegativities of ligand R groups, χR, or ΣχR, as well as with binding energies of both the Fe 2p3/2 and Mn 2p3/2 photoelectron lines. These relationships are consistent with effective communication between molecular fragments of 1-5. From these relationships, prediction of Mn and Fe core electron binding energies in [Mn(R1COCHCOR2)3] complexes from known manganese and/or ferrocenyl redox potentials are, therefore, now possible. Ligand infrared carbonyl stretching frequencies were successfully related to binding energy as a measure of the energy required for inner-sphere reorganization. In particular it became possible to explain why, upon electrochemical oxidation or photoionization, the ferrocenyl FeII inner-shell of 1-5 needs more energy in complexes with ligands bearing electron-withdrawing (CF3) groups than in ligands bearing electron-donating groups such as ferrocenyl. The XPS determined entity Iratio (the ratio between the intensities of the satellite and main metal 2p3/2 photoelectron lines) is an indication not only of the amount of charge transferred, but also of the degree of inner-sphere reorganization. Just as for binding energy, the quantity Iratio was also found to be related to the energy requirements for the inner-sphere reorganization depicted by the vibrational frequency, vco.


[Combination of clofibrate and phenformin in the treatment of endogenous hypertriglyceridaemia (author's transl)].
Combined treatment with clofibrate and phenformin increased the lipid-lowering effect of clofibrate monotherapy in 15 patients with endogenous hypertriglyceridaemia significantly by ca. 10%. The therapeutic success was shown by a reduction in LDL-cholesterol and an additional reduction in VLDL-triglycerides. A clofibrate-induced rise in LDL-cholesterol could not be observed during the combined treatment. Thus combined treatment could be particularly advantageous in the prophylaxis of arteriosclerotic complications of endogenous hypertriglyceridaemia, provided that contra-indications of either of the preparations are excluded.


Epidemiology and the Tobacco Epidemic: How Research on Tobacco and Health Shaped Epidemiology.
In this article, I provide a perspective on the tobacco epidemic and epidemiology, describing the impact of the tobacco-caused disease epidemic on the field of epidemiology. Although there is an enormous body of epidemiologic evidence on the associations of smoking with health, little systematic attention has been given to how decades of research have affected epidemiology and its practice. I address the many advances that resulted from epidemiologic research on smoking and health, such as demonstration of the utility of observational designs and important parameters (the odds ratio and the population attributable risk), guidelines for causal inference, and systematic review approaches. I also cover unintended and adverse consequences for the field, including the strategy of doubt creation and the recruitment of epidemiologists by the tobacco industry to serve its mission. The paradigm of evidence-based action for addressing noncommunicable diseases began with the need to address the epidemic of tobacco-caused disease, an imperative for action documented by epidemiologic research.


[The triglyceride content in the high-density lipoproteins of patients with ischemic heart disease].
The sera and high density lipoprotein (HDL) fraction obtained from donors and patients with coronary heart disease, Functional Class II exercise-induced angina or postinfarction cardiosclerosis were studied for levels of triglycerides (TG) and cholesterol (C) and calculated for percentage of HDL cholesterol of total serum cholesterol, C/TG and HDL C/HDL TG ratios. A TG-enriched HDL fraction was detected, which had an unusual structure. Calculation of the percentage of HDL C of serum total cholesterol levels much more revealed lower concentrations of HDL C.


Effect of Porous Titanium Granules on Bone Regeneration and Primary Stability in Maxillary Sinus: A Human Clinical, Histomorphometric, and Microcomputed Tomography Analyses.
The aim of this randomized controlled study was to comparatively analyze the new bone (NB), residual bone, and graft-bone association in bone biopsies retrieved from augmented maxillary sinus sites by histomorphometry and microcomputed tomography (MicroCT) in a split-mouth model to test the efficacy of porous titanium granules (PTG) in maxillary sinus augmentation. Fifteen patients were included in the study and each patient was treated with bilateral sinus augmentation procedure using xenograft (equine origine, granule size 1000-2000 μm) and xenograft (1 g) + PTG (granule size 700-1000 μm, pore size >50 μm) (1 g), respectively. After a mean of 8.4 months, 30 bone biopsies were retrieved from the implant sites for three-dimensional MicroCT and two-dimensional histomorphometric analyses. Bone volume and vital NB percentages were calculated. Immediate after core biopsy, implants having standard dimensions were placed and implant stability quotient values were recorded at baseline and 3 months follow-up. There were no significant differences between groups according to residual bone height, residual bone width, implant dimensions, and implant stability quotient values (baseline and 3 months). According to MicroCT and two-dimensional histomorphometric analyses, the volume of newly formed bone was 57.05% and 52.67%, and 56.5% and 55.08% for xenograft + PTG and xenograft groups, respectively. No statistically significant differences found between groups according to NB percentages and higher Hounsfield unit values were found for xenograft + PTG group. The findings of the current study supports that PTG, which is a porous, permanent nonresorbable bone substitute, may have a beneficial osteoconductive effect on mechanical strength of NB in augmented maxillary sinus.


Overseas general practitioners (GPs) and prescription behaviour in England.
The UK imports many doctors from abroad, where medical training and experience may differ. This study aims to understand how drug prescription behaviour varies in English GP practices with higher shares of foreign-trained GPs. Results indicate that in general prac- tices with a high proportion of GPs trained outside the UK, there are higher prescriptions for antibiotics, mental health medication, analgesics, antacids, and statins, while controlling for patient and practice characteristics. However, we found no significant impact on pa- tient satisfaction or unplanned hospitalisations, suggesting that this behaviour may be due to over-prescribing. Identifying differences in prescribing habits amongst GPs is crucial in deter- mining best policies for ensuring consistent services across GP practices and reducing health inequalities.


Twenty-Four-Hour Heart Rate Is a Trait but Not State Marker for Depression in a Pilot Randomized Controlled Trial With a Single Infusion of Ketamine.
Background: Abnormalities of heart rate (HR) and its variability are characteristic of major depressive disorder (MDD). However, circadian rhythm is rarely taken into account when statistically exploring state or trait markers for depression. Methods: A 4-day electrocardiogram was recorded for 16 treatment-resistant patients with MDD and 16 age- and sex-matched controls before, and for the patient group only, after a single treatment with the rapid-acting antidepressant ketamine or placebo (clinical trial registration available on https://www.clinicaltrialsregister.eu/ with EUDRACT number 2016-001715-21). Circadian rhythm differences of HR and the root mean square of successive differences (RMSSD) were compared between groups and were explored for classification purposes. Baseline HR/RMSSD were tested as predictors for treatment response, and physiological measures were assessed as state markers. Results: Patients showed higher HR and lower RMSSD alongside marked reductions in HR amplitude and RMSSD variation throughout the day. Excellent classification accuracy was achieved using HR during the night, particularly between 2 and 3 a.m. (90.6%). A positive association between baseline HR and treatment response (r = 0.55, p = 0.046) pointed toward better treatment outcome in patients with higher HR. Heart rate also decreased significantly following treatment but was not associated with improved mood after a single infusion of ketamine. Limitations: Our study had a limited sample size, and patients were treated with concomitant antidepressant medication. Conclusion: Patients with depression show a markedly reduced amplitude for HR and dysregulated RMSSD fluctuation. Higher HR and lower RMSSD in depression remain intact throughout a 24-h day, with the highest classification accuracy during the night. Baseline HR levels show potential for treatment response prediction but did not show potential as state markers in this study. Clinical trial registration: EUDRACT number 2016-001715-21.