Nucleotide selectivity defect and mutator phenotype conferred by a colon cancer-associated DNA polymerase δ mutation in human cells.
Mutations in the POLD1 and POLE genes encoding DNA polymerases δ (Polδ) and ɛ (Polɛ) cause hereditary colorectal cancer (CRC) and have been found in many sporadic colorectal and endometrial tumors. Much attention has been focused on POLE exonuclease domain mutations, which occur frequently in hypermutated DNA mismatch repair (MMR)-proficient tumors and appear to be responsible for the bulk of genomic instability in these tumors. In contrast, somatic POLD1 mutations are seen less frequently and typically occur in MMR-deficient tumors. Their functional significance is often unclear. Here we demonstrate that expression of the cancer-associated POLD1-R689W allele is strongly mutagenic in human cells. The mutation rate increased synergistically when the POLD1-R689W expression was combined with a MMR defect, indicating that the mutator effect of POLD1-R689W results from a high rate of replication errors. Purified human Polδ-R689W has normal exonuclease activity, but the nucleotide selectivity of the enzyme is severely impaired, providing a mechanistic explanation for the increased mutation rate in the POLD1-R689W-expressing cells. The vast majority of mutations induced by the POLD1-R689W are GC→TA transversions and GC→AT transitions, with transversions showing a strong strand bias and a remarkable preference for polypurine/polypyrimidine sequences. The mutational specificity of the Polδ variant matches that of the hypermutated CRC cell line, HCT15, in which this variant was first identified. The results provide compelling evidence for the pathogenic role of the POLD1-R689W mutation in the development of the human tumor and emphasize the need to experimentally determine the significance of Polδ variants present in sporadic tumors.


"Air bubble": a new diagnostic CT sign of perforated pulmonary hydatid cyst.
The greatest difficulty in the CT diagnosis of perforated pulmonary hydatid cyst (PPHC) is the increase in the attenuation numbers following infection. Because of the solid density of infected hydatid cysts, the differentiation from an abscess or neoplasm is usually impossible. The aim of this study was to evaluate the value of "air bubble" as a new CT sign in the diagnosis of PPHC. Sixty-five patients (28 men and 37 women) with PPHC were included in the study. As a control group, 55 patients who had malignant (n = 36) or non-malignant (n = 19) pulmonary diseases were also examined. Radiological diagnosis with classical CT findings was made in only 38 of 65 patients (58.5 %) with PPHC. Air bubble sign was positive in 54 of the patients with PPHC (sensitivity 83.1 %) but only 3 of 55 patients in control group (specificity 94.5 %). When we analyzed the CT scans with classical CT findings including air bubble, the diagnosis of PPHC was made in 61 of patients (93.8 %). It is concluded that "air bubble sign" is a valuable CT finding in the diagnosis of PPHC.


Occurrence and spatial distribution of chemical contaminants in edible fish species collected from UK and proximate marine waters.
The occurrence of a range of regulated and emerging organic environmental contaminants was investigated in 182 samples of edible marine fish sampled mainly from UK marine regions, but extending northerly to the coast of Norway and south to the Algarve. These species (sprats, mackerel, turbot, halibut, herring, grey mullet, sea bass, grey mullet, sardines, etc.) are among those considered to be at the highest risk of contamination with regulated contaminants such as polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs, dioxins), and polychlorinated biphenyls (PCBs), but the occurrence of polybrominated diphenylethers (PBDEs) and polybrominated biphenyls (PBBs) was also investigated. Sub-sets of samples (50-75) were also analysed for emerging contaminants: polychlorinated naphthalenes (PCNs), polybrominated and mixed halogenated dibenzo-p-dioxins, dibenzofurans and biphenyls (PBDD/Fs, PXDD/Fs and PXBs) and perfluoroalkyl substances (PFAS). Contaminant occurrence varied with species and location, but all measured contaminants were detected, with sprats, sea bass, sardines, mackerel, and herring showing higher tissue concentrations. The concentrations of the different contaminants in the various samples were mapped utilising the GPS coordinate data of the capture locations to visualise spatial distribution levels. In terms of catch location, fish sampled from the coasts of southern Britain, north-western France and the Irish Sea appeared to contain proportionately higher levels of some contaminants - e.g. samples from the Irish Sea tended to show higher PCN concentrations, whereas higher levels of PCBs were observed in some fish sampled off the coasts of northern France. Similarly, samples of mullet from the southeast coast of UK showed much higher concentrations of BDE-99 than the other regions. In terms of occurrence trends, PCDD/F and PCB concentrations show a modest decline over the last decade but where limited background data is available for emerging contaminants, there is no evidence of downward trends.


[HIV-1 Rev and related inhibitors].
HIV-1 Rev is an indispensable regulatory factor of the virion protein expression. The interaction between Rev and RRE RNA accelerates the nuclear export of viral mRNA. The unspliced and singly spliced mRNA will be degraded in the absence of Rev, resulting in the interception of HIV-1 replication at the same time. The pivotal role that Rev plays in HIV-1 replication as a trans-acting factor makes it a new target in the research of AIDS drugs. In this review, the function of Rev, Rev-RRE interaction, as well as their related inhibitors are reported.


Exercise gaming - a motivational approach for older adults with vestibular dysfunction.
Purpose The purpose of the study was to identify possible reasons for a modest level of exercise compliance during computer-assisted training for vestibular rehabilitation. Method Qualitative design and analysis of 14 semi-structured interviews with seven participants before and after a period with computer-assisted home training. The interviews evolved around themes, such as the elderly participants' self-efficacy, motivation and acceptance of the technology. Results Age was not an excuse for the modest exercise compliance. The participants were basically self-efficient and accepted the technology, but their knowledge and understanding of the training programme were insufficient. The participants asked for a greater variation in the exercises and asked for closer contact with the physiotherapist. When Mitii is used for vestibular rehabilitation, the system has some limitations. Conclusions The modest level of exercise compliance can be explained by (1) missing variety of exercise speed and duration and lack of introducing new exercises, (2) insufficient interaction with the physiotherapist regarding the participants' performance and lack of social contact with other patients and (3) desire for a deeper understanding of the training programme with supplying information on the parts of the vestibular system addressed by the training. Implications for Rehabilitation Computer-assisted technologies should generate feedback on the quality of user performance and inform the patient of the relevance of the exercise. The technology should support social contact among patients with the same diagnosis and establish contact with the physiotherapist at the hospital advice and feedback. Varity and adjustments to exercises are necessary to maintain motivation and exercise compliance.


Decentralization of health care systems and health outcomes: Evidence from a natural experiment.
While many countries worldwide are shifting responsibilities for their health systems to local levels of government, there is to date insufficient evidence about the potential impact of these policy reforms. We estimate the impact of decentralization of the health services on infant and neonatal mortality using a natural experiment: the devolution of health care decision making powers to Spanish regions. The devolution was implemented gradually and asymmetrically over a twenty-year period (1981-2002). The order in which the regions were decentralized was driven by political factors and hence can be considered exogenous to health outcomes. In addition, we exploit the dynamic effect of decentralization of health services and allow for heterogeneous effects by the two main types of decentralization implemented across regions: full decentralization (political and fiscal powers) versus political decentralization only. Our difference in differences results based on a panel dataset for the 50 Spanish provinces over the period 1980 to 2010 show that the lasting benefit of decentralization accrues only to regions which enjoy almost full fiscal and political powers and which are also among the richest regions.


Furan hydrogenation over Pt(111) and Pt(100) single-crystal surfaces and Pt nanoparticles from 1 to 7 nm: a kinetic and sum frequency generation vibrational spectroscopy study.
Sum frequency generation surface vibrational spectroscopy and kinetic measurements using gas chromatography have been used to systematically study the adsorption and hydrogenation of furan over Pt(111) and Pt(100) single-crystal surfaces and size-controlled 1.0-nm, 3.5-nm and 7.0-nm Pt nanoparticles at Torr pressures (10 Torr of furan, 100 Torr of H(2)) to form dihydrofuran, tetrahydrofuran, and the ring-cracking products butanol and propylene. As determined by SFG, the furan ring lies parallel to all Pt surfaces studied under hydrogenation conditions. Upright THF and the oxametallacycle intermediate are observed over the nanoparticle catalysts under reaction conditions. Butoxy increases in surface concentration over Pt(111) with increasing temperature in agreement with selectivity trends.


Pathophysiology of hantavirus pulmonary syndrome in rhesus macaques.
The pathophysiology of hantavirus pulmonary syndrome (HPS) remains unclear because of a lack of surrogate disease models with which to perform pathogenesis studies. Nonhuman primates (NHP) are considered the gold standard model for studying the underlying immune activation/suppression associated with immunopathogenic viruses such as hantaviruses; however, to date an NHP model for HPS has not been described. Here we show that rhesus macaques infected with Sin Nombre virus (SNV), the primary etiological agent of HPS in North America, propagated in deer mice develop HPS, which is characterized by thrombocytopenia, leukocytosis, and rapid onset of respiratory distress caused by severe interstitial pneumonia. Despite establishing a systemic infection, SNV differentially activated host responses exclusively in the pulmonary endothelium, potentially the mechanism leading to acute severe respiratory distress. This study presents a unique chronological characterization of SNV infection and provides mechanistic data into the pathophysiology of HPS in a closely related surrogate animal model. We anticipate this model will advance our understanding of HPS pathogenesis and will greatly facilitate research toward the development of effective therapeutics and vaccines against hantaviral diseases.


Ac-SDKP ameliorates the progression of experimental autoimmune encephalomyelitis via inhibition of ER stress and oxidative stress in the hippocampus of C57BL/6 mice.
Despite the attention given to the treatment of multiple sclerosis (MS), still no certain cure is available. The main purpose of MS drugs is acting against neuroinflammation which underlies the pathology of MS. Neuroinflammation is associated with endoplasmic reticulum (ER) stress that mediates neural apoptosis. In the present study, we hypothesized that the tetrapeptide N-acetyl-ser-asp-lys-pro (Ac-SDKP) with the previously described anti-fibrotic effects might have anti-inflammatory, anti-oxidative and anti-ER stress roles in the hippocampus. We used myelin oligodendrocyte glycoprotein (MOG) to induce experimental autoimmune encephalomyelitis (EAE), a widely-accepted animal model of MS, in C57BL/6 mice. The protein levels of ER stress-related molecules including caspase-12, C/EBP homologous protein (CHOP), and protein disulfide isomerase (PDI) in the hippocampus were examined by immunoblotting. Hence, reactive oxygen species (ROS) production, lipid peroxidation and antioxidant capacity of the hippocampus were studied. Moreover, hippocampal morphology changes, leukocytes infiltration, and the levels of IL-6 and IL-1β pro-inflammatory cytokines were evaluated. Our results displayed that Ac-SDKP down regulates caspase-12 and CHOP expression in the hippocampus-resident oligodendrocytes of EAE mice. Further, treatment with Ac-SDKP decreased oxidative stress markers and caspase-3 activation in the hippocampus of EAE mice. According to our findings, Ac-SDKP showed beneficial effects against ER stress and oxidative stress in addition to inflammation in the hippocampus of EAE mice. The present study provides the basis for further research on the therapeutic applications of Ac-SDKP to reduce ER stress and oxidative stress-induced apoptosis in neurodegenerative disorders.


Distribution of Norwalk virus within shellfish following bioaccumulation and subsequent depuration by detection using RT-PCR.
Consumption of raw bivalve mollusks contaminated with pathogens from human feces continues to present a human health risk. The purpose of this study was to monitor the uptake, localization, and removal of Norwalk virus (NV) in shellfish (oyster and clam) tissues by analyzing virus distribution in selected dissected tissues. Live shellfish were allowed to bioaccumulate different input titers of NV for time periods from 4 to 24 h. In some experiments, depuration by shellfish that bioaccumulated NV and Escherichia coli bacteria was allowed to proceed for 24 or 48 hours. Dissected stomach (St), digestive diverticula (DD), adductor muscle (AM), and hemolymph cells (HC) tissues were assayed for NV by the reverse transcription polymerase chain reaction (RT-PCR) method. An internal RNA standard control was added to the RT-PCR to identify the presence of inhibitors to RT-PCR. NV titers in DD tissues before and after depuration were estimated using quantitative RT-PCR end-point dilution. NV was found in the alimentary tract (DD or St) at all concentrations of input virus, but was present more frequently after exposure to higher levels of virus. NV was detected in AM and HC only following exposure to higher levels of virus. In experiments where depuration by oysters was continued for 48 h, depuration of bacteria was efficient (95% reduction of bacteria), but minimal (7%) reduction of NV titers from DD tissues was detected. These findings indicate that NV can localize both within and outside the alimentary tract of shellfish, and NV is poorly depurated using conditions favorable for E. coli depuration.


A rapid method to increase the number of F₁ plants in pea (Pisum sativum) breeding programs.
In breeding programs, a large number of F₂ individuals are required to perform the selection process properly, but often few such plants are available. In order to obtain more F₂ seeds, it is necessary to multiply the F₁ plants. We developed a rapid, efficient and reproducible protocol for in vitro shoot regeneration and rooting of seeds using 6-benzylaminopurine. To optimize shoot regeneration, basic medium contained Murashige and Skoog (MS) salts with or without B5 Gamborg vitamins and different concentrations of 6-benzylaminopurine (25, 50 and 75 μM) using five genotypes. We found that modified MS (B5 vitamins + 25 μM 6-benzylaminopurine) is suitable for in vitro shoot regeneration of pea. Thirty-eight hybrid combinations were transferred onto selected medium to produce shoots that were used for root induction on MS medium supplemented with α-naphthalene-acetic acid. Elongated shoots were developed from all hybrid genotypes. This procedure can be used in pea breeding programs and will allow working with a large number of plants even when the F₁ plants produce few seeds.


Prothrombotic disorders in infants and children with cerebral thromboembolism.
To our knowledge, the contribution of prothrombotic conditions to cerebral thromboembolism has never been prospectively studied in a large series of pediatric patients. The Hospital for Sick Children, Toronto, Ontario, established a program in January 1992 to diagnose and treat children (term newborn to 18 years old) with arterial ischemic stroke or sinovenous thrombosis. The routine evaluation for prothrombotic conditions included plasminogen, antithrombin, protein C, free protein S, activated protein C resistance, IgG and IgM anticardiolipin antibody, and lupus anticoagulant. We analyzed samples taken within 2 years of the event. We report results on patients seen from January 1, 1992, to January 1, 1997. Ninety-two patients (47 males and 45 females) entered the program during the study interval. Patients ranged from newborn to 18 years in age. Arterial ischemic stroke occurred in 78% of patients while sinovenous thrombosis occurred in 22%. All were tested for prothrombotic disorders. One or more abnormal results were present in 35 (38%) of the 92 patients. The majority (21/35) had multiple abnormal test results. The abnormal test results were anticardiolipin antibody (33%), plasminogen (9.5%), activated protein C resistance (9%), protein C (7%), antithrombin (12.5%), lupus anticoagulant (8%), and free protein S (11.5%). Male sex predicted the presence of prothrombotic abnormalities (relative risk, 1.7; 95% confidence interval, 1.2-2.5), but stroke type (relative risk, 0.8; 95% confidence interval, 0.7-1.1), age group, and presence of other risk factors did not predict abnormal testing. A significant proportion (38%) of children with cerebral thromboembolism had evidence of prothrombotic conditions. In particular, there was a predominance of children with anticardiolipin antibody (33%). These data support a recommendation that children with cerebral thromboembolism be evaluated for prothrombotic disorders.


An excitatory GABAergic plexus in developing neocortical layer 1.
Layer 1 of the developing rodent somatosensory cortex contains a dense, transient GABAergic fiber plexus. Axons arising from the zona incerta (ZI) of the ventral thalamus contribute to this plexus, as do axons of intrinsic GABAergic cells of layer 1. The function of this early-appearing fiber plexus is not known, but these fibers are positioned to contact the apical dendrites of most postmigratory neurons. Here we show that electrical stimulation of layer 1 results in a GABA(A)-mediated postsynaptic current (PSC) in pyramidal neurons. Gramicidin perforated patch recording demonstrates that the GABAergic layer 1 synapse is excitatory and can trigger action potentials in cortical neurons. In contrast to electrical stimulation, activation of intrinsic layer 1 neurons with a glutamate agonist fails to produce PSCs in pyramidal cells. In addition, responses can be evoked by stimulation of layer 1 at relatively large distances from the recording site. These findings are consistent with a contribution of the widely projecting incertocortical pathway, the only described GABAergic projection to neonatal cortex. Recording of identified neonatal incertocortical neurons reveals a population of active cells that exhibit high frequencies of spontaneous action potentials and are capable of robustly activating neonatal cortical neurons. Because the fiber plexus is confined to layer 1, this pathway provides a spatially restricted excitatory GABAergic innervation of the distal apical dendrites of pyramidal neurons during the peak period of cortical synaptogenesis.


Trichothiodystrophy associated with urologic malformation and primary hypercalciuria.
Trichothiodystrophy (TTD) is a hair abnormality that may be associated with a large number of alterations affecting the skin phenotype and skin appendages, nervous system, eyes, bones, and immune, gonadal, and endocrine systems. We report the first case of TTD associated with a urologic malformation and primary hypercalciuria. Our patient had congenital ichthyosis, physical and mental retardation, and a dysmorphic facies associated with a complex urologic malformation and primary hypercalciuria. Characteristic features of his hair under microscopic examination (trichoschisis, alternating light and dark bands under polarizing microscopy, and a severely defective cuticle) and low sulfur content by radiographic microanalysis confirmed the diagnosis. We discuss the meaning of this new association in the spectrum of abnormalities related to TTD.


Autologous stem cell transplantation versus alternative allogeneic donor transplants in adult acute leukemias.
The availability of alternative sources of stem cells including most recently T-replete haploidentical marrow or peripheral blood, and the increasing use of reduced-intensity conditioning (RIC), renders feasible an allogeneic transplant to almost all patients with acute leukemia up to 70 years of age. Autologous stem cell transplantation (ASCT) for consolidation of complete remission (CR), however, offers in some circumstances an alternative option. Although associated with a higher relapse rate, autologous transplant benefits from a lower non-relapse mortality, the absence of graft-versus-host disease (GVHD), and a better quality of life for long-term survivors. The recent use of intravenous busulfan (IVBU) with high-dose melphalan, better monitoring of minimal residual disease (MRD), and maintenance therapy post autografting bring new interest. Few retrospective studies compared the outcome following alternative donor versus autologous transplants for remission consolidation. Genoidentical and phenoidentical allogeneic stem cell transplantations are undisputed gold standards, but there are no data showing the superiority of alternative allogeneic donor over autologous transplantation, at the time of undetectable MRD, in patients with good- and intermediate-1 risk acute myelocytic leukemia (AML) in first complete remission (CR1), acute promyelocytic leukemia in second complete remission (CR2), and Philadelphia chromosome-positive (Ph(+)) acute lymphocytic leukemia (ALL).


The Antitumour Effect of Prunella vulgaris Extract on Thyroid Cancer Cells In Vitro and In Vivo.
Prunella vulgaris, a traditional Chinese medicine, has been used to treat various benign and malignant tumours for centuries in China. In our previous studies, Prunella vulgaris extract (PVE) was shown to promote apoptosis in differentiated thyroid cancer (DTC) cells. However, whether other mechanisms are involved in the antitumour effect of PVE in thyroid cancer (TC) cells remains unclear. The present study aimed to investigate the antiproliferative and antimigratory effects of PVE on TC cell lines both in vitro and in vivo. First, the TPC-1 and SW579 human TC cell lines were screened by MTT assay for their high level of sensitivity to PVE. Then, the results of cell growth curve and colony formation assay and cell cycle analyses, wound healing, and migration assays demonstrated that PVE inhibited the proliferation and migration of TPC-1 and SW579 cells. Moreover, the antitumour effect of PVE was verified in a subcutaneous xenotransplanted tumour model. Next, MKI67, PCNA, CTNNB1, and CDH1 were screened by qRT-PCR for their significantly differential expression levels in xenograft tissue with and without PVE treatment, and expression of MKI67, PCNA, and CDH1 was verified by Western blot. Finally, an integrated bioinformatics analysis containing protein-protein interaction network, KEGG pathway, and GO analysis was conducted to explore more potential antitumour mechanisms of PVE. In summary, PVE could inhibit the proliferation and migration of TC cells both in vitro and in vivo, which may have been achieved by modulation of the expression of MKI67, PCNA, and CDH1. These data suggest that PVE has the potential to be developed into a new anticancer drug for the treatment of TC.


Increased shoe bending stiffness increases sprint performance.
The purposes of this investigation were to determine if increasing the bending stiffness of sprint shoes increases sprinting performance and to determine whether simple anthropometric factors can be used to predict shoe bending stiffness for optimal performance. Thirty-four athletes were tested using four different shoe conditions--a standard condition consisting of their currently used footwear and three conditions where the bending stiffness was increased systematically. The sprinters performed maximal effort 40 m sprints and their sprint times were recorded from 20 to 40 m. On average, increasing the shoe bending stiffness increased sprint performance. The stiffness each athlete required for his or her maximal performance was subject specific but was not related to subject mass, height, shoe size or skill level. It is speculated that individual differences in the force-length and force-velocity relationships of the calf muscles may influence the appropriate shoe stiffness for each athlete to obtain their maximal performance.


Glucolipotoxicity, β-Cells, and Diabetes: The Emperor Has No Clothes.
Reduction of β-cell mass and function is central to the pathogenesis of type 2 diabetes. The terms glucotoxicity, lipotoxicity, and glucolipotoxicity are used to describe potentially responsible processes. The premise is that chronically elevated glucose levels are toxic to β-cells, that elevated lipid levels in the form of circulating free fatty acids (FFA) also have toxic effects, and that the combination of the two, glucolipotoxicity, is particularly harmful. Much work has shown that high concentrations of FFA can be very damaging to β-cells when used for in vitro experiments, and when infused in large amounts in humans and rodents they produce suppression of insulin secretion. The purpose of this Perspective is to raise doubts about whether the FFA levels found in real-life situations are ever high enough to cause problems. Evidence supporting the importance of glucotoxicity is strong because there is such a tight correlation between defective insulin secretion and rising glucose levels. However, there is virtually no convincing evidence that the alterations in FFA levels occurring during progression to diabetes are pathogenic. Thus, the terms lipotoxicity and glucolipotoxicity should be used with great caution, if at all, because evidence supporting their importance has not yet emerged.


Problems and strategies for bone marrow transplantation in acute leukemia and chronic myelogenous leukemia.
Certain marrow transplant protocols can now result in a 50-70% long disease-free survival and low relapse rates in acute leukemia (AL) in CR1, CR2, or CML following cytoreduction and HLA-identical marrow infusion. Two-thirds of deaths are due to acute and chronic graft-versus-host disease (GVHD) or viral infection. The other deaths are due to toxicities of the cytoreductive treatment. Prevention of GVHD has been tried by treatment after the transplant or treating the marrow (lymphocyte depletion). Cyclosporine (CsA) or CsA plus methotrexate has reduced acute GVHD but not chronic GVHD. Marrow has been treated with monoclonal antibodies and lectins or elutriated to decrease numbers of T lymphocytes. Some studies have been effective, but the majority have shown an increased number of rejections or leukemic relapses. Apart from teratogenic effects, thalidomide has minimal toxicity. It effectively prevents and treats acute and chronic GVHD in rodent models. Clinical trials will soon begin. Mismatched related or matched unrelated donors have been employed in the clinic with limited success. Alternatively, autologous transplantation in acute leukemia has shown promising results. Possible solutions to remaining problems and strategies will be discussed.


Tribal formulations for treatment of pain: a study of the Bede community traditional medicinal practitioners of Porabari Village in Dhaka District, Bangladesh.
The Bedes form one of the largest tribal or indigenous communities in Bangladesh and are popularly known as the boat people or water gypsies because of their preference for living in boats. They travel almost throughout the whole year by boats on the numerous waterways of Bangladesh and earn their livelihood by selling sundry items, performing jugglery acts, catching snakes, and treating village people by the various riversides with their traditional medicinal formulations. Life is hard for the community, and both men and women toil day long. As a result of their strenuous lifestyle, they suffer from various types of pain, and have developed an assortment of formulations for treatment of pain in different parts of the body. Pain is the most common reason for physician consultation in all parts of the world including Bangladesh. Although a number of drugs are available to treat pain, including non-steroidal, steroidal, and narcotic drugs, such drugs usually have side-effects like causing bleeding in the stomach over prolonged use (as in the case of rheumatic pain), or can be addictive. Moreover, pain arising from causes like rheumatism has no proper treatment in allopathic medicine. It was the objective of the present study to document the formulations used by the Bede traditional practitioners for pain treatment, for they claim to have used these formulations over centuries with success. Surveys were conducted among a large Bede community, who reside in boats on the Bangshi River by Porabari village of Savar area in Dhaka district of Bangladesh. Interviews of 30 traditional practitioners were conducted with the help of a semi-structured questionnaire and the guided field-walk method. It was observed that the Bede practitioners used 53 formulations for treatment of various types of pain, the main ingredient of all formulations being medicinal plants. Out of the 53 formulations, 25 were for treatment of rheumatic pain, either exclusively, or along with other types of body pain. A total of 65 plants belonging to 39 families were used in the formulations. The Fabaceae family provided 7 plants followed by the Solanaceae family with 4 plants. 47 out of the 53 formulations were used topically, 5 formulations were orally administered, and 1 formulation had both topical and oral uses. 8 formulations for treatment of rheumatic pain contained Calotropis gigantea, suggesting that the plant has strong potential for further scientific studies leading to discovery of novel efficacious compounds for rheumatic pain treatment.


Research culture in a regional allied health setting.
Research evidence is required to guide best practice, inform policy and improve the health of communities. Current indicators consider allied health research culture to be low. This study aimed to measure the allied health research culture and capacity in a Victorian regional health service. The Research Capacity and Culture tool was used to evaluate research capacity and culture across individual, team and organisation domains. One-way ANOVA was used to determine differences between allied health professions, whereas responses to open-ended questions were themed using open coding. One hundred thirty-six allied health professionals completed the survey. There were statistically significant differences in the organisation domain between social work, physiotherapy and occupational therapy professions; in the team domain, between social work and all other professions. Motivators for conducting research included providing a high-quality service, developing skills and increasing job satisfaction. Barriers included other work roles taking priority, a lack of time and limited research skills. Multi-layered strategies including establishing conjoint research positions are recommended to increase allied health research culture in this regional area.


Effectiveness of Physiotherapy Treatment for Urinary Incontinence in Women: A Systematic Review.
Urinary incontinence (UI) may be defined as involuntary urine loss, which can be diagnosed based on patient-reported measures and is a hygiene and social problem in those who have it, affecting their quality of life negatively. The study aimed to determine the effectiveness of distinct physiotherapy techniques used in the treatment of UI in women through a systematic review of the existing literature. The scales and instruments used for the assessment and follow-up of UI were described. On searching the PubMed, Dialnet, PEDro, and SciELo databases, 16 articles, with information on 1220 patients that comply with the inclusion criteria and conform to the proposed objectives were obtained, limiting the publication period to 2007-2016. The PRISMA statement was adopted. The "Pad Test" is a commonly used diagnostic test and bladder diaries on paper; the Oxford scale was used in the assessment of pelvic floor muscle strength. Distinct protocols and techniques have been described in the treatment of UI in women, namely, pelvic floor exercises, vaginal cones, biofeedback, and electrostimulation. Upon analysis of the content of the articles, the quality of the included clinical trials was determined using the PEDro scale. Studies included in this work propose that physiotherapy treatment may improve UI, the patients' quality of life, and social relations in women. It is necessary to establish group treatment protocols for women with UI, supervised by a physiotherapist to reduce the financial burden incurred from this health problem.


Physiological roles of nonselective cation channels in plants: from salt stress to signalling and development.
Nonselective cation channels (NSCCs) catalyse passive fluxes of cations through plant membranes. NSCCs do not, or only to a small extent, select between monovalent cations, and several are also permeable to divalent cations. Although a number of NSCC genes has been identified in plant genomes, a direct correlation between gene products and in vivo observed currents is still largely absent for most NSCCs. In this review, physiological functions and molecular properties of NSCCs are critically discussed. Recent studies have demonstrated that NSCCs are directly involved in a multitude of stress responses, growth and development, uptake of nutrients and calcium signalling. NSCCs can also function in the perception of external stimuli and as signal transducers for reactive oxygen species, pathogen elicitors, cyclic nucleotides, membrane stretch, amino acids and purines.


Infection with human parvovirus (B19), aplasia of the bone marrow and a rash in hereditary spherocytosis.
Infection with human parvovirus (HPV) B19 was diagnosed in persons with hereditary spherocytosis during an outbreak of erythema infectiosum. A 10-year-old boy had an aplastic crisis of the bone marrow and a maculopapular rash. His mother also had an aplastic crisis, fever, rash and a transiently acellular marrow. Another boy had an aplastic crisis, leucopenia and fever, but did not have a rash. Aplastic crisis and a rash have rarely before been observed together and attributed to infection with HPV.


The lipopolysaccharide Parkinson's disease animal model: mechanistic studies and drug discovery.
Research in the last two decades has unveiled an important role for neuroinflammation in the degeneration of the nigrostriatal dopaminergic (DA) pathway that constitutes the pathological basis of the prevailing movement disorder, Parkinson's disease (PD). Neuroinflammation is characterized by the activation of brain glial cells, primarily microglia and astrocytes that release various soluble factors that include free radicals (reactive oxygen and nitrogen species), cytokines, and lipid metabolites. The majority of these glia-derived factors are proinflammatory and neurotoxic and are particularly deleterious to oxidative damage-vulnerable nigral DA neurons. As a proof of concept, various immunologic stimuli have been employed to directly induce glial activation to model DA neurodegeneration in PD. The bacterial endotoxin, lipopolysaccharide (LPS), has been the most extensively utilized glial activator for the induction of inflammatory DA neurodegeneration. In this review, we will summarize the various in vitro and in vivo LPS PD models. Furthermore, we will highlight the contribution of the LPS PD models to the mechanistic studies of PD pathogenesis and the search for neuroprotective agents for the treatment of PD.


[Case control study of fractures-dislocations of ankle joint with conservative and operative treatment].
To compare the clinical efficacy of grade III, IV supination-eversion fractures-dislocations of ankle joint between manipulative treatment and operative treatment. From September 2007 to December 2008, the clinical data of 60 patients with grade III, IV supination-eversion fractures-dislocations of ankle joint were retrospectively analyzed. There were 32 males and 28 females, ranging in age from 18 to 70 years with an average age of 38.17 years. All patients were respectively treated with manipulative treatment (conservative group, 30 cases) and operative treatment (operative group, 30 cases). The joint function was compared with Mazur standard; the reduction and shifting of fractures were observed with X-ray; the hospitalization day and the therapeutic cost were compared between two groups. All patients were followed up with an average of 15.27 months (ranged, 6 to 25 months). In conservative group, 16 cases got excellent result in joint function, 10 good, 3 fair, 1 poor; in operative group, 20 cases got excellent result, 8 good, 2 fair, 0 poor. In conservative group in the X-ray showed 25 cases obtained excellent and good reduction, 4 fair, 1 poor; and in operative group in the X-ray showed 28 cases obtained excellent and good reduction, 2 fair, 0 poor. There was no significant difference at the joint function and X-ray film after treatment between two groups (P > 0.05). The hospital day was respectively (7.87 +/- 3.34), (17.37 +/- 4.64) d in conservative group and operative group; and the therapeutic cost was respectively (2 506.67 +/- 649.10), (11 473.33 +/- 1 564.90) yuan. There was significant difference at hospital day and therapeutic cost between two groups (P < 0.05). Conservative treatment and operative treatment can both reach a very good result in treating grade III, IV supination-eversion fractures and dislocations of ankle joint. However, conservative treatment has advantage of high safety factor, low therapeutic cost, can reduce medical costs for patients.


Management of unfavorable locoregional prostate carcinoma with radiation and androgen ablation.
This study attempted to define unfavorable locoregional prostate carcinoma and presents the results of treatment with combined radiation and androgen ablation for these patients. Of a group of 938 men with clinically localized N0/NX disease treated with radiation alone, an unfavorable category included all men with prostate specific antigen (PSA) > 20 ng/mL and all men with 10 < PSA < or = 20 ng/mL but with Gleason's grade > 7. One hundred and eighty-five such men treated with radiation alone and an additional 100 men with similar disease received radiation with early androgen ablation. A second cohort was comprised of 229 men with lymphadenectomy proven pelvic lymph node metastases, with 185 receiving early androgen ablation alone and 44 receiving androgen ablation and local radiation. The outcomes, with recurrence or rising PSA as the endpoint, were compared among these various treatment groups using multivariate techniques. Disease outcome with the combined modality treatment was dramatically improved in both cohorts of men. For those with unfavorable N0/NX disease, the failure rate at 5 years decreased from 82% with only radiation therapy to 15% with combined treatment. Likewise, for patients with lymph node disease, the failure rate at 5 years decreased from 58% with only androgen ablation to 10% with combined treatment. For the whole group with unfavorable disease (unfavorable N0/NX and lymph node positive disease) the 6-year failure decreased from 71% with single modality treatment to 13% with bimodality treatment. There was a close relationship between the incidence of lymph node disease and prognostic categories and patients with otherwise unfavorable disease did not have their poor outlook ameliorated by undergoing a negative lymphadenectomy. Unfavorable locoregional prostate carcinoma can be recognized on the basis of pretreatment PSA level, T category, and Gleason's grade without specific evaluation of pelvic lymph node status. Combined local radiation and androgen ablation for patients with unfavorable disease results in a substantial improvement in disease control compared with that achieved by either modality alone. The authors found no improvement in survival because all groups of men had a normal life expectancy to at least 5 years.


Transition metal homeostasis: from yeast to human disease.
Transition metal ions are essential nutrients to all forms of life. Iron, copper, zinc, manganese, cobalt and nickel all have unique chemical and physical properties that make them attractive molecules for use in biological systems. Many of these same properties that allow these metals to provide essential biochemical activities and structural motifs to a multitude of proteins including enzymes and other cellular constituents also lead to a potential for cytotoxicity. Organisms have been required to evolve a number of systems for the efficient uptake, intracellular transport, protein loading and storage of metal ions to ensure that the needs of the cells can be met while minimizing the associated toxic effects. Disruptions in the cellular systems for handling transition metals are observed as a number of diseases ranging from hemochromatosis and anemias to neurodegenerative disorders including Alzheimer's and Parkinson's disease. The yeast Saccharomyces cerevisiae has proved useful as a model organism for the investigation of these processes and many of the genes and biological systems that function in yeast metal homeostasis are conserved throughout eukaryotes to humans. This review focuses on the biological roles of iron, copper, zinc, manganese, nickel and cobalt, the homeostatic mechanisms that function in S. cerevisiae and the human diseases in which these metals have been implicated.


Sequential single-shot imaging of nanoscale dynamic interactions with a table-top soft x-ray laser.
We demonstrate the first real-space recording of nanoscale dynamic interactions using single-shot soft x-ray (SXR) full-field laser microscopy. A sequence of real-space flash images acquired with a table-top SXR laser was used to capture the motion of a rapidly oscillating magnetic nanoprobe. Changes of 30 nm in the oscillation amplitude were detected when the nanoprobe was made to interact with stray fields from a magnetic sample. The table-top visualization of nanoscale dynamics in real space can significantly contribute to the understanding of nanoscale processes and can accelerate the development of new nanodevices.


Transfer of information on palliative home care during the out-of-hours period.
Continuity of end-of-life care for patients receiving palliative care is an important challenge for out-of-hours services in general practice. To investigate how frequent information is transferred on patients receiving palliative care from GPs to the out-of-hours services, to explore the perceptions of GP's on this information transfer and to study the relation between information transfer and the used GP information systems. This is a mixed-method design study. The frequency of information transfer to the out-of-hours services was investigated by analyzing a regional out-of-hours database. Barriers and promoting factors for this transfer of information were investigated by using semi-structured interviews among a purposive sample of GPs from the same region. The relation between information transfer and the GP information system was investigated by a postal questionnaire in a national random selection of GPs. When a palliative patient contacted the out-of-hours service, for 20% of these patients, a transfer of information was available and only half of these transfers included an anticipating end-of-life plan. All interviewed GPs considered continuity of care for these patients as important. However, some doubted whether a transfer of information is relevant for the quality of care. There was no relation between the information transfer and the used GP information systems. For only a minority of patients receiving palliative care, a transfer of information including an anticipating management plan was present. There is a large variation in the opinions of GPs on how to organize continuity of end-of-life care.


Reclassification of Actinomyces humiferus (Gledhill and Casida) as Cellulomonas humilata nom. corrig., comb. nov.
The placement of Actinomyces humiferus within the genus Actinomyces has always been controversial. A humiferus differs from typical members of the genus both phenotypically and in possessing a relatively high DNA G + C content. Comparative 16S rRNA gene sequencing has shown that A. humiferus is related only distantly to other species of the genus Actinomyces and is, in fact, a member of the genus Cellulomonas. On the basis of phylogenetic evidence, it is proposed that A. humiferus be reclassified in the genus Cellulomonas as Cellulomonas humilata nom. corrig., comb. nov.


[Goals and possibilities of therapeutic rehabilitation of oncological patients].
Various manifestations of oncological diseases encountered in the practical work of a therapist are discussed. They are related to both the clinical course of the diseases and their treatment. Characteristics of somatic disorders genesis of which is determined by the active or treated tumour are presented. The necessity of observation of oncological patients at all stages of cancer treatment and after its termination is emphasized. Goals and forms of oncological rehabilitation are described.


Cold adaptation in guinea pig at level of isolated brown adipocyte.
Isolated brown adipocytes were prepared from guinea pigs acclimated to 28 degrees C or exposed to 4-8 degrees C for periods of up to 3 wk. Cells from warm-adapted animals retained respiratory control when stimulated with norepinephrine. Cells from guinea pigs exposed to cold for 4-21 days showed a much greater respiratory response to norepinephrine due to enhanced uncoupling rather than enhanced substrate supply. After 7 days of cold acclimation, norepinephrine-stimulated respiration became uncontrolled and was limited only by the maximal respiratory capacity of the mitochondria. Three weeks of cold acclimation were accompanied by a doubling of total cell number, a doubling of the mitochondrial protein per adipocyte, and a sixfold increase in the norepinephrine-stimulated respiration per in situ mitochondrion with no change in respiratory chain capacity. The induction of norepinephrine-stimulated respiration correlated with the appearance of high-affinity purine nucleotide binding sites on the mitochondria, diagnostic of the uncoupling protein. If the results are extrapolated to the whole animal, they indicate that brown adipose tissue makes little contribution to thermogenesis in the warm-adapted guinea pig but may account for most or all the increment seen on cold adaptation.


Complementary information derived from CRISPR Cas9 mediated gene deletion and suppression.
CRISPR-Cas9 provides the means to perform genome editing and facilitates loss-of-function screens. However, we and others demonstrated that expression of the Cas9 endonuclease induces a gene-independent response that correlates with the number of target sequences in the genome. An alternative approach to suppressing gene expression is to block transcription using a catalytically inactive Cas9 (dCas9). Here we directly compare genome editing by CRISPR-Cas9 (cutting, CRISPRc) and gene suppression using KRAB-dCas9 (CRISPRi) in loss-of-function screens to identify cell essential genes. CRISPRc identified 98% of previously defined cell essential genes. After optimizing library construction by analysing transcriptional start sites (TSS), CRISRPi identified 92% of core cell essential genes and did not show a bias to regions involved in copy number alterations. However, bidirectional promoters scored as false positives in CRISRPi. We conclude that CRISPRc and CRISPRi have different off-target effects and combining these approaches provides complementary information in loss-of-function genetic screens.


Water uptake dynamics under progressive drought stress in diverse accessions of the OryzaSNP panel of rice (Oryza sativa).
In addition to characterising root architecture, evaluating root water uptake ability is important for understanding drought response. A series of three lysimeter studies were conducted using the OryzaSNP panel, which consists of 20 diverse rice (Oryza sativa L.) genotypes. Large genotypic differences in drought response were observed in this genotype panel in terms of plant growth and water uptake. Total water uptake and daily water uptake rates in the drought-stress treatment were correlated with root length density, especially at depths below 30cm. Patterns of water uptake among genotypes remained consistent throughout the stress treatments: genotypes that initially extracted more water were the same genotypes that extracted more water at the end of the study. These results suggest that response to drought by deep root growth, rather than a conservative soil water pattern, seems to be important for lowland rice. Genotypes in the O. sativa type aus group showed some of the greatest water uptake and root growth values. Since the OryzaSNP panel has been genotyped in detail with SNP markers, we expect that these results will be useful for understanding the genetics of rice root growth and function for water uptake in response to drought.


Rhinolaryngoscopy in the allergy office.
Rhinolaryngoscopy is a valuable diagnostic and treatment assessment tool for the allergist. We present a method for office use of the rhinolaryngofiberscope and review our experience with 400 consecutive examinations.


Transcriptomic analysis reveals hub genes and subnetworks related to ROS metabolism in Hylocereus undatus through novel superoxide scavenger trypsin treatment during storage.
It was demonstrated in our previous research that trypsin scavenges superoxide anions. In this study, the mechanisms of storage quality improvement by trypsin were evaluated in H. undatus. Trypsin significantly delayed the weight loss and decreased the levels of ROS and membrane lipid peroxidation. Transcriptome profiles of H. undatus treated with trypsin revealed the pathways and regulatory mechanisms of ROS genes that were up- or downregulated following trypsin treatment by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment analyses. The current results showed that through the regulation of the expression of hub redox enzymes, especially thioredoxin-related proteins, trypsin can maintain low levels of endogenous active oxygen species, reduce malondialdehyde content and delay fruit aging. In addition, the results of protein-protein interaction networks suggested that the downregulated NAD(P) H and lignin pathways might be the key regulatory mechanisms governed by trypsin. Trypsin significantly prolonged the storage life of H. undatus through regulatory on the endogenous ROS metabolism. As a new biopreservative, trypsin is highly efficient, safe and economical. Therefore, trypsin possesses technical feasibility for the quality control of fruit storage.


Application of ICSI for cryptorchid therapy.
Recent advances are provided in assisted reproductive technology and application of ICSI as treatment for infertile patients with previous cryptorchidism. Fertility rates were 25-81% and 8-48% in patients with unilateral and bilateral cryptorchidism, respectively. With the advent of assisted reproductive technology, pregnancy was not possible without sperm. Research in humans has resulted in pregnancy and live births after the injection of haploid germ cells (round spermatids) into the oocytes. In the mouse tetraploid germ cells (primary spermatocytes), nuclei have been injected into oocytes, which undergo meiosis, forming an embryo and live young. In animal models, round spermatids from both cryptorchid and previously cryptorchid testes can initiate normal embryo development when injected into mature oocytes. These cells may be used as substitutes for mature sperm. However, cryptorchidism in humans is often associated with inherent defects of spermatogenesis. With successive breakthroughs in treatment of impaired fertility associated with cryptorchidism, there is an increased risk of genetic abnormalities in the progeny. It is incumbent on clinicians who are involved in reproductive medicine to proceed cautiously with the development and application of assisted reproductive techniques to avoid creating future generations of genetically abnormal individuals.


Natural Orifice Transluminal Endoscopic Surgery-Assisted Laparoscopic Transvesical Bladder Diverticulectomy: Feasibility Study, Points of Technique, and Case Series with Medium-Term Follow-Up.
To demonstrate the feasibility of our novel natural orifice transluminal endoscopic surgery (NOTES)-assisted approach with medium-term follow-up. From March 2012, we included all patients who presented to our clinic with symptomatic or complicated retentive bladder diverticula secondary to long-standing infravesical obstruction. After managing the primary cause, we proceeded in all cases to our novel NOTES-assisted approach. We followed up the patients with abdominal ultrasonography at 6 weeks and 12 months postoperatively. Success was determined as subjective relief of the symptoms and objective disappearance of the diverticula in postoperative retrograde cystogram (RGC). Between March 2012 and August 2014, eight diverticula were treated using our new technique. The surgery was uneventful. The mean operative time was 134.25 ± 44.92 minutes. Blood loss was minimal (>50 mL). Retrograde cystography was performed on the 10th postoperative day. The introduction of the needle holder through the urethral natural orifice (NOTES) facilitated a more optimal direction of the needle holder for suturing the bladder wall due to its parallel position in relation to the trigone and posterolateral walls. This renders this step easier compared with suturing the bladder wall through the transvesical laparoscopic ports. One case had a grade IIIa complication according to the Clavien-Dindo classification of surgical complications. The study is limited by the small number of cases. Laparoscopic transvesical bladder diverticulectomy is a promising and safe procedure with good outcomes. Using the urethra (NOTES assisted) as an extra access to the bladder facilitates diverticular traction and bladder suturing without the need for extra ports. This technique can also be applied together with the novel T-laparoendoscopic single-site surgery approach.


Reducing the incidence of denture stomatitis: are denture cleansers sufficient?
Candida albicans is the predominant oral yeast associated with denture stomatitis. With an increasing population of denture wearers, the incidence of denture stomatitis is increasing. Effective management of these patients will alleviate the morbidity associated with this disease. The aim of this study was to examine the capacity of four denture cleansers to efficiently decontaminate and sterilize surfaces covered by C. albicans biofilms. Sixteen C. albicans strains isolated from denture stomatitis patients and strain ATCC 90028 were grown as mature confluent biofilms on a 96-well format and immersed in Dentural, Medical Interporous, Steradent Active Plus, and Boots Smile denture cleansers according to the manufacturers' instructions or overnight. The metabolic activity and biomass of the biofilms were then quantified, and scanning electron microscopy (SEM) used to examine treated biofilms. Dentural was the most effective denture cleanser, reducing the biomass by greater than 90% after 20 minutes. Steradent Active plus was significantly more effective following 10-minute immersion than overnight (p < 0.001). All cleansers reduced the metabolic activity by greater than 80% following overnight immersion; however, Boots Smile exhibited significantly reduced metabolic activity following only a 15-minute immersion (p < 0.001). SEM revealed residual C. albicans material following Dentural treatment. This study showed that denture cleansers exhibit effective anti-C. albicans biofilm activity, both in terms of removal and disinfection; however, residual biofilm retention that could lead to regrowth and denture colonization was observed. Therefore, alternative mechanical disruptive methods are required to enhance biofilm removal.


Nonenzymatic and enzymatic hydrolysis of alkyl halides: a theoretical study of the SN2 reactions of acetate and hydroxide ions with alkyl chlorides.
The SN2 displacements of chloride ion from CH3Cl, C2H5Cl, and C2H4Cl2 by acetate and hydroxide ions have been investigated, using ab initio molecular orbital theory at the HF/6-31+G(d), MP2/6-31+G(d), and MP4/6-31+G(d) levels of theory. The central barriers (calculated from the initial ion-molecule complex) of the reactions, the differences of the overall reaction energies, and the geometries of the transition states are compared. Essential stereochemical changes before and after the displacement reactions are described for selected cases. The gas phase reactions of hydroxide with CH3Cl, C2H5Cl, and C2H4Cl2 have no overall barrier, but there is a small overall barrier for the reactions of acetate with CH3Cl, C2H5Cl, and C2H4Cl2. A self-consistent reaction field solvation model was used to examine the SN2 reactions between methyl chloride and hydroxide ion and between 1,2-dichloroethane and acetate in solution. As expected, the reactions in polar solvent have a large barrier. However, the transition state structures determined by ab initio calculations change only slightly in the presence of a highly polar solvent as compared with the gas phase. We also calibrated the PM3 method for future study of an enzymatic SN2 displacement of halogen.


Identification of signaling pathways associated with cancer protection in Laron syndrome.
The growth hormone (GH)-insulin-like growth factor-1 (IGF1) pathway emerged in recent years as a critical player in cancer biology. Enhanced expression or activation of specific components of the GH-IGF1 axis, including the IGF1 receptor (IGF1R), is consistently associated with a transformed phenotype. Recent epidemiological studies have shown that patients with Laron syndrome (LS), the best-characterized entity among the congenital IGF1 deficiencies, seem to be protected from cancer development. To identify IGF1-dependent genes and signaling pathways associated with cancer protection in LS, we conducted a genome-wide analysis using immortalized lymphoblastoid cells derived from LS patients and healthy controls of the same gender, age range, and ethnic origin. Our analyses identified a collection of genes that are either over- or under-represented in LS-derived lymphoblastoids. Gene differential expression occurs in several gene families, including cell cycle, metabolic control, cytokine-cytokine receptor interaction, Jak-STAT signaling, and PI3K-AKT signaling. Major differences between LS and healthy controls were also noticed in pathways associated with cell cycle distribution, apoptosis, and autophagy. Our results highlight the key role of the GH-IGF1 axis in the initiation and progression of cancer. Furthermore, data are consistent with the concept that homozygous congenital IGF1 deficiency may confer protection against future tumor development.


[Hormone replacement Up-to-date. Hormone replacement therapy in anti-aging medicine].
The purpose of anti-aging medicine is to raise quality of life (QOL) and to aim at healthy longevity. Melatonin, DHEA(-s) (dehydroepiandrosterone [sulfate]), somatotropin/IGF-I (insulin-like growth factor-I), male and female hormone decrease with aging, that can be prevented by hormone replacement therapy. This therapy has two sides of supplement of the deficit and a healthy increase. Hormone age is "the function age that expressed whether you are equivalent to a hormone secretion state of how old average" and 30 years old or 70-80% of chronological age regard the targeted value of hormone age. We do not decide quantity of hormone replacement uniformly. The reasonable quantity should be determined based on each figure, active mass, life level, and/or blood levels of hormones. Data accumulation for a long term in multiple institutions is important.


Contrast-induced nephropathy--a review of current literature and guidelines.
The use of iodine-based contrast agents always entails the risk of contrast-induced nephropathy (CIN). The recently observed dramatic increase in the number of examinations and therapeutic procedures using iodine-based contrast media led us to conduct a thorough analysis of the growing number of scientific reports and collective works devoted to contrast-induced nephropathy, based on current definitions, epidemiology, pathophysiology, risk factors, successful prophylaxis and guidelines of the European Society of Urogenital Radiology (ESUR). Radiological contrast agents are the third most common cause of nephropathy among in-patients, accounting for 11-12% of cases. CIN is connected with some clinically significant consequences, including increased morbidity, prolonged hospitalisation, increased risk of complications, potential need for dialysis and increased mortality rate. A significant increase in the number of examinations applying iodine-based contrast media in the course of inpatient procedures requires close cooperation of the clinician and radiologist, supported by knowledge of all CIN issues. In order to protect patients from contrast-induced nephropathy, it is necessary to monitor their renal function, indentify patients with risk factors, refer patients for examinations in a responsible manner, and undertake successful preventive measures.


The effects of alphabetic literacy, linguistic-processing demand and tone type on the dichotic listening of lexical tones.
Brain lateralization of lexical tone processing remains a matter of debate. In this study we used a dichotic listening paradigm to examine the influences of the knowledge of Jyutping (a romanization writing system which provides explicit Cantonese tone markers), linguistic-processing demand and tone type on the ear preference pattern of native tone processing in Hong Kong Cantonese speakers. While participants with little knowledge of Jyutping showed a previously reported left-ear advantage (LEA), those with a good level of Jyutping expertise exhibited either a right-ear advantage or bilateral processing during lexical tone identification and contour tone discrimination, respectively. As for the effect of linguistic-processing demand, while an LEA was found in acoustic/phonetic perception situations, this advantage disappeared and was replaced by a bilateral pattern in conditions that involved a greater extent of linguistic processing, suggesting an increased involvement of the left hemisphere. Regarding the effect of tone type, both groups showed an LEA in level tone discrimination, but only the Jyutping group demonstrated a bilateral pattern in contour tone discrimination. Overall, knowledge of written codes of tones, greater degree of linguistic processing and contour tone processing seem to influence the brain lateralization of lexical tone processing in native listeners of Cantonese by increasing the recruitment of the left-hemisphere language network.


[The nucleases of oxytetracycline producing actinomycetes].
The activity of exocellular nucleases, especially RNase, differs among cultures producing oxytetracycline, and belonging or similar to Actinomyces rimosus, and cultures which are not related to this species. The activity of RNase therefore may be regarded as an additional taxonomic characteristic within the species Act. rimosus. Formation of various enzymes involved in synthesis of nucleic acids was studied with the strain of Act. re end of fermentation, the content of the antibiotic and the activity of exocellular and endocellular RNases and DNases in the cultural broth were maximal. The cultural broth therefore may be used as a source of both oxytetracycline and nucleases.


Motion of spin-labeled side chains in T4 lysozyme: effect of side chain structure.
Previous studies have shown that the mobility of nitroxide side chains in a protein, inferred from the electron paramagnetic resonance (EPR) spectra, can be used to classify particular sites as helix surface sites, tertiary contact sites, buried sites, or loop sites. In addition, the sequence dependence of mobility can identify regular secondary structure. However, in the most widely used side chain, an apparent interaction of the nitroxide ring with the protein at some helix surface sites gives rise to EPR spectra degenerate with those at tertiary contact sites. In the present study, we use selected sites in T4 lysozyme to evaluate novel nitroxide side chains designed to resolve this degeneracy. The results indicate that the reagent 3-(methanesulfonylthiomethyl)-2,2, 5,5-tetramethylpyrrolidin-1-yloxy reacts with cysteine to give a nitroxide side chain that has a high contrast in mobility between helix surface and tertiary contact sites, effectively resolving the degeneracy. The reagent 3-(iodomercuriomethyl)-2,2,5,5-tetramethyl-2, 5-dihydro-1H-pyrrol-1-yloxy reacts with cysteine to provide a mercury-linked nitroxide that also shows reduced interaction with the protein at most helix surface sites. Thus, these new side chains may be the preferred choices for structure determination using site-directed spin labeling.


Pasireotide: successful treatment of a sparsely granulated tumour in a resistant case of acromegaly.
The granulation pattern of somatotroph adenomas is well known to be associated with differing clinical and biochemical characteristics, and it has been shown that sparsely granulated tumours respond poorly to commonly used somatostatin receptor ligands (SRLs). We report a challenging case of acromegaly with a sparsely granulated tumour resistant to multiple modalities of treatment, ultimately achieving biochemical control with pasireotide. A 26-year-old lady presented with classical features of acromegaly, which was confirmed by an oral glucose tolerance test. Insulin-like growth factor 1 (IGF1) was 1710 µg/L (103-310 µg/L) and mean growth hormone (GH) was >600 U/L. MRI scan showed a 4 cm pituitary macroadenoma with suprasellar extension and right-sided cavernous sinus invasion. She underwent trans-sphenoidal pituitary surgery. Histology displayed moderate amounts of sparsely granular eosinophilic cytoplasm, staining only for GH. Postoperative investigations showed uncontrolled disease (IGF1:1474 µg/L, mean GH:228 U/L) and residual tumour in the cavernous sinus. She received external beam fractionated radiation. Over the years, she received octreotide LAR (up to 30 mg), lanreotide (up to 120 mg) two weekly, cabergoline, pegvisomant and stereotactic radiosurgery to no avail. Only pegvisomant resulted in an element of disease control; however, this had to be stopped due to abnormal liver function tests. Fifteen years after the diagnosis, she was started on pasireotide 40 mg monthly. Within a month, her IGF1 dropped and has remained within the normal range (103-310 µg/L). Pasireotide has been well tolerated, and there has been significant clinical improvement. Somatostatin receptor subtyping revealed a positivity score of two for both sst5 and sst2a subtypes. Age, size of the tumour, GH levels on presentation, histopathological type and the somatostatin receptor status of the tumour in acromegaly should be reviewed in patients who poorly respond to first-generation somatostatin receptor ligands.Tumours that respond poorly to first-generation somatostatin receptor ligands, especially sparsely granulated somatotroph adenomas, can respond to pasireotide and treatment should be considered early in the management of resistant tumours.Patients with membranous expression of sst5 are likely to be more responsive to pasireotide.


A falls and balance clinic for the elderly.
A Falls and Balance Clinic for the elderly has been developed with the aim of identifying those at risk of subsequent falls, and recommending intervention strategies to reduce this risk. The physical and functional status of 149 clients referred to the Clinic are reported. Neurological and musculoskeletal pathologies were identified as the cause of falls in the majority of clients. Measures of gait velocity and stride length, and ability to stand on one leg were markedly reduced compared with normative data for healthy elderly. A number of other measures of balance, strength, and function are also reported. The results of a questionnaire about home environment indicated that only 28% of those referred had been assessed in their own home in the previous year. Home environment was considered a potential risk in a further 28% of clients and a home visit was instituted in these cases. Other intervention strategies included referral for further investigations (36%), Day Hospital (33%), provision of a home program of balance or strengthening exercises (27%), and medication change (15%). Issues related to the establishment, operation and long term evaluation of the effectiveness of a specialist Falls and Balance Clinic for the elderly are discussed.


Endoscopy for Helicobacter pylori sero-negative young dyspeptic patients: an economic evaluation based on a randomized trial.
A policy of withholding endoscopy in Helicobacter pylori sero-negative dyspeptic patients without sinister symptoms saves up to 36% of endoscopies. However, it is unclear whether the net cost of applying this policy outweighs that of conventional management. To determine the direct (healthcare) and indirect (productivity) costs of applying a strategy of endoscopy versus no endoscopy in H. pylori sero-negative young dyspeptics in the UK. The direct and indirect incremental costs for both strategies were calculated amongst 154 H. pylori seronegative subjects randomized to have an endoscopy or no endoscopy before subsequent management by their general practitioners. The cost per patient of each strategy was calculated using reference values in our clinical setting and sensitivity analysis was used to test different scenarios. The total direct cost rose for the endoscopy group (mean Pound Sterling 103, 95% CI 78 to 127) but did not change for the non-endoscopy group (mean Pound Sterling 6, 95% CI -32 to 44). On average, direct (healthcare) costs for patients in the endoscopy group rose by Pound Sterling 96 (95% CI 51 to 142) more than those for non-endoscopy patients. Indirect (productivity) cost fell for the non-endoscopy group (mean -Pound Sterling 40, 95% CI -220 to 140) compared to a rise for the endoscopy group (mean Pound Sterling 180, 95% CI -60 to 420) (difference not significant). The total cost (including direct and indirect costs) fell for the non-endoscopy group (mean -Pound Sterling 34, 95% CI -228 to 160) but rose for the endoscopy group (mean Pound Sterling 283, 95% CI 32 to 533)--an incremental cost of Pound Sterling 317 (95% CI 0 to 634). For all assumptions in the sensitivity analysis, the mean cost in the endoscopy group was at least Pound Sterling 200 higher than in the non-endoscopy group. It is less expensive to manage H. pylori-negative dyspeptic patients aged under 45 without sinister symptoms by withholding endoscopy.


Hard x-ray Zernike microscopy reaches 30 nm resolution.
Since its invention in 1930, Zernike phase contrast has been a pillar in optical microscopy and more recently in x-ray microscopy, in particular for low-absorption-contrast biological specimens. We experimentally demonstrate that hard-x-ray Zernike microscopy now reaches a lateral resolution below 30 nm while strongly enhancing the contrast, thus opening many new research opportunities in biomedicine and materials science.


Preclinical development of cancer stem cell drugs.
Despite recent progress in cancer treatment, the current cancer chemotherapy can mainly produce remission but often fails to cure cancer due to the existence of cancer stem cells. The emerging cancer stem cell hypothesis offers new insight into the failure of current cancer drugs and suggests new approaches for improved understanding of cancer biology and cancer drug development. In this review, we discuss the concept of cancer stem cells, origin of cancer stem cells and different approaches for isolating or enriching cancer stem cells. We also review the resistance of cancer stem cells to standard chemotherapy and radiation therapy and potential mechanisms for the resistance. Finally, based on the current knowledge on cancer stem cells, we discuss potential approaches for developing new drugs that target cancer stem cells and propose new methods for evaluation of cancer stem cell drugs. Improved cancer treatment is likely to be achieved by a combination of drugs that kill both replicating cancer cells and more quiescent cancer stem cells.


ImmunoConcentration--a new format for solid-phase immunoassays.
A new format for solid-phase immunoassays has been developed in which a monoclonal antibody-coated membrane, incorporated into a cylindrical, disposable device, regulates sample and reagent delivery. We illustrate the method with a two-site, immunoenzymometric assay that can detect human choriogonadotropin at less than 50 int. units/L (4 micrograms/L) in urine and less than 25 int. units/L (2 micrograms/L) in serum and takes less than 5 min to perform. The solid-phase antibody is located in a circular area in the center of the membrane so that in the presence of the hormone, after addition of substrate, a blue enzyme product is generated in this circular area. The high ratio of surface area to volume within the microporous matrix of the membrane assures short diffusion distances and therefore rapid binding of liquid-phase reagents to the solid phase. Pseudo-first-order reaction kinetics describe the binding of antigen to immobilized antibody and the binding of enzyme-labeled antibody to immobilized antigen. The speed and simplicity of this format may facilitate testing for many analytes, both soluble and particulate, as well as serological testing.


Cardioprotection by cardiac progenitor cell-secreted exosomes: role of pregnancy-associated plasma protein-A.
Cell therapy trials using cardiac-resident progenitor cells (CPCs) and bone marrow-derived mesenchymal stem/progenitor cells (BMCs) in patients after myocardial infarction have provided encouraging results. Exosomes, nanosized extracellular vesicles of endosomal origin, figure prominently in the bioactivities of these cells. However, a head-to-head comparison of exosomes from the two cell types has not been performed yet. CPCs and BMCs were derived from cardiac atrial appendage specimens and sternal bone marrow, respectively, from patients (n = 20; age, 69.9 ± 10.9) undergoing heart surgery for aortic valve disease and/or coronary artery disease. Vesicles were purified from cell conditioned media by centrifugation/filtration and ultracentrifugation. Vesicle preparations were predominantly composed of exosomes based on particle size and marker expression (CD9, CD63, CD81, Alix, and TSG-101). CPC-secreted exosomes prevented staurosporine-induced cardiomyocyte apoptosis more effectively than BMC-secreted exosomes. In vivo, CPC-secreted exosomes reduced scar size and improved ventricular function after permanent coronary occlusion in rats more efficiently than BMC-secreted exosomes. Both types of exosomes stimulated blood vessel formation. CPC-secreted exosomes, but not BMC-derived exosomes, enhanced ventricular function after ischaemia/reperfusion. Proteomics profiling identified pregnancy-associated plasma protein-A (PAPP-A) as one of the most highly enriched proteins in CPC vs. BMC exosomes. The active form of PAPP-A was detected on CPC exosome surfaces. These vesicles released insulin-like growth factor-1 (IGF-1) via proteolytic cleavage of IGF-binding protein-4 (IGFBP-4), resulting in IGF-1 receptor activation, intracellular Akt and ERK1/2 phosphorylation, decreased caspase activation, and reduced cardiomyocyte apoptosis. PAPP-A knockdown prevented CPC exosome-mediated cardioprotection both in vitro and in vivo. These results suggest that CPC-secreted exosomes may be more cardioprotective than BMC-secreted exosomes, and that PAPP-A-mediated IGF-1 release may explain the benefit. They illustrate a general mechanism whereby exosomes may function via an active protease on their surface, which releases a ligand in proximity to the transmembrane receptor bound by the ligand.


Establishing ADC-Based Histogram and Texture Features for Early Treatment-Induced Changes in Head and Neck Squamous Cell Carcinoma.
The purpose of this study was to assess baseline variability in histogram and texture features derived from apparent diffusion coefficient (ADC) maps from diffusion-weighted MRI (DW-MRI) examinations and to identify early treatment-induced changes to these features in patients with head and neck squamous cell carcinoma (HNSCC) undergoing definitive chemoradiation. Patients with American Joint Committee on Cancer Stage III-IV (7th edition) HNSCC were prospectively enrolled on an IRB-approved study to undergo two pre-treatment baseline DW-MRI examinations, performed 1 week apart, and a third early intra-treatment DW-MRI examination during the second week of chemoradiation. Forty texture and six histogram features were derived from ADC maps. Repeatability of the features from the baseline ADC maps was assessed with the intra-class correlation coefficient (ICC). A Wilcoxon signed-rank test compared average baseline and early treatment feature changes. Data from nine patients were used for this study. Comparison of the two baseline ADC maps yielded 11 features with an ICC ≥ 0.80, indicating that these features had excellent repeatability: Run Gray-Level Non-Uniformity, Coarseness, Long Zone High Gray-Level, Variance (Histogram Feature), Cluster Shade, Long Zone, Variance (Texture Feature), Run Length Non-Uniformity, Correlation, Cluster Tendency, and ADC Median. The Wilcoxon signed-rank test resulted in four features with significantly different early treatment-induced changes compared to the baseline values: Run Gray-Level Non-Uniformity (p = 0.005), Run Length Non-Uniformity (p = 0.005), Coarseness (p = 0.006), and Variance (Histogram) (p = 0.006). The feasibility of histogram and texture analysis as a potential biomarker is dependent on the baseline variability of each metric, which disqualifies many features.


Attitudes toward physician-nurse collaboration: a cross-cultural study of male and female physicians and nurses in the United States and Mexico.
Inter-professional collaboration between physicians and nurses, within and between cultures, can help contain cost and insure better patient outcomes. Attitude toward such collaboration is a function of the roles prescribed in the culture that guide professional behavior. The purpose of the study was to test three research hypotheses concerning attitudes toward physician-nurse collaboration across genders, disciplines, and cultures. The Jefferson Scale of Attitudes Toward Physician-Nurse Collaboration was administered to 639 physicians and nurses in the United States (n = 267) and Mexico (n = 372). Attitude scores were compared by gender (men, women), discipline (physicians, nurses), and culture (United States, Mexico) by using a three-way factorial analysis of variance design. Findings confirmed the first research hypothesis by demonstrating that both physicians and nurses in the United States would express more positive attitudes toward physician-nurse collaboration than their counterparts in Mexico. The second research hypothesis, positing that nurses as compared to physicians in both countries would express more positive attitudes toward physician-nurse collaboration, was also supported. The third research hypothesis that female physicians would express more positive attitudes toward physician-nurse collaboration than their male counterparts was not confirmed. Collaborative education for medical and nursing students, particularly in cultures with a hierarchical model of inter-professional relationship, is needed to promote positive attitudes toward complementary roles of physicians and nurses. Faculty preparation for collaboration is necessary in such cultures before implementing collaborative education.


Resveratrol induces SIRT1- and energy-stress-independent inhibition of tumor cell regrowth after low-dose platinum treatment.
To investigate resveratrol (RSV) as a calorie restriction (CR) mimetic potentiator of platinum-based cancer drugs. In ovarian carcinoma cell lines, the potentiating effects of RSV were assessed in sulforhodamine B-based growth assays and clonogenic assays. Flow cytometry was used to detect cell cycle effects, siRNA transfections for determining the involvement of SIRT1, and Western blotting for the assessment of altered protein expression and of autophagy. Intracellular ATP levels were detected with a commercial kit. Single-dose RSV co-treatment with cisplatin or carboplatin at inefficiently low doses had the clinically interesting effect of preventing regrowth of cancer cells after drug withdrawal. Of three cell lines tested, metastatic cells with low bioenergetic cellular index (i.e., more glycolytic) were particularly sensitive to combination treatment leading to PUMA induction, acute apoptosis, and autophagy. However, inhibition of regrowth and complete loss of clonogenicity was seen also without these events, in other cells. The underlying mechanism(s) was independent of effects reported to underlie the CR-mimetic cancer-preventive potential of RSV. Thus, SIRT1, estrogen receptors, AMPK activation or upregulation of mitobiogenesis, β-F(1)-ATPase or PTEN were not involved, and ATP levels did not decrease. RSV is an excellent candidate for potentiation of platinum treatment, rather than a cancer therapeutic drug in its own right. While SIRT1-dependent and lifespan-promoting effects of RSV are well-documented and may dominate in normal cells, the observed potentiation of platinum drugs does not require these mechanisms. We suggest that the responses of cancer cells to RSV differ greatly from those of normal cells.


Risk factors and causes of stillbirths among pregnant women in Pakistan.
Globally 3 million stillbirths occur per year, and Pakistan is ranked 3rd among the countries having the highest burden. Despite being a major public health problem, efforts to reduce this figure are insufficient. The aim of the study was to identify and measure the inequalities in stillbirth associated risk factors, causes and fertility risk behaviors. Data were derived from the Pakistan Demographic and Health Surveys (PDHS) 1990-2013. Inequalities on determinants were evaluated using rate differences and rate ratios; time trends computed with annualized reduction rate (ARR). Overall ARR determined for stillbirth was -12.52 percent per annum. The high ARR were recorded for mothers age <20, urban areas, educated mothers and for highest wealth quintile. The relative inequalities were most pronounced for wealth quintiles, education and age of mothers. Stillbirth causes were unexplained antepartum (33%), unexplained intrapartum (21%), intrapartum asphyxia (21%) and antepartum maternal disorders (19%). The high fertility risk behavior was found in mothers with age >34 and birth order >3. The study concluded that to achieve gain in child survival, there is need to promote antenatal care, birth spacing, and family planning programs in developing countries.


Fano Interference in the Optical Absorption of an Individual Gold-Silver Nanodimer.
Fano resonances are central features in the responses of many systems including atoms, molecules, and nanomaterials. They arise as a consequence of interferences between two channels, most frequently associated with two system modes. In plasmonic materials, Fano interferences between optical modes have been shown, experimentally and theoretically, to induce narrow features in their scattering spectra. By investigating individual silver-gold heterodimers, we first experimentally demonstrate that Fano interference is also a key effect in the optical absorption of plasmonic nano-objects, in agreement with theoretical predictions. Conversely to previously investigated systems, the two interacting modes at the origin of absorptive Fano effect are mostly localized on either one or the other dimer component. Experimental results were obtained by selectively monitoring the optical absorption of one dimer component using a two-color nonlinear time-resolved technique. This also opens the way to full optical far-field noncontact investigations of charge or energy exchanges between nano-objects with a spatial resolution much smaller than the optical wavelength.


Neuraminidase subtyping of avian influenza viruses with PrimerHunter-designed primers and quadruplicate primer pools.
We have previously developed a software package called PrimerHunter to design primers for PCR-based virus subtyping. In this study, 9 pairs of primers were designed with PrimerHunter and successfully used to differentiate the 9 neuraminidase (NA) genes of avian influenza viruses (AIVs) in multiple PCR-based assays. Furthermore, primer pools were designed and successfully used to decrease the number of reactions needed for NA subtyping from 9 to 4. The quadruplicate primer-pool method is cost-saving, and was shown to be suitable for the NA subtyping of both cultured AIVs and uncultured AIV swab samples. The primers selected for this study showed excellent sensitivity and specificity in NA subtyping by RT-PCR, SYBR green-based Real-time PCR and Real-time RT-PCR methods. AIV RNA of 2 to 200 copies (varied by NA subtypes) could be detected by these reactions. No unspecific amplification was displayed when detecting RNAs of other avian infectious viruses such as Infectious bronchitis virus, Infectious bursal disease virus and Newcastle disease virus. In summary, this study introduced several sensitive and specific PCR-based assays for NA subtyping of AIVs and also validated again the effectiveness of the PrimerHunter tool for the design of subtyping primers.


Determination using synchrotron radiation-based Fourier transform infrared microspectroscopy of putative stem cells in human adenocarcinoma of the intestine: corresponding benign tissue as a template.
The epithelial-cell layer lining the two morphologically and functionally distinct segments of the mammalian intestinal tract, small intestine, and colon is constantly being renewed. This renewal is necessitated by a harsh lumen environment and is hypothesized to be driven by a small population of stem cells (SCs) that are believed to reside at the base of intestinal crypts. A lack of specific markers has hampered previous attempts to identify their exact location. We obtained tissue sections containing small intestine and colon crypts derived from normal (benign) or adenocarcinoma (AC) human intestine. The samples were floated onto BaF2 windows and analyzed using synchrotron radiation-based Fourier transform infrared microspectroscopy via an aperture size of 10 × 10 μm. Derived infrared (IR) spectral data was then analyzed using principal component analysis and/or linear discriminant analysis. Hypothesized cell types (as a function of aperture location along the length of individual crypts) within benign crypts were classed based on exploratory unsupervised IR spectral point clustering. Scores plots derived from individual small intestine crypts consistently generated one or two distinct spectra that clustered away from the remaining cell categories; these were retrospectively classed as "distinct base region" spectra. In these plots, a clear progression of locations along crypt lengths designated as from putative stem cells (SCs) to transit-amplifying (TA) cells to terminally differentiated (TD) cells was observed in benign small intestine and colon crypts. This progression of spectral points was crypt specific, pointing away from a unifying cell lineage model in human intestinal crypts. On comparison of AC-derived spectra versus corresponding benign, a subpopulation of AC-derived spectra suggested a putative SC-like spectral fingerprint; remaining IR spectra were classed as exhibiting TA cell-like or TD cell-like spectral characteristics. These observations could point to a cancer SC phenotype; an approach capable of identifying their in situ location has enormous therapeutic applications.


Marked motor function improvement in a 32-year-old woman with childhood-onset hypophosphatasia by asfotase alfa therapy: Evaluation based on standardized testing batteries used in Duchenne muscular dystrophy clinical trials.
Hypophosphatasia (HPP) is a rare disorder resulting from biallelic loss-of-function variants or monoallelic dominant negative variants in the ALPL gene. We herein describe the clinical outcome of a 32-year-old woman with childhood-onset HPP caused by compound heterozygous variants in ALPL. Her chief complaints were severe musculoskeletal pain, muscle weakness, and impaired daily activities necessitating assistance in housework and child-rearing in addition to a history of early tooth loss and mildly short stature. Asfotase alfa therapy produced a remarkable increase in muscle strength and daily activities and markedly reduced musculoskeletal pain. Drug efficacy was clearly demonstrated through multiple test batteries (muscle strength test using microFET®2, six-minute walking test, Stair Climb Test, rising-from-floor-time test, and number-of-steps test using Actigraph®) currently adopted as standardized evaluations in Duchenne muscular dystrophy clinical trials since no test batteries for HPP have been established to date. These tests may also be promising for the assessment of HPP.


The efficacy of psychoeducation in managing low back pain: A systematic review.
Low back pain is a relatively common health problem which afflicts many adults, and its prevalence increases with age. Several studies have indicated that psychosocial factors are of importance in low back pain. The aim of this study was to carry out a systematic review of the efficacy of psychoeducation in managing low back pain from evidence provided by randomised controlled trials. The inclusion criteria for studies included in this systematic review were randomised controlled trials; patients with low back pain, with or without sciatica; the inclusion of a psychoeducation (treatment) arm; and age of patients ≥ 17 years. Data extraction revealed the heterogeneous nature of the psychoeducational interventions. Accordingly, it was deemed inappropriate to carry out a formal meta-analysis. Ultimately, nine studies, corresponding to 10 publications, were included in the systematic review. When possible, group contrast mean difference effect sizes were calculated for the studies. Overall, favourable outcomes associated with personalised telephone coaching, while unfavourable outcomes were associated with both Transtheoretical Model-based counselling and motivational enhancement treatment. Other forms of one-to-one counselling were associated with intermediate outcomes. Psychoeducation via personalised telephone coaching was particularly associated with reduced low back pain, reduced daily living disability, improved function and improved recovery expectation. On the basis of this review, the following suggestions are made relating to the design and publication of future studies of the efficacy of psychoeducation in the management of low back pain. First, it would be good to use an experimental design which blinds both the patients and the assessors to group status. Second, it is recommended that all the relevant outcome data from a study are published, either in the corresponding paper or in an on-line supplement. Third, it is important to ensure that the intervention and control groups are matched at baseline. Clearly, baseline group differences can emerge following random allocation of patients into two groups. It may be useful, therefore, to carry out all baseline assessments immediately prior to the randomisation process; an independent assessor could then examine the degree of matching at baseline before the rest of the study proceeds. It is also important that sufficiently large sample sizes be recruited.


Breastfeeding initiation in women with gestational diabetes mellitus.
In the United States, breastfeeding initiation (BFI) is reported for 75% of all live births; however, little information is available regarding mothers affected by gestational diabetes mellitus (GDM). To examine feeding practices and factors associated with BFI in women with GDM and their infants. A total of 303 GDM (58 late preterm and 245 term) pregnancies were studied. Infant feeding preference was ascertained on admission to labor and delivery. Variables known to influence BFI including maternal age, smoking, obesity, racial and educational characteristics were assessed. On admission 188 women intended to BF, 60 intended to feed formula and 55 were undecided. None of the women who wished to feed formula and 27% of the originally undecided later initiated BF. Regardless of feeding preference 163 (54%) of all mothers initiated BF. Similar BFI rates were found for 176 Class A1 and 127 class A2 women. Logistic regression analysis showed that intention to BF was the most significant predictor of BFI. Factors associated with BFI failure included African American race, lower education, smoking, obesity and admission to NICU. Following delivery 264 (87%) infants received well baby care while 39 (13%) were admitted to the NICU. Among 188 women who intended to BF, BFI involved 81% of 160 infants receiving well baby care and 61% of the 28 admitted to the NICU. More than half of women with GDM, who intended to BF, initiated BF. BFI failure remains associated with race, lower education level, smoking, obesity, preference for formula feeding and admission to NICU.


Preoperative prediction of mortality within 1 year after elective thoracic endovascular aortic aneurysm repair.
Thoracic endovascular aortic repair (TEVAR) is known to have a survival benefit over open repair in patients with descending thoracic aneurysms and has become a mainstay of therapy. Because death before 1 year after TEVAR likely indicates an ineffective therapy, we have created a predictive model for death within 1 year using factors available in the preoperative setting. A registry of 526 TEVARs performed at the University of Florida between September 2000 and November 2010 was queried for patients with degenerative descending thoracic aneurysm as their primary pathology. Procedures with emergent or urgent indications were excluded. Preoperatively available variables, such as baseline comorbidities, anatomic-, and procedure-specific planning details, were recorded. Univariate predictors of death were analyzed with multivariable Cox proportional hazards to identify independent predictors of 30-day (death within 30 days) and 1-year mortality (death within 1 year) after TEVAR. A total of 224 patients were identified and evaluated. The 30-day mortality rate was 3% (n = 7) and the 1-year mortality rate was 15% (n = 33). Multivariable predictors of 1-year mortality (hazard ratios [95% confidence interval]) included: age >70 years (5.8 [2.1-16.0]; P = .001), adjunctive intraoperative procedures (eg, brachiocephalic or visceral stents, or both, concomitant arch debranching procedures; 4.5 [1.9-10.8]; P = .001), peripheral arterial disease (3.0 [1.4-6.7]; P = .006), coronary artery disease (2.4 [1.1-4.9]; P = .02), and chronic obstructive pulmonary disease (1.9 [1.0-3.9]; P = .06). A diagnosis of hyperlipidemia was protective (0.4 [0.2-0.7]; P = .006). When patients were grouped into those with one, two, three, or four or more of these risk factors, the predicted 1-year mortality was 1%, 3%, 10%, 27%, and 54%, respectively. Factors are available in the preoperative setting that are predictive of death within 1 year after TEVAR and can guide clinical decision making regarding the timing of repair. Patients with multiple risk factors, such as age ≥ 70 years, coronary artery disease, chronic obstructive pulmonary disease, and a need for an extensive procedure involving adjunctive therapies, have a high predicted mortality within 1 year and may be best served by waiting for a larger aneurysm size to justify the risk of intervention.


The experience of clinician-researchers in occupational therapy.
This study examined the experience of occupational therapy clinicians who do research to illuminate factors that influenced their research, the processes involved, and the outcomes. The qualitative approach of grounded theory was used. Purposive sampling of all research-productive clinicians in acute care hospitals in one Australian city occurred. Fifteen clinicians participated in in-depth interviews that explored their experiences of research. Results were analyzed with the constant comparative method, and six conceptual categories were developed. These categories were further analyzed in terms of their relationships, and a core category that explained and synthesized the data was identified--becoming a clinician-researcher. This category encompassed a process of role change during which the person changed from clinician to clinician-researcher. Conditions for this change were identified, and three key concepts were derived to elaborate the core category. In becoming a clinician-researcher, the person was active in (a) identifying research as significant, (b) constructing actions in relation to research, and (c) evaluating the experience. The findings further the understanding of clinician-researchers through the description of their experience and the empirically based theoretical formulation that explains it.