Cost-effectiveness of rivaroxaban compared with enoxaparin plus a vitamin K antagonist for the treatment of venous thromboembolism.
Venous thromboembolism (VTE), comprised of deep vein thrombosis (DVT) and pulmonary embolism (PE), is commonly treated with a low-molecular-weight heparin such as enoxaparin plus a vitamin K antagonist (VKA) to prevent recurrence. Administration of enoxaparin + VKA is hampered by complexities of laboratory monitoring and frequent dose adjustments. Rivaroxaban, an orally administered anticoagulant, has been compared with enoxaparin + VKA in the EINSTEIN trials. The objective was to evaluate the cost-effectiveness of rivaroxaban compared with enoxaparin + VKA as anticoagulation treatment for acute, symptomatic, objectively-confirmed DVT or PE. A Markov model was built to evaluate the costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios associated with rivaroxaban compared to enoxaparin + VKA in adult patients treated for acute DVT or PE. All patients entered the model in the 'on-treatment' state upon commencement of oral rivaroxaban or enoxaparin + VKA for 3, 6, or 12 months. Transition probabilities were obtained from the EINSTEIN trials during treatment and published literature after treatment. A 3-month cycle length, US payer perspective ($2012), 5-year time horizon and a 3% annual discount rate were used. Treatment with rivaroxaban cost $2,448 per-patient less and was associated with 0.0058 more QALYs compared with enoxaparin + VKA, making it a dominant economic strategy. Upon one-way sensitivity analysis, the model's results were sensitive to the reduction in index VTE hospitalization length-of-stay associated with rivaroxaban compared with enoxaparin + VKA. At a willingness-to-pay threshold of $50,000/QALY, probabilistic sensitivity analysis showed rivaroxaban to be cost-effective compared with enoxaparin + VKA approximately 76% of the time. The model did not account for the benefits associated with an oral and minimally invasive administration of rivaroxaban. 'Real-world' applicability is limited because data from the EINSTEIN trials were used in the model. Also, resource utilization and costs were based on the US healthcare system. Rivaroxaban is a cost-effective option for anticoagulation treatment of acute VTE patients.


Critical review and evaluation of the uterotrophic bioassay for the identification of possible estrogen agonists and antagonists: in support of the validation of the OECD uterotrophic protocols for the laboratory rodent. Organisation for Economic Co-operation and Development.
A current issue for regulatory agencies is endocrine-related modes of action such as those mediated by the estrogen, androgen, and thyroid nuclear receptors. At the national and international levels, the consensus recommendation for the assessment of such modes of action is a tiered series of in vitro and in vivo protocols. The tiered framework begins with screens for structural alerts and then moves to rapid, mechanistic in vitro screening assays, and then to in vivo screening bioassays. The objective of these screens is to identify substances that may warrant testing for endocrine-mediated adverse effects. The final framework tier as needed is to test these substances in long-term bioassays for adverse endocrine-mediated reproductive and/or developmental effects. The subject of this review, the rodent uterotrophic bioassay, is intended to be a rapid in vivo screening bioassay for possible estrogen agonists and based on the response of the estrogen-sensitive uterus. The central metric of bioassay is a statistically significant increase in the weight of the uterus after 3 consecutive days of test substance administration. The extensive background literature is summarized in this review on the mode of action underlying the bioassay and the uterine response to estrogens. The review includes the bioassay's history of development and how its employment has changed and evolved over time. The review describes two major uterotrophic bioassay versions, the intact, immature female and the mature, ovariectomized female, and the protocol factors likely to influence relevance, reproducibility, and reliability of bioassay. The emphasis of the review is the ability of the uterotrophic bioassay to identify the substances of current interest: weak estrogen agonists with binding affinities relative to the natural 17beta-estradiol in the log 0 to log -3 range. Using selected model substances having RBAs in this target range, the bioassay's performance in a hierarchical, tiered approach is evaluated, including the predictive capability of the uterotrophic bioassay based on available reproductive and developmental testing data. The review concludes that the uterotrophic bioassay is reliable and can identify substances that may act via an estrogen-mode of action, supporting the validity of the uterotrophic bioassay and its regulatory use as an in vivo mechanistic screening bioassay for estrogen agonists and antagonists.


Preliminary report on characteristics of women participating in the meeting of the Oral Contraceptive Pill Members Club at Siriraj Hospital.
Oral Contraceptive (OC) services are not frequented a lot in Siriraj Hospital. Therefore, the OC services initiated the Siriraj OC Members Club to increase the number of OC users, develop a 'one-stop-service' clinic and a 'help line' to assist women cope with the side effects during OC use, and provide proper information. Hospital personnel who worked at Sirriaj Hospital were informed about the program of the Siriraj OC Members Club by posters, leaflets, hospital website, and word of mouth. Those who registered as members participated in the half-day meeting of the program. Questionnaire assessment was distributed to all members who attended the meeting. The average age ofparticipants was 31.4 years. The lowest education level was secondary school and the highest was doctorate. Most married members have used at least one kind of contraceptive method OC's and condoms were the most common contraceptive method used in the past. Their source for obtaining OC was drug stores. In general, most women had had irritability and depression. Almost all women expected to have more information about advantages and disadvantages of OC use to cope with fear and side effects of OC use. Women who attended the meeting still need accurate and full information about the OC's. This program proposed to provide them with up-to-date and correct information about the OC. Furthermore, the one-stop-service will save their time and the help-line will assist them to cope with the side effects of OC use.


A historical perspective with current opinion on the management of atrophic mandibular fractures.
The management of atrophic mandibular fractures has been a challenge for maxillofacial surgeons for decades. During the past 70 years, various techniques for treating edentulous mandibular fractures have been advocated. These techniques have been praised, criticized, abandoned, improved, and used in combination with other methods. Although some of the principles of management outlined before the end of World War II are still valid in today's technological era, other concepts did not survive the test of time. The aim of this paper is to examine the evolution of treatment modalities for the management of atrophic mandibular fractures that have been employed over the years. Debates and discussions generated by this topic are included. Current techniques and treatment philosophies with thoughts for future therapies are provided.


Comparative study in vivo and in vitro of uniformly 14C-labelled and 125I-labelled recombinant fibroblast growth factor 2.
Recombinant bovine fibroblast growth factor (FGF2), uniformly labelled with 14C ([14C]FGF2), was purified and showed to be highly stable and to retain full biological activity. Organ distribution of [14C]FGF2 after intravenous injection of young rats was assessed by autoradiography of whole body sections and compared with those obtained with [125I]iodinated FGF2 (125I-FGF2). Thyroid, stomach, intestine, bladder and skin were radioactively labelled only in the case of 125I-FGF2. This tissue-labelling is artefactual, probably due to free iodide binding not observed when using [14C]FGF2. High-resolution autoradiography showed a complex tissue distribution of [14C]FGF2 in kidney and adrenal organs. Incubation of frozen eye sections with [14C]FGF2 showed a specific and high-resolution labelling pattern of ocular tissues. After cellular internalization, [14C]FGF2 was processed into five distinct polypeptides of 16, 14, 8, 7, and 5.5 kDa. The 14-kDa and 7-kDa polypeptides are novel catabolic fragments not detected with radioiodinated FGF2. In terms of stability, tissue distribution specificity, and autoradiographic resolution, [14C]FGF2 proved to have more advantages than 125I-FGF2 for pharmacokinetic and catabolism studies.


Biological and Physicochemical Assessment of Middle Ear Prosthesis.
Polymers modified with bioactive nanoparticles are a promising solution for patients who need a tissue replacement. Modern implants, thanks to bioactive and bactericidal functions, facilitate the healing and regeneration process of the replaced tissue. The aim of this study was to assess whether silver nanoparticles (AgNPs) could support antibacterial function without cytotoxic effect and deterioration of biostability. This article describes biological and physiochemical aspects concerning a new polymeric middle ear implant (Otoimplant) enriched with silver nanoparticles. This kind of prosthesis is a promising implant for the reconstruction of ossicles in ossiculoplasty. We found that incorporation of silver nanoparticles into a polymeric matrix resulted in bactericidal efficacy against Gram-positive and Gram-negative bacteria, both resistant to antibiotics and basic strains. Our prostheses do not show cytotoxic effect and are a suitable biomaterial platform for effective culture of Saos2 and NHOst osteoblastic cells. The in vitro incubation of the samples in distilled water revealed that surface parameters, such as roughness, may slightly increase as a result of unveiling nanoparticles. However, the prolonged immersion does not change mechanical parameters. During one-year incubation, the prosthesis proved to retain stable values of Young's modulus, tensile strength, propagation of longitudinal ultrasonic waves, pH, and conductivity.


Effects of alpha-adrenoceptor agonists and antagonists on duodenal surface epithelial HCO3-secretion in the rat in vivo.
In anesthetized rats a 12 mm segment of duodenum, distal to the Brunner's gland area and devoid of pancreatic and bile secretions, was cannulated in situ. Secretion of HCO3- by the surface epithelium was measured by continuous titration at luminal pH 7.40. Noradrenaline at doses of 25-200 micrograms kg-1 h-1 had no (net) effect on duodenal HCO3- secretion while the non-selective alpha-adrenoceptor antagonist phentolamine (20-1000 micrograms kg-1 intravenously) dose-dependently increased secretion. The phentolamine-induced rise in alkaline secretion was partially inhibited by noradrenaline but this effect was transient and was followed by an increase in secretion in spite of continuous infusion of noradrenaline. The alpha 1-adrenoceptor agonist, phenylephrine (100 and 500 micrograms kg-1 h-1) stimulated HCO3- secretion in a dose-dependent manner and this response was abolished by the alpha 1-adrenoceptor antagonist prazosin (0.5 mg kg-1) while the beta-adrenoceptor antagonist propranolol (1 mg kg-1) was without effect. Basal secretion, as well as secretion stimulated by phentolamine and/or phenylephrine, was inhibited by the alpha 2-adrenoceptor agonist clonidine (0.75-15.0 micrograms kg-1). The results thus strongly suggest that alpha 1-adrenoceptor stimulation increases while alpha 2-adrenoceptor stimulation decreases duodenal surface epithelial HCO3(-)-secretion. This might explain the absence of a net effect of noradrenaline.


Sedation and Analgesia for Dressing Change: A Survey of American Burn Association Burn Centers.
Pain and sedation management for patients undergoing burn dressing change can be challenging. Variations appear to exist in the selection of medications before and during burn dressing change. To determine if institutional variations exist in pain and sedation management for burn dressing change, an online survey was sent to ABA Burn Center nurses and physicians. Three hundred seventy-eight anonymous responses were received from nurses (72%), nurse practitioners (10%), and physicians (18%). Burn centers had adult (22%), pediatric (12%), or pediatric and adult (66%) patients. Eighty percentage of centers had >200 patients/year. Sixty-eight percentage always used a premedication. Oxycodone and morphine or fentanyl was the most frequently used per oral (PO) and intravenous (IV) opioid premedication, respectively. The most common IV premedication anxiolytic were benzodiazepines. Sixty-eight percentage always used a long-acting opioid. Anesthetic regimen was decided case-by-case (47%) or specific protocol (24%). Protocol was followed always (18%) or mostly (55%). Patients' procedural pain could be better controlled 20% of the time. Pain regimen was altered most of the time (25%). Providers differed rarely (39%) and sometimes (44%) regarding preferred regimen. Ketamine was the most common deep sedative. A dedicated anesthesiologist was rarely (33%) consulted, determined case-by-case (33%) or prior failure/excess pain (19%). Acute pain service was never (51%) or rarely (35%) consulted. Pain and sedation management for burn dressing change is difficult and variations in approach exist among burn centers. Such management needs individualized care. Providers must be responsive to pain alterations. Consultation with anesthesia providers may be needed in specific cases. Further studies need to be completed to demonstrate the most effective means of controlling burn pain and evaluating patient outcomes.


Sequence of the WT1 upstream region including the Wit-1 gene.
The Wilms tumor gene WT1 encodes a Cys2His2-type zinc finger protein that can bind DNA and function as a transcriptional regulator. The pathological spectrum of tumorigenesis and various developmental defects produced by different WT1 alterations suggests that WT1 controls a number of subsequent effector genes. To define the role of WT1 in these developmental processes it will be important to elucidate mechanisms that govern expression of WT1 itself. To facilitate mapping of the WT1 promoter region and 5' control elements we have determined the sequence upstream of the WT1 transcription unit. This includes the Wit-1 gene that is transcribed in the opposite direction.


Effect of a new hand-forearm splint on grip strength, pain, and function in patients with tennis elbow.
While the effectiveness of orthoses prescribed for tennis elbow has been reported in several studies, the effect of how they may limit movements which aggravate this condition has not yet been explored. The purpose of this study was to evaluate the effect of a new spiral hand-forearm splint that restricts the movement of the wrist and forearm, on grip strength, pain, and function in patients with tennis elbow. Quasi-experimental design. A total of 15 patients with tennis elbow (mean age 43 years) took part in this study. The amount of pain, grip force, and function were compared using a visual analog scale, Jamar dynamometer, and the Disability of the Arm, Shoulder, and Hand questionnaire, respectively. This was performed at baseline and repeated after 4 weeks of splint use. Active motion of the forearm was measured by a goniometer. The spiral splint significantly relieved pain and improved function and grip force in patients after 4 weeks of application (P < 0.05). The new splint design had a positive effect on the treatment of tennis elbow symptoms which included pain, grip strength, and function. Restriction of rotational movement (e.g. reduction of the supination and pronation of forearm) may have played the main role in this. This new splint design may be considered as a new approach in the conservative treatment and rehabilitation of patients with tennis elbow.


Fabrication of Radially Symmetric Graded Porous Silicon using a Novel Cell Design.
A contactless method using a novel design of the experimental cell for formation of porous silicon with morphological gradient is reported. Fabricated porous silicon layers show a large distribution in porosity, pore size and depth along the radius of the samples. Symmetrical arrangements of morphology gradient were successfully formulated radially on porous films and the formation was attributed to decreasing current density radially inward on the silicon surface exposed to Triton(®) X-100 containing HF based etchant solution. Increasing the surfactant concentration increases the pore depth gradient but has a reverse effect on the pore size distribution. Interestingly, when dimethyl sulfoxide was used instead of Triton(®) X-100 in the etchant solution, no such morphological gradients were observed and a homogeneous porous film was formed.


Genetic markers linked to quantitative traits in poultry.
This study utilized DNA fingerprints and crosses of two genetically distinct lines of layer-type chickens to identify genetic markers linked to quantitative trait loci (QTL). In phase I, backcross (BC1) hens were separately ranked for each of eight traits and then blood pools were produced in groups along each phenotypic distribution. The DNA was isolated from the blood pools and used in a gradient analysis to screen for DNA fingerprint bands that exhibited intensity gradients associated with the phenotypic traits. To identify linkage of bands with QTL and to estimate band effects, F2 progeny were produced in phase II from the phase I BC1 population. A single-trait animal model was used for analysis of associations of all individual DNA fingerprint bands of sires and their progeny phenotypic performance. Twenty fingerprint bands, only two of which had shown trait-associated gradients in phase I, were identified by the animal model analysis of the progeny test as QTL linked (P < or = 0.05) to specific traits of growth, reproduction and egg quality. These 20 bands warrant further study as potentially valuable molecular markers for QTL.


Probiotic strains alleviated OVA-induced food allergy in mice by regulating the gut microbiota and improving the level of indoleacrylic acid in fecal samples.
Food allergy (FA) is a common immune disorder caused by food antigens. Probiotic strains showed alleviating effects on FA, such as the alleviation of FA pathological symptoms, serum OVA-sIgE levels, and the gut microbiota diversity and composition. The results showed that intragastric administration of Lactiplantibacillus plantarum CCFM1189, Limosilactobacillus reuteri CCFM1190, and Bifidobacterium longum CCFM1029 alleviated the weight loss and FA pathological symptoms of FA mice and decreased OVA-specific IgE and histamine (HIS) levels. CCFM1189 and CCFM1190 decreased IL-4, IL-5, and IL-13 levels, while CCFM1189 and CCFM 1029 decreased IL-17 levels. The gut microbiota analysis demonstrated that CCFM1189 increased the abundance of Akkermansia, while CCFM1190 improved immune regulation bacteria such as Faecalibaculum. CCFM1029 increased Bifidobacterium and the bacteria involved in short-chain fatty acid (SCFA) production, such as Dubosiella. L. plantarum CCFM1189 and L. reuteri CCFM1190 improved indoleacrylic acid levels in mouse fecal samples using untargeted metabolomics analysis. In conclusion, CCFM1189, CCFM1190, and CCFM1029 decreased Th2 immune responses and alleviated FA pathological symptoms by regulating the gut microbiota diversity and composition, and altering gut microbial metabolites, which could provide support in clinical tests and probiotic production in the future.


Remodelling of the left anterior descending artery in a porcine model of supravalvular aortic stenosis.
Knowledge of the adaptive mechanisms of structure and function of coronary arteries in response to physical stress is important in human health and disease. To gain a better understanding of the adaptive mechanisms of morphology in the zero-stress state of the coronary arteries in a porcine model of hypertension and flow overload. The effects of simultaneous increases in pressure and flow were examined by studying the left anterior decending (LAD) artery in supravalvular aortic stenosis (SVAS). In this model, the pressure is uniformly increased along the length of the LAD artery trunk, whereas the increase in flow is significantly greater in the proximal than in the distal artery. The longitudinal variation of vessel dimension, medial and adventitial area, opening angle and residual strains were examined in the LAD arteries of aortic-banded (n = 5) and control (n = 5) pigs. Our results show that the wall shear stress was normalized, whereas the circumferential stress was increased, in the proximal portion of the LAD artery after 5 weeks of SVAS. In the distal artery, both shear and circumferential stresses were normalized. The vessel wall area was also increased in the remodelled vessels as the result of an increase in the medial and adventitial area. The major conclusion of this study is that, in the SVAS model, the remodelling process of the coronary artery is consistent with normalization of shear stress despite an increase in the circumferential stress. Furthermore, the remodelling of the zero-stress state is also dominated by flow overload.


Regulation of autoreactive B cell responses to endogenous TLR ligands.
Immune complexes containing DNA and RNA are responsible for disease manifestations found in patients with systemic lupus erythematosus (SLE). B cells contribute to SLE pathology through BCR recognition of endogenous DNA- and RNA- associated autoantigens and delivery of these self-constituents to endosomal TLR9 and TLR7, respectively. B cell activation by these pathways leads to production of class-switched DNA- and RNA-reactive autoantibodies, contributing to an inflammatory amplification loop characteristic of disease. Intriguingly, self-DNA and RNA are typically non-stimulatory for TLR9/7 due to the absence of stimulatory sequences or the presence of molecular modifications. Recent evidence from our laboratory and others suggests that B cell activation by BCR/TLR pathways is tightly regulated by surface-expressed receptors on B cells, and the outcome of activation depends on the balance of stimulatory and inhibitory signals. Either IFNalpha engagement of the type I IFN receptor or loss of IgG ligation of the inhibitory FcgammaRIIB receptor promotes B cell activation by weakly stimulatory DNA and RNA TLR ligands. In this context, autoreactive B cells can respond robustly to common autoantigens. These findings have important implications for the role of B cells in vivo in the pathology of SLE.


Identification of the genetic mechanism that associates L3MBTL3 to multiple sclerosis.
Multiple sclerosis (MS) is a complex and demyelinating disease of the central nervous system. One of the challenges of the post-genome-wide association studies (GWAS) era is to understand the molecular basis of statistical associations to reveal gene networks and potential therapeutic targets. The L3MBTL3 locus has been associated with MS risk by GWAS. To identify the causal variant of the locus, we performed fine mapping in a cohort of 3440 MS patients and 1688 healthy controls. The variant that best explained the association was rs6569648 (P = 4.13E-10, odds ratio = 0.71, 95% confidence interval (CI) = 0.64-0.79), which tagged rs7740107, located in intron 7 of L3MBTL3. The rs7740107 (A/T) variant has been reported to be the best expression and splice quantitative trait locus (eQTL and sQTL) of the region in up to 35 human genotype-tissue expression (GTEx) tissues. By sequencing RNA from blood of 17 MS patients and quantification by digital qPCR, we determined that this eQTL/sQTL originated from the expression of a novel short transcript starting in intron 7 near rs7740107. The short transcript was translated into three proteins starting at different translation initiation codons. These N-terminal truncated proteins lacked the region where L3MBTL3 interacts with the transcriptional regulator Recombination Signal Binding Protein for Immunoglobulin Kappa J Region which, in turn, regulates the Notch signalling pathway. Our data and other functional studies suggest that the genetic mechanism underlying the MS association of rs7740107 affects not only the expression of L3MBTL3 isoforms, but might also involve the Notch signalling pathway.


Hypopigmented mycosis fungoides versus mycosis fungoides with concomitant hypopigmented lesions: same disease or different variants of mycosis fungoides?
Hypopigmented mycosis fungoides (HMF) is a rare subtype of mycosis fungoides (MF). We compared patients with exclusive hypopigmented lesions with a group of MF patients with concomitant different lesions. 20 patients with HMF only and 14 patients with hypopigmented lesions concomitant with other types of lesions (mixed MF, MMF) were selected. Clinical-epidemiological analysis as well as histological and immunohistochemical studies were performed. HMF and MMF preserve some similarities, like predilection for dark-skinned persons and slow progression, but they also present differences: the exclusive variant is associated with early onset and a clear CD8+ immunophenotype, whereas MMF patients tend to present a predominance of CD4+ cell infiltrates. Histological analysis revealed similar findings; relapsing courses were common. Whether patients are suffering from exclusive HMF or MMF, the presence of hypopigmented lesions can be considered a marker of good prognosis in MF, since both groups presented similar data, such as staging and disease duration.


Could antispasmodic drug reduce pain during hysterosalpingo-contrast sonography (HyCoSy) in infertile patients? A randomized double-blind clinical trial.
To assess the effectiveness of an antispasmodic drug, hyoscine-N-butylbromide, in reducing pain during hysterosalpingo-contrast sonography (HyCoSy). Eight hundred and sixteen patients undergoing HyCoSy were randomized to receive 10 mg hyoscine-N-butylbromide (n = 408) or placebo (n = 408) per os, 30 min before the procedure, in a double-blind randomized controlled trial. Immediately after the procedure, the patient was asked to describe any pain experienced in comparison with pain usually suffered during the menstrual cycle, and the operator assigned a pain score between 0 and 4 as follows: 0 (no reaction or discomfort), 1 (slight pain, less than menstrual pain), 2 (moderate pain, exceeding menstrual cramps but no vasovagal reaction), 3 (vasovagal reaction or pain requiring observation in a hospital) and 4 (vasovagal reaction or pain requiring resuscitation). The primary aim was to estimate the difference in pain score, considered as a categorical value, between the active arm of the trial and the control group. The secondary aim was to evaluate if pain is related to tubal patency. There was no difference in pain score between the hyoscine-N-butylbromide group and the placebo group (P = 0.807). There was a negative correlation between pain and tubal patency, regardless of treatment group (P < 0.0001). Administration of 10 mg antispasmodic drug hyoscine-N-butylbromide does not reduce pain in patients undergoing HyCoSy.


Effects of adjuvant chemohormonal therapy on the ovarian and adrenal function of breast cancer patients.
Ovarian and adrenal function were studied in premenopausal breast cancer patients before and at intervals during adjuvant therapy with cyclophosphamide, methotrexate, and 5-fluorouracil (CMF), CMF plus prednisone (CMFP), or CMFP plus tamoxifen (CMFPT). Amenorrhea developed within 10 months of starting therapy in 13 of 15 patients given CMF, 8 of 10 receiving CMFP, and all of 13 CMFPT-treated patients. The amenorrheic patients receiving CMF showed a reduction in their plasma total estrogens and an increase in plasma luteinizing and follicle-stimulating hormones, indicating that these cytotoxic drugs directly suppressed ovarian function. Plasma androstenedione levels, which are derived equally from the ovaries and adrenals before the menopause, were also reduced. Plasma dehydroepiandrosterone sulfate, a steroid predominantly of adrenal origin, was unaffected. CMFP-induced amenorrhea was associated with similar changes in the plasma estrogens and gonadotropins, but patients receiving this combination showed significantly greater reductions in plasma androstenedione and also decreased levels of plasma dehydroepiandrosterone sulfate. Suppression of androstenedione secretion from both the ovaries and adrenals did not affect the total plasma estrogen concentrations. Initially, CMFPT-treated patients showed significant elevations in plasma total estrogens, without a change in the gonadotropin levels. Although the plasma sex hormone-binding capacity was increased during CMFPT therapy, there was only a small reduction in the percentage of free plasma estradiol, with the result that the level of circulating unbound estrogen was increased. The plasma estrogens declined, with a corresponding increase in gonadotropins, after the onset of CMFPT-inducted amenorrhea.


Restriction site-free insertion of PCR products directionally into vectors.
A restriction site-free cloning method has been developed for inserting a PCR product into a vector flexibly and precisely at any desired location with high efficiency. The method uses a pair of DNA integration primers with two portions. The 3' portion isolates the inserts by PCR, and the 5' portion integrates the PCR products into the homologous region of the vector. For mutagenesis, a third portion of mutation-generating sequences can be placed in between the 3' and 5' portions. This method has been used to clone the E. coli gene that codes for peptidyl-tRNA hydrolase, expressing it as a native protein and as a glutathione S-transferase fusion protein. It was also applied to convert a construct of the E. coli fatty acid biosynthesis protein with an N-terminal hexa-histidine tag into a construct with a C-terminal hexa-histidine tag.


The Uganda Memory Project: mothers disclosing their HIV status to their children.
Since 1992, the National Community of Women Living with HIV/AIDS in Uganda has been working to improve the quality of life of Ugandan women living with HIV/AIDS. HIV-positive mothers who were finding it difficult to tell their children about their HIV status started the so-called Memory Project, which tries to help HIV-positive parents give their children the support they need to survive with as little trauma as possible after the deaths of their parents.


[Evaluation of reverse transcription loop-mediated isothermal amplification for detection of avian influenza A H5N1 virus].
A simple and sensitive Reverse Transcription Loop-mediated Isothermal Amplification (RT-LAMP) method was established to provide a new alternative for clinical diagnosis of Avian influenza A H5N1 virus. The method employed a set of six specially designed primers that recognized eight distinct sequences of the target for amplification of nucleic acid under isothermal conditions. In current study, fifty-one experimentally infected animal specimens and viral cultures that had been tested were analyzed by RT-LAMP for NA gene and HA gene, respectively. The amplification process of LAMP was monitored in real-time by the addition of SYBR Green dye. Meanwhile, the result showed high correlation between nested PCR and RT-LAMP. The specificity of the RT-LAMP assay was confirmed by restriction enzyme digestion analysis and sequencing of the amplified product. When the sensitivity of this assay was tested by serial 10-fold dilutions of RNA molecules from specimens, it was found that the RT-LAMP method achieved theoretically a sensitivity of 10 RNA molecules. Thus, we concluded that the RT-LAMP assay has potential usefulness for rapid detection of the Avian influenza A H5N1 virus.


Rhesus monkey lipoprotein(a) binds to lysine Sepharose and U937 monocytoid cells less efficiently than human lipoprotein(a). Evidence for the dominant role of kringle 4(37).
Rhesus lipoprotein(a) (Lp[a]) binds less efficiently than human Lp(a) to lysine-Sepharose and to cultured U937 cells. Studies using elastase-derived plasminogen fragments indicated that neither kringle 5 nor the protease domain of Lp(a) are required in these interactions pointing at an involvement of the K4 region. Comparative structural analyses of both the human and simian apo(a) K4 domain, together with molecular modeling studies, supported the conclusion that K4(37) plays a dominant role in the lysine binding function of apo(a) and that the presence of arginine 72 rather than tryptophan in this kringle can account for the functional deficiency observed with rhesus Lp(a). These in vitro results suggest that rhesus Lp(a) may be less thrombogenic than human Lp(a).


Explosive Fragmentation of Luminescent Diamond Particles.
Development of efficient and cost-effective mass-production techniques for size reduction of high- pressure, high-temperature (HPHT) diamonds with sizes from tens to hundreds of micrometers remains one of the primary goals towards commercial production of fluorescent submicron and nanodiamond (fND). fNDs offer great advantages for many applications, especially in labelling, tracing, and biomedical imaging, owing to their brightness, exceptional photostability, mechanical robustness and intrinsic biocompatibility. This study proposes a novel processing method utilizing explosive fragmentation that can potentially be used for the fabrication of submicron to nanoscale size fluorescent diamond particles. In the proposed method, synthetic HPHT 20 pm and 150 pm microcystalline diamond particles containing color centers are rapidly fragmented in conditions of high explosive detonation. X-ray diffraction and Raman spectroscopy show that the detonation fragmented diamond particles consist of good quality submicron diamonds of ~420-800 nm in size, while fluorescence spectroscopy shows photoluminescence spectra with noticeable changes for large (150 μm) starting microcrystalline diamond particles, and no significant changes in photoluminescence properties for smaller (20 μm) starting microcrystalline diamond particles. The proposed detonation method shows potential as an efficient, cost effective, and industrially scalable alternative to milling for the fragmentation of fluorescent diamond microcrystals into submicron- to nano-size domain.


Informal leadership support: an often overlooked competitive advantage.
As environmental pressures mount, the advantage of using the same strategies and tactics employed by competitors continues to shrink. An alternative is adapting and applying answers successfully employed in other industries to health care organizations. Working with informal influence leaders to share your change management efforts represents one such example. Informal influence leaders offer an often-overlooked source of competitive advantage--they have already earned credibility and respect from others, who regularly look to them for guidance. When sharing their views, they significantly influence the acceptance or rejection of new initiatives. Influence leaders reach into every conversation, every meeting, and every decision made in an organization. The important question is whether they will exert their leadership in support or in opposition to changes you propose. By identifying influence leaders and inviting them to join a group to discuss change initiatives, physician executives can create a positive force for change.


Tunable color generation of transparent composite films reinforced with luminescent nanofillers.
A new composite film based on calcined layered rare earth hydroxides and poly(vinyl alcohol) shows a visible light transmittance comparable to that of the pure matrix, highly reinforced mechanical strength as well as tunable photoluminescence in rolled and folded shapes.


Biology of aortic aneurysms and dissections.
The biology of aortic aneurysm and dissection has evolved to where we now understand the genetic implications of changes in extracellular matrix proteins, smooth muscle cells, and growth factors and how they affect aortic wall homeostasis. These predeterminants are influenced by smoking, hypertension, and atherosclerosis, and the result in an inflammatory response coupled to an accelerated proteolytic cascade that disrupts both elastin and collagen in the aortic wall.


Coat score. A possible explanation for the zebuine selective sweep located on bovine chromosome 5: 47,670,001-48,100,000 bp.
Over 65% of the world's cattle population resides in warm areas where heat stress conditions limit the breed of European taurine cattle. Composite breeds were developed to retain the main traits of both parental breeds. The skin plays a central role in animal response to heat stress. Research on the genetic architecture of skin traits has identified genes and regions related to warm resistance skin features. The aim of this study was to determine whether the indicine proportion accounted for coat type or whether there were genes of large effect segregating in Brangus. Bulls (n = 108) were genotyped using microarrays and their coat score and hair length were evaluated. Indicine-taurine genome-wide composition was estimated and GWAS was performed. Although significant correlations between indicine proportion and traits were not observed, four windows of SNPs on BTA4 and BTA5 explained more than 2% of the trait variance. The GWAS for coat score in summer showed the main peak on BTA5:46,941,446-48,030,219 bp, accounting for 4.65% of the variance. Our results suggest that the variation in coat score and undercoat hair length in Argentinian Brangus bulls is associated with the presence of some particular gene variants, rather than with the whole indicine genetic content.


Hypercholesterolemia is associated with hyperactive cardiac mTORC1 and mTORC2 signaling.
Nutritional excess and hyperlipidemia increase the heart's susceptibility to ischemic injury. Mammalian target of rapamycin (mTOR) controls the cellular response to nutritional status and may play a role in ischemic injury. To explore the effect of hypercholesterolemia on cardiac mTOR signaling, we assessed mTOR signaling in hypercholesterolemic swine (HC) that are also susceptible to increased cardiac ischemia-reperfusion injury. Yucatan pigs were fed a high-fat/high-cholesterol diet for 4 weeks to induce hypercholesterolemia, and mTOR signaling was measured by immunoblotting and immunofluorescence in the non-ischemic left ventricular area. Total myocardial mTOR and raptor levels were markedly increased in the HC group compared to the normocholesterolemic group, and directly correlated with serum cholesterol levels. mTOR exhibited intense perinuclear staining in myocytes only in the HC group. Hypercholesterolemia was associated with hyperactive signaling upstream and downstream of both mTOR complexes, including myocardial Akt, S6K1, 4EBP1, S6 and PKC-alpha, increased levels of cardiac hypertrophy markers, and a trend toward lower levels of myocardial autophagy. Hypercholesterolemia can now be added to the growing list of conditions associated with aberrant mTOR signaling. Hypercholesterolemia produces a unique profile of alterations in cardiac mTOR signaling, which is a potential target in cardiac diseases associated with hypercholesterolemia and nutritional excess.


Stereoselective synthesis of a novel apio analogue of neplanocin A as potential S-adenosylhomocysteine hydrolase inhibitor.
A total synthesis of apio-neplanocin A, which combines properties of apio nucleoside and neplanocin A and is a potential inhibitor of S-adenosylhomocysteine hydrolase, was accomplished starting from D-ribose via stereoselective hydroxymethylation and RCM reaction. [reaction: see text]


Effects of field-contaminated sediments and related water soluble components on haemocyte function and Perkinsus marinus susceptibility and expression in oysters.
This paper reviews and discusses our recent findings on the effects of contaminated sediments (CSs) and related water-soluble fractions (WSFs) on haemocyte function/activity and the onset and progression of an infectious disease caused by the protozoan parasite, Perkinsus marinus (Dermo) in the eastern oyster, Crassostrea virginica. Sediments used to generate WSFs and sediments used for the whole CS exposure experiments were collected in different areas of the southern branch of the Elizabeth River, a heavily polluted sub-estuary of the Chesapeake Bay, USA. The WSFs were dominated by low molecular weight polycyclic aromatic hydrocarbons (PAHs). The CSs used for whole CS exposure experiment had elevated concentrations of high molecular weight PAHs. Polychlorinated biphenyls (PCBs) and metals were also present in the CSs. No PCBs were detected in the WSFs. In vitro exposure of haemocytes to WSFs derived from CSs reduced to haemocytes' chemotaxic, phagocytic, and chemiluminescent responses to some extent. Exposure of oysters to suspended CSs stimulated neutral red uptake, mitochondrial dehydrogenase production and (3)H-leucine incorporation in haemocytes. Exposure of oysters to 0, 15, 30% WSFs increased the oysters' susceptibility to laboratory-induced infection caused by P. marinus. Exposure of oysters to 15, and 30% dilutions of WSFs for 33 days or to 1.0, 1.5, and 2.0g CSs for 30 days significantly elevated the expression/progression of latent P. marinus infection in oysters in a dose-dependent manner.


Use of post-harvest common bean (Phaseolus vulgaris L.) residues in diet of lambs and its effect on finishing performance, rumen fermentation, protozoa population and meat characteristics.
The aim of the experiment was to investigate the replacement value of common bean residues in the diet of finishing lambs as an inexpensive fodder instead of wheat straw or maize silage. Forty Arabi male lambs with average body weight of 18.90 ± 0.6 kg were randomly divided into five treatments with eight replications. The five experimental treatments consisted of control diet, and 50% and 100% replacement of bean residues with wheat straw or 25% and 50% replacement with maize silage in the control diet respectively. Lambs were slaughtered at the end of the experiment to evaluate carcass traits and meat characteristics. Dry matter intake, blood glucose, urea nitrogen, cholesterol and triglyceride concentration were not affected by the experimental treatments. Apparent digestibility of nutrients; total concentration of volatile fatty acids, acetate and butyrate; and total rumen protozoa population were linearly increased by increasing the levels of bean residues, as replacement with wheat straw (p < .05). Replacement of bean residues in control diets instead of wheat straw or maize silage caused a positive linear incremental trend for average daily gain and total weight gain. There was no significant difference in daily gain, final weight and feed conversion ratio among the treatments. Instead of wheat straw or maize silage, replacement bean residues linearly increased chewing, ruminating and eating activities per neutral detergent fibre intake (p < .05). Carcass traits and physicochemical characteristics of meat were not affected by the treatments. It is advisable to use bean residues in the diet of lambs as an alternative to the wheat straw or maize silage, because no adverse effects were observed on rumen fermentation, blood metabolites and performance; moreover, improvement in average daily gain, total weight gain and digestibility of nutrients, and the fact that bean residue is less expensive than wheat straw and maize silage.


BRD4 is a newly characterized transcriptional regulator that represses autophagy and lysosomal function.
As a member of the bromodomain and extraterminal (BET) family, BRD4 (bromodomain containing 4) can bind to acetylated histones and transcription factors, and is also able to recruit various transcriptional regulators. Previous studies have shown that BRD4 mainly plays a positive role in cell growth and cell cycle progression. In a recent study conducted by Sakamaki et al., the authors found that BRD4 acts as a transcriptional repressor in regulating macroautophagy/autophagy and lysosome gene expression, via binding to the histone lysine methyltransferase EHMT2/G9a. The oncoprotein BRD4-NUTM1/NUT also helps block autophagy and lysosome functions. A knockdown of BRD4 allows the retention of MTOR activity during starvation and significantly undermines starvation-induced cell death. However, BRD4 repression only contributes to stimulus-dependent autophagy and aggrephagy, and is not involved in other types of selective autophagy. Taken together, the newly reported repressive role of BRD4 in autophagy adds to our understanding of how autophagy and lysosome functions are regulated at the transcriptional level.


Administration of eptifibatide during endovascular treatment of ruptured cerebral aneurysms reduces the rate of thromboembolic events.
Thromboembolic complications are the most frequent complications of endovascular treatment of ruptured intracranial aneurysms. The optimal protocol to prevent thromboembolic complications during coil embolization does not yet exist. The aim of this study was to investigate the effectiveness and safety of eptifibatide for the prevention of thromboembolic complications during elective coil embolization of ruptured cerebral aneurysms. A consecutive series of 100 patients (group 1) with ruptured intracranial aneurysm were treated using endovascular coil embolization. At the beginning of the procedure, all patients received an intra-arterial bolus (0.2 mg/kg) of eptifibatide. The following data were collected: degree of aneurysmal occlusion after treatment, thromboembolic and hemorrhagic complications and other intraoperative adverse events. The results were compared with those from a control group (group 2) which were analyzed retrospectively. Group 2 consisted of 100 previous patients with ruptured aneurysm managed with coil embolization who had received heparin and/or aspirin at the beginning of the procedure. (1) Patient populations in groups 1 and 2 were considered statistically comparable, except that group 1 (eptifibatide) included more wide-necked aneurysms (p = 0.011). (2) There were less thromboembolic complications in group 1 (p = 0.011): seven intraoperative complications in group 1 versus 20 in group 2. (3) Intraoperative hemorrhagic complications were statistically comparable in both groups (p = 1). Eptifibatide was effective in lowering the intraoperative thromboembolic complication rate in ruptured aneurysms treated with coil embolization and did not increase the hemorrhagic risk.


Successful multimodality treatment for locally advanced primary thymic adenocarcinoma: report of a case.
Although the optimal treatment strategy for locally advanced thymic carcinomas has yet to be determined, complete resection of the tumor after induction chemoradiotherapy (CRT) can sometimes provide a good chance of being cured. A 61-year-old woman was diagnosed with locally advanced primary thymic carcinoma, which invaded bilateral brachiocephalic veins and superior vena cava with intraluminal tumor thrombus. Induction CRT was performed, and a partial response to the treatment was achieved. Subsequent radical surgery was successfully performed by the median full sternotomy with a right transmanubrial osteomuscular sparing approach (TMA). The patient is currently alive and has remained disease-free for a year. The TMA is useful for extensive surgery of locally advanced thymic carcinoma because it can provide good exposure of the operative field without post-operative functional limitation of upper limbs.


Leptin enhances the effect of transforming growth factor beta in increasing type I collagen formation.
Hepatic fibrosis produced by carbon tetrachloride and by Schistosoma masoni is markedly decreased in leptin deficient ob/ob mice as compared to control mice. Leptin is present in activated rat stellate cells, which are the principal collagen producing cells in the liver. The purpose of this study was to identify the leptin receptor and to determine the effects of leptin on type I collagen expression in the human stellate cell line, LX-1. Leptin protein was detected in the LX-1 cells. The leptin receptor (OB-R) was demonstrated by immunofluorescent staining and confocal microscopy. However, only the short forms (Ob-R(s)), but not the long forms (Ob-R(l)), of leptin receptor mRNA expression were detected. Leptin increased alpha(1)(I) collagen mRNA and type I collagen production. Leptin did not increase TGFbeta1 mRNA or protein in the cultured LX-1 cells. Leptin, however, increased TGFbeta type II receptor mRNA and protein and augmented the effect of TGFbeta1 on collagen production. In conclusion, this study shows that the effect of leptin in increasing type I collagen production in stellate cells is mediated by actions of leptin in increasing the effectiveness of TGFbeta on fibrogenesis by means of an enhancement of the TGFbeta type II receptor.


Complementation of expression of carcinoembryonic antigen and tumor associated glycoprotein-72 (TAG-72) in human colon adenocarcinomas.
Enzyme-labeled monoclonal antibodies (MAbs) were used in an immunohistochemical, dual-staining study of 10 colon adenocarcinomas. MAbs B72.3 and COL-4, reactive with the high molecular weight tumor-associated glycoprotein-72 (TAG-72) antigen and carcinoembryonic antigen (CEA), respectively, were labeled with horseradish peroxidase or alkaline phosphatase. Dual staining using the two MAbs on a single tissue section (formalin-fixed, paraffin-embedded) showed that greater numbers of carcinoma cells could be detected by using the combination of the two MAbs than could be detected by use of either MAb alone. In many tumors, some carcinoma cells reacted with MAb B72.3, some reacted with MAb COL-4, and some cells reacted with both MAbs. Only 1 of 10 carcinomas showed greater than 75% reactive cells when stained with each MAb individually. In 9 of 10 cases, however, greater than 75% of cells reacted when the combination of MAbs was used. Cell surface and cytoplasmic patterns of reactivity were observed with both MAbs while some pools of extracellular mucin were composed of both TAG-72 and CEA. This study supports the rationale for the use of a combination of anti-TAG-72 and anti-CEA MAbs for in vitro immunologic detection and potential in vivo immunodiagnostic and immunotherapeutic applications for these MAbs in colon adenocarcinoma patients.


Quantitative assessment of the risk of human activities on landscape fragmentation: A case study of Northeast China Tiger and Leopard National Park.
Risk assessment of human activities on landscape fragmentation in nature reserves can effectively balance the conflict between wildlife conservation and human development. However, previous studies had been unable to quantitatively assess the risk of human activities on landscape fragmentation. Thus, we constructed a risk assessment methodology to quantitatively assess the risk of different human activities on the Landscape Fragmentation Composite Index (LFCI) in the Northeast China Tiger and Leopard National Park (NCTLNP). First, we fitted the relationship curve between LFCI and different human activity factors based on the Generalized Additive Model (GAM) to determine the impact patterns of each factor on LFCI. Secondly, we identified impact risk areas of each human activity factor on LFCI by the location of threshold points in the curve and analyzed their spatiotemporal variation characteristics from 2015 to 2020. The results show that the relationship between LFCI and Land Use Intensity (LUI) showed an inverted "U" shape, the relationship with Population Density (POPD) showed a "rising-flat-rising" trend, and the relationship with Traffic Accessibility (TA) and Industrial and Mining Activity (IMA) showed a positive correlation after a flat interval. In addition, we found that the LUI and IMA impact risk areas were widely distributed and remained stable for five years. But the POPD impact risk area was mainly distributed around settlements and expanded by 6.6 % from 2015 to 2020. The TA impact risk area was distributed in strips and expanded by 16.38 % from 2015 to 2017 due to the construction of the G331 national road. And the joint impact risk area of these four factors expanded by 1.55 times in five years. Our research can provide a reference for ecological risk assessment under the impact of human activities on other nature reserves in the world.


Therapeutic Potential of Menstrual Blood-Derived Stem Cell Transplantation for Intrauterine Adhesions.
An increasing number of women experience intrauterine adhesion as a result of intrauterine operations, such as induced abortion, which can cause infertility, recurrent abortion and amenorrhea. Although some strategies have been applied clinically, such as hysteroscopy adhesiolysis of intrauterine adhesions, the results have not been promising. As regenerative medicine develops, research on menstrual blood-derived stem cell transplantation is increasing due to the properties of these cells, including self-renewal, differentiation, angiogenesis, anti-inflammation and immunomodulation. As a result, menstrual blood-derived stem cells may be an ideal cell source for the treatment of intrauterine adhesion. Excitingly, it has been reported that autologous menstrual blood stem cells could recovery injured endometrium and improve infertility in patients with refractory intrauterine adhesion. In this review, we discuss the possible potential of menstrual blood-derived stem cell transplantation for intrauterine adhesion, including the antifibrosis, angiogenesis, anti-inflammation and immunoregulation properties of the cells, which brings hopes for clinical therapy.


HFE C282Y homozygosity is associated with an increased risk of total hip replacement for osteoarthritis.
The evidence for an association between mutations in the HFE (hemochromatosis) gene and the risk of hip or knee osteoarthritis is inconsistent. Total joint replacement is considered a surrogate measure for symptomatic end-stage osteoarthritis. We examined the relationship between HFE gene mutations and risk of total hip and knee replacement using a prospective cohort study. The Melbourne Collaborative Cohort Study recruited participants between 1990 and 1994. Participants born in Australia, New Zealand, the United Kingdom, or Ireland (n = 27,848) were genotyped for the HFE C282Y mutation. Total hip and knee replacements for osteoarthritis during 2001 to 2009 were ascertained from the Australian Orthopaedic Association National Joint Replacement Registry. Hazard ratios (HR)/odds ratios (OR) and confidence intervals (CI) were obtained from Cox regression or logistic regression. Compared with those with no C282Y mutation, C282Y homozygotes had an increased risk of single total hip replacement (HR 1.94, 95% CI 1.04-3.62) and bilateral total hip replacement (OR 5.86, 95% CI 2.36-14.57) for osteoarthritis, adjusting for age, sex, body mass index, and educational level. Only 3 C282Y homozygotes had single total knee replacement; the HR was 0.51 (95% CI 0.16-1.57). C282Y/H63D compound heterozygosity was not related to the risk of total hip or knee replacement. HFE C282Y homozygosity was associated with an increased risk of both single and bilateral total hip replacement for osteoarthritis.


Comparative genome analysis of three Group A Streptococcus dysgalactiae subsp. equisimilis strains isolated in Japan.
Introduction. Streptococcus dysgalactiae subsp. equisimilis (SDSE) is a β-hemolytic streptococcus that causes severe invasive streptococcal infections, especially in the elderly and people with underlying diseases. SDSE strains are primarily characterized by Lancefield group G or C antigens.Hypothesis/Gap Statement. We have previously reported the prevalence of Lancefield group A SDSE (GA-SDSE) strains in Japan and have analysed the draft genome sequences of these strains. As GA-SDSE is a rare type of SDSE, only one complete genome has been sequenced to date.Aim. The present study is focused on genetic characteristics of GA-SDSE strains. In order to examine molecular characteristics, we also tested growth inhibition of other streptococci by GA-SDSE.Methodology. We determined the complete genome sequences of three GA-SDSE strains by two new generation sequencing systems (short-read and long-read sequencing data). Using the sequences, we also conducted a comparative analysis of GA-SDSE and group C/G SDSE strains. In addition, we tested multiplex and quantitative PCRs targeting the GA-SDSE, group G SDSE, and S. pyogenes.Results. We found a group-specific conserved region in GA-SDSE strains that is composed of genes encoding predicted anti-bacteriocin and streptococcal lantibiotic (Sal) proteins. Multiplex and quantitative PCRs targeting the GA-SDSE-specific region were able to distinguish between GA-SDSE, other SDSE, and S. pyogenes strains. The growth of GA-SDSE was suppressed in the presence of group G SDSE, indicating a possible explanation for the low frequency of isolation of GA-SDSE.Conclusion. The comparative genome analysis shows that the genome of GA-SDSE has a distinct arrangement, enabling the differentiation between S. pyogenes, GA-SDSE, and other SDSE strains using our PCR methods.


Influence of two administration rates of propofol at induction of anaesthesia on its relative potency in cats: a pilot study.
Objectives This was a randomised, blinded trial to investigate the influence of administration rate on the dose of propofol required for the orotracheal intubation of cats. Methods Twenty-four female domestic cats undergoing ovariohysterectomy were premedicated with oral tramadol (6 mg/kg) or intramuscular tramadol (4 mg/kg), and intramuscular dexmedetomidine (0.007 mg/kg). Oral or intramuscular (IM) tramadol was administered 60 or 30 mins prior to induction of anaesthesia, respectively. Dexmedetomidine was administered 30 mins prior to anaesthetic induction. Sedation scores were established prior to anaesthesia induction with propofol intravenously at 4 mg/kg/min (fast) or 1 mg/kg/min (slow) to effect until orotracheal intubation was achieved without coughing. If coughing occurred, the intubation process was paused for 15 s. Four groups were determined: IM tramadol/propofol fast (GIMF, n = 6); IM tramadol/propofol slow (GIMS, n = 6); oral tramadol/propofol fast (GOF, n = 6); oral tramadol/propofol slow (GOS, n = 6). The Shapiro-Wilk test was used to evaluate for normality of residuals. Sedation scores and propofol anaesthetic induction doses were compared between GIMF and GIMS groups, and between GOF and GOS groups using the Mann-Whitney test and the t-test, respectively ( P = 0.05). The presence of hypotension (mean arterial blood pressure <60 mmHg) or apnoea (no breathing for 30 s or more) within the first 15 mins postintubation was recorded. Results The median sedation scores for GIMF and GOF were not significantly different compared with those for GIMS ( P = 0.94) and GOS ( P = 0.70). However, the mean ± SD propofol anaesthetic induction doses were higher in GIMF (9.1 ± 1.8 mg/kg) and GOF (7.9 ± 1.7 mg/kg) than in GIMS (5.1 ± 1.5 mg/kg; P <0.01) and GOS (5.4 ± 0.3 mg/kg; P <0.01). No hypotension or apnoea were detected. Conclusions and relevance Using the slower anaesthetic induction rate resulted in an increase in propofol relative potency.


In the shadow of Darwin: Anton de Bary's origin of myxomycetology and a molecular phylogeny of the plasmodial slime molds.
In his Origin of Species (John Murray, London, 1859), Charles Darwin described the theory of descent with modification by means of natural selection and postulated that all life may have evolved from one or a few simple kinds of organisms. However, Darwin's concept of evolutionary change is entirely based on observations of populations of animals and plants. He briefly mentioned 'lower algae', but ignored amoebae, bacteria and other micro-organisms. In 1859, Anton de Bary, the founder of mycology and plant pathology, published a seminal paper on the biology and taxonomy of the plasmodial slime molds (myxomycetes). These heterotrophic protists are known primarily as a large composite mass, the plasmodium, in which single nuclei are suspended in a common 'naked' cytoplasm that is surrounded by a plasma membrane. Here we summarize the contents of de Bary's 1859 publication and highlight the significance of this scientific classic with respect to the establishment of the kingdom Protoctista (protists such as amoebae), the development of the protoplasmic theory of the cell, the introduction of the concept of symbiosis and the rejection of the dogma of spontaneous generation. We describe the life cycle of the myxomycetes, present new observations on the myxamoebae and propose a higher-order phylogeny based on elongation factor-1 alpha gene sequences. Our results document the congruence between the morphology-based taxonomy of the myxomycetes and molecular data. In addition, we show that free-living amoebae, common protists in the soil, are among the closest living relatives of the myxomycetes and conclude that de Bary's 'Amoeba-hypothesis' on the evolutionary origin of the plasmodial slime molds may have been correct.


Dimer Interface of the Human Serotonin Transporter and Effect of the Membrane Composition.
The oligomeric state of membrane proteins has recently emerged in many cases as having an effect on their function. However, the intrinsic dynamics of their spatial organization in cells and model systems makes it challenging to characterize. Here we use molecular dynamics (MD) simulations at multiple resolutions to determine the dimer conformation of the human serotonin transporter (hSERT). From self-assembly simulations we predict dimer candidates and subsequently quantify their relative strength. We use umbrella sampling (US) replica exchange MD simulations for which we present extensive analysis of their efficiency and improved sampling compared to regular US MD simulations. The data shows that the most stable hSERT dimer interface is symmetrical and involves transmembrane helix 12 (TM12), similar to the crystal structure of the bacterial homologue LeuT, but with a slightly different orientation. We also describe the supramolecular organization of hSERT from a 250 μs self-assembly simulation. Finally, the effects of the presence of phosphatidylinositol bisphosphate or cholesterol in the membrane model has been quantified for the TM12-TM12 predicted interface. Collectively, the presented data bring new insight to the area of protein and lipid interplay in biological membranes.


Wrist bone mineral density utility in diagnosing hip osteoporosis in postmenopausal women.
Osteoporosis is a common bone disease that increases with age. Wrist bone mineral density (BMD) has significant correlation with other skeletal sites and it could be used as a diagnostic method for osteoporosis. The purpose of this study was to evaluate the role of wrist BMD in diagnosing osteoporosis in postmenopausal women. In this cross-sectional study, 99 postmenopausal women with mean age of 57 ± 6.9 (range 50-76) years were evaluated. BMD of nondominant wrist, lumbar spine (L2-L4) and femur bone using a dual-energy X-ray absorptiometry (DXA) device as well as lateral lumbosacral X-ray for degenerative joint disease (DJD) evaluation were measured. Mean T-score of wrist was lower than hip and lumbar area. Osteopenia and osteoporosis were observed in 40.4% and 59.6% in the wrist, 38.4% and 24.2% in the hip and 36.4% and 49.5% in lumbar-spine BMD measurements, respectively. There was positive correlation between wrist BMD with hip BMD (r = 0.468,p < 0.001) and lumbar BMD (r = 0.322, p = 0.001). DJD due to lumbosacral X-ray was reported in 84 cases (84.8%) including mild DJD in 45 (53.5%), moderate DJD in 33 (39.3%) and severe DJD in 6 (7.2%). Our results showed that wrist BMD has better accuracy than lumbar BMD in diagnosing osteoporosis in postmenopausal women.


Structural Basis of Mitochondrial Scaffolds by Prohibitin Complexes: Insight into a Role of the Coiled-Coil Region.
The coiled-coil motif mediates subunit oligomerization and scaffolding and underlies several fundamental biologic processes. Prohibitins (PHBs), mitochondrial inner membrane proteins involved in mitochondrial homeostasis and signal transduction, are predicted to have a coiled-coil motif, but their structural features are poorly understood. Here we solved the crystal structure of the heptad repeat (HR) region of PHB2 at 1.7-Å resolution, showing that it assembles into a dimeric, antiparallel coiled-coil with a unique negatively charged area essential for the PHB interactome in mitochondria. Disruption of the HR coiled-coil abolishes well-ordered PHB complexes and the mitochondrial tubular networks accompanying PHB-dependent signaling. Using a proximity-dependent biotin identification (BioID) technique in live cells, we mapped a number of mitochondrial intermembrane space proteins whose association with PHB2 relies on the HR coiled-coil region. Elucidation of the PHB complex structure in mitochondria provides insight into essential PHB interactomes required for mitochondrial dynamics as well as signal transduction.


Fractures in medieval Scotland.
The prevalence of fractures in medieval Scotland is assessed, particular attention being given to excavations of cemeteries beside three Carmelite cemeteries, at Aberdeen, Perth and Linlithgow, and another one at Whithorn Abbey. In the friaries the prevalence of fractures was 7.6% and in Whithorn it was 5.0%. These figures are comparable with an estimated prevalence of 7.2% for individuals between 0 and 65 years in present day Scotland. Males were more at risk of fractures than females, but a small group from both genders had been struck on the head by weapons. A study from a rural cemetery in England indicates that both male and female peasants had a much higher risk of fractures than their urban counterparts.


Biogeographical Regionalization of Wine Yeast Communities in Greece and Environmental Drivers of Species Distribution at a Local Scale.
Recent research has expanded our understanding on vineyard-associated fungal community assembly, suggesting non-random distribution and implicating regional differences in the wine terroir effect. Here, we focused on the culturable fraction of the fungal community that resides on grapes and determine wine quality, the so-called wine yeast populations. We aimed to analyze local-scale yeast community assemblages and to test whether the hypothesis of biogeographical patterns also applies to wine yeasts in particular. Surveying 34 vineyards across four main viticultural zones in Greece showed significant trends in vineyard-specific patterns. At a local scale, viticultural regions were also linked to distinct yeast community compositions. Importantly, major yeast populations directly related to wine fermentation contributed significantly to the delimitation of regions, highlighting their potential influence on the regionality of wine characteristics. In terms of the microbial terroir influence, yeast communities within an area were temporarily stable, which is critical for the regional character of the wine. Community structure could be explained only partially by environmental features. Maximum temperature, elevation, and net precipitation were the highest correlated variables with the yeast community biogeographic patterns. Finally, we also showed that certain environmental factors may drive the population size of specific yeast populations. The present results indicate that the wine yeast community has a geographical character at local scale, which is an important feature of the microbial terroir concept and thus for the wine industry.


Magnetic cell separation using antibody binding with protein a expressed on bacterial magnetic particles.
Bacterial magnetic particles (BacMPs) are efficient platforms of proteins for surface display systems. In this study, mononuclear cells from peripheral blood were separated using BacMPs expressing protein A on the BacMP membrane surface (protein A-BacMPs), which were complexed with the Fc fragment of anti-mouse IgG antibody. The procedure of positive selection involves incubation of mononuclear cells and mouse monoclonal antibodies against different cell surface antigens (CD8, CD14, CD19, CD20) prior to treatment with protein A-BacMP binding with rabbit anti-mouse IgG secondary antibodies. Flow cytometric analysis showed that approximately 97.5 +/- 1.7% of CD19(+) and CD20(+) cells were involved in the positive fraction after magnetic separation. The ratio of the negative cells in the negative fraction was approximately 97.6 +/-1.4%. This indicates that CD19(+) and CD20(+) cells can be efficiently separated from mononuclear cells. Stem cell marker (CD34) positive cells were also separated using protein A-BacMP binding with antibody. May-Grunwald Giemsa stain showed a high nuclear/cytoplasm ratio, which indicates a typical staining pattern of stem cells. The separated cells had the capability of colony formation as hematopoietic stem cells. Furthermore, the inhibitory effect of magnetic cell separation on CD14(+) cells was evaluated by measurement of cytokine in the culture supernatant by ELISA when the cells were cultured with or without lipopolysaccharide (LPS). The induction of IL1-beta, TNFalpha, and IL6 was observed in the presence of 1 ng/mL LPS in all fractions. On the other hand, in the absence of LPS, BacMPs had little immunopotentiation to CD14(+) cells as well as that of artificial magnetic particles, although TNFalpha and IL6 were slightly induced in the absence of LPS in the positive fraction.


Significance of CD44v6 expression in gynecologic malignancies.
Variants of CD44 have been proposed to be important in cancer invasion and metastasis. The purpose of this study was to evaluate the diagnostic and prognostic value of CD44v6 expression in gynecologic malignancies. Immunohistochemistry was used to determine the expression of CD44v6 in samples from a series of 65 cases of early cervical cancer, 76 cases of endometrial samples and 57 cases of serous epithelial ovarian tumors. We analyzed the expression of CD44v6 and correlated the findings with clinicopathological factors. In the cervical series, CD44v6 was detected in 60 cases of cervical cancer (92.3%). The immunoreactivity was decreased when stromal invasion reached a depth of more than 5 mm (P < 0.05). However, it was not correlated with other clinicopathological factors. In the endometrial series, CD44v6 was detected in one endometrial hyperplasia (6.7%) and in 24 endometrial cancers (100%), while it was not detected in the proliferative endometrium (P < 0.05). Immunoreactivity was decreased in grade 2 and 3 endometrial cancers compared with grade 1 (P < 0.05). In the ovarian series, CD44v6 was not detected in the benign tumors, but it was detected in four borderline malignancies (27%) and 12 carcinomas (40%). Immunoreactivity was not correlated with clinicopathological factors of ovarian cancer. CD44v6 may be involved in stromal invasion of early squamous cervical carcinomas and in the cellular differentiation of endometrial cancer. In addition, it may be useful for early diagnosis of endometrial cancer.


A comparative analysis of biomass and clean fuel exposure on pulmonary function during cooking among rural women in Tamilnadu, India.
It is of interest to document data on the comparative analysis of biomass and clean fuel exposure on pulmonary function during cooking among rural women. The study consisted of 100 biomass and 100 LPG fuel using women with no smoking habits and other related illness Parameters such as FVC, FEV1, FEV1/FVC, PEFR, FEF25-75%were obtained using the computerized spirometry to assess the pulmonary function in these subjects. The collected data were analyzed using the Student t-test method and Pearson correlation. The exposure index for biomass fuel users is 69.78±27.25 showing high exposure duration during cooking. The parameters for pulmonary functions significantly declined in FVC (42.34±13.6), FEV1 (45.55±15.98), PEFR (34.11±14.78) and FEF25-75% (45.56±23.00) for biomass fuel user. However, this is not true for FEV1/FVC ratio (107.56±16.9). The increase in PFT suggests the restrictive and obstructive patterns of pulmonary diseases. There was a negative correlation between increased duration of cooking and the value of FEV1/FVC (r = -0.2961), FEF25-75% (r = -0.3519) and PEFR (r = -0.2868). Thus, the deformation of pulmonary function due to extended exposure of biomass fuel for cooking women in rural Tamilnadu is shown using parameter features such as high exposure index, overcrowded area and improper ventilated houses.


Adult tethered cord syndrome: relative to spinal cord length and filum thickness.
The adults with tethered cord syndrome (TCS) are divided into two groups: group-1 adult TCS patients with spinal dysraphism; and group-2 patients without dysraphism who develop signs and symptoms in adulthood. A significant number of group-2 patients failed to show elongation of the spinal cord and abnormally thick filum terminale. This paper reports the combinations of the location of the caudal end of the spinal cord and the thickness of the filum terminale in 104 patients with group-2 adult TCS. The caudal end of the spinal cord was found at the L2-3 intervertebral space or above in 37 patients (35.6%) and below L2-3 level in 67 patients (64.4%). The diameter of the filum was <2 mm in 60 patients (57.7%) and > or =2 mm in 44 patients (42.3%). These data clearly indicate that the pre-operative diagnosis of adult TCS must rely primarily on the neurological symptomatology and the specific imaging feature, posterior displacement of the conus and filum that attach the posterior arachnid membrane.


[Consequences of the ambivalence about openness and transparency].
Personnel at the general intensive care unit at the University of Heidelberg Children's Hospital aim for a maximum of openness and transparency for parents regarding everything relevant to their own child. In this context ward nurses were interviewed about diverse aspects of their work. Aside from technical-medical activities, nurses regarded the relationship to the parents to be a central point in their work. The recognize that the relationship to the parents influences the relationship to the child and partially even the nursing of the child. Nurses are in favor of openness and transparency in relating to parents, however, reality reveals contradictions. Nurses differentiated attitude and the consequences for physicians, psychologists and parents are discussed. A case example is presented.


Human herpes virus 8-unrelated primary effusion lymphoma-like lymphoma presenting with cardiac tamponade: A case report.
Primary effusion lymphoma (PEL) is a rare disease of lymphomatous effusion in the body cavities in the absence of detectable mass and lymphadenopathy. PEL is predominantly related to the immunosuppressed patients infected with human herpes virus 8 (HHV-8). PEL-like lymphoma is negative for HHV-8 and human immunodeficiency virus (HIV) unlike PEL. The pathogenesis and prognosis of PEL-like lymphoma are unclear and there is no established treatment yet. A 73-year-old male patient was admitted for evaluation of dyspnea on exertion with 1-week duration. His relevant examinations were completed. PEL-like lymphoma was diagnosed. The patient received chemotherapy including rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP), and palliative whole-brain radiotherapy, sequentially. He died 3 months after the diagnosis. Although the prognosis of PEL-like lymphoma may be better than PEL, our case showed poor disease course despite chemotherapy.


Health-Promoting Home and Workplace Neighborhoods: Associations With Multiple Facets of Men's Health.
Despite the importance of healthy settings for health promotion, little is known about how neighborhood characteristics affect men's health. The present study aims to explore the associations between perceptions of home and workplace neighborhoods with diverse health outcomes, and to examine mediating mechanisms. A sample of 669 men members of labor unions in Quebec, Canada, completed a questionnaire assessing social and physical aspects of their work and home neighborhoods (the Health-Promoting Neighborhood Questionnaire) as well as subjective and objective health outcomes (perceived health, positive mental health, body mass index) and potential mediators (health behaviors, self-efficacy). Structural equation modeling (path analysis) revealed that the Health-Promoting Neighborhood Questionnaire was associated with all three health outcomes, either directly or indirectly through health behaviors and self-efficacy. Both home and workplace neighborhoods were associated with men's health, home neighborhood being more strongly associated. The findings suggest that physical and social aspects of neighborhood might contribute to men's health. The study highlights positive environmental levers for urban planners, policy makers, and health professionals to promote men's health.


A non-hepatotropic parasite infection increases mortality in the acetaminophen-induced acute liver failure murine model: possible roles for IL-5 and IL-6.
We evaluated the effects of a non-hepatotropic parasite infection (Taenia crassiceps) on the outcome of acetaminophen-induced acute liver failure in mice. Uninfected and T. crassiceps infected mice orally received either 300 mg/kg acetaminophen or water as vehicle (n = 5 per group). Survival analysis, hepatocyte necrosis, alanine aminotransferase (ALT) levels, CYP2E1 protein, interleukin (IL-) 5, and IL-6 were assessed for all groups. All infected mice died within 16 h after exposure to acetaminophen (Tc+APAP group), whereas only one-third of uninfected animals exposed to acetaminophen (APAP group) died. Uninfected (Control group) and infected (Tc group) mice that received the vehicle showed no liver damage. Tc+APAP mice exhibited massive liver necrosis characterised by marked balloning degeneration of hepatocytes and higher serum ALT compared to Control, Tc, and APAP animals. Liver tissue from Tc+APAP mice also displayed increased expression of CYP2E1 protein and higher mRNA and protein levels of IL-5 and IL-6 compared to the other groups. These findings suggest that non-hepatotropic parasite infections may increase mortality following acute liver failure by promoting hepatocyte necrosis via IL-5 and IL-6-dependent CYP2E1 overproduction. This study identifies new potential risk factors associated with severe acute liver failure in patients.


Nuclear magnetic resonance relaxation times and plasmalemma water exchange in ivy bark.
Measurement of nuclear magnetic resonance (NMR) relaxation times (transverse [T(2)] and longitudinal [T(1)]) for Hedera helix L. cv. Thorndale (ivy) bark water indicates the presence of at least two populations of water with different relaxation characteristics. One population of water with short T(2) and T(1) was found to be composed of both hydration water and extracellular free water. The second population of water with long T(2) and T(1) was identified as intracellular bulk water.NMR relaxation of extracellular water protons is controlled by cell wall surface effects, possibly due to binding of paramagnetic cations by the cell walls. NMR relaxation of intracellular water protons is controlled by both water exchange to the extracellular environment and chemical exchange with a population of protons that is chemically shifted from that of the bulk water. The relaxation time of intracellular water is not measurably affected, either by intracellular paramagnetic ions or by increased viscosity of intracellular water. Manganese flux into the cells occurs at 1.7 x 10(-15) moles cm(-2) seconds(-1) and is independent of extracellular Mn(2+) concentration in the range 5 to 20 mm.The intracellular-extracellular water exchange time of ivy bark was found to be predominantly limited by membrane water permeability. A diffusional water permeability coefficient (P(d)) of approximately 3 x 10(-2) cm seconds(-1) was calculated for ivy cell membranes at 20 C.


Corticotropin-releasing factor-binding protein is produced by human placenta and intrauterine tissues.
CRF circulates in high concentration in pregnant woman. It is produced by the placenta and the other intrauterine tissues (maternal decidua, amnion, and chorion). Recently, a CRF-binding protein (CRF-BP) has been identified and cloned. It binds the circulating CRF, reducing its biological action during pregnancy. Liver is the major source of CRF-BP. The aim of the present study was to evaluate whether human placenta and intrauterine tissues produce CRF-BP. The localization of mRNA and immune CRF-BP by in situ hybridization and immunohistochemistry, respectively, was performed. Antisense and sense riboprobes synthesized from a fragment of human CRF-BP cRNA and a specific rabbit anti-hCRF-BP serum was used. The syncytial layer of placental villi at term intensely expressed CRF-BP mRNA and immunoreactivity, whereas rare positively hybridized cells were observed within the cytotrophoblasts and mesenchymal cells. Large decidual cells, amniotic epithelial cells, and chorionic cytotrophoblast stained positively for CRF-BP mRNA and protein. Control sections collected from the same tissues failed to show any positive localization of sense strand cRNA probe and antiserum preadsorbed with immunogen. Finally, the addition of recombinant CRF-BP to human cultured placental cells significantly decreased CRF-induced ACTH release, with a dose-dependent effect. The present data show that local production of CRF-BP occurs in human trophoblast and intrauterine tissues and may represent one of the major mechanisms used by targets tissues to control CRF activity during pregnancy.


Black soldier fly larvae effectively degrade lincomycin from pharmaceutical industry wastes.
Lincomycin fermentation residues (LFR) are the byproducts from the pharmaceutical industry, and contain high concentrations of antibiotics that could pose a threat to the environment. Here, we report that black soldier fly larvae (BSFL) and associated microbiota can effectively degrade LFR and accelerate the degradation of lincomycin in LFR. The degradation rate of lincomycin in LFR can reach 84.9% after 12 days of BSFL-mediated bioconversion, which is 3-fold greater than that accomplished with natural composting. The rapid degradation was partially carried out by the BSFL-associated microbiota, contributing 22.0% of the degradation in the final composts. Based on microbiome analysis, we found that the structure of microbiota from both BSFL guts and BSFL composts changed significantly during the bioconversion, and that several bacterial genera were correlated with lincomycin degradation. The roles of the associated microbiota in the degradation were further verified by the ability of two larval intestinal bacterial isolates and one bacterial isolate from BSFL composts to lincomycin degradation. The synergy between BSFL and the isolated strains resulted in a 2-fold increase in degradation compared to that achieved by microbial degradation alone. Furthermore, we determined that the degradation was correlated with the induction of several antibiotic resistant genes (ARGs) associated with lincomycin degradation in larval guts and BSFL composts. Moreover, the environmental conditions in the BSFL composts were found to be conducive to the degradation. In conclusion, these findings demonstrate that the BSFL-mediated bioconversion of LFR could effectively reduce residual lincomycin and that the associated microbiota play crucial roles in the process.


Psychologic distress and QOL in medical staff after a disaster: A longitudinal 4-year study.
Aiming to improve post-disaster care of medical staff, we conducted an early and ongoing assessment of post-disaster psychologic distress and quality of life (QOL) in one center of a disaster-response hospital. Twelve days after the Great East Japan Earthquake, as the Fukushima Daiichi Nuclear Power Plant crisis was unfolding, we began a survey to examine the physical and mental state of medical staff to assess their motivation toward work. Surveys were administered in March 2011 (Survey 1), March 2012 (Survey 2), March 2013 (Survey 3), March 2014 (Survey 4), and March 2015 (Survey 5). Participants completed the Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), EuroQol (EQ-5D), and MOS Short-Form 36-item Health Survey (SF-36). Although BDI scores significantly improved over time following Survey 1, participants in their 30s had significantly higher Survey 2 scores than those in their 40s/50s, and significantly higher Survey 3 scores than those in their 20s. STAI scores significantly improved over time following Survey 1. However, participants in their 30s had significantly higher Survey 3 scores than those in their 20s. EQ-5D scores did not significantly vary among survey time points or age groups. SF-36 physical functioning, role physical, social functioning, role emotional, and mental health subscale scores significantly improved over time. In conclusion, post-disaster longitudinal changes, including recovery period, differed among age groups. Thus, age should be taken into account in longitudinal evaluations of psychologic distress and QOL in medical staff after a disaster and, as more recent events suggest, during a pandemic.


Evaluation of complicated migraine in childhood.
We report on 3 patients with complicated migraine of childhood. Family history was positive for migraine in each case, and all experienced the acute onset pf neurologic deficits in associated with throbbing hemicranium. Abnormalities of cerebral blood flow determinations, electroencephalograms and cerebral arteriograms in addition to persistent neurologic sequelae were demonstrated. We propose that complicated migraine of childhood is not an entirely benign symptom complex.


Plumeria rubra L.- A review on its ethnopharmacological, morphological, phytochemical, pharmacological and toxicological studies.
Plumeria rubra L. (Apocynaceae) is a deciduous, commonly ornamental, tropical plant grown in home premises, parks, gardens, graveyards, because of its beautiful and attractive flowers of various colours and size. The different parts of the plant are used traditionally to treat various diseases and conditions like leprosy, inflammation, diabetic mellitus, ulcers, wounds, itching, acne, toothache, earache, tongue cleaning, pain, asthma, constipation and antifertility. The main aim of this review is to provide an overview and critically analyze the reported ethnomedical uses, phytochemistry, pharmacological activities and toxicological studies of P. rubra and to identify the remaining gaps and thus supply a basis for further investigations. The review also focuses towards drawing attention of people and researchers about the wide spread pharmaceutical properties of the plant for its better utilization in the coming future. All the relevant data and information on P. rubra was gathered using various databases such as PubMed, Springer, Taylor and Francis imprints, NCBI (National Center for Biotechnology Information), Science direct, Google scholar, Chemspider, SciFinder, research and review articles from peer-reviewed journals and unpublished data such as Phd thesis, etc. Some other 'grey literature' sources such as webpages, ethnobotanical books, chapters, wikipedia were also studied. More than 110 chemical constituents have been isolated from P. rubra including iridoids, terpenoids, flavonoids and flavonoid glycosides, alkaloids, glycosides, fatty acid esters, carbohydrates, animo acids, lignan, coumarin, volatile oils, etc. The important chemical constituents responsible for pharmacological activities of the plant are fulvoplumierin, plumieride, rubrinol, lupeol, oleanolic acid, stigmasterol, taraxasteryl acetate, plumieride-p-E-coumarate, rubranonoside, rubrajalellol, plumericin, isoplumericin, etc. The plant possess a wide range of pharmacological activities present namely antibacterial, antiviral, anti-inflammatory, antipyretic, antidiabetic, hepatoprotective, anticancer, anthelmintic, antifertility and many other activities. P. rubra is a valuable medicinal source and further study in this topic can validate the traditional and ethnobotanical use of the plant. However, many aspects of the plant have not been studied yet. The pharmacological activity of active chemical constituent isolated from the plant is proven only for a couple of activities hence, lack of bio-guided isolation strategies is observed. Further studies on bioavailability, pharmacokinetics, mechanism of action and structural activity relationship studies of isolated pure compounds will contribute more in understanding their pharmacological effects. Higher doses of plant extracts are administered to experimental animals, therefore their toxicity and side effects in humans are needed to be thoroughly studied, although no side effect or toxicity is seen or observed in experimental animals. Studies are also essential to investigate the long term in vivo toxicity and clinical efficacy of the plant.


Rorschach findings for patients with pseudoseizures.
This study used the Rorschach test to investigate the possible differences between a carefully selected group of 16 patients with pseudoseizures, defined as spontaneous behavior resembling partial complex epilepsy and with or without tonic clonic generalization, and a group of 12 epileptic patients with partial complex seizures. Analysis of the structural data of protocols does not support a significant difference in the Rorschach findings between the two groups.


Neuroscience-informed computer-assisted cognitive training in schizophrenia.
Schizophrenia is a heterogeneous psychiatric syndrome characterized by psychosis. It is also a neurodevelopmental disorder. In the earliest phases of the illness, at-risk individuals exhibit subtle, nonspecific symptoms, including cognitive dysfunction and progressive brain volumetric loss. Generally, schizophrenia is characterized by abnormal/inefficient neural system operations and neural oscillatory activity, as well as functional disconnectivity across frontal-temporo parietal and frontal-subcortical networks; it thus may best be described as a widespread neural oscillatory connectomopathy. Despite earlier views of schizophrenia as an inevitably progressive neurodegenerative disease, emerging evidence indicates that endogenous neuroplastic capacity is retained. An active area of research is directed at understanding how best to harness this learning-induced neuroplasticity to enhance neural system functioning, improve cognition, and prevent-and possibly even reverse-disease progression. In this review, we present an overview of results from the most widely used computer-assisted cognitive-training programs in schizophrenia, contrasting a broad neuropsychological rehabilitation approach with a targeted cognitive-training approach. We then review studies on the neurobiological effects of these two training methods. Finally, we discuss future directions with a focus on the "oscillatory connectome" as a key area of investigation for developing the most precise and scientifically informed treatment approaches for this illness.


Validity and reliability of the St George's Respiratory Questionnaire after adaptation to a different language and culture: the Spanish example.
We describe the adaptation into Spanish of the St George's Respiratory Questionnaire (SGRQ), a self-administered questionnaire developed by Jones et al. (1991) covering three domains of health in airways disease patients: symptoms, activity and impacts. For the adaptation, the forward and back-translation method by bilinguals was used, together with professional committee and lay panel. Once tested for feasibility and comprehension, 318 male chronic obstructive pulmonary disease (COPD) patients with a wide range of disease severity completed the Spanish version of the SGRQ. The clinical status of the patients was evaluated concurrently with the measurement of health status. Lung function was assessed in the 2 months before or after the questionnaire administration. The Spanish version of the SGRQ was acceptable and easy to understand. Cronbach's alpha reliability coefficient was 0.94 for the overall scale and 0.72 for "Symptoms", 0.89 for "Activity", and 0.89 for "Impacts" subscales. Correlation coefficients between the overall score and dyspnoea and % forced expiratory volume in one second (FEV1) were 0.59 and -0.45, respectively, and these correlations were higher than those observed between the clinical variables and the Nottingham Health Profile, a generic measure of health-related quality of life. Results of the study suggest that the Spanish version of the SGRQ is conceptually equivalent to the original, and similarly reliable and valid. Although further studies should complete the adaptation work, results suggest that the SGRQ may already be used in Spain and in international studies involving Spanish respiratory patients. According to the present approach, it appears to be feasible to adapt a specific questionnaire on health-related quality of life in respiratory disease to another language and culture.


Thymic Egress Is Regulated by T Cell-Derived LTβR Signal and via Distinct Thymic Portal Endothelial Cells.
Thymic blood vessels at the perivascular space (PVS) are the critical site for both homing of hematopoietic progenitor cells (HPCs) and egress of mature thymocytes. It has been intriguing how different opposite migrations can happen in the same place. A subset of specialized thymic portal endothelial cells (TPECs) associated with PVS has been identified to function as the entry site for HPCs. However, the cellular basis and mechanism underlying egress of mature thymocytes has not been well defined. In this study, using various conventional and conditional gene-deficient mouse models, we first confirmed the role of endothelial lymphotoxin beta receptor (LTβR) for thymic egress and ruled out the role of LTβR from epithelial cells or dendritic cells. In addition, we found that T cell-derived ligands lymphotoxin (LT) and LIGHT are required for thymic egress, suggesting a crosstalk between T cells and endothelial cells (ECs) for thymic egress control. Furthermore, immunofluorescence staining analysis interestingly showed that TPECs are also the exit site for mature thymocytes. Single-cell transcriptomic analysis of thymic endothelial cells suggested that TPECs are heterogeneous and can be further divided into two subsets depending on BST-1 expression level. Importantly, BST-1hi population is associated with thymic egressing thymocytes while BST-1lo/- population is associated with HPC settling. Thus, we have defined a LT/LIGHT-LTβR signaling-mediated cellular crosstalk regulating thymic egress and uncovered distinct subsets of TPECs controlling thymic homing and egress, respectively.


Ultrastructural Comparison of Cyanidium caldarium Wild Type and III-C Mutant Lacking Phycobilisomes.
Cyanidium caldarium wild type and III-C mutant lacking phycobilisomes were compared with respect to the ultrastructural organization of particles on the freeze-fractured thylakoid membrane.In the wild type, the particles on the exoplasmic fracture face were arranged in the same manner as that reported for the phycobilisomes on the membrane surface. The phycobilisomes constitute the major part of the photosystem II antenna and their absence in the III-C mutant was accompanied by a completely different arrangement of the particles on the exoplasmic fracture face.The density of these particles was almost two times higher in the mutant than in the wild type while that of the particles on the protoplasmic fracture face was about the same.The relative densities of the particles on the exoplasmic fracture face in the two organisms was consistent with the 2-fold higher photosystem II to photosystem I ratio in the mutant compared to the wild type as determined by measurements of the field indicating absorbance changes.These particles were 100 Angstroms in both organisms.It is concluded that the particles on the exoplasmic fracture face in Cyanidium are probably substructural units of the particles observed on the same surface in higher plants and green algae and attributed to photosystem II.


Gene-specific response of dynamic ventricular repolarization to sympathetic stimulation in LQT1, LQT2 and LQT3 forms of congenital long QT syndrome.
Differences in the sensitivity of the genotype of the congenital long QT syndrome to sympathetic stimulation have been suggested. This study compared the influence of sympathetic stimulation on continuous corrected QT (QTc) intervals between LQT1, LQT2 and LQT3 forms of the congenital long QT syndrome. We recorded a 12-lead electrocardiogram continuously before and after bolus injection (0.1 microg x kg(-1)) of epinephrine followed by continuous infusion (0.1 microg x kg(-1) min(-1)) in 12 LQT1, 10 LQT2, 6 LQT3, and 13 control patients. The QT intervals and previous RR intervals of all beats were measured semi-automatically, and the QTc intervals of all beats were calculated by Bazett's method. The dynamic response of the RR interval to epinephrine was no different between the four groups. The QTc was prolonged remarkably (477+/-42 to 631+/- 59 ms; P<0.0005, % delta prolongation =+32%) as the RR was maximally decreased (at peak of epinephrine), and remained prolonged at steady state conditions of epinephrine (556+/-56 ms; P<0.0005 vs baseline, +17%) in LQT1 patients. Epinephrine also prolonged the QTc dramatically (502+/-23 to 620+/-39 ms; P<0.0005, +24%) at peak of epinephrine in LQT2 patients, but this shortened to baseline levels at steady state (531+/-25 ms; P=ns vs baseline, +6%). The QTc was much less prolonged at peak of epinephrine in LQT3 (478+/-44 to 532+/-41 ms; P<0.05, +11%) and controls (394+/-21 to 456+/-18 ms; P<0.0005, +16%) than in LQT1 and LQT2 patients, and shortened to the baseline levels (LQT3; 466+/-49 ms, -3%, controls; 397+/-16 ms, +1%; P=ns vs baseline) at steady state. Our data suggest that the dynamic response of ventricular repolarization to sympathetic stimulation differs between LQT1, LQT2 and LQT3 syndromes, and may explain why the trigger of cardiac events differs between the genotypes.