Critical revision of the medical treatment of gout in Brazil.
Gout is considered the most common form of inflammatory arthritis in men over 40 years. The authors present a brief review of the current treatment of gout and discuss the existing pharmacological limitations in Brazil for the treatment of this disease. Although allopurinol is still the main drug administered for decreasing serum levels of uric acid in gout patients in this country, the authors also present data that show a great opportunity for the Brazilian drug market for the treatment of hyperuricemia and gout and especially for patients using private and public (SUS) health care systems.


Head and neck tumor sites differ in prevalence and spectrum of p53 alterations but these have limited prognostic value.
The tumor site is a strong clinical factor in head and neck squamous cell carcinoma (HNSCC). To clarify the biologic and clinical role of p53 alterations in HNSCC, we have examined the prevalence and the nature of p53 alterations in a large cohort of tumors from the different sites. For immunohistochemical analysis of p53 protein expression, we introduced tyramide signal amplification immunohistochemistry (TSA-IHC) on a tissue microarray. This allowed the discrimination between normal low-level expression and reduced or lost expression. Two hundred fifty-three tumors were subjected to mutational analysis by genomic DNA sequencing, employing also the p53 GeneChip from Affymetrix. The prevalence of all p53 alterations, i.e., mutations, overexpression and loss of expression, was significantly higher in hypopharyngeal tumors than in the other sites (p = 0.001). Laryngeal tumors showed the lowest rate of p53 alterations, but revealed a distinct mutation spectrum: most mutations affected exon 5 (p = 0.013) and the S2' domain (p = 0.002), and most hot-spot 248 mutations occurred in the larynx (p < 0.001). Sequencing by p53GeneChip technology was shown to be only insignificantly more sensitive than dideoxy sequencing. In agreement with p53 mutations occurring prior to invasiveness, their prevalence did not increase with tumor stage, and all mutation classes lacked prognostic significance. The large patient cohort of this study showed that p53 is differentially affected in the different tumor sites of the head and neck, but its mode of inactivation does not play a major role in tumor progression.


Assessing the clinical utility of major indices for nonalcoholic fatty liver disease in East Asian populations.
Nonalcoholic fatty liver disease (NAFLD) is currently the most common form of chronic liver disease. The growing prevalence of NAFLD is strongly associated with the high incidence of metabolic syndrome. NAFLD affects as much as 19% of the US population with a disproportionate impact on minority racial groups such as Asian Americans. If not promptly managed, NAFLD may progress to more feared complications. Liver indices for NAFLD screening have been proposed but were often developed using study populations with different anthropometrics than patients of East Asian descent. This review compares the accuracy of five indices for NAFLD screening in Asian cohorts. The Fatty Liver Index performed well in multiple large-scale community studies, although other indices may be more suited for specific patient cohorts. This is important, as the utilization of liver indices could accelerate screening for NAFLD for early management and to reduce liver disease-related health disparities among Asian Americans.


Comparison of SYNTAX and Gensini Scores in the Decision of Surgery or Percutaneous Revascularization in Patients With Multivessel Coronary Artery Disease.
Many scoring systems have been developed to determine the extent of coronary artery disease (CAD) in patients with multi-vessel disease. The most widely used of these are Synergy between percutaneous coronary intervention with Taxus and cardiac surgery (SYNTAX) and Gensini scoring. Gensini scoring system can successfully show coronary plaque burden. In our study, we aimed to test the predictive power of SYNTAX and Gensini scores for surgical or percutaneous intervention decisions made by the cardiac team in patients with three-vessel disease. A total of 476 patients without ST-elevation myocardial infarction with the three-vessel disease were included in the study. SYNTAX and Gensini scores of the patients were calculated from their coronary angiographies. Receiver operating characteristic curve (ROC-curve) analysis was performed using both scores. Both the SYNTAX score and Gensini score were able to predict heart team decisions (AUC: 0.759, 0.680; p<0.001). Diabetes and smoking were more common in patients who were decided to have surgery (p<0.001). In the light of our study results, the decisions to be made with the SYNTAX score will be closer to the decisions of the heart team than the Gensini score.


Nonculprit plaques in patients with acute coronary syndromes have more vulnerable features compared with those with non-acute coronary syndromes: a 3-vessel optical coherence tomography study.
Patients with acute coronary syndrome (ACS) have a higher incidence of recurrent ischemic events. The aim of this study was to compare the plaque characteristics of nonculprit lesions between ACS and non-ACS patients using optical coherence tomography (OCT) imaging. Patients who had 3-vessel OCT imaging were selected from the Massachusetts General Hospital (MGH) OCT Registry. MGH registry is a multicenter registry of patients undergoing OCT. The prevalence and characteristics of nonculprit plaques were compared between ACS and non-ACS patients. A total of 248 nonculprit plaques were found in 104 patients: 45 plaques in 17 ACS patients and 203 plaques in 87 non-ACS patients. Compared with plaques of non-ACS patients, plaques of ACS patients had a wider lipid arc (147.3 ± 29.5° versus 116.2 ± 33.7°, P<0.001), a longer lipid length (10.7 ± 5.9 mm versus 7.0 ± 3.7 mm, P=0.002), a larger lipid volume index [averaged lipid arc×lipid length] (1605.5 ± 1013.1 versus 853.4 ± 570.8, P<0.001), and a thinner fibrous cap (70.2 ± 20.2 µm versus 103.3 ± 46.8 µm, P<0.001). Moreover, thin-cap fibroatheroma (64.7% versus 14.9%, P<0.001), macrophage (82.4% versus 37.9%, P=0.001), and thrombus (29.4% versus 1.1%, P<0.001) were more frequent in ACS patients. Although the prevalence of microchannel did not differ between the groups, the closest distance from the lumen to microchannel was shorter in ACS subjects than in non-ACS (104.6 ± 67.0 µm versus 198.3 ± 133.0 µm, P=0.027). Nonculprit lesions in patients with ACS have more vulnerable plaque characteristics compared with those with non-ACS. Neovascularization was more frequently located close to the lumen in patients with ACS.


Phase I/II study of G3139 (Bcl-2 antisense oligonucleotide) in combination with doxorubicin and docetaxel in breast cancer.
Preclinical data showed enhancement of breast cancer cell death when G3139 was combined with anthracyclines and taxanes. We evaluated the efficacy and safety of a Bcl-2 antisense oligonucleotide, G3139, in combination with doxorubicin (A) and docetaxel (T) in patients with locally advanced breast cancer (LABC). Following a brief phase I to determine the phase II dose, patients with locally advanced breast cancer received G3139 administered by continuous i.v. infusion for 5 to 7 days with bolus A (50 mg/m2) and T (75 mg/m2) administered on either day 3 or 6 of therapy with G3139. Cycles were repeated every 21 days x 6 in the neoadjuvant setting. Serial plasma samples were obtained for pharmacokinetic analysis. Tissue samples were obtained before and after therapy for pharmacodynamic analysis of Bcl-2 expression. Thirty patients (median age, 49 years; range, 24-71 years) received 160 cycles. During the phase I portion of the trial, the dose of G3139 was escalated from 3 to 7 mg/kg/d (i.v. for 5 days) in combination with AT. During the phase II portion of the trial, several doses and schedules of G3139 were evaluated. There were no pathologic complete responses. Pharmacodynamic studies showed limited Bcl-2 down-regulation in the primary tumors. G3139 in combination with doxorubicin and docetaxel is well tolerated. No pathologic complete response was seen and pharmacodynamic studies showed very little down-regulation of Bcl-2 in primary tumors, perhaps related to issues with insufficient drug delivery to the intact tumor.


The standardization of vaccines: a discussion.
Many changes have been made in the World Health Organization's (WHO) requirements for the production and control of both the killed and live (oral) poliovirus vaccines since their initial formulations in 1959 and 1962, respectively. The major changes in the production of killed vaccine concern the cell substrates used from primary tissue to passaged primary tissue or even a continuous cell line such as Vero. It has been shown also that there is no longer the necessity to test for residual infectious virus by the inoculation of monkeys, since cell cultures are much more sensitive for this purpose. For the live vaccine, a more uniform test for the titration of virus content has been introduced. Furthermore, international agreement on the details of the test for neurovirulence in monkeys has been reached. The expression of the immunogen of poliovirus in eukaryotic cells has been achieved, but whether it becomes a commercial proposition replacing one or both of our present vaccines remains to be seen.


[Effects of hepatitis B virus X gene on p21(WAF1) expression through p53-dependent and p53-independent pathways].
It was reported that the hepatitis B virus X could inhibit the function of p53 and have contrary effects on p21(WAF1), a downstream gene of p53, but the mechanism is not clear up to now. So this study was designed to investigate HBx's effect on p21(WAF1) gene. After co-transfection of sense or antisense wild type p53 gene (wtp53) with HBx into SMMC-7721 and HBx alone transfection into other hepatoma cell lines with different endogenous status of p53, we evaluated the luciferase expression level under the p21(WAF1) promoter by detecting the luciferase activity and alteration of cell cycle in these transfected cell lines by flow cytometry. Expressions of p53 and p21 (WAF1) in hepatoma cells after transfected with HBx were also estimated by Western blot analysis. The luciferase activity (1.007+/-0.098) in SMMC-7721 cells cotransfected with HBx and sense-wtp53 was higher than that in cells with wtp53 gene alone (0.490+/-0.012, P< 0.05), and also was depressed in the other experimental groups transfected with HBx (P< 0.05). Western blot analysis showed that after transfected with HBx, p53 expression was elevated in all hepatoma cell lines with different endogenous status of p53, and the expression of p21(WAF1) and luciferase activity under the p21(WAF1) promoter (0.053+/-0.010 vs. 0.094+/-0.013, P< 0.05) were both decreased in SMMC-7721 cells with low expression of p53, but relatively increased in HepG2 cell line with high expression of p53 (1.252+/-0.052 vs. 0.767+/-0.031, P< 0.05). Flow cytometry showed that fewer SMMC-7721 (42.31%) and Hep3B (36.96%) cells were arrested in G(0)/G(1) phase in transiently transfected HBx groups than in the control groups (47.10% and 42.90%), which was the opposite case in HepG2 cell line (63.62% vs. 57.42%). Moreover, after stably transfected with pcDNA3HBx, HepG2 cells reduced in G(0)/G(1) phase in compared with the control group (57.31% vs 61.49%). HBx may not only increase the expression of p21(WAF1) by introducing the accumulation of p53 in cytoplasm but also inhibit the transcriptional activity of p21(WAF1) promoter in a p53-independent manner.


Identifications of inhibitors of IgE production by human lymphocytes isolated from 'Cha Chuukanbohon Nou 6' tea leaves.
Tea (Camellia sinensis L.) is consumed all over the world and in especially large quantities in Japan and China, where it has been used not only as a daily beverage but also for medicinal purposes for thousands of years. Tea has been found to exhibit various bioregulatory activities, including antiallergic, anticarcinogenic, antimetastatic, antioxidative, antihypertensive, antihypercholesterolemic, anti-dental caries and antibacterial effects, and to influence intestinal flora. Cha Chuukanbohon Nou 6 is a tea cultivar improved by the National Institute of Vegetable and Tea Science (NIVTS) in Japan. On comparing chemical constituents of 11 varieties of tea leaves by high-performance liquid chromatography, we found two new major compounds in Cha Chuukanbohon Nou 6. Nuclear magnetic resonance spectroscopy revealed these compounds to be theogallin and 1,2-di-O-galloyl-4,6-O-(S)-hexahydroxydiphenoyl-beta-D-glucopyranose. The two were similar in chemical structure to strictinin, an inhibitor of immunoglobulin (Ig) production. Thus their effects on the production of Igs by peripheral blood lymphocytes were tested. Both compounds, like strictinin, inhibited IgE production. The results suggest Cha Chuukanbohon Nou 6 to be the basis of an antiallergic beverage.


Tardive Blepharospasm and Meige Syndrome during Treatment with Quetiapine and Olanzapine.
Meige syndrome, which has been presented in tardive syndromes, is a form of blepharospasm accompanied by oromandibular dystonia with manifestations over the face, jaw, and neck. A blepharospasm can be induced by antihistamines, dopaminomimetic or sympathomimetic drugs, or long-term exposure to dopamine antagonists. Atypical antipsychotics have less extrapyramidal side effects because of a weak dopamine D2 receptor binding affinity or a strong antagonistic effect to serotonin 5-HT2a receptor and have been known to cause less tardive dyskinesia than typical antipsychotics. Thus, in literature, atypical antipsychotics are recommended for the treatment of psychosis in cases of tardive dyskinesia. The potential risk factors associated with the development of tardive dyskinesia are extrapyramidal symptoms' history, diabetes mellitus, affective disorder, female gender, older age, and long-term therapy with neuroleptics at higher dosages. As reported below, a patient with an affective disorder who had quetiapine-induced oromandibular dystonia and olanzapine-induced Meige syndrome after antipsychotic augmentation in different stages of the disease process was presented.


A giant choledochal cyst in infancy: a case report.
Choledochal cyst is a dilation that encloses the intrahepatic or both extra- and intrahepatic portions of the biliary ducts. Postnatally, ultrasonography is the initial diagnostic modality of choice, allowing for precise measurements of intra- or extrahepatic duct dilatation and identification of stones and sludge. Symptoms depend on the age at presentation. Common bile duct malformations should be considered as a differential diagnosis of a cystic mass regardless of the cyst's size or patient's age, especially in children presenting with abdominal pain, jaundice, and palpable mass. To the best of our knowledge, we report the largest choledochal cyst in infancy.


Peroneal neuropathy following liver transplantation: possible predisposing factors and outcome.
Perioperative peroneal neuropathy is an uncommon complication following operations remote from the leg or in supine position including liver transplant. We retrospectively reviewed the medical records of 132 living-donor liver transplant recipients done at our center between September 2006 and December 2008. Various potential preoperative, intraoperative, and postoperative factors were studied in the cases that developed perioperative peroneal neuropathy. Peroneal neuropathy was reported in 7 recipients (5.3%) following liver transplant. Apart from intraoperative positioning, other identifiable predisposing factors appear to be poor nutritional status, tall and slender body shape, alcoholic liver disease, and higher pretransplant model for endstage liver disease score. All patients were treated conservatively, including nutritionally balanced diet and vitamin supplements combined with physical rehabilitation therapy. The motor power returned to normal within 6 months in all 7 patients. Perioperative peroneal neuropathy may be contributed by various preoperative factors apart from intraoperative nerve compression. It can be effectively prevented by being aware of the predisposing factors and implicating adequate precautions perioperatively.


Caught in the middle: case study of a brachial (sentry) lymph node recurrence after resection and locoregional breast radiotherapy.
To reduce local recurrence, adjuvant locoregional radiotherapy is given routinely for post-mastectomy breast patients with 4 or more positive lymph nodes. Most institutions adopt a 3- or 4-field radiotherapy technique, in which the field and shielding placements are informed by bony anatomic landmarks viewed on digitally reconstructed radiographs.Here, we report on a 40-year-old woman who underwent a lumpectomy with axillary node dissection, followed by chemotherapy, completion mastectomy, and adjuvant locoregional radiotherapy (50 Gy in 25 fractions) for a multicentric pT1cN2aM0 invasive ductal carcinoma of the right breast. At 9 months after radiotherapy, she presented with a palpable brachial lymph node, a major draining node of the upper extremity, in the axilla, abutting the previous anterior supraclavicular and axillary radiation fields. This occurrence highlights the potential superolateral border of the level i axillary nodal chain and its relationship to the upper extremity lymphatics via the brachial ("sentry") node. Adapting the delineated nodal target volume in locoregional radiotherapy of the breast for disease with extensive nodal involvement or other high-risk pathologic indications may be warranted in certain situations. Careful imaging and an informed discussion with the patient is needed before deciding to treat the sentry node and including the acromial-clavicular joints, balanced with the potential increased risk of lymphedema.


Replication of the RNA segments of a bipartite viral genome is coordinated by a transactivating subgenomic RNA.
The insect nodavirus Flock house virus (FHV) has a small genome divided between two segments of positive-sense RNA, RNA1 and RNA2. RNA1 encodes the RNA-dependent RNA polymerase (RdRp) catalytic subunit and templates the synthesis of a subgenomic RNA (RNA3) that encodes two small nonstructural proteins. Replication of RNA2, which encodes a precursor to the viral capsid proteins, suppresses RNA3 synthesis. Here we report that RNA1 mutants deficient in RNA3 synthesis failed to support RNA2 replication. This effect was not caused by alterations in the RdRp catalytic subunit nor by a lack of the proteins encoded by RNA3. Furthermore, RNA3 supplied in trans from an exogenous source restored RNA2 replication. These data indicate that RNA3 transactivates the replication of RNA2, a novel property for a viral RNA. We propose that the RNA3 dependence of RNA2 replication serves to coordinate replication of the FHV genome segments.


Interventions to maximize facial cleanliness and achieve environmental improvement for trachoma elimination: A review of the grey literature.
Efforts are underway to scale-up the facial cleanliness and environmental improvement (F&E) components of the World Health Organization's SAFE strategy for elimination of trachoma as a public health problem. Improving understanding of the F&E intervention landscape could inform advancements prior to scale-up, and lead to more effective and sustained behavior change. We systematically searched for relevant grey literature published from January 1965 through August 2016. Publications were eligible for review if they described interventions addressing F&E in the context of trachoma elimination programs. Subsequent to screening, we mapped attributes of F&E interventions. We then employed three behavior change frameworks to synthesize mapped data and identify potential intervention gaps. We identified 27 documents meeting inclusion criteria. With the exception of some recent programming, F&E interventions have largely focused on intermediate and distal antecedents of behavior change. Evidence from our analyses suggests many interventions are not designed to address documented determinants of improved F&E practices. No reviewed documents endorsed inclusion of intervention components related to behavioral maintenance or resilience-factors critical for sustaining improved behaviors. If left unaddressed, identified gaps in intervention content may continue to challenge uptake and sustainability of improved F&E behaviors. Stakeholders designing and implementing trachoma elimination programs should review their F&E intervention content and delivery approaches with an eye toward improvement, including better alignment with established behavior change theories and empirical evidence. Implementation should move beyond information dissemination, and appropriately employ a variety of behavior change techniques to address more proximal influencers of change.


The mechanism of action of novel antipsychotic drugs.
It is no longer tenable to attribute all the antipsychotic action of antipsychotic drugs to dopamine (DA) D2 receptor blockade and subsequent development of depolarization inactivation of the mesolimbic or mesocortical DA neurons. The chief evidence for this position is that clozapine (CLOZ) does not differ from typical antipsychotic drugs in these regards but is more effective than typical neuroleptic drugs. The mechanism of action of atypical antipsychotic drugs related to CLOZ may involve reduction of dopaminergic activity in the mesolimbic system by a variety of mechanisms, including D1 and D2 receptor blockade. Relatively higher affinity for the serotonin (5HT)2 receptor than for the D2 receptor may also be important to the action of CLOZ-like compounds. Enhanced DA release in the mesocortical system may be relevant to the effectiveness of these agents in treating negative symptoms. Several other classes of new agents alter the dopaminergic system by means of alternative mechanisms. Partial DA agonists may modulate DA neurotransmission more adequately than pure antagonists by producing a mix of direct agonist and antagonistic effects. DA autoreceptor agonists and 5HT3 antagonists appear to act by diminishing the release of DA from some, but not all, DA neurons. Substituted benzamides are "pure" D2 antagonists with some in vivo selectivity for limbic D2 over striatal D2 receptors. Highly selective D1 antagonists have been proposed to produce equivalent antipsychotic activity and fewer extrapyramidal symptoms than D2 antagonists. Antagonists of the recently identified D3 receptors are being sought. Excessive stimulation of the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptor, leading to neurotoxicity or diminished activation of this receptor, is the target of novel approaches to treating schizophrenia. Phencyclidine (PCP) antagonists that would activate the NMDA receptor and sigma receptor antagonists are of interest as antipsychotic agents. Therapeutic strategies for treating schizophrenia, schizophrenia-related disorders, and other psychoses will likely be genuinely diverse in the next decade.


Expression of a translationally fused TAP-tagged plasma membrane proton pump in Arabidopsis thaliana.
The Arabidopsis thaliana plasma membrane proton ATPase genes, AHA1 and AHA2, are the two most highly expressed isoforms of an 11 gene family and are collectively essential for embryo development. We report the translational fusion of a tandem affinity-purification tag to the 5' end of the AHA1 open reading frame in a genomic clone. Stable expression of TAP-tagged AHA1 in Arabidopsis rescues the embryonic lethal phenotype of endogenous double aha1/aha2 knockdowns. Western blots of SDS-PAGE and Blue Native gels show enrichment of AHA1 in plasma membrane fractions and indicate a hexameric quaternary structure. TAP-tagged AHA1 rescue lines exhibited reduced vertical root growth. Analysis of the plasma membrane and soluble proteomes identified several plasma membrane-localized proteins with alterred abundance in TAP-tagged AHA1 rescue lines compared to wild type. Using affinity-purification mass spectrometry, we uniquely identified two additional AHA isoforms, AHA9 and AHA11, which copurified with TAP-tagged AHA1. In conclusion, we have generated transgenic Arabidopsis lines in which a TAP-tagged AHA1 transgene has complemented all essential endogenous AHA1 and AHA2 functions and have shown that these plants can be used to purify AHA1 protein and to identify in planta interacting proteins by mass spectrometry.


Datura stramonium Leaf Extract Exhibits Anti-inflammatory Activity in CCL4-Induced Hepatic Injury Model by Modulating Oxidative Stress Markers and iNOS/Nrf2 Expression.
Inflammation is a frequent phenomenon in the pathogenesis of hepatic disorders leading to fibrosis and cirrhosis. Phytopharmaceuticals developed from traditional medicine can provide effective therapeutic alternatives to conventional medications. Datura stramonium (DS) has reported traditional uses in inflammatory diseases. In this study, we have tried to validate its potential as a source of anti-inflammatory agents. Powdered leaf part of DS was extracted using ethyl acetate (EA) to provide the extract (DSL-EA). Lymphocyte and macrophage viability and acute toxicity assays established the safety profile, while nitric oxide (NO) scavenging assay estimated the in vitro anti-inflammatory potential. Noninvasive anti-inflammatory, antidepressant, and antinociceptive activities were monitored using BALB/c mice using low and high doses (150 and 250 mg/kg). Major inflammatory studies were performed on Sprague-Dawley male rats using CCl4-induced liver injury model. Disease induction was initiated by intraperitoneal injections of CCl4 (1 mL/kg of 30% CCl4 in olive oil). The rats were divided into six groups. The anti-inflammatory potential of DSL-EA in low and high doses (150 and 300 mg/kg, respectively) was assessed through hematological, biochemical, liver antioxidant defense, oxidative stress markers, and histological studies as well as the expression of Nrf2 and iNOS. DSL-EA exhibited prominent in vitro NO scavenging (IC50: 7.625 ± 0.51 μg/mL) and in vivo anti-inflammatory activity in paw and anal edema models. In CCl4 model, hematological investigations revealed vasotonic effects. Liver functionality was significantly (P < 0.001 - 0.05) improved in DSL-EA-treated rats. The activity level of endogenous antioxidant enzymes in liver tissues was improved in a manner identical to silymarin. The extract reduced the percent concentration of oxidative stress markers in liver tissues. Furthermore, DSL-EA displayed restorative effects on histological parameters (H and E and Masson's trichrome staining). Immunohistochemistry studies showed marked decline in Nrf2 expression, while overexpression of iNOS was also observed in disease control rats. The damage was distinctly reversed by the extract.


The role of Akt in the signaling pathway of the glycoprotein Ib-IX induced platelet activation.
The platelet von Willebrand factor (vWF) receptor, glycoprotein Ib-IX (GPIb-IX), mediates platelet adhesion and induces signaling leading to integrin activation. Phosphoinositol 3-kinase (PI3K) is important in GPIb-IX-mediated signaling. PI3K-dependent signaling mechanisms, however, are unclear. We show that GPIb-IX-induced platelet aggregation and stable adhesion under flow were impaired in mouse platelets deficient in PI3K effectors, Akt1 and Akt2, and in human platelets treated with an Akt inhibitor, SH-6. Akt1 and Akt2 play important roles in early GPIb-IX signaling independent of Syk, adenosine diphosphate (ADP), or thromboxane A2 (TXA2), in addition to their recognized roles in ADP- and TXA2-dependent secondary amplification pathways. Knockout of Akt1 or Akt2 diminished platelet spreading on vWF but not on immobilized fibrinogen. Thus, Akt1 and Akt2 are both required only in the GPIb-IX-mediated integrin activation (inside-out signaling). In contrast, PI3K inhibitors abolished platelet spreading on both vWF and fibrinogen, indicating a role for PI3K in integrin outside-in signaling distinct from that in GPIb-IX-mediated inside-out signaling. Furthermore, Akt1- or Akt2-deficiency diminished vWF-induced cGMP elevation, and their inhibitory effects on GPIb-IX-dependent platelet adhesion were reversed by exogenous cGMP. Thus, Akt1 and Akt2 mediate GPIb-IX signaling via the cGMP-dependent signaling pathway.


Direct Bioelectricity Generation from Sago Hampas by Clostridium beijerinckii SR1 Using Microbial Fuel Cell.
Microbial fuel cells offer a technology for simultaneous biomass degradation and biological electricity generation. Microbial fuel cells have the ability to utilize a wide range of biomass including carbohydrates, such as starch. Sago hampas is a starchy biomass that has 58% starch content. With this significant amount of starch content in the sago hampas, it has a high potential to be utilized as a carbon source for the bioelectricity generation using microbial fuel cells by Clostridium beijerinckii SR1. The maximum power density obtained from 20 g/L of sago hampas was 73.8 mW/cm2 with stable cell voltage output of 211.7 mV. The total substrate consumed was 95.1% with the respect of 10.7% coulombic efficiency. The results obtained were almost comparable to the sago hampas hydrolysate with the maximum power density 56.5 mW/cm2. These results demonstrate the feasibility of solid biomass to be utilized for the power generation in fuel cells as well as high substrate degradation efficiency. Thus, this approach provides a promising way to exploit sago hampas for bioenergy generation.


Synthetic Biology Tools for Genome and Transcriptome Engineering of Solventogenic Clostridium.
Strains of Clostridium genus are used for production of various value-added products including fuels and chemicals. Development of any commercially viable production process requires a combination of both strain and fermentation process development strategies. The strain development in Clostridium sp. could be achieved by random mutagenesis, and targeted gene alteration methods. However, strain improvement in Clostridium sp. by targeted gene alteration method was challenging due to the lack of efficient tools for genome and transcriptome engineering in this organism. Recently, various synthetic biology tools have been developed to facilitate the strain engineering of solventogenic Clostridium. In this review, we consolidated the recent advancements in toolbox development for genome and transcriptome engineering in solventogenic Clostridium. Here we reviewed the genome-engineering tools employing mobile group II intron, pyrE alleles exchange, and CRISPR/Cas9 with their application for strain development of Clostridium sp. Next, transcriptome engineering tools such as untranslated region (UTR) engineering and synthetic sRNA techniques were also discussed in context of Clostridium strain engineering. Application of any of these discussed techniques will facilitate the metabolic engineering of clostridia for development of improved strains with respect to requisite functional attributes. This might lead to the development of an economically viable butanol production process with improved titer, yield and productivity.


Brain activation associated with deep brain stimulation causing dissociation in a patient with Tourette's syndrome.
Dissociation involves a disruption in the integrated functions of consciousness, memory, identity, or perception of the environment. Attempts at localizing dissociative responses have yielded contradictory results regarding brain activation, laterality, and regional involvement. Here, we used a single-day split-dose activation paradigm with single photon emission computed tomography and 99m-Tc ethylcysteinatedimer as a brain perfusion tracer in a patient with Tourette's syndrome undergoing bilateral high-frequency thalamic stimulation for the treatment of tics who developed an alternate personality state during right thalamic stimulation. We documented increased regional cerebral blood flow in bilateral prefrontal and left temporal brain areas during the alternate identity state. We conclude that our findings support the temporal lobe as well as the frontolimbic disconnection hypotheses of dissociation.


Dengue fever outbreak in Lahore.
Dengue fever has now affected all the major cities of country. About 41,354 patients underwent antibody screening for dengue fever from Shaukat Khanum Memorial Cancer Hospital, Lahore, during the epidemic period (October 1st 2010 to December 20th 2010). Out of them, 1294 (3.1%) patients were positive for IgM antibodies, and 124 (0.3%) for IgG antibodies. A total of 722 (1.7%) patients were borderline positive for IgM antibodies and 108 (0.26%) were borderline positive for IgG antibodies. Dengue fever has emerged as a global problem over the last 5 years. It has also hit Lahore badly especially after the floods in 2010. High index of suspicion should be there in case of related symptoms.


Differential regulation of cerebellar granule neurons by two types of quisqualate receptors.
Stimulation of the quisqualate (QA) subtype of glutamate receptor increased the expression of phosphate activated glutaminase (needed for neurotransmitter glutamate synthesis) and the ability to release neurotransmitter glutamate in cultures of glutamatergic cerebellar granule neurons. In contrast, QA had no significant effects on the lactate dehydrogenase activity and amount of protein. The QA-mediated elevation in glutaminase activity was blocked by the ionotropic QA receptor antagonist CNQX and mimicked by the ionotropic QA receptor agonist AMPA, but not by the metatropic QA receptor agonist t-ACPD. The increase in Ca2+ influx essentially through activation of L-type channels, and not the mobilization of internal Ca2+ stores, was responsible for these QA receptor-mediated long-term changes in cerebellar granule neurons.


Cryopreserved amniotic membrane in the treatment of limb skin defects of aplasia cutis congenita: a case study.
To report the efficacy and long-term outcomes of treating the skin defects of aplasia cutis congenita (ACC) with cryopreserved amniotic membrane (AM). Human amnion was obtained from the caesarean delivery of a full-term healthy pregnancy and processed in a sterile laminar flow hood, and cryopreserved in liquid nitrogen. The structure of the AM was investigated histologically and the viability of the epithelial cells was assessed after cryopreservation and compared with fresh AM and with AM preserved in phosphate-buffered saline (PBS) at 4°C. The cryopreserved AM was applied onto the lower limb skin defects of a one-month old baby with ACC. Timely AM changes were performed as necessary until the wounds healed. The structure of the cryopreserved AM was intact, with little visible difference compared with fresh AM. The viability of the epithelial cells was partially lost but still much better retained than in those preserved in PBS at 4°C. The limb skin defects were gradually re-epithelialised upon application of the AM and were completely healed after one month. The 4-month and 2-year follow-ups presented good skin texture and colour, without hypertrophic scar formation. In this case study, cryopreservation of AM presented a well preserved stromal compartment and viable epithelial layer. It also offered features such as pain relief, good attachment and adhesiveness, improved wound healing and suppressed scar formation in the treatment of ACC skin defects.


The misidentification of bacterial genes as human cDNAs: was the human D-1 tumor antigen gene acquired from bacteria?
The initial analysis of the draft copy of the human genome sequence revealed the presence of several genes that were proposed to have been directly transferred from bacteria. We investigated the human D-1 antigen as a potential lateral transfer event. We report that although the human D-1 antigen seems to be an excellent candidate for lateral transfer, it is a contaminating bacterial sequence present in a human cDNA library that was included in the human genome analysis. Furthermore, several other genes present in the publicly available databases that were included in the analysis of the human genome are also likely contaminating bacterial sequences present in cDNA libraries.


[The age at first intercourse has been stable since the 1960s, and early coital debut is linked to sexual risk situations].
This article reviews the 17 most robust Danish studies performed 1944-2006, in which coital debut was included as a specific variable. Women and men born before 1920 had their first sexual intercourse at the mean age of 21 and 20 years, respectively. Today, however, the median age of debut for both sexes is 16 years. The decrease in coital debut age culminated in the late 1960s, and no major changes have since occurred. Early debut is linked to sexual risk-taking and sexually transmitted infections. One fourth of current Danish adolescents do not use any protection at their sexual debut, and strengthened preventive measures are still needed.


Effects of ploidy and mating type on virulence of Candida albicans.
Candida albicans is the most common fungal pathogen of humans. The recent discovery of sexuality in this organism has led to the demonstration of a mating type locus which is usually heterozygous, although some isolates are homozygous. Tetraploids can be formed between homozygotes of the opposite mating type. However, the role of the mating process and tetraploid formation in virulence has not been investigated. We describe here experiments using a murine model of disseminated candidiasis which demonstrate that in three strains, including CAI-4, the most commonly used strain background, tetraploids are less virulent than diploids and can undergo changes in ploidy during infection. In contrast to reports with other strains, we find that MTL homozygotes are almost as virulent as the heterozygotes. These results show that the level of ploidy in Candida albicans can affect virulence, but the mating type configuration does not necessarily do so.


Exercise: Teaching myocytes new tricks.
Endurance exercise training promotes numerous cellular adaptations in both cardiac myocytes and skeletal muscle fibers. For example, exercise training fosters changes in mitochondrial function due to increased mitochondrial protein expression and accelerated mitochondrial turnover. Additionally, endurance exercise training alters the abundance of numerous cytosolic and mitochondrial proteins in both cardiac and skeletal muscle myocytes, resulting in a protective phenotype in the active fibers; this exercise-induced protection of cardiac and skeletal muscle fibers is often referred to as "exercise preconditioning." As few as 3-5 consecutive days of endurance exercise training result in a preconditioned cardiac phenotype that is sheltered against ischemia-reperfusion-induced injury. Similarly, endurance exercise training results in preconditioned skeletal muscle fibers that are resistant to a variety of stresses (e.g., heat stress, exercise-induced oxidative stress, and inactivity-induced atrophy). Many studies have probed the mechanisms responsible for exercise-induced preconditioning of cardiac and skeletal muscle fibers; these studies are important, because they provide an improved understanding of the biochemical mechanisms responsible for exercise-induced preconditioning, which has the potential to lead to innovative pharmacological therapies aimed at minimizing stress-induced injury to cardiac and skeletal muscle. This review summarizes the development of exercise-induced protection of cardiac myocytes and skeletal muscle fibers and highlights the putative mechanisms responsible for exercise-induced protection in the heart and skeletal muscles.


Relationship of Glucagon-like Peptide 1 and Peptide YY with Catch-up Growth in Children Born Small for Gestational Age.
Children born small for gestational age (SGA) are at a greater risk of developing insulin resistance, type 2 diabetes, and cardiovascular disease in adulthood. Gastrointestinal peptides regulate glucose and lipid metabolism and act on the hypothalamus to regulate energy homeostasis. This study aimed to explore whether gastrointestinal peptides are involved in metabolic disorders in SGA, which remains unclear. We detected the secretion of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) in prepubertal children born SGA, compared the differences between catch-up growth and persistent short stature, and analyzed their correlations with glucose and lipid metabolism. GLP-1, PYY, insulin-like factor 1, glucose, insulin, and lipid concentrations were analyzed in prepubertal children aged 4-10 years in three groups: short SGA, catch-up growth SGA, and normal growth appropriate for gestational age (AGA). The fasting GLP-1 and PYY concentrations were significantly lower in the SGA group than in the AGA group (p<0.05), and the GLP-1 level in infants born SGA with catch-up growth was lower than that in the short SGA group (p<0.05). In the SGA population, GLP-1 showed a weak correlation with catch-up growth (r = -0.326) and fasting insulin (r = 0.331). Lower GLP-1 concentrations may be associated with abnormal glucose metabolism in prepubertal children born SGA with catch-up growth. Impaired intestinal L cell function may be involved in the development of metabolic complications in SGA children.


Total gastrectomy: twenty years' experience.
The management and treatment of patients with gastric cancer is all encompassing. It includes preoperative care, operative resection postoperative sympathetic encouragement with therapeutic and nutritional guidance. This has been the experience with 62 human beings afflicted with malignant disease of the stomach. The end result has been that approximately 50% of these patients survived five years or more. This is a comparative favorable percentage when considering cancer elsewhere in the gastrointestinal tract. What is more enlightening is that the patients were comfortable and able to enjoy a pleasant personal diet during the five or more years following surgery. This salubrious state is attributed to the preservation of a small segment of stomach which enabled the intrinsic factor in the gastric mucosa to participate in and contribute to the normal hemopoietic physiological process.


[A giant ureteral stone: case report and literature review].
The article reports a case of a 68-year-old female patient with a giant ureteral stone of 12 cm in length, localized at the upper and middle third of the right ureter. The patient had undergone right ureterolithotomy with DJ-stent placement. Her postoperative period was uneventful. The distinctive feature of this case was that the patient had neither obstruction of urine flow through the urinary tract, nor metabolic disorders that could cause the formation of the giant ureteral stone.


IL-37 As a Potential Biotherapeutics of Inflammatory Diseases.
Interleukin-37 (IL-37) was discovered as a new member of pro-inflammatory IL-1 superfamily. However, further studies suggested that IL-37 plays a critical anti-inflammatory role in innate and adaptive immunity. IL-37 may suppress the inflammatory process via intracellular SMAD family member 3 (SMAD3) and extracellular IL-18 Receptor alpha (IL-18Rα) signaling pathway, respectively. Meanwhile, the abnormal expression of IL-37 was observed in immune-mediated inflammatory diseases, such as inflammatory bowel disease, rheumatoid arthritis, atherosclerosis, systemic lupus erythematosus, asthma, and multiple sclerosis, which suggest IL-37 is a potential therapeutic target for these diseases. In this review, we summarize the anti-inflammatory mechanism of IL-37 and discuss the critical roles of IL-37 in the pathogenesis of these diseases. Further studies are required to confirm the effectiveness of IL-37 as a novel target for these inflammatory diseases.


3D printing-mediated microporous starch hydrogels for wound hemostasis.
Starch hydrogels with biodegradability and cytocompatibility are good alternatives to traditional dressings. Herein, oxidized starch hydrogel loaded with coagulation factor Ca2+ ions (CaOMS) is successfully constructed by green hot-extrusion 3D printing technology (HE-3DP). In vitro study demonstrated the good water absorbing capacity (845.15-1194.20%) and blood cell and platelet adhesion of CaOMS to assist hemostasis owing to the boosted network structure density, gel strength, and the release of activated Ca2+ ions. More importantly, in vivo experiments further demonstrated CaOMS could maintain the weight loss caused by blood loss from wounds and has excellent hemostatic (65 s) and wound healing properties by promoting the secretion of epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF) expression. The advantages of CaOMS, including rapid and effective hemostasis, effective wound healing, low cost, easy usage, and adaptability to fit various wound shapes, make it a promising biomaterial for achieving fast hemostasis and wound healing.


Drug development for children: how is pharma tackling an unmet need?
The laws and regulatory processes that govern the pharmaceutical industry have previously had the unintended consequence of excluding children in the drug development process. Many of the medicines prescribed to children consist of either an unlicensed form of a launched drug or an off-label form (ie, a form outside of the terms of the license, such as in an unapproved dose or for use in a different disease or age group). Medicines prescribed to children in such ways may have an increased risk of causing adverse drug reactions. New legislation in the EU, along with legislation in the US, provide the pharmaceutical industry with positive financial incentives to consider children in the drug development process. From the stage of identifying new molecular entities, to juvenile animal testing, to phase I to IV clinical trials and formulation development, industry practice has improved in several areas with relation to pediatrics; however, other areas remain to benefit from these legislative changes.


Persistent genital arousal disorder: confluent patient history of agitated depression, paroxetine cessation, and a tarlov cyst.
We report a case of a woman suffering from persistent genital arousal disorder (PGAD) after paroxetine cessation. She was admitted to a psychiatric department and diagnosed with agitated depression. Physical investigation showed no gynaecological or neurological explanation; however, a pelvic MRI scan revealed a Tarlov cyst. Size and placement of the cyst could not explain the patient's symptoms; thus neurosurgical approach would not be helpful. Her depression was treated with antidepressant with little effect. Electroconvulsive therapy improved the patient's symptoms though they did not fully resolve. More awareness of PGAD and thorough interdisciplinary conferences are necessary to insure an unequivocal treatment strategy.


MDSINE: Microbial Dynamical Systems INference Engine for microbiome time-series analyses.
Predicting dynamics of host-microbial ecosystems is crucial for the rational design of bacteriotherapies. We present MDSINE, a suite of algorithms for inferring dynamical systems models from microbiome time-series data and predicting temporal behaviors. Using simulated data, we demonstrate that MDSINE significantly outperforms the existing inference method. We then show MDSINE's utility on two new gnotobiotic mice datasets, investigating infection with Clostridium difficile and an immune-modulatory probiotic. Using these datasets, we demonstrate new capabilities, including accurate forecasting of microbial dynamics, prediction of stable sub-communities that inhibit pathogen growth, and identification of bacteria most crucial to community integrity in response to perturbations.


Input-Specific Plasticity and Homeostasis at the Drosophila Larval Neuromuscular Junction.
Synaptic connections undergo activity-dependent plasticity during development and learning, as well as homeostatic re-adjustment to ensure stability. Little is known about the relationship between these processes, particularly in vivo. We addressed this with novel quantal resolution imaging of transmission during locomotive behavior at glutamatergic synapses of the Drosophila larval neuromuscular junction. We find that two motor input types, Ib and Is, provide distinct forms of excitatory drive during crawling and differ in key transmission properties. Although both inputs vary in transmission probability, active Is synapses are more reliable. High-frequency firing "wakes up" silent Ib synapses and depresses Is synapses. Strikingly, homeostatic compensation in presynaptic strength only occurs at Ib synapses. This specialization is associated with distinct regulation of postsynaptic CaMKII. Thus, basal synaptic strength, short-term plasticity, and homeostasis are determined input-specifically, generating a functional diversity that sculpts excitatory transmission and behavioral function.


Adrenomedullin Regulates IL-1β Gene Expression in F4/80+ Macrophages during Synovial Inflammation.
Adrenomedullin (AM) plays an important role in the regulation of inflammatory processes; however, the role and expression of AM in synovial inflammation have not been determined. To investigate the expression and role of AM in inflamed synovial tissue (ST), the gene expression profiles of AM in the ST, including synovial macrophages and fibroblasts, of a murine patellar surgical dislocation model were characterized. In addition, the effects of interleukin- (IL-) 1β and AM in cultured synovial cells were also examined. CD11c+ macrophages were found to be elevated in ST of the surgically dislocated patella. Higher gene expression of CD11c, IL-1β, AM, receptor activity-modifying proteins 2 (RAMP2), and 3 (RAMP3) was also observed in ST obtained from the dislocated side. AM expression was also significantly increased in synovial fibroblasts and macrophages in response to IL-1β treatment. Synovial macrophages also highly expressed RAMP3 compared to fibroblasts and this expression was further stimulated by exogenously added IL-1β. Further, the treatment of the F4/80-positive cell fraction obtained from ST with AM inhibited IL-1β expression. Taken together, these findings demonstrated that AM was produced by synovial fibroblasts and macrophages in inflamed ST and that increased levels of AM may exert anti-inflammatory effects on synovial macrophages.


MDMA-evoked changes in [11C]raclopride and [11C]NMSP binding in living pig brain.
Positron emission tomography (PET) studies with radiolabeled dopamine D2-like receptor ligands reveal d-amphetamine-evoked increases in the competition from endogenous dopamine. However, the corresponding effects of methylenedioxymethamphetamine (MDMA, "Ecstasy"), which releases catecholamines and also serotonin, are unknown. Using PET, we measured the binding potentials (pBs) of the benzamide [11C]raclopride and the butyrophenone N-[11C]methylspiperone ([11C]NMSP) in brain of living pigs first in a baseline condition and at 45 and 165 min after infusion of (+/-)-MDMA-HCl (1 mg/kg, i.v.). Concomitant studies of cerebral blood flow did not reveal significant perfusion changes in the cerebellum reference region or in striatum, supporting the present use of reference tissue methods for the mapping of MDMA-evoked pB changes. Relative to the baseline pB of [11C]raclopride for dopamine D(2/3) receptors in striatum (pB = 1.5-2.2), MDMA-treatment reduced pB by 35% in the first posttreatment scan and by 22% in the second posttreatment scan, comparable to changes typically evoked by d-amphetamine at a similar dose. In most previous studies, the in vivo binding of butyrophenones has been nearly insensitive to d-amphetamine-evoked dopamine release. However, we found the baseline pB of [11C]NMSP for dopamine D2-like receptors in striatum (pB = 4-5) was decreased by 30% in the first post-MDMA scan and by 50% in the second post-MDMA scan, irrespective of assumptions about the extent of equilibrium binding attained during the 90-min-long PET recordings. Distinct properties of MDMA such as simultaneous release of dopamine and serotonin in brain may account for the present finding of progressive decline in the availability of [11C]NMSP binding sites in striatum.


Comparison between spot urine and overnight urine in the estimation of 24-hour excretion of urine protein, sodium and kallikrein.
To compare the value of spot urine and overnight 9-hour urine in the estimation of 24-hour urinary sodium excretion (UNaV), protein excretion (UpV) and kallikrein excretion (UKaV), we measured the concentration of sodium, protein, kallikrein and creatinine in spot urine, overnight 9-hour urine, and 24-hour urine samples obtained from 21 patients with various renal diseases. They ranged in age from 16 to 75 years with 10 males and 11 females. Urinary protein was measured by the Coomassie Blue dye-binding method. Urinary kallikrein activity was measured by assay of its amidase activity on synthetic substrate S-2266. The results showed that the 9-hour UpV and 9-hour urine P/Cr ratio was better correlated with the 24-hour UpV than the spot urine P/Cr ratio (at 9-11 AM), and the 9-hour UKaV and spot urine Ka/Cr ratio were better correlated with the 24-hour UKaV than the 9-hour Ka/Cr ratio. Only the 9-hour UNaV was correlated with the 24-hour UNaV. We conclude that overnight 9-hour urine, in view of its lower cost, equal effectiveness and convenience, is the best method to substitute for 24-hour urine collection in the evaluation of Na, P and Ka excretion in patients with renal diseases.


Association of obesity, gender, age and occupation with carpal tunnel syndrome.
The present study determines the association of obesity, gender, age and occupation in patients with carpal tunnel syndrome (CTS) in a New Zealand population. Analysis of questionnaires and clinical review of patients who had undergone surgical decompression of the median nerve in the carpal tunnel. The age and gender distribution of 655 hands (512 patients) that had undergone carpal tunnel release (CTR) were compared with the age and gender distribution of the New Zealand population. The results indicate that the 3-year-period prevalence of CTS in females is more than double that in males. Proportionally there were more patients over age 55 than in the general population. The findings also indicate that, proportionally, six times the number of females who worked in moderate manual work underwent CTR compared with the general female population and proportionally twice the number of males who worked in heavy office/clerical work underwent CTR compared with the general male population. It was also found that CTR patients are twice as likely to be overweight (body mass index [BMI] > 25) than the general population and female patients are twice as likely to be obese (BMI > 30) than the general population. Carpal tunnel syndrome is more than twice as common in females as it is in males, and patients aged more than 55 years are more likely to suffer from CTS. Females with CTS are more likely to work in moderate manual work and males with CTS are more likely to work in heavy office/clerical work. Obesity and CTS are related statistically.


Rapid cortical motor output map changes assessed by the triple stimulation technique.
The amplitudes of motor evoked potentials (MEPs) were mapped by transcranial magnetic stimulation (TMS) using the triple stimulation technique (TST) in 11 normal individuals. Stimuli were given while the subjects were (a) distracted, (b) concentrating on their target (recorded) hand, and (c) concentrating on their contralateral hand. Within seconds, the proportion of excited motor units increased, similarly in all subjects, by an average of 70% from (a) to (b), and by 48% from (a) to (c). At the optimal stimulation site, results obtained with the TST were compared to those of conventional MEPs. The TST proved superior in detecting the rapid changes of the motor output caused by the non-specific mental tasks studied.


The cells of equine blood and their development.
Based on morphologie studies on bone marrow, lymphnode and blood preparations the cells of equine blood and their developmental stages are described and illustrated with 32 coloured photographs.


The Role of pH and Ionic Strength in the Attraction-Repulsion Balance of Fibrinogen Interactions.
Fibrinogen (Fg) self-assembly is sensitive to the physicochemical properties of an environment like pH and ionic strength. These parameters tune the direction and strength of noncovalent physical driving forces determining protein intermolecular interactions. The attraction-repulsion balance in intermolecular interactions of the multidomain protein Fg at pH values 3.5, 7.4, and 9.5 and varying ionic strengths of the water medium has been analyzed by the complex diffusive approach, proposed by us previously. The concentration dependence of protein collective diffusion was analyzed within the phenomenological approach, based on the frictional formalism of nonequilibrium thermodynamics proposed by H. Vink. The analysis of protein diffusion data has shown the fundamental difference in the physical nature and direction of interaction forces between protein molecules at different conditions. The paired interaction potential of protein molecules was characterized in terms of second virial coefficients and Hamaker constants within the Deryaguin-Landau-Verwey-Overbeek theory and the "porous" colloid particle model. Our results indicated the maximum Hamaker constant and dominance of the van der Waals attraction between Fg molecules at pH 7.4. The increase in pH up to 9.5 results in the zero values of the second virial coefficient and Hamaker constant, corresponding to the full reciprocal compensation for electrostatic repulsion and van der Waals attraction. In the acidic medium (pH 3.5), the strong electrostatic repulsion substantially exceeds the van der Waals attraction. A high ionic strength is characterized by a significant decrease of all intermolecular interactions, which is expressed in almost zero values of virial coefficients and the Hamaker constant. Thus, it is experimentally shown that the physiological conditions of the Fg environment (pH 7.4 and slight ionic strength) provide a high probability for peak physical attraction between fibrinogen molecules, which is used in nature to facilitate blood clotting.


Fuckbuddy partnerships among men who have sex with men - a marker of sexually transmitted infection risk.
'Fuckbuddies' are a type of regular sexual partner with whom men have ongoing sexual contact, generally in the absence of romantic attachment. We surveyed 989 men who have sex with men (MSM) at the Melbourne Sexual Health Centre, Australia, with the aim of determining the frequency of 'fuckbuddy' partnerships among sexual health clinic attendees and assessing their sexual risk. The majority (60%) of 1139 regular partnerships were described as 'fuckbuddies'. Most MSM (63%) with a 'fuckbuddy' had multiple 'fuckbuddies'. MSM with 'fuckbuddies' were more likely to also have casual sexual partners (odds ratio [OR] 5.7; 95% confidence interval 3.6-8.9) and had more casual sexual partners (median of 4 versus 1, p < 0.001) and more rectal chlamydia (12.4% versus 5.7%; adjusted OR 2.3; p < 0.05) than MSM without 'fuckbuddies', and this risk persisted after adjusting for total numbers of sexual partners. Our findings suggest that patients with 'fuckbuddies' are at particular risk of sexually transmitted infections. We argue that clinicians should specifically ask about 'fuckbuddy' partnerships as part of their risk assessment during patient interviews, as these patients may benefit from HIV prevention strategies such as pre-exposure prophylaxis (PrEP).


Metabolism of procainamide in the perfused rat liver.
We have previously produced evidence that procainamide forms a reactive metabolite. This study of the metabolism of procainamide in a perfused rat liver was aimed at providing clues to the identity of this reactive metabolite. Several metabolites were found that had not been previously described and three of these were identified. Probably the most significant of these metabolites is the phenol, N-acetyl-3-hydroxyprocainamide. This phenol could have been formed from either a hydroxylamine or an arene oxide intermediate and either of these could represent a reactive metabolite. In contrast to the metabolism of procainamide, the phenol metabolite, N-acetyl-3-hydroxyprocainamide, is not formed in significant quantities from N-acetylprocainamide. This implies that oxidation of procainamide to 3-hydroxyprocainamide precedes acetylation to give N-acetyl-3-hydroxyprocainamide. As N-acetylation of procainamide decreases both its toxicity and the formation of the oxidative phenol metabolite, among the hypotheses to be explored is relationship between the formation of the phenol metabolite and the toxicity of procainamide. The other metabolites that were identified were N-acetylprocainamide N-oxide and N-acetyl-4-aminohippuric acid.


Comparison of visual results and higher-order aberrations after small incision lenticule extraction (SMILE): high myopia vs. mild to moderate myopia.
To compare the refractive results and higher-order aberrations (HOAs) after small incision lenticule extraction (SMILE) in high myopia and mild to moderate myopia patients. This prospective study included 165 eyes (86 patients) undergoing SMILE. According to the preoperative spherical equivalent (SE), treated eyes were divided into two groups: the high myopia group (more than -6.0 D, group-H) and the mild to moderate group (less than -6.0 D, group-M). Follow-up intervals were at 1 day, 10 days, 1 month and 3 months postoperatively. We obtained the following parameters: uncorrected (UDVA) and corrected distance visual acuity (CDVA), SE, efficacy and safety index, and HOAs. Preoperative SE was -7.16 ± 0.93 D in group-H and -4.34 ± 0.97 D in group-M. At 3 months postoperatively, the SE in group-H and group-M was -0.20 ± 0.37 D and 0.01 ± 0.19 D (t = - 4.11, P<0.05), respectively. It was found that 77% and 98% had an UDVA of 20/20, 98% and 99% had a CDVA of 20/20 in group-H and group-M, respectively, while 87% and 95% had a SE within ±0.5 D and ±1.0 D in group-H, and 98% and 100% in group-M. The efficacy indexes were 0.98 ± 0.18 in group-H and 1.05 ± 0.10 in group-M (t = - 3.084, p < 0.05). The safety indexes were 1.06 ± 0.09 and 1.06 ± 0.09 (t = 0.153, p > 0.05), respectively. There were significant increases in total HOAs, 3rd-order coma, and 4th-order spherical aberrations. SMILE is an effective and safe surgery for correcting myopia. But the target correction amount in high myopia patients should be adjusted to avoid undercorrection and acquired more satisfaction. SMILE induced increases of HOAs. ChiTrial registration number: ChiCTR-OON-16009164 . Retrospectively registered: 06.September.2016.


Biocultural correlates of gross motor coordination in prepubescent children: A cross-sectional study.
This study aimed to explore the association of gross motor coordination (GMC) with a matrix of biocultural factors in prepubescent children, taking into account weight status, somatic maturation, sociodemographic variables, and type of school. One hundred twenty-nine prepubescent children, of both sexes, aged between 8.00 and 8.99, were assessed for GMC (Körperkoordinationstest Für Kinder - KTK), weight status, biological maturation (predicted mature stature), sex, mother's education level and type of school. Binary logistic regression was used to examine the relationship between higher values of KTK and associated biocultural factors. Normoponderal children are more likely to attain better total KTK scores than those with overweight or obesity (OR: 2.942; LC 95%: 1.189, 7.280). In addition, children who are more advanced in terms of biological maturation exhibited significantly lower odds of being in the high KTK category than their less advanced peers (OR: 0.670; LC 95%: 0.474,0.946). Sex, mother's education level and the type of school are not associated with higher performance on KTK. Weight status and biological maturation are associated with motor competence in prepubescent children. Future studies should consider additional correlates to better understand the complex interactions between biological, psychosocial and behavioral factors in the prediction of motor competence.


Thermally grown ZnO nanosheets for high efficiency dye-sensitized solar cells.
High efficiency dye-sensitized solar cells (DSSCs) were fabricated using ZnO nanosheet electrodes. ZnO nanosheets were synthesized on top of fluorine-doped tin oxide (FTO) glass using Zn(OAc)2 as a precursor in the gold catalyzed chemical vapor deposition (CVD) method at a temperature of 800-900 degrees C. The synthesized materials were characterized by X-ray diffraction (XRD), field emission-scanning electron microscopy (FE-SEM), and Raman and photoluminescence (PL) spectroscopy. Typical DSSCs with ZnO nanosheets achieved moderately good conversion efficiency eta of approximately 2.12% with short-circuit current density J(SC) = 3.56 mA/cm2, open-circuit voltage V(OC) = 0.831 V, and fill factor FF = 71%. The high J(SC) and eta are attributed to high dye absorption through high surface ZnO nanosheets, which increased the light harvesting. The lower recombination rate was also observed in the ZnO nanosheet electrodes, resulting in high values of V(OC) and FF in the DSSCs.


PEG-PCL-based nanomedicines: A biodegradable drug delivery system and its application.
The lack of efficient therapeutic options for many severe disorders including cancer spurs demand for improved drug delivery technologies. Nanoscale drug delivery systems based on poly(ethylene glycol)-poly(ε-caprolactone) copolymers (PEG-PCL) represent a strategy to implement therapies with enhanced drug accumulation at the site of action and decreased off-target effects. In this review, we discuss state-of-the-art nanomedicines based on PEG-PCL that have been investigated in a preclinical setting. We summarize the various synthesis routes and different preparation methods used for the production of PEG-PCL nanoparticles. Additionally, we review physico-chemical properties including biodegradability, biocompatibility, and drug loading. Finally, we highlight recent therapeutic applications investigated in vitro and in vivo using advanced systems such as triggered release, multi-component therapies, theranostics, or gene delivery systems.


Munc13 Is a Molecular Target of Bryostatin 1.
Bryostatin 1 is a natural macrolide shown to improve neuronal connections and enhance memory in mice. Its mechanism of action is largely attributed to the modulation of novel and conventional protein kinase Cs (PKCs) by binding to their regulatory C1 domains. Munc13-1 is a C1 domain-containing protein that shares common endogenous and exogenous activators with novel and conventional PKC subtypes. Given the essential role of Munc13-1 in the priming of synaptic vesicles and neuronal transmission overall, we explored the potential interaction between bryostatin 1 and Munc13-1. Our results indicate that in vitro bryostatin 1 binds to both the isolated C1 domain of Munc13-1 ( Ki = 8.07 ± 0.90 nM) and the full-length Munc13-1 protein ( Ki = 0.45 ± 0.04 nM). Furthermore, confocal microscopy and immunoblot analysis demonstrated that in intact HT22 cells bryostatin 1 mimics the actions of phorbol esters, a previously established class of Munc13-1 activators, and induces plasma membrane translocation of Munc13-1, a hallmark of its activation. Consistently, bryostatin 1 had no effect on the Munc13-1H567K construct that is insensitive to phorbol esters. Effects of bryostatin 1 on the other Munc13 family members, ubMunc13-2 and bMunc13-2, resembled those of Munc13-1 for translocation. Lastly, we observed an increased level of expression of Munc13-1 following a 24 h incubation with bryostatin 1 in both HT22 and primary mouse hippocampal cells. This study characterizes Munc13-1 as a molecular target of bryostatin 1. Considering the crucial role of Munc13-1 in neuronal function, these findings provide strong support for the potential role of Munc13s in the actions of bryostatin 1.


SBR treatment of tank truck cleaning wastewater: sludge characteristics, chemical and ecotoxicological effluent quality.
A lab-scale activated sludge sequencing batch reactor (SBR) was used to treat tank truck cleaning (TTC) wastewater with different operational strategies (identified as different stages). The first stage was an adaptation period for the seed sludge that originated from a continuous fed industrial plant treating TTC wastewater. The first stage was followed by a dynamic reactor operation based on the oxygen uptake rate (OUR). Thirdly, dynamic SBR control based on OUR treated a daily changing influent. Lastly, the reactor was operated with a gradually shortened fixed cycle. During operation, sludge settling evolved from nearly no settling to good settling sludge in 16 days. The sludge volume index improved from 200 to 70 mL gMLSS-1 in 16 days and remained stable during the whole reactor operation. The average soluble chemical oxygen demand (sCOD) removal varied from 87.0% to 91.3% in the different stages while significant differences in the food to mass ratio were observed, varying from 0.11 (stage I) to 0.37 kgCOD.(kgMLVSS day)-1 (stage III). Effluent toxicity measurements were performed with Aliivibrio fischeri, Daphnia magna and Pseudokirchneriella subcapitata. Low sensitivity of Aliivibrio was observed. A few samples were acutely toxic for Daphnia; 50% of the tested effluent samples showed an inhibition of 100% for Pseudokirchneriella.


Predictors of Outcome and Severity in Adult Filipino Patients with Febrile Neutropenia.
Aim. The study aimed to describe the profile of Filipino febrile neutropenia patients and to determine parameters associated with severe outcomes. Methods. This is a retrospective study of Filipino febrile neutropenia patients admitted to the Philippine General Hospital. Patients were described in terms of clinical presentation and stratified according to the presence or absence of severe outcomes. Prognostic factors were then identified using regression analysis. Results. 115 febrile episodes in 102 patients were identified. Regression analysis yielded prolonged fever >7 days prior to admission (OR 2.43; 95% CI, 0.77-7.74), isolation of a pathogen on cultures (OR 2.69; 95% CI, 1.04-6.98), and nadir absolute neutrophil count (ANC) < 100 during admission (OR 1.96; 95% CI, 0.75-5.12) as significant predictors of poor outcome. Factors that significantly correlated with better outcome were granulocyte colony-stimulating factor (G-CSF) use (OR 0.31; 95% CI, 0.11-0.85) and completeness of antibiotic therapy (OR 0.26; 95% CI, 0.10-0.67). Conclusion. Prolonged fever >7 days prior to admission, positive pathogen on cultures, and nadir ANC < 100 during admission predicted severe outcomes, whereas G-CSF use and complete antibiotic therapy were associated with better outcomes. These prognostic variables might be useful in identifying patients that need more intensive treatment and monitoring.


A bio-economic analysis of a sustainable agricultural transition using green biorefinery.
Traditional pig production often relies on cereal-based feed, which has adverse environmental effects, e.g. nitrogen leaching and greenhouse gas (GHG) emissions. Alternative production systems are therefore sought to improve the sustainability of pig production. A promising alternative is to use proteinaceous feed from grass, produced in a green bio-refinery (GBR), to substitute part of the cereals in the feed. Cultivation of grass on arable land can reduce nitrogen leaching and pesticide application, and increase carbon storage. The GBR using grass as feedstock also produces valuable byproducts, e.g. fibre and biogas. In this study we combine a life-cycle analysis (LCA) and a cost-benefit analysis to compare the economic and environmental effects of producing the pig feed to produce 1ton of pork using two feeding systems. We apply this approach to the intensive Danish pork production as a case study. The results show that compared with traditional cereal-based feeding system for producing a ton of pork, using proteinaceous concentrate from small-scale GBR will (1) decrease the average feed cost by 5.01%; (2) produce a profit of 96€ before tax in the GBR; and (3) decrease the nitrogen leaching (NO3-N) by 28.2%. However, in most of the scenarios (except for G2), the nitrogen emissions into the air (N2O-N) will also increase because of the increased N fertilizer application compared to a cereal-based system. In most of the scenarios (except for S1 and G1), the energy and land use will also be saved. However, some important factors, e.g. the soil characteristics, pressed juice fraction in fresh biomass and scale of GBR, could subvert the conclusion about energy and land use saving in the alternative feeding system.


Induction of cortical granule exocytosis of pig oocytes by spermatozoa during meiotic maturation.
Pig oocytes were examined to test their ability to undergo cortical granule exocytosis upon penetration by spermatozoa during meiotic maturation. Immature or maturing oocytes (cultured in vitro for 0 h, 26 h and 46 h) were inseminated with ejaculated boar spermatozoa in vitro. Before and after insemination, oocytes were stained with peanut agglutinin labelled with fluorescein isothiocyanate and the cortical granule distributions were examined under the fluorescent microscope and the laser confocal microscope. Before insemination, all the oocytes at the germinal vesicle stage showed a uniform distribution of cortical granules throughout the cortical cytoplasm. The granules migrated centrifugally during maturation and were distributed just beneath the oolemma in the oocytes after germinal vesicle breakdown, forming a monolayer in metaphase I or metaphase II. Cortical granules were still present in all penetrated oocytes at the germinal vesicle stage 18 h after insemination; in contrast, 26% and 84% of the oocytes inseminated at the stages of germinal vesicle breakdown or at metaphase I and II, respectively, completely released their cortical granules. Nuclear activation rates of penetrated oocytes were 0%, 38% and 96% in oocytes cultured for 0 h, 26 h and 46 h, respectively. Of the nuclear-activated oocytes, 67% (oocytes cultured for 26 h) and 88% (oocytes cultured for 46 h) released cortical granules completely. Complete cortical granule exocytosis was not observed in nuclear-inactivated oocytes. Of the nuclear-activated oocytes, 67% (oocytes cultured for 26 h) and 80% (oocytes cultured for 46 h) of monospermic oocytes and 67% (oocytes cultured for 26 h) and 91% (oocytes cultured for 46 h) of polyspermic oocytes released cortical granules, and no statistical difference was observed between oocytes cultured for 26 h or 46 h, or between monospermic and polyspermic oocytes. The proportion of oocytes with cortical granule exocytosis increased as insemination time increased and was greatest 18 h after insemination in oocytes cultured for 26 h and 46 h; no obvious changes were observed when the insemination time was prolonged to 24 h. These results indicate that pig oocytes develop the ability to release cortical granules after penetration by spermatozoa following germinal vesicle breakdown, and that this ability is not fully developed until metaphase II. Cortical granule exocytosis is accompanied by nuclear activation, suggesting that both nuclear and cytoplasmic maturation are responsible for the cortical reaction. Polyspermy may be a result of a complete failure of cortical granule exocytosis in immature oocytes and delayed CG exocytosis in matured oocytes.


[Intussusception and Rectal Prolapse: A Common Cause for Defecation Disorders].
A rectal prolapse is mainly a disease of the elderly population, occurring more frequently among women. The medical practitioner has an important role in the recognition and initiation of therapy for rectal prolapse. Appropriate therapy can have an important impact on symptom reduction and healthcare resources. Surgical therapy includes perineal or transabdominal surgery, with increasing use of minimally invasive techniques such as mesh rectopexy. This operation is indicated and feasible regardless of age. The management of the rectal prolapse in specialized pelvic floor centres with interdisciplinary expertise for diagnosis and therapy is recommended.


Professional staff education. Quantifying costs and outcomes.
In today's cost-conscious marketplace, it is critical to identify the true costs of professional staff development within a healthcare organization. Many hidden costs can be difficult to quantify. This article will help administrators identify these costs, and decide whether their professional staff education would be done better internally or using outside resources.


Role of macrophages in tumor progression and therapy (Review).
The number and phenotype of macrophages are closely related to tumor growth and prognosis. Macrophages are recruited to (and polarized at) the tumor site thereby promoting tumor growth, stimulating tumor angiogenesis, facilitating tumor cell migration, and creating a favorable environment for subsequent colonization by (and survival of) tumor cells. These phenomena contribute to the formation of an immunosuppressive tumor microenvironment (TME) and therefore speed up tumor cell proliferation and metastasis and reduce the efficacy of antitumor factors and therapies. The ability of macrophages to remodel the TME through interactions with other cells and corresponding changes in their number, activity, and phenotype during conventional therapies, as well as the association between these changes and drug resistance, make tumor‑associated macrophages a new target for antitumor therapies. In this review, advantages and limitations of the existing antitumor strategies targeting macrophages in Traditional Chinese and Western medicine were analyzed, starting with the effect of macrophages on tumors and their interactions with other cells and then the role of macrophages in conventional treatments was explored. Possible directions of future developments in this field from an all‑around multitarget standpoint were also examined.


Might the kinetic behavior of hormone-sensitive lipase reflect the absence of the lid domain?
Hormone-sensitive lipase (HSL) is thought to contribute importantly to the mobilization of fatty acids from the triacylglycerols (TAGs) stored in adipocytes, providing the main source of energy in mammals. To investigate the HSL substrate specificity more closely, we systematically assessed the lipolytic activity of recombinant human HSL on solutions and emulsions of various vinyl esters and TAG substrates, using the pH-stat assay technique. Recombinant human HSL activity on solutions of partly soluble vinyl esters or TAG was found to range from 35 to 90% of the maximum activity measured with the same substrates in the emulsified state. The possible existence of a lipid-water interface due to the formation of small aggregates of vinyl esters or TAG in solution may account for the HSL activity observed below the solubility limit of the substrate. Recombinant human HSL also hydrolyzes insoluble medium- and long-chain acylglycerols such as trioctanoylglycerol, dioleoylglycerol, and olive oil, and can therefore be classified as a true lipase. Preincubation of the recombinant HSL with a serine esterase inhibitor such as diethyl p-nitrophenyl phosphate in 1:100 molar excess leads to complete HSL inhibition within 15 min. This result indicates that the catalytic serine of HSL is highly reactive and that it is readily accessible. Similar behavior was also observed with lipases with no lid domain covering their active site, or with a deletion in the lid domain. The 3-D structure of HSL, which still remains to be determined, may therefore lack the lid domain known to exist in various other lipases.


Chemical profiles of scent gland secretions in the cyphophthalmid opilionid harvestmen, Siro duricorius and S. exilis.
Gas chromatographic-mass spectrometric analyses of the scent gland secretions of Siro duricorius and S. exilis (Opiliones, Cyphophthalmi, Sironidae) revealed a set of 24 components, comprising a series of saturated and unsaturated methyl ketones (C11-C15) and four naphthoquinones. Whereas the scent gland secretions of S. duricorius, collected in Austria, and S. exilis from USA were qualitatively nearly indistinguishable (with the exception of acetophenone that was specific to S. duricorius), they distinctly differed in their relative quantitative compositions: major components of the secretion of S. duricorius were 7-tridecen-2-one, tridecan-2-one, undecan-2-one, 1,4-naphthoquinone, 6-methyl-1,4-naphthoquinone (tentatively identified only), and 4-chloro-1,2-naphthoquinone. In contrast, in S. exilis a compound tentatively identified as 6-methyl-4-chloro-1,2-naphthoquinone was present in large amounts (in S. duricorius a trace component), whereas undecan-2-one only occurred in minor quantities. Secretion profiles of juveniles and adults (both sexes) of each species showed high correspondence. This is the first report on the chemistry of scent gland secretions of the opilionid suborder Cyphophthalmi. 4-Chloro-1,2-naphthoquinone was identified as a new exocrine product of arthropods, whereas 1,4-naphthoquinone and the tentatively identified 6-methyl-1,4-naphthoquinone are known constituents of exocrine secretions from one species of palpatorid opilionids, Phalangium opilio. In contrast, all ketones identified were new for opilionid scent glands, although similar ketones are characteristic of scent gland secretions of palpatorid genera Leiobunum and Hadrobunus. With regard to the near-basic position of Cyphophthalmi in currently proposed phylogenetic trees of Opiliones, naphthoquinones and ketones from Siro may represent the condition ancestral to the (derived) naphthoquinone- and ketone-rich secretions in phalangid Palpatores.


Translating High-Throughput Phenotyping into Genetic Gain.
Inability to efficiently implement high-throughput field phenotyping is increasingly perceived as a key component that limits genetic gain in breeding programs. Field phenotyping must be integrated into a wider context than just choosing the correct selection traits, deployment tools, evaluation platforms, or basic data-management methods. Phenotyping means more than conducting such activities in a resource-efficient manner; it also requires appropriate trial management and spatial variability handling, definition of key constraining conditions prevalent in the target population of environments, and the development of more comprehensive data management, including crop modeling. This review will provide a wide perspective on how field phenotyping is best implemented. It will also outline how to bridge the gap between breeders and 'phenotypers' in an effective manner.


Contributions of arachidonic acid derivatives and substance P to the sensitization of cutaneous nociceptors.
1. The role of presumed chemical mediators of inflammation in the heat-induced sensitization of cutaneous C-polymodal nociceptors (CPNs) was examined in a rabbit ear preparation maintained in vitro by intra-arterial perfusion with a solution free of protein and cellular elements. 2. In this preparation, CPNs consistently showed enhanced responsiveness after repeated exposure of their receptive fields to noxious levels of heat. The average magnitude of sensitization was quantitatively similar to that observed in vivo, suggesting that blood-born factors are not essential for development of sensitization. 3. Sensitization in one-half of randomly selected CPNs was blocked or reduced when the perfusate contained a cyclooxygenase inhibitor, indomethacin or dipyrone, or the dual cyclooxygenase/lipoxygenase inhibitor, BW755C, even though initial responsiveness to heat and pressure was unaltered. These observations suggest that arachidonic acid breakdown products, possibly prostaglandins, are intermediaries in the sensitization of some, but not all, C-fiber nociceptors of the skin. In addition, heat-induced sensitization for some C-fiber cutaneous nociceptors is the result of processes that are at least partially independent of those involved in excitation. 4. Substance P (SP) or the putative SP antagonists, [D-Pro2, D-Trp7.9]-SP or [D-Pro2, D-Phe7, D-Trip9]-SP, produced no significant effect on heat-responsiveness or sensitization, although ongoing activity may have marginally increased over control levels after repeated heat stimulations. We conclude that SP in an in vitro preparation is not involved in the enhancement of cutaneous C-fiber nociceptor responsiveness after repeated thermal insults.


Personal knowing in cancer nursing.
Nursing practice involves the use of different types of knowledge. This article provides an analysis of personal knowing, one type of nursing knowledge. It uses an example from the cancer nursing literature that reflects the creative and expressive dimensions of personal knowing. The author discusses the social/political process used to determine the validity of this way of knowing and comments on the invaluable contribution that the practice of personal knowing and all types of nursing knowledge lend to the discipline of nursing and to the art and science of cancer nursing.


A plea for conservative treatment of large, unruptured omphaloceles.
Forty-six babies with an unruptured omphalocele were admitted over a 10-year period. The conservative treatment consisted of the application of mercurochrome or an antibiotic powder, while the primary surgical treatment consisted of either full-layer closure or silastic sac insertion. Liver containing omphaloceles were considered large. Of the 25 babies without associated life-threatening congenital anomalies, all 9 with a small omphalocele survived, irrespective of the method of treatment. Sixteen babies had a large omphalocele of which all 8 conservatively treated babies survived against only 4 of the 7 who underwent surgery. The remaining baby, weighting 960 g, died prior to treatment, due to respiratory distress. Eighteen of the 21 babies with associated life-threatening congenital anomalies died, irrespective the extent of the defect. Although the conservative treatment of the large defects did not result in an improved survival rate, therapy-related complications did not occur. From this study it appears that large unruptured omphaloceles should be treated conservatively. Babies not doing well with a small omphalocele or a large one treated conservatively, will have one or more major associated anomalies, necessitating urgent diagnosis and treatment.


Effects of Temperature on the Age-Stage, Two-Sex Life Table of Bradysia odoriphaga (Diptera: Sciaridae).
The demographics of Bradysia odoriphaga were examined with an age-stage, two-sex life table that was developed at 15, 20, 25, and 30°C under controlled conditions. The intrinsic rate of increase and mean generation time were 0.0574 and 48.08 d at 15°C, 0.1175 and 30.09 d at 20°C, 0.1369 and 26.31 d at 25°C, and 0.1247 and 26.55 d at 30°C, respectively. The gross reproductive rate (GRR), the net reproductive rate (R0), and the pre-adult survivorship (la) were consistent with the relationship R0<la×GRR<GRR. Development was slower at 15°C than at the other temperatures. The mean duration of the total pre-adult stages was 38.01, 27.62, 23.74, and 24.10 d at 15, 20, 25, and 30°C, respectively. The highest values for the intrinsic rate of increase, finite rate of increase, and fecundity (0.1369 d(-1), 1.147 d(-1), and 50.53 eggs, respectively) and the shortest mean generation time were at 25°C. Still, B. odoriphaga was able to develop, survive, and reproduce across the entire temperature range (15-30°C). This study provides insight into the temperature-dependent phenology of B. odoriphaga and will contribute to the modeling of its population dynamics and to its management in the field.


Ascorbic acid protects against levodopa-induced neurotoxicity on a catecholamine-rich human neuroblastoma cell line.
Levodopa, at concentrations of 0.25 x 10(-4) M or larger, is toxic for the human neuroblastoma cell NB69. Toxicity is associated with high levels of quinones, increased activity of complex II-III, and lack of changes of complex I of the mitochondrial respiratory chain. Deprenyl, which does not alter the production of quinones, has a partial protective effect. Tocopherol, 23 or 115 x 10(-6) M, lacks significant preventive effect on levodopa toxicity, but ascorbic acid, 10(-3) M, prevents levodopa toxicity and quinone formation. Deprenyl, 10(-4) M, provides additional protection in cultures treated with levodopa and ascorbic acid. Our results indicate that ascorbic acid and deprenyl prevent levodopa neurotoxicity by unrelated mechanisms. Both compounds should be considered as complementary drugs to test for slowing the progression of Parkinson's disease.


Genome-Wide SNP Data Revealed the Extent of Linkage Disequilibrium, Persistence of Phase and Effective Population Size in Purebred and Crossbred Buffalo Populations.
Linkage disequilibrium (LD) is a useful parameter for guiding the accuracy and power of both genome-wide association studies (GWAS) and genomic selection (GS) among different livestock species. The present study evaluated the extent of LD, persistence of phase and effective population size (Ne) for the purebred (Mediterranean buffalo; n = 411) and crossbred [Mediterranean × Jianghan × Nili-Ravi buffalo, n = 9; Murrah × Nili-Ravi × local (Xilin or Fuzhong) buffalo, n = 36] buffalo populations using the 90K Buffalo SNP genotyping array. The results showed that the average square of correlation coefficient (r 2) between adjacent SNP was 0.13 ± 0.19 across all autosomes for purebred and 0.09 ± 0.13 for crossbred, and the most rapid decline in LD was observed over the first 200 kb. Estimated r 2 ≥ 0.2 extended up to ~50 kb in crossbred and 170 kb in purebred populations, while average r 2 values ≥0.3 were respectively observed in the ~10 and 60 kb in the crossbred and purebred populations. The largest phase correlation (R P, C = 0.47) was observed at the distance of 100 kb, suggesting that this phase was not actively preserved between the two populations. Estimated Ne for the purebred and crossbred population at the current generation was 387 and 113 individuals, respectively. These findings may provide useful information to guide the GS and GWAS in buffaloes.


Prevention and treatment of postpartum hemorrhage: new advances for low-resource settings.
Postpartum hemorrhage due to uterine atony is the primary direct cause of maternal mortality globally. Management strategies in developed countries involve crystalloid fluid replacement, blood transfusions, and surgery. These definitive therapies are often not accessible in developing countries. Long transports from home or primary health care facilities, a dearth of skilled providers, and lack of intravenous fluids and/or a safe blood supply often create long delays in instituting appropriate treatment. We review the evidence for active management of third-stage labor and for the use of specific uterotonics. New strategies to prevent and manage postpartum hemorrhage in developing countries, such as community-based use of misoprostol, oxytocin in the Uniject delivery system, the non-inflatable antishock garment to stabilize and resuscitate hypovolemic shock, and the balloon condom catheter to treat intractable uterine bleeding are reviewed. New directions for clinical and operations research are suggested.


Spontaneous decompression of a posterior fossa arachnoid cyst: a case report.
The authors present a case of spontaneous regression of a posterior fossa, supracerebellar arachnoid cyst causing hydrocephalus in a 7-month-old male child. The patient presented with macrocrania, bulging fontanelle and upgaze paresis of the eyes. There was complete improvement of these symptoms on the morning of the day of surgery without any obvious precipitating factors, including trauma. CT scan showed complete resolution of the cyst and hydrocephalus. The child was doing well at 1 year of follow-up. To the best of our knowledge, this is the first case report of spontaneous resolution of a posterior fossa arachnoid cyst.


Clinical Significance of PD1 and PDL1 in Human Breast Cancer.
Programmed death 1 (PD1) and its ligand programmed death ligand 1 (PDL1) form a pathway which when activated is thought to result in suppression of antitumor adaptive responses, influencing antitumor immunity. With potential targeted therapies emerging against PDL1, we investigated the clinical significance of mRNA expression levels of PD1 and PDL1 in our breast cancer cohort to explore its association with disease progression and prognosis. Previous studies evaluating the expression of PD1 and PDL1 (mRNA or protein) and its association with prognosis in breast cancer showed both positive and negative correlations and hence remain controversial. Quantitative polymerase chain reaction was used to determine transcript expression levels of PD1 and PDL1 in a cohort consisting of primary breast cancer tissues (n=127) and matching non-neoplastic background tissues (n=33) with available clinical and pathological information. Two-sample two-tailed t-test, Kaplan-Meier survival analysis and Wilcoxon tests were performed. Significant PDL1 transcript level reductions were seen in patients who developed metastases, as well as those who had local recurrence, compared to patients who remained disease-free. Higher PDL1 transcript levels were also associated with better overall and disease-free survival. Significantly higher transcript expression levels of PD1 were found in tumor tissue, whilst a general increase in PDL1 expression was found in tumor tissues, although this did not reach statistical significance. Our study demonstrates higher levels of expression of PDL1 are associated with favorable clinical outcome.


Identification and initial characterization of 6,000 expressed sequenced tags (ESTs) from rat normal-growing cartilage and swarm rat chondrosarcoma cDNA libraries.
Chondrosarcoma is the second most common type of skeletal malignancy with a survival rate at five years for histological grade III of only 29 percent. The development of a reliable chondrosarcoma animal model could enable the study of tumor growth and progression, the effect of the host on tumor behavior, and the effectiveness of various therapeutic modalities. The Swarm rat chondrosarcoma is a tumor tissue line that has been maintained through the years by serial subcutaneous injections, and the histochemical characteristics of the tumor have remained essentially similar in all transplants over the years. This study was designed to initiate the characterization of the Swarm rat chondrosarcoma model by gene expression profiling as compared to normal-growing rat cartilage. Analysis of the gene expression from both libraries revealed a complex pattern of gene expression, including many genes not yet reported to be expressed by chondrocytes. It suggests that the biochemical characterization of growing cartilage and chondrosarcoma reported to date has only begun to describe the complexity of these tissues.


Effect of gamma radiation and oregano essential oil on murein and ATP concentration of Listeria monocytogenes.
The effects of gamma radiation and of oregano essential oil alone or in combination with radiation on murein composition of Listeria monocytogenes and on the intracellular and extracellular concentration of ATP were evaluated. The bacterial strain was treated with two radiation doses, 1.2 kGy to induce cell damage and 3.5 kGy to cause cell death. Oregano essential oil was used at 0.020 and 0.025% (wt/vol), which is the MIC. All treatments had a significant effect (P < or = 0.05) on the murein composition, although some muropeptides did not seem to be affected by the treatment. Each treatment influenced differently the relative percentage and number of muropeptides. There was a significant correlation (P < or = 0.05) between the reduction of intracellular ATP and increase in extracellular ATP, following treatment of the cells with oregano oil. The reduction of intracellular ATP was even more important when essential oil was combined with irradiation, but irradiation of L. monocytogenes alone induced a significant decrease (P < or = 0.05) of the internal ATP without affecting the external ATP. Transmission electron microscopic observation revealed that oregano oil and irradiation have an effect on cell wall structure.


Screening for early childhood hearing loss in Nigeria.
Newborn hearing screening has been recognized as an essential component of public health care in early childhood in developed countries. However, such screening is yet to be widely embraced in the developing world. The new national health policy in Nigeria seeks, for the first time, to reduce the impact of permanent hearing loss on early childhood development through early detection and timely intervention services. The aim of this paper is to ascertain if newborn hearing screening satisfies the conventional criteria for a screening programme as an early detection strategy in this developing country. A review of the available literature shows that permanent childhood hearing loss is a significant health condition and its detection through screening with oto-acoustic emissions and/or auditory brainstem response is feasible in the target population. Amplification with hearing aids is an effective and preferred option for early intervention by parents. The risk of maternal anxiety from potential false-positives or the psychological cost of false assurance from false-negatives is unlikely to outweigh the benefit of screening. Newborn hearing screening is therefore a potential early detection strategy for permanent childhood hearing loss in Nigeria.