Genomic features in the breakpoint regions between syntenic blocks.
We study the largely unaligned regions between the syntenic blocks conserved in humans and mice, based on data extracted from the UCSC genome browser. These regions contain evolutionary breakpoints caused by inversion, translocation and other processes. We suggest explanations for the limited amount of genomic alignment in the neighbourhoods of breakpoints. We discount inferences of extensive breakpoint reuse as artefacts introduced during the reconstruction of syntenic blocks. We find that the number, size and distribution of small aligned fragments in the breakpoint regions depend on the origin of the neighbouring blocks and the other blocks on the same chromosome. We account for this and for the generalized loss of alignment in the regions partially by artefacts due to alignment protocols and partially by mutational processes operative only after the rearrangement event. These results are consistent with breakpoints occurring randomly over virtually the entire genome.


Aberrant Levels of miRNAs in Bone Marrow Microenvironment and Peripheral Blood of Myeloma Patients and Disease Progression.
The bone marrow (BM) microenvironment of multiple myeloma (MM) is reported to play a role in the biology of disease. In this study, we found that the extracellular BM microenvironment in MM contains a unique miRNA signature detectable by miRNA microarray and quantitative real-time PCR, which is partially represented in the peripheral blood. Eleven miRNAs were significantly decreased in both BM and serum of MM patients in comparison with controls. Evaluation of these miRNAs in plasma of a separate cohort of MM patients and controls confirmed significantly aberrant levels of let-7a, let-7b, let-7i, miR-15b, miR-16, and miR-20a in both serum and plasma. We then studied the myeloma precursor diseases and found that a subset of the MM miRNAs exhibited aberrant expression in monoclonal gammopathy of undetermined significance and smoldering myeloma. miRNA analysis of enriched CD138(+) plasma cells from MM and monoclonal gammopathy of undetermined significance found that most of the validated MM BM signature miRNAs were significantly decreased in MM plasma cells. Gene expression profiling indicated that multiple targets of the decreased miRNAs found increased expression in MM plasma cells, including ATF2, HRAS, HDAC4, TGFB1, TGFBR1, and mitogen-activated protein kinases. The findings suggest that these miRNAs are detectable in aberrant levels in the peripheral blood of patients with plasma cell proliferation and may play a role in aberrant plasma cell proliferation and disease progression.


Tissue distribution of the mRNA for a rhesus monkey major histocompatibility class Ib molecule, Mamu-AG.
We identified recently a novel major histocompatibility complex (MHC) class I locus in the rhesus monkey, Mamu-AG, which is expressed in the placenta and encodes molecules that share unique characteristics of human HL4-G. We established locus-specific reverse transcription-polymerase chain reaction (RT-PCR) and ribonuclease protection assays to determine whether Mamu-AG is expressed in other rhesus monkey tissues. With an RT-PCR assay, Mamu-AG mRNA was detected in placenta, amniotic membranes, kidney, spleen, eye, brain, lung, spinal cord, liver and occasionally heart, but was undetectable in lymph nodes, salivary glands, peripheral blood lymphocytes (PBL), large and small intestine, skeletal muscle or skin. Examination of endocrine organs demonstrated the presence of Mamu-AG transcripts in pituitary, testes, ovary and adrenal glands but not in pancreas or thyroid. Quantitative analysis using a ribonuclease protection assay demonstrated that the highest level of Mamu-AG mRNA expression was consistently in the placenta and amniotic membranes, while expression was moderate in a few tissues (testis, adrenal) and low to undetectable in all other tissues. These results suggest that the Mamu-AG mRNA, like the mRNA for the human MHC class Ib gene HLA-G, is expressed at high levels in the placenta, but also has restricted low-level expression in other tissues.


Spontaneous Tumor Lysis Syndrome in Small Cell Lung Cancer.
Tumor lysis syndrome (TLS) is a life-threatening oncologic complication caused by the lysis of a vast number of malignant cells resulting in metabolic derangements and organ dysfunction. TLS can occur spontaneously before initiation of any therapies often referred to as spontaneous tumor lysis syndrome (STLS), or shortly after the induction of chemotherapy, radiotherapy, or cytolytic antibody therapy. TLS is vastly seen in patients with hematological malignancies with high rapid cell turnover rates such as Burkitt lymphoma, acute myelogenous leukemia, and acute lymphocytic leukemia, and is rarely observed in solid tumors. However, TLS can occur in solid tumors, and there are multiple reports in the literature on the occurrence of TLS in various solid tumors. In this article, we report a case of STLS in small cell lung cancer followed by a brief review of the occurrence of TLS and STLS in small cell lung cancer.


Two-electron time-delay interference in atomic double ionization by attosecond pulses.
A two-color two-photon atomic double ionization experiment using subfemtosecond uv pulses can be designed such that the sequential two-color process dominates and one electron is ejected by each pulse. Nonetheless, ab initio calculations show that, for sufficiently short pulses, a prominent interference pattern in the joint energy distribution of the sequentially ejected electrons can be observed that is due to their indistinguishability and the exchange symmetry of the wave function.


Magnetic polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol micelles for docetaxel delivery in breast cancer: an in vitro study on two cell lines of breast cancer.
The aim of the present study was to load docetaxel (DCT) and Fe3O4 magnetic nanoparticles (MNPs) in polymeric micelles to concentrate them by an external magnetic field in target tissues. Oleic acid (OA) coated MNPs were prepared by hydrothermal method. The micelles were characterized for their zeta potential, particle size, drug loading and release efficacy. Fe loading efficacy was determined by atomic absorption. The magnetic micelles were characterized by Fourier transform infrared (FT-IR) spectroscopy, thermogravimetric analysis (TGA), transmission electron microscopy and vibrating sample magnetometer (VSM). The cytotoxicity of the micelles was studied by MTT assay on L929 fibroblast cells and also on two breast cancer cell lines of MCF-7 and MDA-MB-231. The optimum formulation showed 70% drug loading efficiency, zeta potential of -2.58 mV, particle size of 144.3 nm and drug release efficiency within 24 h of 68.9% at pH 5.5. Fe was loaded in these nanomicelles 290 μg/100 ml. TGA results confirmed the coating of MNPs with OA and polymeric micelles. The VSM analysis confirmed superparamagnetic property of the micelles. DCT loaded in micelles showed significantly more cytotoxicity compared to free drug on MCF-7 and MDA-MB-231 cells, but blank magnetic micelles had no significant cytotoxicity on normal fibroblast cells.


Reflections on a decade of research by ASEAN dental faculties: analysis of publications from ISI-WOS databases from 2000 to 2009.
This communication analyzed research publications in dentistry in the Institute of Scientific Information Web of Science databases of 10 dental faculties in the Association of South-East Asian Nations (ASEAN) from 2000 to 2009. The term used for the "all-document types" search was "Faculty of Dentistry/College of Dentistry." Abstracts presented at regional meetings were also included in the analysis. The Times Higher Education System QS World University Rankings showed that universities in the region fare poorly in world university rankings. Only the National University of Singapore and Nanyang Technological University appeared in the top 100 in 2009; 19 universities in the region, including Indonesia, Malaysia, the Philippines, Singapore, and Thailand, appeared in the top 500. Data from the databases showed that research publications by dental institutes in the region fall short of their Asian counterparts. Singapore and Thailand are the most active in dental research of the ASEAN countries.


Clostridium difficle Enteropathy Is Associated With a Higher Risk for Acute Kidney Injury in Patients With an Ileostomy-A Case-Control Study.
Clostridium difficile infection (CDI) is traditionally considered a colon-affecting disease with frequent pseudomembrane formation. However, multiple case reports have documented the existence of CDI in the small bowel, and the literature on outcome of C difficile enteropathy (CDE) is sparse. The aims of our study are to identify risk factors and to assess patient-related outcomes associated with CDE. This is a case-control study involving 112 patients at our tertiary care center. Patients with an ileostomy who tested positive for C difficile toxins were assigned to the study group (n = 34). The control group included patients with an ileostomy who tested negative for the C difficile toxins (n = 78). Via chart review, we collected data on baseline characteristics, laboratory values, potential risk factors, and outcome measures. Patients in the study and control groups were comparable in baseline and laboratory characteristics. In univariate analysis, CDE was associated with a history of smoking (hazard ratio [HR], 2.1; 95% confidence interval [CI], 1.06-4.3; P = 0.034), the presence of alcohol use (HR, 3.7; 95% CI, 1.05-12.8; P = 0.042), and older median age at the time of ileostomy (HR, 1.2; 95% CI, 1.07-1.3; P = 0.001). In multivariate analysis, no significant association between established CDI risk factors (eg, prior exposure to antibiotics and the use of proton pump inhibitors or histamine 2 receptor blockers) and the risk for the CDE was found. Only a history of alcohol intake was found to be associated with CDE (HR, 3.9; 95% CI, 1.09-14.1; P = 0.036). No significant difference in mortality was found in the study and control groups (2.9% vs 1.3%, P = 0.52), but patients with CDE were more likely to have acute kidney injury (AKI) than those without CDE (odds ratio, 4.0; 95% CI, 1.2-13.0. P = 0.023). We identified a history of alcohol use a risk factor for CDE. Furthermore, CDE was found be associated with an increased risk for developing AKI.


Crystal structures of the archaeal RNase P protein Rpp38 in complex with RNA fragments containing a K-turn motif.
A characteristic feature of archaeal ribonuclease P (RNase P) RNAs is that they have extended helices P12.1 and P12.2 containing kink-turn (K-turn) motifs to which the archaeal RNase P protein Rpp38, a homologue of the human RNase P protein Rpp38, specifically binds. PhoRpp38 from the hyperthermophilic archaeon Pyrococcus horikoshii is involved in the elevation of the optimum temperature of the reconstituted RNase P by binding the K-turns in P12.1 and P12.2. Previously, the crystal structure of PhoRpp38 in complex with the K-turn in P12.2 was determined at 3.4 Å resolution. In this study, the crystal structure of PhoRpp38 in complex with the K-turn in P12.2 was improved to 2.1 Å resolution and the structure of PhoRpp38 in complex with the K-turn in P12.1 was also determined at a resolution of 3.1 Å. Both structures revealed that Lys35, Asn38 and Glu39 in PhoRpp38 interact with characteristic G·A and A·G pairs in the K-turn, while Thr37, Asp59, Lys84, Glu94, Ala96 and Ala98 in PhoRpp38 interact with the three-nucleotide bulge in the K-turn. Moreover, an extended stem-loop containing P10-P12.2 in complex with PhoRpp38, as well as PhoRpp21 and PhoRpp29, which are the archaeal homologues of the human proteins Rpp21 and Rpp29, respectively, was affinity-purified and crystallized. The crystals thus grown diffracted to a resolution of 6.35 Å. Structure determination of the crystals will demonstrate the previously proposed secondary structure of stem-loops including helices P12.1 and P12.2 and will also provide insight into the structural organization of the specificity domain in P. horikoshii RNase P RNA.


Detection of co-colonization with Streptococcus pneumoniae by algorithmic use of conventional and molecular methods.
Detection of pneumococcal carriage by multiple co-colonizing serotypes is important in assessing the benefits of pneumococcal conjugate vaccine (PCV). Various methods differing in sensitivity, cost and technical complexity have been employed to detect multiple serotypes of pneumococcus in respiratory specimens. We have developed an algorithmic method to detect all known serotypes that preserves the relative abundance of specific serotypes by using Quellung-guided molecular techniques. The method involves culturing respiratory swabs followed by serotyping of 100 colonies by either capsular (10 colonies) or PCR (90 colonies) reactions on 96-well plates. The method was evaluated using 102 nasal swabs from children carrying pneumococcus. Multiple serotypes were detected in 22% of carriers, compared to 3% by World Health Organization (WHO)-recommended morphology-based selection of 1 to 3 colonies. Our method, with a processing cost of $87, could detect subdominant strains making up as low as 1% of the population. The method is affordable, practical, and capable of detecting all known serotypes without false positive reactions or change in the native distribution of multiple serotypes.


Progression of antral and body gastritis in patients with active and healed duodenal ulcer and duodenitis.
The dynamics of the antral and body mucosa has been studied in biopsy specimens obtained during endoscopy of patients with duodenal ulcer (103 cases), patients with duodenal ulcer scars (108 cases), and patients with duodenitis (44 cases). A representative Finnish population sample consisting of 434 subjects was used as reference material. The antral mucosa of all patient series showed an increase in the severity and prevalence of gastritis similar to that of the general population, whereas virtually no progression of gastritis with age was seen in the body mucosa, which remained normal or at the stage of superficial gastritis up to geriatric age. In contrast, in the present controls and in all earlier population samples studied by us so far, there was a significant and steady increase in the severity and prevalence of body gastritis with age. It is concluded that the age behavior of the antral and body mucosa was in duodenal ulcer scars and duodenitis similar to that of patients with active duodenal ulcer. The persistence of normal conditions in the acid-secreting area may serve as one explanation of the strong tendency of the disease to recur. In addition, it is tentatively concluded that in duodenal ulcer disease there are factors that have a 'protecting' influence on the body glands and which are abolished by antrectomy, according to our earlier studies.


Physiologically Based Pharmacokinetic Model of All-trans-Retinoic Acid with Application to Cancer Populations and Drug Interactions.
All-trans retinoic acid (atRA) is a front-line treatment of acute promyelocytic leukemia (APL). Due to its activity in regulating the cell cycle, it has also been evaluated for the treatment of other cancers. However, the efficacy of atRA has been limited by atRA inducing its own metabolism during therapy, resulting in a decrease of atRA exposure during continuous dosing. Frequent relapse occurs in patients receiving atRA monotherapy. In an attempt to combat therapy resistance, inhibitors of atRA metabolism have been developed. Of these, ketoconazole and liarozole have shown some benefits, but their usage is limited by side effects and low potency toward the cytochrome P450 26A1 isoform (CYP26A1), the main atRA hydroxylase. We determined the pharmacokinetic basis of therapy resistance to atRA and tested whether the complex disposition kinetics of atRA could be predicted in healthy subjects and in cancer patients in the presence and absence of inhibitors of atRA metabolism using physiologically based pharmacokinetic (PBPK) modeling. A PBPK model of atRA disposition was developed and verified in healthy individuals and in cancer patients. The population-based PBPK model of atRA disposition incorporated saturable metabolic clearance of atRA, induction of CYP26A1 by atRA, and the absorption and distribution kinetics of atRA. It accurately predicted the changes in atRA exposure after continuous dosing and when coadministered with ketoconazole and liarozole. The developed model will be useful in interpretation of atRA disposition and efficacy, design of novel dosing strategies, and development of next-generation atRA metabolism inhibitors.


Human papillomavirus 16 E5 induces bi-nucleated cell formation by cell-cell fusion.
Human papillomaviruses (HPV) 16 is a DNA virus encoding three oncogenes--E5, E6, and E7. The E6 and E7 proteins have well-established roles as inhibitors of tumor suppression, but the contribution of E5 to malignant transformation is controversial. Using spontaneously immortalized human keratinocytes (HaCaT cells), we demonstrate that expression of HPV16 E5 is necessary and sufficient for the formation of bi-nucleated cells, a common characteristic of precancerous cervical lesions. Expression of E5 from non-carcinogenic HPV6b does not produce bi-nucleate cells. Video microscopy and biochemical analyses reveal that bi-nucleates arise through cell-cell fusion. Although most E5-induced bi-nucleates fail to propagate, co-expression of HPV16 E6/E7 enhances the proliferation of these cells. Expression of HPV16 E6/E7 also increases bi-nucleated cell colony formation. These findings identify a new role for HPV16 E5 and support a model in which complementary roles of the HPV16 oncogenes lead to the induction of carcinogenesis.


Porphyromonas somerae sp. nov., a pathogen isolated from humans and distinct from porphyromonas levii.
Porphyromonas levii is an anaerobic, pigmented gram-negative bacillus originally isolated from bovine rumen. We describe 58 human clinical strains of P. levii-like organisms, isolated from various human clinical specimens that are phenotypically similar to the type strain of P. levii, a rumen isolate (ATCC 29147). Our biochemical, comparative 16S rRNA sequence analyses, and DNAlpha-DNA relatedness studies indicate that the human P. levii-like organisms are similar to each other but genetically different from the P. levii type strain isolated from bovine rumen. We therefore propose the name Porphyromonas somerae to encompass the human P. levii-like organisms. P. somerae was predominantly isolated from patients with chronic skin and soft tissue or bone infections, especially in the lower extremities.


Three-dimensional finite element analysis of stress distribution and displacement of the maxilla following surgically assisted rapid maxillary expansion.
The aim of this study was to investigate the displacement and stress distributions during surgically assisted rapid maxillary expansion under different surgical conditions. 3-dimensional finite element model of a maxilla with a Hyrax appliance was constructed and an expansion force of 6000 grams was applied using the expansion screw. According to the surgical procedures, 5 groups including a control group without surgery (Group I) were simulated. The experimental groups were as follows; Group II (Le Fort I osteotomy), Group III (Le Fort I osteotomy and paramedian osteotomy), Group IV (Le Fort I osteotomy and pterygomaxillary separation), and Group V (Le Fort I osteotomy, paramedian osteotomy, and pterygomaxillary separation). Displacement of the maxilla gradually increased from Group 1 to Group 5 in all three planes of space, indicating that combination of the Le Fort I osteotomy with paramedian osteotomy and pterygomaxillary separation produce greatest displacement of the maxilla. By surgical relief, the stress exerted on anchor teeth was significantly reduced. The results suggested that the combination of Le Fort I and paramedian osteotomy with pterygomaxillary separation is an effective procedure for increasing the expansion of the maxilla with lower side effects caused by excessive stresses around the anchor teeth.


Clinical Comparison of Spleen-Preserving Distal Pancreatectomy With or Without Splenic Vessel Preservation: A Systematic Review and Meta-Analysis.
Spleen-preserving distal pancreatectomy with splenic vessel preservation (SVP) and only the save of short gastric and left gastroepiploic vessels called the Warshaw technique (WT) are the optimal procedures to resect benign or borderline malignant tumors of the left pancreas. The aim of this meta-analysis was to assess the intra- and postoperative outcomes between SVP and the WT. We searched studies that compared the intra- and postoperative outcomes between SVP and the WT from PubMed, Embase, and the Cochrane Library (2004-2017). Dichotomous and continuous variables were calculated by the odds ratios and weighted mean differences with 95% confidence intervals. Eighteen retrospective studies, including 1039 patients, were eligible for our analysis. Six hundred seventy-nine patients (65.4%) underwent SVP, and 360 patients (34.6%) underwent the WT. Although the estimated blood loss in patients undergoing the WT was less than that in those undergoing SVP (P < .00001), SVP had a lower incidence of clinically relevant postoperative pancreatic fistula (P = .03), splenic infarcts (P < .00001), intra- and postoperative splenectomies (P = .0009), and gastric varices (P < .00001) than the WT. In addition, the tumor size of patients who underwent SVP was smaller (P = .006). Both SVP and the WT are feasible and effective surgical techniques. SVP should be given priority to reduce postoperative complications, and the WT should be regarded as a salvage operation to preserve the spleen based on the preoperative evaluation or in the case of uncontrolled bleeding during SVP.


Emissive Pt(II) complexes bearing both cyclometalated ligand and 2-pyridyl hexafluoropropoxide ancillary chelate.
A new series of mono-cyclometalated Pt(II) complexes 1-4 with chelating 2-pyridyl hexafluoropropoxide as the ancillary ligand were synthesized. Single crystal X-ray diffraction studies were examined, giving evidence for the occurrence of pi pi stacking between the cyclometalated ligands, but a lack of intermolecular Pt ... Pt interaction. Among these complexes, the benzo[h]quinoline analogue 2a shows the greatest degree of pi pi stacking, which is also confirmed by the observation of additional, large Stokes shifted emission attributed to the aggregated counterparts in solid thin film. All these Pt(II) complexes are highly emissive in solid state, whereas except for 4-phenylquinazoline analogues 4a and 4b, complexes 1-3 in solution are subject to dominant radiationless deactivation induced, in part, by the solvent collision to the square planar Pt(II) framework. Electroluminescent OLEDs employing 2-phenylpyridine analogue 1b as the dopants were fabricated, rendering satisfactory performance data suited for future improvement.


Evolution of the patient-first approach: a dual-trained, single-neurosurgeon experience with 2002 consecutive intracranial aneurysm treatments.
The paradigm for intracranial aneurysm (IA) treatment is shifting toward a hybrid approach involving open and endovascular techniques. The authors chronicled the evolution of IA treatment by retrospectively examining a large series of IA cases treated by a single dual-trained neurosurgeon, focusing on evolving technology relative to the choice of treatment options, perioperative morbidity, and mortality. The aneurysm database at the authors' institution was searched to identify consecutive patients treated with endovascular or open microsurgical approaches by one neurosurgeon during an 18-year time span. Patients were included regardless of IA rupture status, location or morphology, or treatment modality. Data collected were baseline clinical characteristics, aneurysm size, treatment modality, operative complications, in-hospital mortality, and retreatment rate. A total of 1858 patients with 2002 IA treatments were included in the study. Three-hundred fifty IAs (17.5%) were ruptured. Open microsurgery was performed in 504 aneurysms (25.2%) and endovascular surgery in 1498 (74.8%). Endovascular IA treatments trended toward a growing use of flow diversion during the last 11 years. In-hospital mortality was 1.7% overall, including 7.0% in ruptured and 0.5% in unruptured cases. The overall complication rate was 3.3%, including 3.4% for microsurgical cases and 3.3% for endovascular cases. The rate of retreatment was 3.6% after clipping and 10.7% for endovascular treatment. This study demonstrates complementary use of open and endovascular approaches for IA treatment. By customizing treatment to the patient, comparable rates of procedural complications, mortality, and retreatment were achieved for both endovascular and microsurgical approaches.


An augmented passive immune therapy to treat fulminant bacterial infections.
In the early 1900s, passive immunization/antibody therapy was used to treat a variety of human ailments such as hypoimmunoglobulinemia, cancer and infectious disease. The advent of antibiotic therapy had relegated this type of therapy obsolete for treatment of infectious diseases. Emergence of multi-drug resistant pathogens along with novel monoclonal antibody production techniques has rekindled the interest in passive immunization (PI). An increase in the number of monoclonal antibody patent applications in the recent past suggests a renewed commercial interest in PI. Despite these developments, antibody therapy for infectious diseases has limitations including the need for large or frequent dosages. P4, a 28-amino acid peptide is a multi-lineage cellular activator. P4, along with infectious disease (i.e. Pathogen) specific immunoglobulin, has been shown in vitro and in vivo in mice to potentiate innate immunity. This review will discuss the progress made in passive antibody therapy, the challenges still to be surmounted, and the potential expanded role of an immune-potentiating peptide (bio-molecule) in the quest to utilize and revitalize passive immunization.


Evolution, growth, and status of managed care in the United States.
While under attack in the United States, managed care/competition is being viewed by a number of European and other countries as a remedy in their struggle to control rising health care costs. While many fundamentals of American managed care have their roots in the British health system, significant differences exist between the two systems. While managed care, which can be loosely defined as any system of delivering health services in which care is delivered by a specified network of providers who agree to comply with the care approaches established through a case management process, has had a 100-year history in the United States, it wasn't until the mid-1970's that it began to gain national recognition. All health maintenance organizations (HMOs) are managed care organizations (MCOs) but not all MCOs are HMOs. The two other categories of MCOs are, preferred provider organizations (PPOs) and point of service plans (POS). Currently, three-quarters of Americans with health insurance are enrolled in managed care plans and there are 160 million Americans enrolled in such plans. A major on-going debate occurring in the United States is in regard to the comparative quality of care provided by MCOs and traditional fee-for-service plans. The study results to date have been equivocal. Another controversial managed care issue is the use of gag clauses in contracts between the MCOs and their providers. These clauses limit providers from being totally open and honest with patients about, for example, alternative treatment possibilities or the details of provider reimbursement. Since the failure of U.S. health care reform in 1994, there has been a more focused turn to the marketplace to provide the impetus for reducing costs. As a result, health care plans and providers have become more like traditional businesses which must focus on the bottom line to survive. In a marketplace where purchasers of care look for low bidders, it should be remembered that the level and quality of care a society receives is usually commensurate with the level of resources that it is willing to expend.


Localization of galactocerebroside in oligodendrocytes, myelin sheath and choroid plexus.
The location of galactocerebroside in brain was investigated by using a specific anti-galactocerebroside antibody which was purified by affinity chromatography. It was found that galactocerebroside is distributed not only in oligodendrocytes and myelin but also in epithelial cells of the ependymal layer of the ventricle and choroid plexus. Biochemical analysis also revealed the presence of galactocerebroside and its sulfated derivative, sulfatide, in the choroid plexus.


Effect of colchicine on angiotensin receptors in rabbit aorta.
Colchicine (10(-5) M) significantly depressed the dose-response curve for angiotensin in isolated rabbit aortic strips. A lower maximal response was observed without apparent change in receptor affinity for angiotensin, as can be judged by unchanged ED50 values. Colchicine also diminished the dose-response curve for norepinephrine. The angiotensinase activity in cell membrane fraction and high-speed supernate was significantly inhibited. Colchicine did not change the specific receptor binding of radioactive angiotensin to either cell membrane fraction or supernate. It is concluded that colchicine possibly depresses the response to angiotensin through a mechanism involving a site beyond membrane receptors.


Antagonistic effects of extracts from Artemisia rupetris L. and Leontopodium leontopodioides to CC chemokine receptor 2b (CCR2b).
The present study was designed to establish a suitable assay to explore CCR2b receptor antagonists from the natural products of Artemisia rupetris and Leontopodium leontopodioides. An aequorin assay was developed as a cell-based assay suitable for 384-well microplate and used for screening CCR2b receptor antagonists from natural products. Through establishing suitable conditions, the assay was shown to be suitable for screening of CCR2b receptor antagonists. Seven compounds were identified in preliminary screening. Five of them showed evident dose-response relationship in secondary screening. The structure-activity relationship study suggested that 7-position hydroxyl group of flavonoids was necessary, a polar group should be introduced on the 3-position, and the substituents on 2-position benzene ring of flavonoids have little influence on the potentency of the inhibition activity on CCR2b receptor. The ortho-position dihydroxyl structure in quinic acid compounds may be important. In conclusion, Compounds HR-1, 5, 7, and AR-20, 35 showed activity as antagonist of CCR2b receptor, which shed lights on the development of novel drugs as CCR2b receptor antagonists for preventing inflammation related diseases.


Cyclic changes of cervical mucus enzymes related to the time of ovulation II. Amino peptidase and esterase.
The enzymes amino peptidase and esterase were identified in human cervical mucus. Their concentration was serially determined during a menstrual cycle in 5 normal ovulatory women and correlated with the time of ovulation as monitored by the basal body temperature and radioimmunoassay of serum luteinizing hormone (LH), progesterone, and estradiol (E2). The activity of both enzymes decreased at midcycle just before the LH surge and began to rise after ovulation. The preovulatory decline in enzyme activity was significant for esterase but not for amino peptidase. The site of production and functional significance of these enzymes are not at present identified.


Development of a sedation protocol using orally administered tiletamine-zolazepam-acepromazine in free-roaming dogs.
To investigate the sedative effects in dogs of tiletamine-zolazepam-acepromazine (TZA) or ketamine-flunitrazepam (KF) administered orally and to evaluate the effectiveness of encapsulated TZA for capturing free-roaming dogs. Experimental study followed by a field trial. Six research dogs and 27 free-roaming dogs. In a pilot study, six research dogs were administered liquid TZA (20 mg kg-1 tiletamine-zolazepam and 2 mg kg-1 acepromazine) or liquid KF (50 mg kg-1 ketamine and 2 mg kg-1 flunitrazepam) orally: treatment 1, forcefully squirting liquid medication into the mouth; treatment 2, encapsulating liquid medication for administration in canned food; treatment 3, administering liquid medication mixed with gravy. Sedation was scored. A follow-up field trial attempted capture of 27 free-roaming dogs. In the pilot study, the median time (range) to lateral recumbency (% dogs) after TZA administration was: treatment 1, 47.5 (35-80) minutes (67%); treatment 2, 30 (15-65) minutes (83%); and treatment 3, 75 (45-110) minutes (100%). No dogs in KF treatment 2 or 3 achieved lateral recumbency. Based on these results, 20 free-roaming dogs were offered encapsulated TZA in canned food: TZ (20 mg kg-1) and acepromazine (2 mg kg-1). Of these, no further drugs to four dogs (one dog captured), 10 dogs were administered a second dose within 30 minutes (five dogs captured) and six dogs were administered TZ (5 mg kg-1) and xylazine (1.1-2.2 mg kg-1) intramuscularly by blow dart (six dogs captured). Seven dogs were initially offered twice the TZA dose (five dogs captured). In total, 63% free-roaming dogs were captured after administration of encapsulated TZA in canned food. Oral administration of encapsulated TZA in canned dog food can aid in the capture of free-roaming dogs, but additional drugs may be required. The sedation onset time and medication palatability influenced the capture rate.


Winter warming is ecologically more relevant than summer warming in a cool-temperate grassland.
Climate change affects all seasons, but warming is more pronounced in winter than summer at mid- and high latitudes. Winter warming can have profound ecological effects, which are rarely compared to the effects of summer warming, and causal explanations are not well established. We compared mild aboveground infrared warming in winter to warming in summer in a semi-natural, cool-temperate grassland in Germany for four years. Aboveground plant biomass increased following winter warming (+18%) and was unaffected by summer warming. Winter warming affected the composition of the plant community more than summer warming, favoring productive species. Winter warming increased soil respiration more than summer warming. Prolonged growing seasons and changes in plant-community composition accounted for the increased aboveground biomass production. Winter warming stimulated ecological processes, despite causing frost damage to plant roots and microorganisms during an extremely cold period when warming reduced the thermal insulation provided by snow. Future warming beyond such intermittent frosts may therefore further increase the accelerating effects of winter warming on ecological processes.


Agreement between a frequency-weighted filter for continuous biomechanical measurements of repetitive wrist flexion against a load and published psychophysical data.
A previous pilot study demonstrated that a force and frequency-weighted filter network could be developed for processing continuous biomechanical measures of repetitive wrist motions and exertions. The current study achieves the objective by modelling subjective discomfort for repetitive wrist flexion using controlled posture, pace and force. A three-level fractional factorial experiment was conducted involving repetitive wrist flexion (2 s/motion, 6 s/motion, 10 s/motion) from a neutral posture to a given angle (10 degrees, 28 degrees, 45 degrees) against a controlled resistance (5 N, 25 N, 50 N) using a Box Behnken design. Ten subjects participated. Discomfort was reported on a 10 cm visual analogue scale. Results of response surface regression analysis revealed that main effects of force, wrist flexion angle, and repetition were all significant (p < 0.05) and that no second-order effects were observed. Linear regression analysis on these factors established a discomfort model on which the filter characteristics were based. The pure error test model revealed no significant lack of fit (p > 0.05). The continuous model was compared and agreed with discrete psychophysical data from other published studies. The model was used for generating parameters for a force and frequency-weighted digital filter that weighs continuous wrist postural signals with corresponding force in proportion to the equal discomfort function as a function of frequency of repetition. These filters will enable integration of large quantities of biomechanical data in field studies.


Advanced backcross QTL analysis and comparative mapping with RIL QTL studies and GWAS provide an overview of QTL and marker haplotype diversity for resistance to Aphanomyces root rot in pea (Pisum sativum).
Aphanomyces euteiches is the most damaging soilborne pea pathogen in France. Breeding of pea resistant varieties combining a diversity of quantitative trait loci (QTL) is a promising strategy considering previous research achievements in dissecting polygenic resistance to A. euteiches. The objective of this study was to provide an overview of the diversity of QTL and marker haplotypes for resistance to A. euteiches, by integrating a novel QTL mapping study in advanced backcross (AB) populations with previous QTL analyses and genome-wide association study (GWAS) using common markers. QTL analysis was performed in two AB populations derived from the cross between the susceptible spring pea variety "Eden" and the two new sources of partial resistance "E11" and "LISA". The two AB populations were genotyped using 993 and 478 single nucleotide polymorphism (SNP) markers, respectively, and phenotyped for resistance to A. euteiches in controlled conditions and in infested fields at two locations. GWAS and QTL mapping previously reported in the pea-Aphanomyces collection and from four recombinant inbred line (RIL) populations, respectively, were updated using a total of 1,850 additional markers, including the markers used in the Eden x E11 and Eden x LISA populations analysis. A total of 29 resistance-associated SNPs and 171 resistance QTL were identified by GWAS and RIL or AB QTL analyses, respectively, which highlighted 10 consistent genetic regions confirming the previously reported QTL. No new consistent resistance QTL was detected from both Eden x E11 and Eden x LISA AB populations. However, a high diversity of resistance haplotypes was identified at 11 linkage disequilibrium (LD) blocks underlying consistent genetic regions, especially in 14 new sources of resistance from the pea-Aphanomyces collection. An accumulation of favorable haplotypes at these 11 blocks was confirmed in the most resistant pea lines of the collection. This study provides new SNP markers and rare haplotypes associated with the diversity of Aphanomyces root rot resistance QTL investigated, which will be useful for QTL pyramiding strategies to increase resistance levels in future pea varieties.


Occurrence of pap-, sfa-, and afa-related sequences among F165-positive Escherichia coli from diseased animals.
A total of 160 Escherichia coli positive for F165 fimbrial antigen and isolated from diarrheic and septicemic animals, were examined for the presence of the pap, afa, and sfa/foc operons or related nucleotide sequences using colony hybridization. Most isolates shared DNA sequences with the pap operon sequences alone or in association with afa or sfa. Thus, our results indicate that F165-positive E. coli from diseased animals share DNA sequences with operons coding for adhesins important in human extra-intestinal disease and that multiple adhesin systems are often found in single isolates. However, 20% of the F165-positive isolates did not show any homology with the probes representing the three adhesin systems, suggesting that one of the operons responsible for F165 production could be different from the pap, sfa/foc, and afa operons.


From prefrontal leukotomy to deep brain stimulation: the historical transformation of psychosurgery and the emergence of neuroethics.
The history of psychosurgery is described and analyzed. This historical perspective largely begins with analysis of the work of Egas Moniz in the development of the leukotomy, and follows the rise and fall of its popularity in the 1900s. The reemergence of psychosurgical procedures and the development of new therapeutic technologies such as vagus nerve stimulation and deep brain stimulation are discussed. In addition, an introduction to the field of neuroethics is provided, given its importance in any discussion about surgical therapy for psychiatric patients.


Aerosol Delivery Through an Adult High-Flow Nasal Cannula Circuit Using Low-Flow Oxygen.
There has been a growing trend toward delivering aerosolized medications using high-flow nasal cannula (HFNC). In some cases, patients who do not require high-flow oxygen to maintain adequate oxygenation may benefit from aerosol delivery while receiving low-flow oxygen via HFNC. The objective of this study was to quantify and compare the relative pulmonary and systemic delivery of salbutamol, with 2 different nebulizers, in patients with COPD receiving low-flow oxygen therapy through an HFNC. Subjects were randomized to receive study doses of 5 mg salbutamol nebulized by either a jet nebulizer or a vibrating mesh nebulizer with a T-piece or spacer on days 1, 3, and 5 of admission. Subjects using the large spacer also received 2 puffs (100 μg each) of salbutamol via a pressurized metered-dose-inhaler prior to the nebulizer dose. Urinary salbutamol excretion 30 min post-inhalation and pooled samples of urinary salbutamol excretion up to 24 h post-inhalation were measured. On day 2, ex vivo studies were performed with salbutamol collected on filters placed between the HFNC and nebulizer, with drug eluted from filters and analyzed to determine inhaled dose. Twelve subjects (6 females), age 51.3 ± 11.2 y, were included. The vibrating mesh nebulizer demonstrated higher urinary salbutamol excretion at 30 min and 24 h post-inhalation compared to a jet nebulizer (P = .001 and P = .02, respectively). No significant difference was found between the T-piece and large-spacer configurations, even though the spacer provided a significantly larger emitted aerosol dose at the opening of the HFNC (P = .002). Aerosolized medication could be efficiently combined with low-flow oxygen, via HFNC, in COPD subjects without the need to interrupt the gas supply. The vibrating mesh nebulizer delivered larger doses to subjects compared to the jet nebulizer. However, there was no benefit of using the large spacer with HFNC in low-flow delivery, because the small inner diameter of the HFNC does not allow larger aerosol droplet sizes (preserved by the spacer) to reach the subject.


The Acute Physiological and Perceptual Responses Between Bodyweight and Treadmill Running High-Intensity Interval Exercises.
The purpose of this study was to compare the acute physiological, perceptual, and enjoyment responses between bodyweight high-intensity interval exercise (BW-HIIE) and treadmill running high-intensity interval exercise HIIE (RUN-HIIE). Twelve adults [age: 29.5 ± 5.3 years; weight: 70.9 ± 15.0 kg; height: 167.9 ± 8.9 cm; peak oxygen consumption (VO2 peak): 48.7 ± 6.5 ml min-1·kg-1] performed both RUN-HIIE and BW-HIIE. RUN-HIIE consisted of two sets of 5, 60-s (s) run intervals at 100% of the speed achieved during VO2 peak testing followed by 60s of walking at 4.02 km/h. BW-HIIE consisted of two sets of 5, 60s 'all-out' effort calisthenic exercises followed by 60s of marching in place at 100 steps per minute. Oxygen consumption (VO2), blood lactate (Blac), heart rate (HR), and rating of perceived exertion (RPE) were measured during exercise. Physical activity enjoyment (PACES) was assessed post-exercise. Creatine Kinase (CK) was measured before exercise and 48-h post-exercise. Muscle soreness was assessed before exercise, post-exercise, and 48-h post-exercise. Oxygen consumption relative to VO2 peak was higher (p < 0.001) during RUN-HIIE (88 ± 3%) compared to BW-HIIE (77 ± 4%). HR relative to HRpeak was higher (p = 0.002) for RUN-HIIE (93 ± 1%) compared to BW-HIIE (88 ± 2%). Blac was higher (p < 0.001) after BW-HIIE (11.2 ± 3.2 mmol/l) compared to RUN-HIIE (6.9 ± 2.0 mmol/l). Average RPE achieved was higher (p = 0.003) during BW-HIIE (16 ± 2) than RUN-HIIE (14 ± 2). PACES was similar for RUN-HIIE and BW-HIIE (p > 0.05). No differences (p > 0.05) in CK were observed between RUN-HIIE and BW-HIIE. Our results indicate 'all-out' calisthenic exercise can elicit vigorous cardiorespiratory, Blac, and RPE responses. Implementing this style of exercise into training requires minimal space, no equipment, and may elicit cardiometabolic adaptations seen with traditional forms of high-intensity exercise.


Comprehensive analysis of the role of a four-gene signature based on EMT in the prognosis, immunity, and treatment of lung squamous cell carcinoma.
Epithelial-mesenchymal transition (EMT), a biological process through which epithelial cells transform into mesenchymal cells, contributes to tumor progression and metastasis. However, a comprehensive analysis of the role of EMT-related genes in Lung squamous cell carcinoma (LUSC) is still lacking. In this study, data were downloaded from available databases, including The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database. The association between differentially expressed EMT-related genes (EMT-RDGs) and LUSC prognosis, drug sensitivity, mutation, and immunity was analyzed using bioinformatics methods. In the results, Lasso and univariate Cox regression analyses identified four EMT-RDGs that were differentially expressed, and used to establish a prognostic model capable of distinguishing between high- and low-risk groups. Then, prognostic factors were identified by multivariate Cox regression analysis and used to construct a nomogram. The high-risk group had a significantly poorer prognosis than the low-risk group. The tumor immune environment was significantly different between the two groups, with the low-risk group exhibiting a better response to immunotherapy. In addition, the half-maximal inhibitory concentration prediction indicating that the constructed model could effectively predict sensitivity to chemotherapy. This study provides new reference for further exploration of new clinical therapeutic strategies for LUSC.


Impact of moderate-severe persistent allergic rhinitis on thoraco-abdominal kinematics and respiratory muscle function.
Objective: To assess thoraco-abdominal kinematics, respiratory muscle strength and electromyographic activity of the diaphragm (EAdi) in moderate-severe allergic rhinitis (AR) patients. Methods: A cross-sectional study involving 40 individuals (20 in the AR group) and 20 in the control group [CG]) was conducted. Ventilatory pattern and chest wall volume distribution (optoelectronic plethysmography), respiratory muscle strength (manovacuometry and sniff nasal inspiratory pressure [SNIP]), and EAdi were assessed in both groups. Results: The AR patients had impaired thoraco-abdominal kinematics (reduced total chest wall volume) (p = 0.004), lower values of total respiratory cycle time (p = 0.014) and expiratory time (p = 0.006). They also presented an increase of percentage contribution of the abdominal rib cage (p = 0.475) and respiratory rate (p = 0.019). A positive correlation among pulmonary rib cage tidal volume and MIP (r = 0.544; p < 0.001), SNIP (r = 0.615; p < 0.001), and MEP (r = 0.604; p < 0.001) was observed. After adjusting for age, BMI and gender through multivariate analysis, the individuals with AR presented lower values of MIP (β = -24.341; p < 0.001), MEP (β = -0.277; p < 0.001), SNIP (β = -34.687; p < 0.001) and RMS (β = -0.041; p = 0.017). Conclusions: The individuals with moderate-severe persistent AR had worse respiratory muscle strength, diaphragm activation and chest wall volume distribution with a higher abdominal contribution to tidal volume than the control group. These findings reinforce the notion that the upper and lower airways work in an integrated and synergistic manner.


Relationship of Speed, Agility, Neuromuscular Power, and Selected Anthropometrical Variables and Performance Results of Male and Female Junior Tennis Players.
The aim of the study was to analyses the relation between the selected speed, agility, and neuromuscular power test items. The sample of subjects consisted of 154 male and 152 female young tennis players. Using six motor and three anthropometrical tests we investigate differences between males and females and between two age categories. Finally, we analyzed the relation between motor and anthropometrical tests and a player's tennis performance. The correlation between the two agility test items and 5-m sprint is very large in male players, while only moderate with 20-m sprint in female category. Male tennis players have higher correlations between speed test items and neuromuscular test items. The speed test item (5-m sprint) has large correlation with a player's tennis performance. One-way analysis of variance results indicated that young male tennis players performed significantly better than females in all motor test items. Significant differences between genders have not been revealed only in the body mass index. Differences between the males aged 18& under and 16& under have been noted as significant in all test items, except the vertical jump, while differences between the females have been noted as significant in three anthropometrical tests, quarter jump, and the fan-drill test. Regression analyses have shown that the system of prediction variables explains a relatively small part of variance (46%--males and 40%--females). In both genders, it has been revealed that test items measuring speed significantly influence a player's tennis performance.


Selective benzylic and allylic alkylation of protic nucleophiles with sulfonamides through double Lewis acid catalyzed cleavage of sp3 carbon-nitrogen bonds.
The acid-catalyzed benzylic and allylic alkylation of protic nucleophiles is fundamentally important for the formation of carbon-carbon and carbon-heteroatom bonds, and it is a formidable challenge for benzylic and allylic amine derivatives to be used as the alkylating agents. Herein we report a highly efficient benzylic and allylic alkylation of protic carbon and sulfur nucleophiles with sulfonamides through double Lewis acid catalyzed cleavage of sp(3) carbon-nitrogen bonds at room temperature. In the presence of a catalytic amount of inexpensive ZnCl(2)-TMSCl (TMSCl: chlorotrimethylsilane), 1,3-diketones, beta-keto esters, beta-keto amides, malononitrile, aromatic compounds, thiols, and thioacetic acid can couple with a broad range of tosyl-activated benzylic and allylic amines to give diversely functionalized products in good to excellent yields and with high regioselectivity. Furthermore, the cross-coupling reaction of 1,3-dicarbonyl compounds with benzylic propargylic amine derivatives has been successfully applied to the one-step synthesis of polysubstituted furans and benzofurans.


Post-operative opioid pain management patterns for patients who receive hip surgery.
Identifying optimal, post-operative opioid management strategies is a priority of health providers and government agencies. At present, there are no studies we are aware of that have formally investigated opioid prescribing patterns for post-operative non-arthroplasty orthopedic conditions such as femoroacetabular impingement, nor has any study investigated the influence of opioid prescription patterns on health care costs and utilization. We aimed to investigate a subgrouping scheme associated with post-operative opioid prescription strategies and measure the subgroups' direct and indirect health care utilization and costs in individuals undergoing non-arthroplasty orthopedic hip surgery. The study was an observational cohort of routine military clinical practices. We used cluster analysis to characterize pre-operative (12 months) and post-operative (24 months) opioid prescription patterns. Linear mixed effects modeling (with statistical controls for baseline status) identified opioid prescription pattern subgroups and identified subgroup differences in health care utilization and costs. Two distinct clusters were identified representing 1) short-duration, high total days' supply (SD-HD), and 2) long-duration, lesser total days' supply (LD-LD) post-operative prescription patterns. Significantly higher costs and health care utilization for both hip-related and non-hip-related variables were consistently identified in the SD-HD group. Long-term opioid prescription use has been identified as a concern, but our findings demonstrate that LD-LD post-operative opioid management for hip surgery recipients was associated with lower costs and utilization. Whether these management patterns were a reflection of pre-operative health status, impacted pain-related outcomes, or can be replicated in other orthopedic procedures remains a consideration for future studies. NA.


Development and application of physiologically based pharmacokinetic-modeling tools to support drug discovery.
Physiologically based pharmacokinetic (PBPK) modeling integrates physicochemical (PC) and in vitro pharmacokinetic (PK) data using a mechanistic framework of principal ADME (absorption, distribution, metabolism, and excretion) processes into a physiologically based whole-body model. Absorption, distribution, and clearance are modeled by combining compound-specific PC and PK properties with physiological processes. Thereby, isolated in vitro data can be upgraded by means of predicting full concentration-time profiles prior to animal experiments. The integrative process of PBPK modeling leads to a better understanding of the specific ADME processes driving the PK behavior in vivo, and has the power to rationally select experiments for a more focussed PK project support. This article presents a generic disposition model based on tissue-composition-based distribution and directly scaled hepatic clearance. This model can be used in drug discovery to identify the critical PK issues of compound classes and to rationally guide the optimization path of the compounds toward a viable development candidate. Starting with a generic PBPK model, which is empirically based on the most common PK processes, the model will be gradually tailored to the specifics of drug candidates as more and more experimental data become available. This will lead to a growing understanding of the 'drug in the making', allowing a range of predictions to be made for various purposes and conditions. The stage is set for a wide penetration of PK modeling and simulations to form an intrinsic part of a project starting from lead discovery, to lead optimization and candidate selection, to preclinical profiling and clinical trials.


Phthalocyanine photodynamic therapy: disparate effects of pharmacologic inhibitors on cutaneous photosensitivity and on tumor regression.
The phthalocyanines are promising second-generation photosensitizers that are being evaluated for the photodynamic therapy (PDT) of malignant tumors. In vivo studies with the silicon phthalocyanine Pc 4 have shown that it is highly effective at causing regression of RIF-1 tumors in C3H/HeN mice in PDT protocols. Because cutaneous photosensitivity is the major complication of photosensitizers used for PDT, experiments were performed to evaluate the effect of inhibitors of the inflammatory response (cyproheptadine, dexamethasone, pentoxifylline, and tumor necrosis factor alpha [TNF-alpha] antibodies) on Pc 4-induced cutaneous photosensitivity and tumor regression. The C3H/HeN mice were injected with either Pc 4 or Photofrin and were exposed to 86 J/cm2 of filtered radiation emitted from a solar simulator. Animals were irradiated at 1, 3, 7, 10, 14 and 28 days postinjection. Cutaneous photosensitivity was assessed using the murine ear-swelling response. Cyproheptadine, dexamethasone, pentoxifylline and TNF-alpha antibodies were administered prior to illumination to assess their ability to block Pc 4-induced cutaneous photosensitivity and to evaluate whether such treatment adversely influenced Pc 4 PDT-induced tumor regression. Compared to Photofrin, Pc 4 produced cutaneous photosensitivity that was transient, resolving within 24 h, and that could be elicited for only 10 days after administration. In contrast, Photofrin caused photosensitivity that required 4 days to resolve and could be elicited for at least 1 month after it was administered. The Pc 4-induced cutaneous photosensitivity could be blocked by corticosteroids and an inhibitor of vasoactive amines (cyproheptadine). The TNF-alpha gene transcription was found to increase in keratinocytes following treatment with Pc 4 and light. The anti-TNF-alpha antibodies and pentoxifylline, an inhibitor of cytokine transcription, also prevented cutaneous photosensitivity, implicating TNF-alpha in the pathogenesis of Pc 4-induced cutaneous photosensitivity. None of these agents had any effect on Pc 4 PDT-induced tumor regression. Cyproheptadine, dexamethasone, pentoxifylline and TNF-alpha antibodies may be valuable pharmacologic agents in the management of cutaneous photosensitivity associated with PDT without altering the efficacy of this new therapeutic modality. The findings suggest that it should be possible to devise PDT protocols that block cutaneous photosensitivity without impairing the anti-tumor response to the agents.


[Acute pyelonephritis treated under "home hospitalization." Ten years' experience].
We present the experience of the Vitoria-Gasteiz Hospital at Home Unit in the treatment of acute pyelonephritis, including an analysis of potential predictors of failure. A total of 369 episodes of acute pyelonephritis without septic shock or renoureteral obstruction are described. After initiating intravenous antibiotic therapy in the hospital emergency department, all patients were referred to the HH. We analyzed the characteristics of the cases and the relationship between several clinical factors and failure of HH care, defined as the need to readmit the patient to conventional hospitalization. During the study period, 280 women and 89 men (age 16-88 years) met the inclusion criteria. Mean length of HH stay was 5 days and duration of intravenous therapy was 3 days. Sixteen of the 369 cases (4%) had to be readmitted to the hospital because of hypotension, vomiting, pain, fever, or signs of obstruction on ultrasound or because they requested it (four patients). Patients who were readmitted had a higher maximum temperature (mean 39.4 vs. 38.7 degrees C; p = 0.006) than those who remained at the HH. There were no differences between the groups with respect to the other clinical variables studied. The evolution of all 16 hospitalized patients was favorable; only one required a urological intervention. Hospital at home care was an effective alternative for managing acute pyelonephritis without shock in 96% of cases referred by the emergency department, and obviated conventional hospital admission, which is usually indicated for this disease.


Expression of neurotransmitter receptors and Ca2+ channels in the adult fornix and optic nerve.
Using Xenopus oocytes, we have investigated the presence of mRNA coding for neurotransmitter receptors and channels in the adult bovine fornix and optic nerve. Oocytes injected with mRNA from either area, expressed comparable levels of functional receptors to several neurotransmitters, including glutamate and angiotensin II, as well as voltage-activated Ca2+ channels. Glutamate receptors were mainly of the AMPA/kainate type and were expressed in astrocyte cultures from the regions studied, suggesting that the receptors are present at least in this type of glial cells in vivo. These results show that the white matter areas in the adult brain express receptors and channels. These molecules may play an important role in the transfer of information between axons and glial cells.


Ward sister--teacher or facilitator? An investigation into the behavioural characteristics of effective ward teachers.
The ward sister role is increasingly coming under study. This paper summarizes research into learning in the ward environment. The study being one of several on a similar theme, to have been published in the past 2 years. The research concentrated in particular on the behavioural characteristics of trained nurses perceived as good teachers. Attitudes and perceptions of teaching and learning were investigated by interviewing trained and trainee nurses. The data concerning good teachers collected at interviews were developed into a questionnaire and the results factor analysed. In the third phase of the study trained nurse-trainee verbal communications were observed and analysed to determine any relationship between verbal behaviours and effective teaching. The findings of the study led to the conclusion that on the job teaching of nurses is a complex global act in which the role model presented to the learner has a powerful influence while it could not be said conclusively that a link between effective teaching and verbal behaviour was identified, a trend towards a more participative mode of communication was noted in two identified good teachers.


Gastric lymphomas: chemotherapy as a primary treatment.
Twenty-one of 65 patients with gastric lymphoma have been treated with combination chemotherapy; 17 patients had chemotherapy as primary treatment, and 4 had it for residual disease after incomplete surgical resection. Three of these patients were in stage III and 18 were in stage IV of the disease, according to the TNM Staging Classification. CHOP-Bleo or CHOP combination was given to 17 patients, and the COPP-Bleo regimen to three; the last one was treated with COP. Sixteen of the 18 stage IV patients entered into complete remission after 6 to 10 courses of CHOP or COPP-Bleo; there was one partial response and one failure. Six complete responders had a surgical restaging performed and none of them had gross evidence of residual disease; all of them had partial gastrectomy and in five cases there was no microscopical evidence of disease; in one of the resected stomachs, a focus of residual disease was discovered involving the submucosa but without compromise of the serosa. Fourteen (77.7%) of these patients are alive with no evidence of disease 1-10 (X = 3.8 years); one patient died with recurrent disease at 30 months; another patient died of other causes after 3 years; one patient is alive with disease at 18+ months. All the remaining 16 stage IV patients who were not given chemotherapy have died, median survival time being 5 months.(ABSTRACT TRUNCATED AT 250 WORDS)


Impaired FEF25-75 values may predict bronchial reversibility in allergic children with rhinitis or asthma.
FEV1 is considered an important parameter for asthma diagnosis and follow-up. However, it has been proposed that FEF25-75 could be more sensitive than FEV1 to detect slight airways obstruction. Bronchial reversibility defined by positive response to bronchodilation test. The aim of the present study was to define whether an impaired FEF25-75 value (less than 65 percent of predicted) may be predictive for reversibility in a large cohort of allergic children with rhinitis or asthma. Six hundred allergic children were recruited: 300 with controlled asthma and 300 with allergic rhinitis. All of them were evaluated by performing spirometry, bronchodilation test, and skin prick test. Two predictors were significantly associated with bronchial reversibility: i) an impaired FEF25-75 value (less than 65 percent of predicted), and ii) sensitization to perennial allergens. It was more relevant in children with rhinitis (ORAdj:8.9 and 2.2 respectively). In conclusion, this study, conducted in real life, could suggest that an impaired FEF25-75 value (less than 65 percent of predicted) may be considered a reliable marker of bronchial reversibility, mainly in children with allergic rhinitis.


Primacy of functional knowledge in semantic representations: the case of living and nonliving things.
In 3 experiments, participants decided whether sensory and functional features were true of living and nonliving concepts. In Experiments 1 and 2, concepts were presented twice: test phase followed study phase after either 3 min (Experiment 1) or 3 s (Experiment 2). At test, concepts were paired with the same feature as that at study, or a different feature from either the same modality (within-modality priming) or another modality (cross-modality priming). In both experiments functional decisions were faster than sensory decisions for living and nonliving concepts. Whilst no semantic priming occurred between study and test in Experiment 1, the shorter study-test interval of Experiment 2 did lead to test phase semantic priming. Here there was greater within- than cross-modality priming for sensory decisions, but equivalent within- and cross-modality priming for functional decisions owing to significantly greater facilitation of functional decisions from prior sensory decisions than vice versa. Experiment 3 involved a single verification phase: For half the participants the feature name preceded the concept name, and for half the concept name preceded the feature name. The functional processing advantage persisted irrespective of presentation order. Results suggest that functional information is central to the representation of all concepts: Function is processed faster than sensory information and is activated obligatorily.


Exhausting T cells in CLL.
In this issue of Blood, Riches and colleagues provide an in-depth characterization of T cells and particularly CD8+ T cells from patients with chronic lymphocytic leukemia (CLL). They demonstrate that CD8+ T cells exhibit defects in proliferation, cytotoxicity, and increased expression of inhibitory receptors and thus exhibit features of T-cell exhaustion.


[Risks and prognosis for success of a pregnancy following replacement of a heart valve (author's transl)].
After replacement of a heart valve a pregnancy is possible in the complaint categories I and II. Treatment with anti-coagulation is necessary for plastic heart valves. To avoid teratogenic effects the early pregnancy is best managed with heparin although stillbirth and early intra-uterine death are more common than with Marcumar. A treatment with heparin 10,000 units subcutaneously twice throughout all of the pregnancy is recommended. According to the literature 2/3 of the pregnancy with anti-coagulation result in the normal delivery of a healthy infant. Of 202 women in the reproductive age group with artificial heart valves, 150 were followed by a questionnaire. 25 women desired children. 10 women had pregnancies. 1 had two pregnancies, 1 had three pregnancies, 3 healthy infants were born.


Surgery after combination therapy with a tyrosine kinase inhibitor and anti-PD-1 antibody in sarcomatoid hepatocellular carcinoma: case report and literature review.
Although surgery is the preferred treatment for sarcomatoid hepatocellular carcinoma (SHC), the prognosis remains considerably poor due to early postoperative recurrence and metastasis. Reports on surgery after combined treatment with a tyrosine kinase inhibitor and anti-programmed cell death (PD)-1 antibody are unavailable. A 69-year-old male patient with SHC was admitted to our hospital for treatment of a liver tumor that was detected on ultrasonography. Abdominal computed tomography with triple-phase enhancement revealed a lesion in the right hepatic lobe that measured 86.0 mm × 75.0 mm × 71.0 mm. Biopsy revealed a pathological diagnosis of liver sarcoma or sarcomatoid carcinoma. The patient subsequently received transcatheter arterial chemo-embolization, as he did not consent to surgery. More than two months later, he received a combination of lenvatinib with camrelizumab, as computed tomography showed an increase in the lesion size (to 123.0 mm × 90.0 mm × 80.0 mm) and lateral growth posterior to the upper pole of the right kidney. Liver resection was performed after 6 months of systemic therapy; pathological examination confirmed a diagnosis of SHC and showed extensive necrosis of tumor cells. Combined treatment with lenvatinib and camrelizumab was continued for 6 months after surgery. The patient has survived for over 24 months after initial diagnosis and is currently tumor-free. Combined systemic therapy with a tyrosine kinase inhibitor and anti-PD-1 antibody may represent a feasible treatment strategy for improving resectability in cases of unresectable SHC. The outcomes with this combination may also be explored in cases of resectable SHC that have a high-risk of recurrence; this may improve the therapeutic effect.


GOCI image enhancement using an MTF compensation technique for coastal water applications.
The Geostationary Ocean Color Imager (GOCI) is the first optical sensor in geostationary orbit for monitoring the ocean environment around the Korean Peninsula. This paper discusses on-orbit modulation transfer function (MTF) estimation with the pulse-source method and its compensation results for the GOCI. Additionally, by analyzing the relationship between the MTF compensation effect and the accuracy of the secondary ocean product, we confirmed the optimal MTF compensation parameter for enhancing image quality without variation in the accuracy. In this study, MTF assessment was performed using a natural target because the GOCI system has a spatial resolution of 500 m. For MTF compensation with the Wiener filter, we fitted a point spread function with a Gaussian curve controlled by a standard deviation value (σ). After a parametric analysis for finding the optimal degradation model, the σ value of 0.4 was determined to be an optimal indicator. Finally, the MTF value was enhanced from 0.1645 to 0.2152 without degradation of the accuracy of the ocean color product. Enhanced GOCI images by MTF compensation are expected to recognize small-scale ocean products in coastal areas with sharpened geometric performance.


Commentary: profiling by appearance and assumption: beyond race and ethnicity.
In this issue, Acquaviva and Mintz highlight issues regarding racial profiling in medicine and how it is perpetuated through medical education: Physicians are taught to make subjective determinations of race and/or ethnicity in case presentations, and such assumptions may affect patient care. The author of this commentary believes that the discussion should be broadened to include profiling on the basis of general appearance. The author reports personal experiences as someone who has profiled and been profiled by appearance-sometimes by skin color, sometimes by other physical attributes. In the two cases detailed here, patient care could have been affected had the author not become aware of his practices in such situations. The author advocates raising awareness of profiling in the broader sense through training.


Visible-Light-Promoted C-H Arylation by Merging Palladium Catalysis with Organic Photoredox Catalysis.
The use of a dual palladium/organic photoredox catalytic system enables the directed arylation of arenes with aryldiazonium salts with a broad substrate scope at room temperature under mild reaction conditions. This study thus serves as not only an alternative route for the biaryl motifs but also a new example for the application of an organic photoredox catalyst.


An examination of nervous system revealed unexpected immunoreactivity of both secretory apparatus and excretory canals in plerocercoids of two broad tapeworms (Cestoda: Diphyllobothriidea).
Dibothriocephalus ditremus and Dibothriocephalus latus are diphyllobothriidean tapeworms autochthonous to Europe. Their larval stages (plerocercoids) may seriously alter health of their intermediate fish hosts (D. ditremus) or cause intestinal diphyllobothriosis of the final human host (D. latus). Despite numerous data on the internal structure of broad tapeworms, many aspects of the morphology and physiology related to host–parasite co-existence remain unclear for these 2 species. The main objective of this work was to elucidate functional morphology of the frontal part (scolex) of plerocercoids, which is crucial for their establishment in fish tissues and for an early attachment in final hosts. The whole-mount specimens were labelled with different antibodies and examined by confocal microscope to capture their complex 3-dimensional microanatomy. Both species exhibited similar general pattern of immunofluorescent signal, although some differences were observed. In the nervous system, FMRF amide-like immunoreactivity (IR) occurred in the bi-lobed brain, 2 main nerve cords and surrounding nerve plexuses. Differences between the species were found in the structure of the brain commissures and the size of the sensilla. Synapsin IR examined in D. ditremus occurred mainly around FMRF amide-like IR brain lobes and main cords. The unexpected finding was an occurrence of FMRF amide-like IR in terminal reservoirs of secretory gland ducts and excretory canals, which has not been observed previously in any tapeworm species. This may indicate that secretory/excretory products, which play a key role in host–parasite relationships, are likely to contain FMRF amide-related peptide/s.


An Experimental Study of the Effects of External Physiological Parameters on the Photoplethysmography Signals in the Context of Local Blood Pressure (Hydrostatic Pressure Changes).
A comprehensive study of the effect of a wide range of controlled human subject motion on Photoplethysmographic signals is reported. The investigation includes testing of two separate groups of 5 and 18 subjects who were asked to undertake set exercises whilst simultaneously monitoring a wide range of physiological parameters including Breathing Rate, Heart Rate and Localised Blood Pressure using commercial clinical sensing systems. The unique finger mounted PPG probe equipped with miniature three axis accelerometers for undertaking this investigation was a purpose built in-house version which is designed to facilitate reproducible application to a wide range of human subjects and the study of motion. The subjects were required to undertake several motion based exercises including standing, sitting and lying down and transitions between these states. They were also required to undertake set arm movements including arm-swinging and wrist rotation. A comprehensive set of experimental results corresponding to all motion inducing exercises have been recorded and analysed including the baseline (BL) value (DC component) and the amplitude of the oscillation of the PPG. All physiological parameters were also recorded as a simultaneous time varying waveform. The effects of the motion and specifically the localised Blood Pressure (BP) have been studied and related to possible influences of the Autonomic Nervous System (ANS) and hemodynamic pressure variations. It is envisaged that a comprehensive study of the effect of motion and the localised pressure fluctuations will provide valuable information for the future minimisation of motion artefact effect on the PPG signals of this probe and allow the accurate assessment of total haemoglobin concentration which is the primary function of the probe.


Tus prevents overreplication of oriC plasmid DNA.
Minichromosome plasmid DNA templates containing oriC and two Ter sites, oriented as they are on the Escherichia coli chromosome, have been used to study the role of Tus in termination of bidirectional replication. In replication reactions reconstituted with purified proteins where it could be demonstrated that each active template was replicating bidirectionally, Tus was required to prevent extensive overreplication. In the presence of Tus, both replication forks terminated DNA synthesis at one or the other Ter site in an apparent stepwise manner. First, the progress of one replication fork was arrested by a properly oriented Tus-Ter complex. Then, either because of steric hindrance resulting from the stalled replication machinery of the first fork or because of the formation of a branched DNA structure, the progression of the second opposing fork was halted at the same site on the DNA template. In the absence of Tus, overreplication required DNA ligase and arose via a template strand-switching mechanism. Thus, the role of Tus in E. coli is more likely to prevent overreplication rather than to ensure accurate termination.


46,XX SRY-negative true hermaphrodite siblings.
The sex-determining region on the Y chromosome (SRY) gene guides male sexual development. However, individuals with sex reversal syndrome (46,XX males and 46,XX true hermaphrodites) lack the SRY gene and yet can still develop testes. We present 2 siblings with XX true hermaphroditism. Most cases of sex reversal syndrome are sporadic; however, reports have been published of familial occurrence, suggesting that 46,XX maleness and 46,XX true hermaphroditism are actually different manifestations of the same disorder of gonadal development, likely an autosomal dominant mutation with variable penetrance or an X-linked mutation.


Cascade cyclization and acyl migration of propargylic esters with isocyanides: rapid access to substituted furans.
A novel rearrangement of ester-activated propargylic acetate with isocyanide has been disclosed. This protocol enables a quick synthesis of polysubstituted furan derivatives. The reaction outcome also reveals that the ester group is employed for the construction of a furan ring and an acyl migration is observed.


Microstructure and Properties of ER50-6 Steel Fabricated by Wire Arc Additive Manufacturing.
In this paper, ER50-6 steel was fabricated by wire arc additive manufacturing (WAAM) with an A-W GTAW system. The microstructure, mechanical properties, and corrosion behaviors of ER50-6 steel by WAAM were studied. The results showed that, with the GMAW current increased, from the bottom to the top of the sample, the microstructure was fine ferrite and granular pearlite, ferrite equiaxed grains with fine grains at grain boundaries, and columnar ferrite, respectively. The average hardness in the vertical direction of samples 1# and 2# was 146 and 153 HV, respectively. The hardness of sample 2# increased because of the refinement of grain. The pores in the sample increased as the bypass current increased. The higher bypass current also has a deterioration effect on the corrosion behavior of ER50-6 steel.


Dynamic Evolution from Negative to Positive Photocharging in Colloidal CdS Quantum Dots.
The optical properties of colloidal semiconductor nanocrystals are largely influenced by the trapping of charge carriers on the nanocrystal surface. Different concentrations of electron and hole traps and different rates of their capture to the traps provide dynamical charging of otherwise neutral nanocrystals. We study the photocharging formation and evolution dynamics in CdS colloidal quantum dots with native oleic acid surface ligands. A time-resolved technique with three laser pulses (pump, orientation, and probe) is developed to monitor the photocharging dynamics with picosecond resolution on wide time scales ranging from picoseconds to milliseconds. The detection is based on measuring the coherent spin dynamics of electrons, allowing us to distinguish the type of carrier in the QD core (electron or hole). We find that although initially negative photocharging happens because of fast hole trapping, it eventually evolves to positive photocharging due to electron trapping and hole detrapping. The positive photocharging lasts up to hundreds of microseconds at room temperature. These findings give insight into the photocharging process and provide valuable information for understanding the mechanisms responsible for the emission blinking in colloidal nanostructures.


Peak muscle mass in young men and sarcopenia in the ageing male.
The prevalence of sarcopenia increases with age. The diagnosis of sarcopenia relies in part on normative data on muscle mass, but these data are lacking. This study provides population-based reference data on muscle mass in young men, and these results may be used clinically for the diagnosis of sarcopenia in men. The ageing population increases the prevalence of sarcopenia. Estimation of normative data on muscle mass in young men during the peak of anabolic hormones is necessary for the diagnosis of sarcopenia in ageing males. The purposes of this study were to provide population-based reference data on lean body mass (LBM) in young men during the time of peak levels of GH/IGF-1 and testosterone and further to apply the reference data on a population-based sample of men aged 60-74 years to estimate the prevalence of sarcopenia. This is a cross-sectional, population-based single-centre study. Our participants are from random selection of 783 men, aged 20-29 years, and 600 men, aged 60-74 years. LBM was assessed by dual-energy X-ray absorptiometry (DXA). LBM T-scores were calculated on the basis of LBM in the young participants. Muscle function in the lower extremities was measured using a leg extension power (LEP) rig in the ageing participants. Total lean body mass (TLB) was (mean (SD)) 64.7 kg (6.8) in the young and 60.4 kg (6.4) in the ageing men (p<0.001). Lower extremity lean mass (LELB) was 22.0 kg (2.6) in the young and 19.2 kg (2.4) in the ageing men (p<0.001). In the ageing men, TLB and LELB T-scores were -0.64 (0.94) and -1.09 (0.94). A total of 4.8 and 8.5% had a TLB or LELB T-score of less than -2 and a LEP in the lowest quartile. This study provides population-based reference data on LBM in men, and these data may be used clinically for the diagnosis of sarcopenia.


Delayed Guillain-Barré Syndrome after Bariatric Surgery: A Report of Three Cases.
Surgeries carry a risk of complications. Polyneuropathies, including Guillain-Barré syndrome (GBS), are potential complications of bariatric surgery. The incidence of these conditions is expected to increase as these surgeries become increasingly popular. We present a case report of three patients who developed a polyneuropathy after bariatric surgery. GBS was diagnosed in each patient, with nutritional deficiencies being suspected as a contributing factor. All patients began a 5-day intravenous immunoglobulin course in addition to receiving rehabilitative support, multivitamins, intravenous thiamine, vitamin D (therapeutic dose), and selenium. The patients' symptoms improved but did not completely resolve. GBS can be a complication of bariatric surgery. Although a clear cause-effect relationship cannot be established for the present cases, the cumulative literature on the subject suggests that it is important to include it as a potential risk when counseling patients for such surgeries.


Development of switchable polymers to address the dilemma of stability and cargo release in polycationic nucleic acid carriers.
Cationic polymer gene delivery vehicles that effectively resist premature serum degradation often have difficulty releasing their nucleic acid cargoes. In this work, we report a pH-sensitive polymer (SP), poly(oligo(ethylene glycol) monomethyl ether methacrylate)-co-poly(2-(dimethylamino)ethyl methacrylate)-block- poly(propargyl methacrylate-graft-propyl-(4-methoxy-benzylidene)-amine) (p(PMA-PMBA)-b-(p(OEGMA-DMAEMA)), for successful in vitro and in vivo gene transfer. In the physiological condition, the hydrophobization of p(OEGMA-DMAEMA) polycations by p(PMA-PMBA) significantly enhanced the stability of its polyplexes counterpart. In endosomes, the polymer undergoes an acid-triggered hydrophilic transition through the cleavage of benzoic imines, thus allowing the vector to quickly release nucleic acid cargo due to the loss of hydrophobic functionalization. Compared to a pH-insensitive polymer (IP), SP exhibited more significant luciferase plasmid delivery efficiency with HeLa cells in vitro and with in vivo intraventricular brain injections. Therefore, the polymer designed here is a good solution to address the dilemma of stability and cargo release in gene delivery, and may have broad potential applications in therapeutic agent delivery.


Density fluctuations near the liquid-gas critical point of a confined fluid.
We report the results of an experimental study of the effect of a dilute silica network on liquid-gas critical phenomena in carbon dioxide (CO2). Using small-angle neutron scattering, we measured the correlation length of the density fluctuations in bulk (xi(bulk)) and confined CO2 (xi(conf)) as a function of temperature and average fluid density. We find that quenched disorder induced by an aerogel suppresses density fluctuations: xi(conf) loses the Ising model divergence characteristic of xi(bulk) and does not exceed the size of pores in the homogeneous region.


Overlapping representations of food and social stimuli in mouse VTA dopamine neurons.
Dopamine neurons of the ventral tegmental area (VTADA) respond to food and social stimuli and contribute to both forms of motivation. However, it is unclear whether the same or different VTADA neurons encode these different stimuli. To address this question, we performed two-photon calcium imaging in mice presented with food and conspecifics and found statistically significant overlap in the populations responsive to both stimuli. Both hunger and opposite-sex social experience further increased the proportion of neurons that respond to both stimuli, implying that increasing motivation for one stimulus increases overlap. In addition, single-nucleus RNA sequencing revealed significant co-expression of feeding- and social-hormone-related genes in individual VTADA neurons. Taken together, our functional and transcriptional data suggest overlapping VTADA populations underlie food and social motivation.


Protective effects of aqueous extract of Solanum nigrum Linn. leaves in rat models of oral mucositis.
Oral mucositis is one of the most debilitating side effects in patient undergoing chemotherapy or chemoradiotherapy. Leaves of the plant Solanum nigrum are used in folklore medicine to treat oral ulcers in India. However, no pharmacological investigation has been carried out till date. Aqueous extract of Solanum nigrum leaves (AESN) was prepared and subjected to various phytochemical screening. HPLC analysis of the ethyl acetate fraction was carried out. The aqueous extract (100 and 200 mg/kg) was further evaluated for its protective effect on two rat models: (a) busulfan plus infrared radiation (chemoradiotherapy) induced oral mucositis and (b) methotrexate (chemotherapy) induced oral mucositis. Various parameters including body weight change, food intake, and mortality were measured. AESN showed protective effect in both models of oral mucositis; however, the higher dose was more effective in chemotherapy induced oral mucositis. A reduction in oral mucositis score (P < 0.05) was observed in the treatment groups. Significant (P < 0.05) improvement in food intake was also observed in AESN treated groups. Aqueous extract of Solanum nigrum leaves has protective effect on chemotherapy and chemoradiotherapy induced oral mucositis in rats.


Questionnaires Measuring Patients' Spiritual Needs: A Narrative Literature Review.
The objective of the present review was to collect published spiritual needs questionnaires and to present a clear image of the research condition of this domain. First, an electronic search was conducted with no limits on time span (until June 2015) or language in the following databases: PubMed, Scopus, Ovid, ProQuest and Google Scholar. All derivations of the keywords religion and spiritual alongside need and its synonyms were included in the search. Researches that introduced new tools was then selected and included in the study. Due to the limited quantity of questionnaires in this domain and with no consideration given to the existence or lack of exact standardization information, all of the questionnaires were included in the final report. Eight questionnaires were found: patients spiritual needs assessment scale (PSNAS), spiritual needs inventory (SNI), spiritual interests related to illness tool (SpIRIT), spiritual needs questionnaire (SpNQ), spiritual needs assessment for patients (SNAP), spiritual needs scale (SNS), spiritual care needs inventory (SCNI), and spiritual needs questionnaire for palliative care. These questionnaires have been designed from a limited medical perspective and often involve cultural concepts which complicate their cross-cultural applicability.


The Frankia alni symbiotic transcriptome.
The actinobacteria Frankia spp. are able to induce the formation of nodules on the roots of a large spectrum of actinorhizal plants, where they convert dinitrogen to ammonia in exchange for plant photosynthates. In the present study, transcriptional analyses were performed on nitrogen-replete free-living Frankia alni cells and on Alnus glutinosa nodule bacteria, using whole-genome microarrays. Distribution of nodule-induced genes on the genome was found to be mostly over regions with high synteny between three Frankia spp. genomes, while nodule-repressed genes, which were mostly hypothetical and not conserved, were spread around the genome. Genes known to be related to nitrogen fixation were highly induced, nif (nitrogenase), hup2 (hydrogenase uptake), suf (sulfur-iron cluster), and shc (hopanoids synthesis). The expression of genes involved in ammonium assimilation and transport was strongly modified, suggesting that bacteria ammonium assimilation was limited. Genes involved in particular in transcriptional regulation, signaling processes, protein drug export, protein secretion, lipopolysaccharide, and peptidoglycan biosynthesis that may play a role in symbiosis were also identified. We also showed that this Frankia symbiotic transcriptome was highly similar among phylogenetically distant plant families Betulaceae and Myricaceae. Finally, comparison with rhizobia transcriptome suggested that F. alni is metabolically more active in symbiosis than rhizobia.


[Synthesis and antiinflammation activity of aromatic aminoketone compounds, a new type of PAF-receptor antagonist].
A series of aromatic aminoketones were synthesized by Mannich reaction. Structures of these compounds were confirmed by 1H NMR, MS and HRMS or element analysis. Pharmacological screening showed that most target compounds inhibited the release of beta-glucuronidase in polymorphonuclear leucocytes by PAF (platelet activating factor) and compounds MA12, MA13, MA18, MA21 and MA33 were more active. The study suggests that target compounds are potential PAF receptor antagonists and their anti-inflammatory activities are due to the inhibition of release of lysosomal enzyme.


Membrane localization of the pertussis toxin-sensitive G-protein subunits alpha i-2 and alpha i-3 and expression of a metallothionein-alpha i-2 fusion gene in LLC-PK1 cells.
The renal epithelial cell line LLC-PK1 has topographically distinct regulatory roles for the alpha subunits of pertussis toxin-sensitive guanine nucleotide regulatory proteins (alpha i subunit); these include the inhibition of adenylyl cyclase at the basolateral membrane and the stimulation of Na+ channel activity at the apical membrane. We now report that LLC-PK1 cells contain two members of the alpha i protein family, alpha i-2 and alpha i-3, which have distinct cellular locations consistent with their diverse functional roles. By using specific alpha i antibodies and immunofluorescence, the alpha i-2 subunit was found to be localized to the basolateral membrane, whereas the alpha i-3 subunit was concentrated in the Golgi and was also detectable at low levels on apical membranes in some cells. Induction of a chimeric mouse metallothionein 1-rat or canine alpha i-2 gene stably transfected into the LLC-PK1 cells produced an increase in the content of the alpha i-2 subunit, which was targeted only to the basolateral membrane. These findings suggest that alpha i subunit specificity for effectors may be achieved in polarized renal epithelial cells by their geographic segregation to different cellular membranes. The LLC-PK1 cell stably transfected with the metallothionein-alpha i-2 fusion gene will provide a model for the study of guanine nucleotide regulatory protein function in epithelia.


Forensic analysis of soman exposure using characteristic fragment ions from protein adducts.
The verification of exposure to nerve agents is a serious challenge, especially in cases of soman (GD) poisoning. Protein adducts are reliable biomarkers, that provide forensic information and evidence during incidents of terrorism or sporadic poisoning. Mass spectrometry, coupled with a proteomics approach, was established for the forensic analysis of GD-based protein adducts. The fragmentation pathways of GD-based protein adducts were investigated for the first time using electrospray ionization tandem mass spectrometry. Three abundant natural loss product ions, [M+2H-54]2+ (loss of two carbon cations), [M+2H-72]2+ (loss of tert-butyl and methyl moieties), and [M+2H-84]2+ (loss of the pinacolyl moieties), were observed in each of the GD-labeled adducts, and the product ions were independent of protein structure and exposure route. A unique mechanism for the formation of product ions involving GD-protein adducts is proposed here. These findings support the development of a simple and precise forensic analysis technique to rapidly verify GD poisoning using these three GD-related product ions.


Developing an Inclusive and Welcoming LGBTQ Clinic.
People who identify as lesbian, gay, bisexual, transgender, queer, and questioning (LGBTQ) are underserved and face barriers to knowledgeable health care. Most health systems are ill prepared to provide care that addresses the needs of the LGBTQ community. Basic steps to developing an LGBTQ welcoming health care program are presented. It can be adapted to diverse health care models, from obstetrics and gynecology and other primary care services whether public or private and to hospitals and specialty clinics. This LGBTQ inclusive health care model was developed in collaboration with the LGBTQ community, a multidisciplinary team of health care providers, and professionals of Law and Information Technology.


The Effects of Oral Cryotherapy on Chemotherapy-Induced Oral Mucositis in Patients Undergoing Autologous Transplantation of Blood Stem Cells: A Clinical Trial.
Oral mucositis is one of the irritating side effects of chemotherapy in patients undergoing bone marrow transplantation. However, up until now, the common methods of oral mucositis therapy have failed to show significant effects. The aim of this study was to investigate the effects of local cryotherapy on the intensity of chemotherapy-induced oral mucositis in autologous bone marrow transplantation patients. In this single, blinded, randomized clinical trial, 29 patients undergoing stem cell transplantation in Iran were selected by convenience sampling, and randomly allocated to control (n = 13) and intervention groups (n = 16). In the intervention group, cryotherapy was applied, while the control group received a normal saline mouthwash. The severity of the mucositis and neutrophil rate were investigated in five periods, based on the world health organization (WHO) scales. The data were analyzed using descriptive statistics, the Mann-Whitney test, repeated measures analysis of variance (ANOVA), and linear regression. In both groups, the mucositis reached its peak intensity on the 7th day, and the least intensity was obtained on the 21st day. The neutrophil rate reached the minimum value on the 7th day, then increased up to the 21st day. The two groups showed no significant differences between the mucositis severity on the 14th and 21st days (P = 0.164), while the severity of the mucositis in the cryotherapy group was significantly less than that in the saline mouthwash group (1.81 < 2.54 and 0.13 < 0.92, respectively) on the 7th and 14th days (P < 0.05). There was no significant difference in the neutrophil rate between the groups. The results showed that cryotherapy is more effective than the saline mouthwash in reducing the severity of mucositis. This method is recommended for the prevention of mucositis in bone marrow transplantation.


[Serum interferon in newborn infants and their mothers].
The results from a study on serum interferon in newborns and their mothers are described. The newborns infants receive serum interferon transplacentally in a relative part of the examined cases. Coincidence in the levels of interferon in newborns and their mothers is found in 50% of the cases. Intrauterine synthesized interferon (5.8%) with considerable concentration is also established, due probably to ascendant virus infection.


Borderline personality disorder and bone marrow transplantation: ethical considerations and review.
Bone marrow transplantation (BMT) is rapidly becoming a part of conventional cancer treatment. However, it remains a 'last-ditch' treatment option for patients who have exhausted other treatment modalities. Patients experience a significant amount of emotional distress during all stages of the BMT process. Patients with personality disorders experience even more emotional distress than average and their behavior is often detrimental to effective patient-staff interactions. A case of a borderline patient is presented with a discussion of the ethical issues involved in the evaluation of these patients and the determination of their appropriateness for transplant.