Construction of a Novel Polychlorinated Biphenyl-Degrading Bacterium: Utilization of 3,4'-Dichlorobiphenyl by Pseudomonas acidovorans M3GY.
Pseudomonas acidovorans M3GY is a recombinant bacterium with the novel capacity to utilize a biphenyl congener chlorinated on both rings, 3,4'-dichlorobiphenyl (3,4'-DCBP), as a sole carbon and energy source. Strain M3GY was constructed with a continuous amalgamated culture apparatus (L. Kröckel and D. D. Focht, Appl. Environ. Microbiol. 53:2470-2475, 1987) with P. acidovorans CC1(19), a chloroacetate and biphenyl degrader, and Pseudomonas sp. strain CB15(1), a biphenyl and 3-chlorobenzoate degrader. Genetic and phenotypic data showed the recipient parental strain to be P. acidovorans CC1 and the donor parental strain to be Pseudomonas sp. strain CB15. In growth experiments with 3,4'-DCBP as a sole source of carbon, cultures of strain M3GY increased in absorbance from 0.07 to 0.39 in 29 days while reaching a protein concentration of 58 mug ml and 67% substrate dehalogenation. 4-Chlorobenzoate was identified from culture supernatants of strain M3GY by gas chromatography-infrared spectrometry-mass spectrometry; this would be consistent with the oxidation of the m-chlorinated ring through the standard biphenyl pathway. 4-Chlorobenzoate was converted to 4-chlorocatechol, which was metabolized through the meta-fission pathway. The construction of P. acidovorans M3GY, with the novel capability to utilize 3,4'-DCBP, thus involves the complete use of meta-fission pathways for sequential rupture of the biphenyl and chlorobenzoate rings.


[Nonspecific immunity factors in calves in relation to the corticosteroid hormone content].
Studied were a total of 133 blood samples from 19 calves to follow up the level of cortizol from birth up to the age of 3 months (at the 4th and 24th hour, on the 10th day, and at 1 and 3 months of age). It was found that in relatively constant concentrations of the total protein the ratio of the albumin and the globulin fraction varied in accordance with the level of cortizol. The concentration of cortizol at birth was high (60.3 ng/cm3). It was demonstrated that the high level of cortizol had a suppressive action with regard to the absorption of colostral gamma-globulins. The drop of the cortizol level led to the rise of the gamma-globulin amount in the blood. The factors of unspecific resistance were also followed up, such as lysozyme and complement- and phagocyte-activity. A direct dependence was established between the cortizol level and the gamma-globulin concentration and the indices of natural resistance.


The effects of intradermal vaccination with DNA encoding for the T-cell receptor on the induction of experimental autoimmune encephalomyelitis in B10.PL mice.
Intradermal gene administration was found to induce a more profound immune response than direct intramuscular gene injection. We performed intradermal vaccination of B10.PL mice with DNA encoding for the V 8.2 region of the T-cell receptors (TCR). Three weeks later, these mice were immunized with rat myelin basic protein (MBP). Daily mean clinical scores and mortality rate were lower in this group compared with controls. The proliferative responses of lymph node cells to rat MBP were slightly less in the vaccination groups than in the control groups (p < 0.05). However, we detected no differences between the two groups with regard to the production of MBP-specific IgG, IgG1, & IgG2a antibodies. The levels of cytokine mRNA expression in the vaccination groups were observed higher than in the control groups without antigen-specific stimulation, but all of cytokine expressions between the vaccination and control groups after antigen-specific stimulation were identical. These results demonstrate that intradermal DNA vaccines encoding for TCR might prove to be useful in the control of autoimmune disease.


Effects of Dexmedetomidine and Propofol on Postoperative Analgesia and the Cellular Immune Function of Patients Undergoing Radical Gastrectomy for Gastric Cancer.
In order to optimize the anesthesia scheme and improve the effect of surgical treatment, the effects of dexmedetomidine and propofol on postoperative analgesia and cellular immune function of patients undergoing radical gastrectomy for gastric cancer have been analyzed. A total of 86 patients admitted to our hospital from March 2021 to March 2022 who received laparoscopic radical gastritis were selected. The combined dexmedetomidine group (n = 43) and the control group (n = 43) are grouped by the random number table method, respectively. Anesthesia induction regimens of dexmedetomidine combined with propofol and conventional propofol are treated, and the changes in serum stress index, immune function index, analgesia score, and pain score are observed. The results show that the postoperative stress response, analgesic effect, and immune function of patients receiving dexmedetomidine combined with propofol anesthesia are significantly better than those receiving conventional anesthesia, and the incidence of postoperative complications in the dexmedetomidine combined group is significantly lower than that in the control group. The results demonstrate that dexmedetomidine combined with propofol anesthesia intervention has high security in undergoing radical gastrectomy for gastric cancer.


Contrasting effects of maize litter and litter-derived biochar on the temperature sensitivity of paddy soil organic matter decomposition.
Organic matter input regulates the rate and temperature sensitivity (expressed as Q 10) of soil organic matter (SOM) decomposition by changing microbial composition and activities. It remains unclear how the incorporation of litter-made biochar instead of litter affects the Q 10 of SOM decomposition. Using a unique combination of two-and three-source partitioning methods (isotopic discrimination between C3/C4 pathways and 14C labeling), we investigated: (1) how maize litter versus litter-made biochar (of C4 origin) addition influenced the Q 10 of SOM (C3 origin) under 10°C warming, and (2) how the litter or biochar amendments affected the Q 10 of 14C-labeled fresh organic matter (FOM) after long-term incubation. Compared with biochar addition, litter increased the rates and Q 10 of mass-specific respiration, SOM and FOM decomposition, as well as the contents of SOM-derived dissolved organic C (DOC) and total phospholipid fatty acids (PLFA). Litter-amended soils have much higher activities (V max) of β-glucosidase, N-acetyl-β-glucosaminidase, and leucine aminopeptidase, suggesting larger enzyme pools than in soils with biochar. The Q 10 of enzyme V max (1.6-2.0) and K m (1.2-1.4) were similar between litter-and biochar-amended soils, and remained stable with warming. However, warming reduced microbial biomass (PLFA) and enzyme activity (V max), suggesting decreased enzyme production associated with smaller microbial biomass or faster enzyme turnover at higher temperatures. Reductions in PLFA content and enzyme V max due to warming were larger in litter-amended soils (by 31%) than in the control and biochar-amended soils (by 4-11%), implying the active litter-feeding microorganisms have a smaller degree of heat tolerance than the inactive microorganisms under biochar amendments. The reduction in enzyme activity (V max) by warming was lower in soils with biochar than in the control soil. Our modeling suggested that the higher Q 10 in litter-amended soils was mainly caused by faster C loss under warming, linked to reductions in microbial biomass and growth efficiency, rather than the slightly increased SOM-originated substrate availability (DOC). Overall, using straw-made biochar instead of straw per se as a soil amendment lowers the Q 10 of SOM and FOM by making microbial communities and enzyme pools more temperature-tolerant, and consequently reduces SOM losses under warming.


Solution conformation of C-linked antifreeze glycoprotein analogues and modulation of ice recrystallization.
Antifreeze glycoproteins (AFGPs) are a unique class of proteins that are found in many organisms inhabiting subzero environments and ensure their survival by preventing ice growth in vivo. During the last several years, our laboratory has synthesized functional C-linked AFGP analogues (3 and 5) that possess custom-tailored antifreeze activity suitable for medical, commercial, and industrial applications. These compounds are potent inhibitors of ice recrystallization and do not exhibit thermal hysteresis. The current study explores how changes in the length of the amide-containing side chain between the carbohydrate moiety and the polypeptide backbone in 5 influences ice recrystallization inhibition (IRI) activity. Analogue 5 (n = 3, where n is the number of carbons in the side chain) was a potent inhibitor of ice recrystallization, while 4, 6, and 7 (n = 4, 2, and 1, respectively) exhibited no IRI activity. The solution conformation of the polypeptide backbone in C-linked AFGP analogues 4-7 was examined using circular dichroism (CD) spectroscopy. The results suggested that all of the analogues exhibit a random coil conformation in solution and that the dramatic increase in IRI activity observed with 5 is not due to a change in long-range solution conformation. Variable-temperature (1)H NMR studies on truncated analogues 26-28 failed to elucidate the presence of persistent intramolecular bonds between the amide in the side chain and the peptide backbone. Molecular dynamics simulations performed on these analogues also failed to show persistent intramolecular hydrogen bonds. However, the simulations did indicate that the side chain of IRI-active analogue 26 (n = 3) adopts a unique short-range solution conformation in which it is folded back onto the peptide backbone, orienting the more hydrophilic face of the carbohydrate moiety away from the bulk solvent. In contrast, the solution conformation of IRI-inactive analogues 25, 27, and 28 had fully extended side chains, with the carbohydrate moiety being exposed to bulk solvent. These results illustrate how subtle changes in conformation and carbohydrate orientation dramatically influence IRI activity in C-linked AFGP analogues.


Description of 48 cases of multiple myeloma seen in the hematology laboratory of the CHU-Joseph Ravoahangy Andrianavalona, Antananarivo, Madagascar.
Monoclonal gammopathies are common abnormalities and their incidence increases with age. They are detected in roughly 3 % of people older over 50 years and up to 7 % of those over 70 years. Multiple myeloma (MM) is characterized by the proliferation of plasma cells within the bone marrow and excess secretion of monoclonal immunoglobulins. In Madagascar, late performance of biological examinations such as serum protein electrophoresis overestimates MM rates. We studied 54 patient records between March 2009 and January 2015 in the biology laboratory of the Joseph Ravoahangy Andrianavalona university hospital in Antananarivo (Madagascar). Monoclonal gammopathy was associated with multiple myeloma in most cases (88.9 %). Patients' median age was 64.2 years. Men were slightly more affected than women. It is discovered most frequently due to bone symptoms (83.3 %), and anemia is always present. Monoclonal gammopathy is mostly IgG. The bone marrow study showed medullary plasmacytosis. This disease appears most often in the elderly and has a slight male predominance. Bone marrow cytology is mandatory for diagnosis.


B-Site Fe/Re Cation-Ordering Control and Its Influence on the Magnetic Properties of Sr2FeReO6 Oxide Powders.
Double-perovskite oxide Sr2FeReO6 (SFRO) powders have promising applications in spintronics due to their half-metallicity and high Curie temperature. However, their magnetic properties suffer from the existence of anti-site defects (ASDs). Here, we report on the synthesis of SFRO powders by the sol-gel process. The B-site cationic ordering degree (η) and its influence on magnetic properties are investigated. The results demonstrate that the η value is well controlled by the annealing temperature, which is as high as 85% when annealing at 1100 °C. However, the annealing atmospheres (e.g., N2 or Ar) have little effect on the η value. At room temperature, the SFRO powders crystallize in a tetragonal crystal structure (space group I4/m). They have a relatively uniform morphology and the molar ratios of Sr, Fe, and Re elements are close to 2:1:1. XPS spectra identified that Sr, Fe, and Re elements presented as Sr2+, Fe3+, and Re5+ ions, respectively, and the O element presented as O2-. The SFRO samples annealed at 1100 °C in N2, exhibiting the highest saturation magnetization (MS = 2.61 μB/f.u. at 2 K), which was ascribed to their smallest ASD content (7.45%) with an anti-phase boundary-like morphology compared to those annealed at 1000 °C (ASDs = 10.7%) or 1200 °C (ASDs = 10.95%).


Metastatic primary duodenal adeno-carcinoma responding to metronomic oral cyclophosphamide chemotherapy.
Primary adenocarcinoma of duodenum is a very rare tumour with a prevalence of only 0.3 to 1% of among all the tumours of gastrointestinal tracts. Localised tumours, if resected have good prognosis but those with metastates entails a poor prognosis, where generally palliation may be the only feasible option. Low dose continous cytotoxic treatment or metronomic chemotherapy prevents neoangiogenesis and chemoresistance thereby, provides excellent symptom relief and palliation in many advanced heavily pretreated solid malignancies. It offers as an affordable, less toxic therapy with moderate to good efficacy. Here we report a case of a 52 year female who, presented with history of maleana, pallor and pedal edema for last 2 months. Her performance status was poor (KPS 40) and she had enlarged left supraclavicular lymph node, palpable liver and vague mass in paraumbilical region. Upper GI endoscopy revealed large ulceroproliferative growth in the D2 segment and HPE showed moderately differentiated adenocarcinoma. CT scan revealed paratracheal and retroperitoneal lymphadenopathy and bone scan revealed vertebral metastasis. Patient received oral cyclophosphamide and hematinic and vitamin support, along with radiation to spine. There was near complete clinical response, and progression free period of about 32 weeks. Thus, single agent cyclophosphamide in the present case provided near total clinical response and prolonged period of freedom from disease progression with excellent palliation of symptoms. Hence in patient of advanced and metastatic small bowel cancer, with poor performance status metronomic therapy with single agent cyclophosphamide may provide viable option both for treatment and palliation.


Medical applications of polymeric materials.
This review presents a critical analysis of the use of polymeric materials in medicine, other than orthopedic and dental applications. Primary focus is on problem areas with various polymers and plastics in disposable products, implants, and devices, including artificial heart valves, cardiovascular prostheses, cardiopulmonary bypass, and hemodialysis. Several problems are presented especially in the biological evaluation of polymeric materials and devices, including species-related hematological differences and the role of the complement system in blood compatibility. Finally, examples of newer medical applications of polymeric materials are discussed, such as controlled drug delivery, polymeric drugs, and artificial skin.


Cellular and molecular basis of the asbestos-related diseases.
Asbestosis is an inflammatory and fibrotic process of the alveolar structures mediated, at least in part, by cytokines released by "activated" alveolar macrophages. The process of phagocytosis and "activation" of alveolar macrophages is poorly understood. Are all macrophages activated or only subpopulations? Which cytokines are up-regulated? How does the local milieu modulate profibrotic and antifibrotic mediators? Is protein release accompanied by up-regulation of gene transcription? Is there an ordered sequence of cytokine activity? What roles do neutrophils and lymphocytes play? How can disease progression best be quantified absent further exposure? Answers to these questions are important to direct rational strategies at interdicting the fibrotic process. The question of cancer and asbestos is more vexing. The processes of inflammation, fibrosis, and carcinogenesis appear to be closely intertwined. For example, proto-oncogenes such as c-sis (PDGF B-chain) are up-regulated in activated alveolar macrophages from fibrotic lungs; these and possibly others may play an important role in asbestos carcinogenesis. Second, asbestos can transfect DNA into cells. Furthermore, DNA can adhere to asbestos fibers, and these fibers are capable of direct transmigration into cells. The questions of the mechanisms of cigarette smoke cocarcinogenicity and latency remain. Lastly, if the bronchial epithelium is highly metaplastic throughout from cigarette smoking, what triggers a single (or several) nidus of cells to transform into carcinoma? Malignant mesothelioma poses the most challenging questions because of association with brief asbestos exposure by history. Mesothelial cells are susceptible to minute environmental manipulations, and changes occur after exposure to all fiber types. Yet epidemiologic studies point toward long amphiboles as having greater mesothelioma risk. To test this hypothesis, experimental data must be generated differentiating tumorigenesis risk from short, chrysotile fibers that can migrate to the parietal pleura from the associations of long amphiboles persisting in lung tissue. Despite the future decreasing numbers of clinical cases of asbestos-related disease, solving the important mechanistic questions remaining will contribute significantly to our understanding of fibrosis and cancer.


NEWBORNS WITH KASABACH-MERRITT PHENOMENON-ASSOCIATED KAPOSIFORM HEMANGIOENDOTHELIOMA: A REPORT OF 6 CASES.
Combination of kaposiform hemangioendothelioma (KHE) and Kasabach-Merritt phenomenon (KMP) in newborn children is a life-threatening constellation. The purpose of the study is the choice of the diagnostic and treatment methods in these patients and evaluating the effectiveness of treatment using radiological methods of investigation. The study enrolled 6 newborn patients with KHE within a period 2013 - 2018. MRI (CT) performed to make the diagnosis and evaluate treatment response. Hypervascular mass accompanied by reticular lymphedema, hyper intensive in T2 WI; isointensive in T1 WI, intense contrast enhancement, heterogeneous diffusion restriction were unique MRI characteristics of KHE. The sustained remission was achieved with treatment by propranolol (n=2), vincristine (n=1), and their combination (n=3).


Hyaluronidase 2 Deficiency Causes Increased Mesenchymal Cells, Congenital Heart Defects, and Heart Failure.
Hyaluronan (HA) is required for endothelial-to-mesenchymal transition and normal heart development in the mouse. Heart abnormalities in hyaluronidase 2 (HYAL2)-deficient (Hyal2-/- ) mice and humans suggested removal of HA is also important for normal heart development. We have performed longitudinal studies of heart structure and function in Hyal2-/- mice to determine when, and how, HYAL2 deficiency leads to these abnormalities. Echocardiography revealed atrial enlargement, atrial tissue masses, and valvular thickening at 4 weeks of age, as well as diastolic dysfunction that progressed with age, in Hyal2-/- mice. These abnormalities were associated with increased HA, vimentin-positive cells, and fibrosis in Hyal2-/- compared with control mice. Based on the severity of heart dysfunction, acute and chronic groups of Hyal2-/- mice that died at an average of 12 and 25 weeks respectively, were defined. Increased HA levels and mesenchymal cells, but not vascular endothelial growth factor in Hyal2-/- embryonic hearts, suggest that HYAL2 is important to inhibit endothelial-to-mesenchymal transition. Consistent with this, in wild-type embryos, HYAL2 and HA were readily detected, and HA levels decreased with age. These data demonstrate that disruption of normal HA catabolism in Hyal2-/- mice causes increased HA, which may promote endothelial-to-mesenchymal transition and proliferation of mesenchymal cells. Excess endothelial-to-mesenchymal transition, resulting in increased mesenchymal cells, is the likely cause of morphological heart abnormalities in both humans and mice. In mice, these abnormalities result in progressive and severe diastolic dysfunction, culminating in heart failure.


Sirolimus-based immunosuppression in liver transplantation for hepatocellular carcinoma: a meta-analysis.
Sirolimus (SRL) is a novel immunosuppressant with antitumor properties. We performed a meta-analysis to determine whether SRL can improve patient survival and decrease the risks of tumor recurrence in patients with a pretransplant diagnosis of hepatocellular carcinoma (HCC). We searched databases for controlled clinical trials assessing the survival and oncological benefits of SRL for liver transplant recipients with pretransplant HCC. Five studies with a total of 2950 participants were included in this study. In comparison with SRL-free regimens, SRL-based regimens improved overall survival at 1 [odds ratio (OR) = 4.53, 95% confidence interval (95% CI) = 2.31-8.89], 3 (OR = 1.97, 95% CI = 1.29-3.00), and 5 years (OR = 2.47, 95% CI = 1.72-3.55). The pooled results showed that in comparison with SRL-free regimens, SRL-based regimens decreased tumor recurrence (OR = 0.42, 95% CI = 0.21-0.83). No significant differences in the frequencies of episodes of major posttransplant complications were observed between the groups. In conclusion, SRL is generally safe and prolongs patient survival in liver transplant recipients with pretransplant HCC.


Aortic valve sparing and restoration with autologous pericardial leaflet extension is an effective alternative in pediatric patients.
We sought to evaluate the durability and efficacy of aortic valve repair with autologous pericardial leaflet extension in children. From 1997 through 2006, 54 patients underwent aortic valve repair with autologous pericardial leaflet extension at a mean age 8.4 +/- 5.3 years (range, 0 to 17 years). Primary endpoints were early and late mortality, freedom of reoperation, and late valve function. Thirty-day and late mortality were one in 54 (1.8%) and two in 53 (3.7%), respectively. There were seven re-operations in six patients, and one patient was re-operated twice. Re-operations were re-repairs in four cases and replacements in three cases. The mean interval between original repair and re-operation was 4.3 +/- 2.5 years. Mean severity grade of post-repair intraoperative aortic regurgitation (AR) was 0.3 (range, grade 0 to 4). At late follow-up, 87.7% of all patients had no AR or only a trace (grade 0-1). Seven patients (12.9%) had mild AR (grade 2-3) and none severe (grade 4); 94.4% had no aortic stenosis or only a trace (grade 0-1), 5.5% had mild (grade 2-3), and none severe. This technique delays potential complications from other approaches to valve pathology and allows a normal growth of the aortic annulus. Although, our data show that this technique has a low mortality and morbidity, more studies are needed to elucidate durability and late outcome.


Sustainable Growth Drivers: Unveiling the Role Played by Carbon Productivity.
In global climate change, improving carbon productivity holds great importance for China's sustainable growth. Based on panel data of 30 Chinese provinces and cities from 1997-2017, the drivers, spatial effects, and convergence characteristics of carbon productivity in China are explored by combining a factor decomposition framework and a spatial panel model. The findings show that (1) China's carbon productivity shows continuous positive growth, and the substitution effect of capital for energy dominates this changing pattern; (2) There is a β-convergence trend and club convergence in China's carbon productivity, and the spatial technology spillover accelerates the convergence rate; (3) With its accelerated industrial transformation and technological upgrading, China's current carbon productivity converges faster than its earlier stage, and the role of physical capital investment has gradually shifted to suppression. In contrast, the positive push of human capital investment has been strengthened; (4) From the perspective of the realization mechanism, the convergence of carbon productivity in China mainly comes from the convergence of energy restructuring and capital-energy substitution. These findings can help China narrow the inter-provincial carbon productivity gap in terms of improving factor structure, upgrading technology, etc., and provide references for sustainable growth decision making in China and around the world.


Adrenergic influence on bile secretion--an experimental study in the cat.
The influence on bile secretion of electrical stimulation of the splanchnic nerves and arterial infusion of adrenergic agonists was studied in anaesthetized cats. The bile salt secretion was supported by a continuous intravenous infusion of sodium glycocholate. Electrical stimulation of the splanchnic nerves reduced the volume outflow of bile from 0.71 to 0.44 ml h-1 kg-1 body wt and raised the bile acid concentration in bile, while the bile salt secretion rate was not affected. This response was reduced but not blocked by pretreatment with phentolamine, an alpha-adrenergic blocker, at a dose that prevented the blood pressure response. Infusion of noradrenaline, a mainly alpha-adrenergic agonist, into the hepatic artery mimicked the response. Infusion of isoprenaline, a beta-adrenergic agonist, also reduced the volume outflow of bile from the liver. The biliary clearances of mannitol and polyethylene glycol 900, both of which are suggested to reflect canalicular events, were reduced by stimulation of the splanchnic nerves and infusion of noradrenaline. It is concluded that stimulation of the alpha-adrenergic receptors reduces the bile acid-independent bile secretion. This reduction in bile flow induced by stimulation of the splanchnic nerves and infusion of noradrenaline is elicited mainly at the canalicular level.


Nursing Teaching Curriculum Setting by Introducing Postcompetency Model under the Vision of Internet Informatization.
The nursing curriculum is to be modernized to improve the student's skills in meeting the recent trends in medical and healthcare fields. The curriculum improvements are based on expert recommendations, authors, and informative data from different web sources. The challenging task is to improve the readability and understandability of the curriculum to real-time standards. Considering the above facts, this article introduces a refined curriculum with Internet information analysis (RC-IIA) method. The proposed method incorporates the distributed Internet, journal, and previous curriculum information within the active nursing syllabus. This prevents repetitions and less-informative content within the active curriculum. Besides, classification learning for knowledge-based representations is used within the curriculum to improve competency. Based on the refined information, a recommendation-based curriculum is preferred for varying information across different standards. The proposed analysis method relies on existing and distributed information across multiple curriculum providers for leveraging the visibility and prolonging the stealth of the nursing curriculum.


[The ideal curriculum for undergraduate clinical practice training in clinical laboratory medical education].
A model core curriculum for medical education is proposed to serve as an essential basis of material to be mastered. The fundamental laboratory techniques specified by this curriculum are the following five items. 1. Ability to appropriately record a 12-lead EKG. 2. Ability to perform urinalysis. 3. Ability to prepare and examine blood smear samples. 4. Ability to select and preserve microbiological samples for analysis, and to perform Gram staining analysis. 5. Ability to perform and evaluate pregnancy test. However, many other laboratory skill items are permitted in the model curriculum, as emphasized by the individual university. Therefore, reforms require appropriate changes in the educational programs for laboratory practice on the undergraduate level. In the Toyama Medical and Pharmaceutical University, all students must study compulsory fundamental laboratory technique in the first semester of the 5th year and, in addition, 6th graders in the last two months may choose an advanced clinical training course including genetic examinations. An important feature of our clinical training program is to introduce problem-based learning(PBL) tutorial education, which utilizes reversed CPC(R-CPC). An additional elective curriculum in clinical laboratory practice will be required, providing unique training programs based on student needs, the educational principles of each university and the specialties of the instructors.


Drug-Loaded Magnetic Microhydrogel as Microwave Susceptible Agents for Cancer Multimodality Treatment and MR Imaging.
Microwave (MW) ablation has been widely recognized as one of prominent protocols for clinical cancer treatment with advantages of minimally invasive treatment, convenient operation and consistent intra-tumoral temperature. However, microwave therapeutic approach still has the risk of overheating the surrounding healthy tissues, which thus necessitates susceptible agent to concentrate the heat and enhance the treatment efficiency with lower microwave power while avoiding side effects. Herein, a doxorubicin (DOX)-loaded magnetic nanocomposite calcium alginate microhydrogel (Fe₃O₄@DOX/CAM) as microwave susceptible and MR contrast agent has been developed for in vivo tumor multimodality therapy. Membrane emulsification method was employed for the fabrication of the monodispersed microhydrogel with rather uniform size distribution. Even under microwave irradiation at extremely low microwave power (2 W), enough heat (∼50 °C) can be induced by the microhydrogel. Except for as an excellent susceptible agent for microwave thermotherapy, the as-prepared Fe₃O₄@DOX/CAM can achieve microwave responsive DOX delivery, as it was noticed that microwave heating can actually facilitate drug release. Moreover, such multifunctional Fe₃O₄@DOX/CAM can be administered by intra-tumoral injection to achieve MW thermotherapy combined with sustainable chemotherapy. Meanwhile, the magnetic nanoparticles incorporated within the microhydrogel can be applied for T₂-weighted MR image during the cancer treatment. In summary, our observations on such Fe₃O₄@DOX/CAM suggest an effective microwave susceptible agent for cancer multimodality treatment and imaging.


Effects of the 5-HT6 receptor antagonist idalopirdine on extracellular levels of monoamines, glutamate and acetylcholine in the rat medial prefrontal cortex.
Idalopirdine (Lu AE58054) is a high affinity and selective antagonist for the human serotonin 5-HT6 receptor (Ki 0.83nM) in phase III development for mild-to-moderate Alzheimer's disease as an adjunct therapy to acetylcholinesterase inhibitors (AChEIs). We have studied the effects of idalopirdine on extracellular levels of monoamines, glutamate and acetylcholine in the medial prefrontal cortex (mPFC) of freely-moving rats using microdialysis. Idalopirdine (10mg/kg p.o.) increased extracellular levels of dopamine, noradrenaline and glutamate in the mPFC and showed a trend to increase serotonin levels. No effect was observed on acetylcholine levels. The AChEI donepezil (1.3mg/kg s.c.) significantly increased the levels of acetylcholine. Pretreatment with idalopirdine 2h prior to donepezil administration potentiated the effect of donepezil on extracellular acetylcholine levels. The idalopirdine potentiation of donepezil-induced increase in acetylcholine levels was also observed during local infusion of idalopirdine (6µg/ml) into the mPFC by reverse dialysis. The data from the current study may provide a mechanistic model for the pro-cognitive effects observed with administration of idalopirdine in donepezil-treated patients with Alzheimer's disease observed in the phase 2 studies (Wilkinson et al. 2014).


Computed tomography in the diagnosis of subcapsular and perirenal hematoma.
Six patients are described in whom subcapsular and perirenal hematomas were demonstrated by computed tomography. This new diagnostic tool provided a rapid noninvasive means of visualizing the hematoma, its extent, location, and relationship to renal parenchyma. Serial examinations were used to follow progress of the hematomas toward resolution. Correlation is made with conventional rediography, angiography, and gray scale ultrasound.


Combining a scientific approach and prototyping in the design of EHCR systems.
In this paper, it is emphasized that electronic medical record systems cannot totally be developed in the traditional way. The underlying process of how physicians or nurses are searching for information is not fully understood. Therefore, a method that combines a scientific approach and prototyping is advocated. With the help of this advocated approach, these questions could be answered in a way that was also scientifically sound. In this contribution, two examples of the use of this method are presented. One concerns the determination of the optimum granularity of the narrative parts of the electronic healthcare record (EHCR) and the other concerns the use and impact of stand-alone protocol systems.


Pramlintide as an adjunct to insulin therapy improves long-term glycemic and weight control in patients with type 2 diabetes: a 1-year randomized controlled trial.
Mealtime amylin replacement with the human amylin analog pramlintide, as an adjunct to mealtime insulin replacement, reduces postprandial glucose excursions in patients with type 2 diabetes. The aim of the present study was to assess the long-term efficacy and safety of pramlintide in this patient population. In a 52-week, double-blind, placebo-controlled, parallel-group, multicenter study, 656 patients with type 2 diabetes (age 57 +/- 10 years, diabetes duration 12 +/- 7 years, BMI 34.0 +/- 7.0 kg/m(2), HbA(1c) 9.1 +/- 1.2%, mean +/- SD) treated with insulin (alone or in combination with sulfonylureas and/or metformin) were randomized to receive additional preprandial subcutaneous injections of either placebo or pramlintide (60 micro g TID, 90 microg BID, or 120 microg BID). Treatment with pramlintide 120 micro g BID led to a sustained reduction from baseline in HbA(1c) (-0.68 and -0.62% at weeks 26 and 52, respectively), which was significantly greater than that seen with placebo (P < 0.05). The proportion of patients achieving an HbA(1c) <8% was approximately twofold greater with pramlintide (120 microg BID) than with placebo (46 vs. 28%, P < 0.05). The glycemic improvement with pramlintide 120 micro g BID was accompanied by a mean weight loss (-1.4 kg vs. +0.7 kg with placebo at week 52, P < 0.05) and occurred without an overall increase in the severe hypoglycemia event rate. The most common adverse event associated with pramlintide use was transient, mild-to-moderate nausea. Mealtime amylin replacement with pramlintide 120 microg BID, as an adjunct to insulin therapy, improves long-term glycemic and weight control in patients with type 2 diabetes.


Comprehensive prediction of immune microenvironment and hot and cold tumor differentiation in cutaneous melanoma based on necroptosis-related lncRNA.
As per research, causing cancer cells to necroptosis might be used as a therapy to combat cancer drug susceptibility. Long non-coding RNA (lncRNA) modulates the necroptosis process in Skin Cutaneous Melanoma (SKCM), even though the precise mechanism by which it does so has yet been unknown. RNA sequencing and clinical evidence of SKCM patients were accessed from The Cancer Genome Atlas database, and normal skin tissue sequencing data was available from the Genotype-Tissue Expression database. Person correlation analysis, differential screening, and univariate Cox regression were successively utilized to identify necroptosis-related hub lncRNAs. Following this, we adopt the least absolute shrinkage and selection operator regression analysis to construct a risk model. The model was evaluated on various clinical characteristics using many integrated approaches to ensure it generated accurate predictions. Through risk score comparisons and consistent cluster analysis, SKCM patients were sorted either high-risk or low-risk subgroups as well as distinct clusters. Finally, the effect of immune microenvironment, m7G methylation, and viable anti-cancer drugs in risk groups and potential clusters was evaluated in further detail. Included USP30-AS1, LINC01711, LINC00520, NRIR, BASP1-AS1, and LINC02178, the 6 necroptosis-related hub lncRNAs were utilized to construct a novel prediction model with excellent accuracy and sensitivity, which was not influenced by confounding clinical factors. Immune-related, necroptosis, and apoptosis pathways were enhanced in the model structure, as shown by Gene Set Enrichment Analysis findings. TME score, immune factors, immune checkpoint-related genes, m7G methylation-related genes, and anti-cancer drug sensitivity differed significantly between the high-risk and low-risk groups. Cluster 2 was identified as a hot tumor with a better immune response and therapeutic effect. Our study may provide potential biomarkers for predicting prognosis in SKCM and provide personalized clinical therapy for patients based on hot and cold tumor classification.


Adherence to burn center referral criteria: are patients appropriately being referred?
The American Burn Association (ABA) has an established set of criteria for burn center referral to guide healthcare providers and improve patient outcomes. As U.S. healthcare becomes increasingly focused on improving quality of care (ie, pay-for-performance initiatives), assessing and monitoring the referral patterns to burn centers is critical in providing optimal burn care. Few studies have compared admission, treatment, and discharge patterns at burn centers and nonburn centers. Our goal was to compare practice and referral guidelines for patients with burn injuries by reviewing every discharge record in our state over a 2-year period. The study was conducted in a retrospective fashion using our state's hospital association patient database of International Classification of Diseases, 9th revision (ICD-9) discharge codes, querying 940.00 to 948.99, over the period of October 1, 2005, to September 30, 2007. Additional variables abstracted included the discharging hospital, outcome, race, gender, payor status, length of stay, procedures, and age. Adherence to referral criteria was established by comparing the discharge ICD-9 codes with the burn center referral criteria established by the ABA and American College of Surgeons Committee on Trauma in Guidelines for the Operation of Burn Centers. Injury patterns were analyzed using the 2 burn centers in our state and the remaining 107 nonburn centers providing care to burn patients. A total of 2036 adult patients aged 18 to 106 years sustained burn injuries requiring hospital admission, and 1416 (70%) met ABA referral criteria based on ICD-9 codes. Of the 1084 patients treated at burn centers, 88% met referral criteria. Of the 952 burns treated entirely at nonburn centers, 48% met referral criteria but were not transferred. The most common burns treated at nonburn centers included injuries to the hand, wrist, face, neck, and lower extremity. The mean number of criteria met by patients treated at nonburn centers was 1.5, and all deaths occurring at nonburn centers met referral criteria. A significantly higher percentage of patients with Medicare were not transferred from nonburn centers (P < or = .00001), and a significantly higher percentage of patients were discharged to nursing homes as opposed to home (P = .01) from nonburn centers. Forty-seven percent of the patients sustaining burn injuries in our state receive all of their acute inpatient care at nonburn centers, and almost half of these met ABA burn center referral criteria. Given the disparity in discharge placement and immediate availability of burn specialists in our state, all patients meeting ABA referral criteria should be referred to burn centers. More focused outreach and education for initial providers may help improve access and referral to burn centers.


Evaluation of serological tests detecting Chlamydophila pneumoniae-specific immunoglobulin M antibody.
To evaluate a newly developed enzyme-linked immunosorbent assay (ELISA) (Hitazyme C. pneumoniae) detecting Chlamydophila pneumoniae-specific immunoglobulin M (IgM) antibody, we compared the assay with culturing, immunoblotting and the microimmunofluorescence (MIF) test. Two hundred five patients with stable chronic lung diseases without acute respiratory tract infections (ARTIs) and 116 healthy volunteers without ARTIs were enrolled in this study. Nasopharyngeal swab specimens and sera were obtained from all subjects for isolation and serological testing of C. pneumoniae. C. pneumoniae IgM-positive results were observed in 16.5% of patients with stable chronic lung diseases and in 8.6% of asymptomatic healthy subjects. However, there were no positive cases with cell culture, immunoblot or MIF test. In addition, no cases with a significant increase in IgA or IgG antibody titer for the ELISA kit and MIF test between paired sera were observed in the followed-up groups. IgM-positive cases were more frequent among patients with chronic obstructive pulmonary disease (p=0.1566), collagen disease-associated interstitial lung disease (p<0.0001) and cryptogenic organizing pneumonia (p=0.0199) than among the healthy subjects. Our results indicate that IgM-positive results with the ELISA kit do not always reflect acute C. pneumoniae infections. Further studies are needed, to determine an appropriate cut-off level and the possible causes of the false-positive results in the ELISA kit, such as other underlying conditions.


Live birth rate according to maternal age and previous number of recurrent miscarriages.
In Japan, marital age and women's age at the first pregnancy are continuing to increase year by year. However, information concerning subsequent live birth rate according to maternal age and number of previous recurrent miscarriages is limited. We studied a total of 1250 unexplained patients suffering two or more consecutive miscarriages. We examined the live birth rate at the first pregnancy and the cumulative success rate for birth of at least one child after examination. The live birth rate of women in their 40s was 58.1%, which was similar to that of women who were 35-39 years old (58.4%) at the first pregnancy, as found after examination. From logistic regression, women's age and the number of previous miscarriages independently decreased the live birth rate in subsequent pregnancies (p(s)) as well as cumulative pregnancies (p(c)), as follows: logit (p(s)) = 3.964 - 0.0652 x (age) - 0.408 x (previous number of miscarriages), logit(p(c)) = 6.806 - 0.1130 x (age) - 0.514 x (previous number of miscarriages). The information concerning the live birth rate can be given to each patient before subsequent pregnancy.


Anti-proliferative effects of 1,2-diphenylethane oestrogens and anti-oestrogens on human breast cancer cells.
The anti-tumour activities of 1,2-diphenylethane oestrogens (hexoestrol and orthohexoestrol) and anti-oestrogens (metahexoestrol, tetramethylHES, and metatetramethylHES) were studied on the human MCF-7 and MDA-MB-231 breast cancer cell lines. On the E2R-positive MCF-7 cell line, all test compounds exhibited a dose-dependent inhibition of cell proliferation, but no correlation between anti-proliferative activity and binding affinity for the E2R was found. Tested on the E2R-negative MDA-MB-231 cell line, metahexoestrol also showed dose-dependent inhibitory effects, but higher concentrations were necessary than on the MCF-7 cell line. From this it is concluded that the anti-proliferative effect is specific and at least partially mediated via the E2R. Combination of metahexoestrol (10(-6)M) with E2 (10(-9) to 10(-7)M) gave no rescue effect. It is therefore suggested that this compound might be useful for therapy in the presence of high oestrogen levels, i.e. in pre-menopausal patients. The test compounds (10(-8) to 10(-6)M) could rescue the inhibitory effect of tamoxifen (10(-6)M) in a dose-dependent manner, except in the cases of metahexoestrol (10(-6)M) and tetramethylHES (10(-6)M). The latter compound exhibited a strongly additive effect at this concentration.


Coronary arteriovenous fistula as a cause for reversible thallium-201 perfusion defect.
Exercise 201Tl SPECT imaging has become routinely accepted and utilized as a major screening test for atherosclerotic coronary artery disease. In appropriate clinical situations, an abnormal 201Tl study usually will require a subsequent coronary angiogram to confirm the presence of an abnormality and to define its pathologic anatomy. Although most reversible thallium defects will prove to be secondary to significant coronary artery atherosclerosis, congenital coronary or cardiac anomalies can occasionally be responsible, and it is useful to be aware of these, particularly in the evaluation of relatively young symptomatic patients. We report, for the first time, a coronary arteriovenous fistula as the cause for an exercise-induced reversible 201Tl perfusion abnormality.


Gender's Effect on a School-Based Intervention in The Prepubertal Growth Spurt.
Children aged 10-11 years pass through a dynamic developmental period marked by rapid changes in body size, shape, and composition, all of which are sexually dimorphic. The purpose of this study was to analyze the effects of gender on a school-based intervention in the prepubertal growth spurt. One hundred twenty-five healthy children (58 boys, 67 girls), fifth and sixth grade students from an urban public elementary school in Portugal (10.8 ± 0.4 years), were randomly assigned into two experimental groups: a strength training group (19 boys, 22 girls), and an endurance training group (21 boys, 24 girls); and a control group (18 boys, 21 girls; no training program). Training program for the two experimental groups was conducted twice a week for 8 weeks. Compared with the values at the beginning of the protocol, both strength and endurance training programs produced significant improvements (p< 0.05) in vertical and horizontal jumps, a 1 kg and 3 kg medicine ball throw, a 20 m sprint and VO2max, for both boys and girls. No significant changes were observed related to gender in training-induced strength (p> 0.05, η_p^2= 0.16, Power= 0.29) and aerobic (p> 0.05, η_p^2= 0.05, Power= 0.28) capacity. The results of the present study should be taken into consideration in order to optimize strength training school-based programs.


Taking phylogenetics beyond pattern analysis: can models of genome dynamics guide predictions about homoplasy in morphological and behavioral data sets?
Despite the considerable amount of interest in phylogeny reconstruction, patterns of homoplasy in morphological and behavioral data have received only limited attention to date, whereas the patterns of homoplasy in molecular data are relatively well understood. First, because the number of alternative molecular character states is strictly limited (particularly for nucleotide sequence data), higher rates of substitution generate higher levels of homoplasy. Second, depending on the relative proportions of constrained and unconstrained sites, each molecular data set has a time frame of applicability outside of which resolution becomes ambiguous. There is good evidence to suggest that numbers of alternative character states for morphological and even behavioral data may be similarly limited and that higher rates of evolution are often linked to higher rates of homoplasy. Like molecular data sets, morphological and behavioral data sets contain rapidly evolving characters as well as more conservative elements. Morphologies and behaviors related to sexual recognition and reproduction show low levels of intraspecific variation, but high levels of lability between species, making them crucial for species identification but often poor as markers of relationship at greater time depths. The organization theory of speciation derived by Carson is a model based on genome dynamics, and it predicts exactly this window of applicability for characters related to sexual reproduction. Nonsexual characters related to environmental adaptation should be applicable at greater phylogenetic depths. A better understanding of patterns of homoplasy enables a more sophisticated approach to the assessment of the relative reliabilities of alternative tree topologies.


Gonadotrophin-releasing hormone analogues and endometriosis: current strategies and new insights.
Endometriosis is an estrogen-dependent chronic inflammatory disease affecting 5% to 10% of women in reproductive age and has been reported also in adolescents. Its main clinical presentations are chronic pelvic pain and infertility. To provide a comprehensive review of the recently published data concerning the mechanism of action of gonadotrophin-releasing hormone analogues (GnRHas) as well as to analyze their role in the management of endometriosis-associated pain and infertility in addition to its value in adolescent cases. Furthermore, to provide practical recommendations and new insights based on the best available information. Systematic search was performed of the Cochrane Library and Medical Literature Analysis and Retrieval System Online database looking for the different trials, reviews and various guidelines relating to GnRHas usage in the management of endometriosis-associated pain, infertility and in adolescent cases. From a pathophysiological perspective, there is a growing scientific evidence that GnRHas exert its therapeutic effects by their classical pituitary downregulation and via a direct effect on the endometrial cells themselves. Accordingly, they represent an important medical option for the management of different aspects of this enigmatic disease. GnRHas have a valuable strategic role in treatment of endometriosis-associated pain and infertility as well as in adolescents above 16 years.


Land use, water and Mediterranean landscapes: modelling long-term dynamics of complex socio-ecological systems.
The evolution of Mediterranean landscapes during the Holocene has been increasingly governed by the complex interactions of water and human land use. Different land-use practices change the amount of water flowing across the surface and infiltrating the soil, and change water's ability to move surface sediments. Conversely, water amplifies the impacts of human land use and extends the ecological footprint of human activities far beyond the borders of towns and fields. Advances in computational modelling offer new tools to study the complex feedbacks between land use, land cover, topography and surface water. The Mediterranean Landscape Dynamics project (MedLand) is building a modelling laboratory where experiments can be carried out on the long-term impacts of agropastoral land use, and whose results can be tested against the archaeological record. These computational experiments are providing new insights into the socio-ecological consequences of human decisions at varying temporal and spatial scales.


Identifying clinicians' priorities for the implementation of best practices in cognitive rehabilitation post-acquired brain injury.
To identify clinicians' perceptions of current levels of implementation of cognitive rehabilitation best practices, as well as individual and consensual group priorities for implementing cognitive rehabilitation interventions as part of a multi-site integrated knowledge translation initiative. A two-step consensus-building methodology was used, that is the Technique for Research of Information by Animation of a Group of Experts (TRIAGE), including a cross-sectional electronic survey followed by consensual in-person group discussions to identify implementation priorities from a list of evidence-based practices for cognitive rehabilitation following traumatic brain injury and stroke. Thirty-eight professionals from three rehabilitation teams (n = 9, 13 and 16) participated, including neuropsychologists, occupational therapists, speech-language pathologists, educators, clinical coordinators and program managers. Descriptive statistics were used to document the perceived levels of implementation as well as individual and consensual group priorities. Most of the best practices (81-100%) were perceived as at least partially implemented by a minimum of 50% of the participants but only 20-25% of the practices were considered fully implemented. Findings suggest that current practices are mostly consistent with general cognitive rehabilitation principles suggested in guidelines but that further efforts are needed to support the application of specific cognitive rehabilitation strategies and interventions. Executive function and self-awareness retraining, as well as interventions promoting the generalization of skills, were among the highest implementation priorities. Consensual in-person group discussions, included as part of the TRIAGE process, also helped to define and operationalize these best practices into more specific intervention components according to the teams' needs and priorities. TRIAGE consensus-building methodology can be used to engage stakeholders and support clinicians' decision-making regarding the identification of implementation priorities in cognitive rehabilitation post-ABI in order to tailor the implementation process to local needs.IMPLICATIONS FOR REHABILITATIONThe Technique for Research of Information by Animation of a Group of Experts (TRIAGE) can be used to support clinicians' decision-making regarding the identification of implementation priorities in cognitive rehabilitation post-ABI.The combination of individual consultations followed by consensual in-person group discussions, as part of the TRIAGE process, may help clinicians in defining and operationalizing best practices into more specific intervention components to implement.Effective implementation strategies are needed to support the use of specific cognitive rehabilitation interventions in prioritized areas, such as executive function and self-awareness retraining, as well as generalization of skills.Some differences in clinicians' perceived priorities point up the importance of tailoring implementation to local needs and contexts from the early stages in the process.


Shear bond strengths of calcium silicate-based sealer to dentin and calcium silicate-impregnated gutta-percha.
To compare the shear bond strengths of a calcium silicate-based root canal sealer (CSS), to dentin or calcium silicate-impregnated gutta-percha (CSGP), with the shear bond strengths of an epoxy resin-based sealer. For sealer/dentin testing, 40 hemisectioned roots were divided into 2 groups. Coronal root dentin discs were bonded with CSS or epoxy resin-based sealer. For sealer/core material testing, CSGP and conventional gutta-percha discs were bonded with a matching sealer (N = 20 per group). The shear bond strengths were tested using a universal testing machine. The failed modes were analyzed using stereomicroscopy and scanning electron microscopy. The CSS sealer had significantly higher shear bond strength to dentin than did epoxy resin-based sealer (P < .01). However, shear bond strengths of the 2 sealers to core materials did not significantly differ (P = .74). The remnants of the CSS sealer adhering to dentin or calcium silicate gutta-percha disc were observed. The CSS sealer had better adhesion to dentin than did epoxy resin-based sealer. However, the bond of the CSS sealer to impregnated gutta-percha was not superior to the epoxy resin-based sealer bonded to conventional gutta-percha.


Structural basis of substrate specificity and regiochemistry in the MycF/TylF family of sugar O-methyltransferases.
Sugar moieties in natural products are frequently modified by O-methylation. In the biosynthesis of the macrolide antibiotic mycinamicin, methylation of a 6'-deoxyallose substituent occurs in a stepwise manner first at the 2'- and then the 3'-hydroxyl groups to produce the mycinose moiety in the final product. The timing and placement of the O-methylations impact final stage C-H functionalization reactions mediated by the P450 monooxygenase MycG. The structural basis of pathway ordering and substrate specificity is unknown. A series of crystal structures of MycF, the 3'-O-methyltransferase, including the free enzyme and complexes with S-adenosyl homocysteine (SAH), substrate, product, and unnatural substrates, show that SAM binding induces substantial ordering that creates the binding site for the natural substrate, and a bound metal ion positions the substrate for catalysis. A single amino acid substitution relaxed the 2'-methoxy specificity but retained regiospecificity. The engineered variant produced a new mycinamicin analog, demonstrating the utility of structural information to facilitate bioengineering approaches for the chemoenzymatic synthesis of complex small molecules containing modified sugars. Using the MycF substrate complex and the modeled substrate complex of a 4'-specific homologue, active site residues were identified that correlate with the 3' or 4' specificity of MycF family members and define the protein and substrate features that direct the regiochemistry of methyltransfer. This classification scheme will be useful in the annotation of new secondary metabolite pathways that utilize this family of enzymes.


Evaluation of thermoregulation of horses (Equus caballus) submitted to two methods of post-exercise cooling, in hot and humid climate conditions, in the Eastern Amazon.
In Brazil, the study on equine thermoregulation has not shown considerable advances, moreover, in the Amazon, this is a little explored aspect. This study aims to evaluate the thermoregulation of horses submitted to two methods of post-exercise cooling, in the climatic conditions of the Eastern Amazon. The experiment was conducted at Centro Hipico, Ananindeua, Para, for 15 days. Ten male horses, castrated of the Brazilian breed, aged 13 years and with an average weight of 482.3 kg were used. Equestrianism, which was exercised with pre-established protocol in the arena and track, for 30 min. After the exercise, the animals were divided into two groups for application of the treatments, which were two cooling methods, such as a bath with water at room temperature (about 25°C) and a hiper cooling method (6-9°C). During the experimental period, air temperature (AT) and relative humidity (RH) data were recorded and the Temperature and Humidity Index (THI) was calculated. Data from the rectal temperature (RT), heart rate (HR), respiratory rate (RR) and Body surface temperature (BST) of the animals were also measured at three moments: before exercise, after exercise and after applying the cooling methods. The adaptability index used was the Benezra Thermal Comfort Index (BTCI). The BST was performed with the help of infrared thermograph, which were the left side of the neck, thorax, rump, and right side to the armpi, before the exercise, after the exercise and after applying the cooling methods. The statistical design was completely randomized. Analysis of variance was performed using the GLM Procedure of SAS 9.1.3. After the application of the cooling techniques in the animals, the AT and THI were higher and the highest RH values were found before the exercise (87.21%). The highest RT, RR, HR, BST, and BTCI values were observed after exercise. There was no significant dierence (P > 0.05) between cooling methods. There was a highly significant and positive correlation (P < 0.01) between all physiological variables (RT, RR, HR, and BST) and the Iberian Index with AT and THI and negative with RH (P < 0.01), thus demonstrating the influence of the environment on the thermoregulation of animals. It is concluded the evaluation of stress, welfare and thermoregulation of horses submitted to two methods of post-exercise cooling, in the climatic conditions of the Eastern Amazon, demonstrated that the studied cooling methods showed to reduce the rectal temperature, the respiratory rate, the heart rate and the body surface temperature with equal efficiency. However, in terms of practical ease of use, the room temperature water cooling method has proven to be more practical.


A Mechanistic Understanding of Axon Degeneration in Chemotherapy-Induced Peripheral Neuropathy.
Chemotherapeutic agents cause many short and long term toxic side effects to peripheral nervous system (PNS) that drastically alter quality of life. Chemotherapy-induced peripheral neuropathy (CIPN) is a common and enduring disorder caused by several anti-neoplastic agents. CIPN typically presents with neuropathic pain, numbness of distal extremities, and/or oversensitivity to thermal or mechanical stimuli. This adverse side effect often requires a reduction in chemotherapy dosage or even discontinuation of treatment. Currently there are no effective treatment options for CIPN. While the underlying mechanisms for CIPN are not understood, current data identify a "dying back" axon degeneration of distal nerve endings as the major pathology in this disorder. Therefore, mechanistic understanding of axon degeneration will provide insights into the pathway and molecular players responsible for CIPN. Here, we review recent findings that expand our understanding of the pathogenesis of CIPN and discuss pathways that may be shared with the axonal degeneration that occurs during developmental axon pruning and during injury-induced Wallerian degeneration. These mechanistic insights provide new avenues for development of therapies to prevent or treat CIPN.


Identification of bull protamine disulfides.
We have identified the disulfide cross-links in bull protamine by titrating intact bull sperm with dithiothreitol (DTT) and following the modification of each cysteine residue with tritiated iodoacetate. The derivatization of each cysteine was monitored by a combination of HPLC, peptide mapping, and protein sequencing. Analyses of total free sulfhydryls show that all seven of the bull protamine cysteines are cross-linked as disulfides in mature sperm. The first disulfide is reduced at a DTT:protamine cysteine (DTT:Cys) ratio of 0.3 and the last at a ratio of 2.0. Intra- and intermolecular disulfides were identified by correlating the reduction of specific disulfides with the dissociation of protamine from DNA in partially reduced sperm and sperm treated with N,N'-ethylenedimaleimide, a bifunctional disulfide cross-linking agent. Three intermolecular and two intramolecular disulfides were identified. The results of these experiments demonstrate that the amino- and carboxy-terminal ends of the bull protamine molecule are folded inward toward the center of the molecule and are locked in place, each by a single intramolecular disulfide bridge. Three intermolecular disulfides cross-link neighboring protamine molecules around the DNA helix in such a manner that the protamines cannot be dissociated from DNA without first reducing the interprotamine disulfides.


I(-)⋅CH(3)X (X=Cl,Br,I) photodetachment: The effect of electron-molecule interactions in cluster anion photodetachment spectra and angular distributions.
The electron kinetic energy dependence of the photoelectron spectra and angular distributions of I(-)⋅CH(3)X (X=Cl,Br,I) cluster anions are measured via velocity mapped imaging at wavelengths between 350 and 270 nm. Processes analogous to those encountered in free CH(3)X-electron interactions are revealed. In particular, the presence and energies of resonances associated with a low lying σ(∗) state have a marked effect on the results of I(-)⋅CH(3)X photoexcitation. These effects (vibrational excitation, product anion production, and alteration of the photoelectron angular distribution) are far more prominent for I(-)⋅CH(3)I. However, in the vicinity of the (2)P(1/2) threshold there is a sharp deviation in the (2)P(3/2) channel angular distribution and an enhancement of the (2)P(3/2) channel vibrational structure of all three cluster anions. These latter effects are specific to the cluster anion environment through the relaxation of the partner excited I atom and subsequent electronic autodetachment.


Application of mechanical and manual sutures enclosing the bronchus.
The mechanical suture was introduced into thoracic surgical procedures by Amonosow and Androsow, Soviet surgeons, in the late 50s. The aim of the paper is to compare the incidence of bronchopleural fistulae that develop after the mechanical suture has been applied in bronchus surgery with the corresponding figures for traditional manual sutures. In the period of January 1997-March 1999 a series of 524 anatomical lung parenchyma resections was performed at the Department of Thoracic Surgery, Medical Academy of Gdańsk. In 460 cases (87.8%) the indication for the procedure came from primary lung carcinoma, and in 64 cases (12.2%) from tuberculosis, hamartoma, arteriovenous fistula, inflammatory lesions, asperpilloma, and metastases to the lungs. Depending on the way the bronchus was surgically closed the patients were subgrouped as follows: group I comprised 209 subjects (40.6%) whose bronchus was closed with a mechanical TA Premium Auto Suture, and group II that embraced 306 subjects (59.4%) whose bronchus was closed with a manual PDS 3/0 or Maxon 3/0 suture. The bronchopleural fistula developed in 11 cases of which 5/216 (2.3%) had the bronchus stump closed with a mechanical suture, and 6/308 (2.0%) cases had it closed with a manual suture. Of 11 cases of bronchopleural fistula 10 cases were noted after pneumonectomy. After the right side pneumonectomy, one fistula was discovered following the application of mechanical suture and six fistulas were found when the manual suture was used. After the left side pneumonectomy, no fistulae were discovered when the manual suture was used, and 3 those found were exclusively present when the mechanical suture was applied.


Boosting Effect of Amphiphilic Random Copolymers for Bicontinuous Phases.
Amphiphilic random copolymers, poly(oxyethylene)/poly(oxypropylene) butyl ethers (C4EmPn), have been used as raw materials for cosmetics. This paper reports on the influence of amphiphilic random copolymers on mixtures of n-decane, water, and a nonionic surfactant, hexa(oxyethylene) dodecyl ether (C12E6). Bicontinuous phases are formed from decane/water/C12E6 mixtures at high C12E6 weight fractions (> 70 wt%). Adding C4EmPn to decane/water/C12E6 mixtures brings about the formation of bicontinuous phases and a decrease in the amount of the surfactant required for their formation, indicating efficiency boosting. The bicontinuous phase formation region in the phase diagram of the decane/water/C12E6+C4E5P5 system is largest at a specific C4E5P5 weight fraction in the C12E6/C4E5P5 mixture. When a hydrophobic polymer, in which the poly(ethylene oxide) group in C4EmPn is absent, is added to decane/water/C12E6 mixtures, no efficiency boosting is observed. These results suggest that the adjustment of the hydrophilicity-hydrophobicity balance of C12E6/C4EmPn mixture causes the efficiency boosting.


Scalable and Reconfigurable Green Electronic Textiles with Personalized Comfort Management.
Electronic textiles, inherited with the wearability of conventional clothes, are deemed fundamental for emerging wearable electronics, particularly in the Internet of Things era. However, the electronic waste produced by electronic textiles will further exacerbate the severe pollution in traditional textiles. Here, we develop a large-scale green electronic textile using renewable bio-based polylactic acid and sustainable eutectic gallium-indium alloys. The green electronic textile is extremely abrasion resistant and can degrade naturally in the environment even if abrasion produces infinitesimal amounts of microplastics. The mass loss and performance change rates of the reconstituted green electronic textiles are all below 5.4% after going through the full-cycle recycling procedure. This green electronic textile delivers high physiological comfort (including electronic comfort and thermal-moisture comfort), enables wireless power supply (without constraints by, e.g., wires and ports), has 2 orders of magnitude better air and moisture permeability than the body requires, and can lower skin temperature by 5.2 °C.


Vesicle transfer and cell fusion: Emerging concepts of cell-cell communication in the tumor microenvironment.
Cell-cell fusion and vesicle-mediated transfer are fundamental biological processes that are emerging as novel mechanisms for re-programming cells in the tumor microenvironment. Both cell-cell fusion and intercellular transfer of vesicles (including microvesicles and exosomes) allow for the transfer of information among tumor cells, between tumor cells and tumor stroma, and between tumor cells and the host immune system, which could have profound implications for our understanding of tumor initiation and progression. The National Cancer Institute's Division of Cancer Biology sponsored a recent workshop (December 4-6, 2010) entitled, Vesicle Transfer and Cell Fusion: Emerging Concepts of Cell-Cell Communication in the Tumor Microenvironment to assess the current state of the science in these two scientific areas. Co-chaired by Drs. Huang-Ge Zhang (University of Louisville) and Madhav Dhodapkar (Yale University) this workshop brought together, for the first time at the NIH, leaders in the field to assess the effects of vesicle transfer and cell-cell fusion on cancer initiation, progression and metastasis. This meeting report includes brief summaries of the presentations and identifies the major questions, roadblocks, and opportunities. The meeting report is presented here to highlight research priorities and to stimulate basic and translational research efforts to better understand the contributions of cell-cell fusion and vesicle transfer to cancer.


[Applications of polymerase chain reaction in identifying the D1S80 (pMCT 118) locus in forensic DNA analysis].
The value of the amplified fragment length polymorphism at the D1S80 locus was examples by means of examples of forensic casework (paternity and identification cases). Parameters, like PCR conditions, limit of detection and analysis of mixed samples are discussed. In a population study the allele and genotype frequencies of 154 individuals from the area of Bonn were determined. The distribution of genotypes was in agreement with expected values according to the Hardy-Weinberg equilibrium. There was no deviation from other published Middle European studies.


The frequency of common skin conditions in preschool-aged children in Australia: seborrheic dermatitis and pityriasis capitis (cradle cap).
To determine the prevalence and severity of seborrheic dermatitis and pityriasis capitis in Australian preschool-aged children. A stratified cross-sectional skin survey using cluster sampling of centers throughout Victoria, Australia. The study population included children attending child care centers, preschools, and Maternal and Child Health Centers, with the reference population being Australian children 5 years and younger. Of the 1,634 children in the original sample, 1.116 children aged 11 days to 5 years 11 months were included in the study. Parents completed a questionnaire recording demographic information and personal and family history of skin problems and related diseases. A dermatologist performed a total skin examination, including the diaper area for children younger than 12 months. The age- and sex-specific prevalence rates and site and severity of seborrheic dermatitis and pityriasis capitis were measured. The overall age- and sex-adjusted prevalence of seborrheic dermatitis was 10.0% (95% confidence interval [CI], 8.2%-11.7%): 10.4% (95% CI, 7.8%-12.9%) in boys and 9.5% (95% CI, 7.0%-12.0%) in girls. This was highest in the first 3 months of life, decreasing rapidly by the age of 1 year, after which it slowly decreased over the next 4 years. Most (71.9%) had disease classified as minimal to mild. Pityriasis capitis occurred in 41.7% (95% CI, 38.8%-44.6%) of the 1,116 children examined, with 85.8% categorized as minimal to mild only. Seborrheic dermatitis and pityriasis capitis are common in early childhood. Most children have minimal to mild disease that would require little if any treatment. Education programs directed at those caring for preschool-aged children are needed to provide information on simple preventative measures and treatment, if necessary, that could easily reduce the morbidity associated with these very common conditions.


'I was in control of it from the start': A qualitative study of men's experiences of positive adjustment following a heart attack.
A qualitative design was used to explore the experience of positive adjustment following a heart attack. Ten men attending a cardiac rehabilitation programme completed in-depth semi-structured interviews. An overarching theme: 'I was in control of it from the start' emerged with six subthemes, relating to intrapersonal and interpersonal factors and processes. The subthemes reflected the importance of identifying controllable versus non-controllable factors and employing adaptive coping strategies.


Impact of pain in health related quality of life of patients with systemic sclerosis.
Systemic sclerosis (SSc) has an heterogenous clinical pattern, with variable organ involvement and degrees of severity. Like in other rheumatic diseases, the self-questionnaires have been used to evaluate SSc globally. The aim of the study is as to evaluate the quality of life (QoL) in patients with either diffuse or limited SSc, and to examine the impact of pain on the QoL scores. Patients with SSc, either diffuse or limited SSc, were included in a cross-sectional study. The QoL was evaluated with the short-form 36 (SF-36) and the functional repercussion with the SSc-modified Health Assessment Questionnaire (S-HAQ). A total of 89 patients (67 with diffuse and 22 with limited SSc) were included. The SF-36 score values were lower in SSc patients than those reported in the general population. The physical component scores (PCS) of the SF-36 was significantly worse in diffuse compared with limited SSc (P < 0.05). The PCS was significantly negatively related to the number of clinical manifestations (ANOVA, P < 0.0001). The mental component score (MCS) was not influenced by the type of SSc or the number of clinical manifestations presented by the patient. The QoL of SSc patients was highly correlated with pain (R = 0.69) and disability (R = 0.70). Interestingly, the QoL of SSc patients was only slightly correlated with cutaneous (R = 0.42) and pulmonary involvement (R = 0.57). The QoL of patients with SSc is strongly influenced by the type of SSc, the burden of clinical manifestations, the functional disability and by the pain, whatever its cause. The treatment of pain should be considered as priority to improve the QoL of SSc patients.


Barriers in the management of tuberculosis in rawalpindi, pakistan: a qualitative study.
Tuberculosis (TB) is a contagious, airborne disease and remains a major global public health hazard. TB is a major cause of mortality and is affecting millions of people in low-income and middle-income countries. Worldwide, one person out of three is infected with the Mycobacterium tuberculosis. Timely diagnosis and treatment are the two key factors for better outcomes. Non-adherence to TB treatment is an important barrier for TB control programs. This study was designed to understand the barriers encountered by TB patients when seeking health care. A qualitative study was conducted during the months of August and December 2010 on 15 health facilities. In-depth interviews were conducted with 23 TB patients (13 males and 10 females) aged 15-65 years. In addition, 15 health personnel were also interviewed. Most patients were found to be well informed about the idea of taking TB medications under direct supervision and its overall importance. However, many of them were not convinced with either drugs or treatment protocols. We found that limited knowledge of patients, loss of employment, financial burden, social stigma and long distance from health facility were the main barriers for TB adherence. More patient-centred interventions and attention to the barriers are required to improve the treatment adherence. Direct observation of patients and regular home visits by health workers can reduce the risk of non-adherence.


Twenty-one-gauge needles provide more cellular samples than twenty-five-gauge needles in fine-needle aspiration biopsy of the thyroid but may not provide increased diagnostic accuracy.
The technique of fine-needle aspiration (FNA) biopsy of the thyroid is important to evaluate malignancy in thyroid nodules. Eighty-five percent of thyroid FNA procedures lead to sufficient cellular material for diagnosis. With more cells aspirated, the chance of sufficiency for diagnosis increases. Large-bore needles lead to more cellular material being aspirated but bloodier specimens that may interfere with cytologic interpretation. Small-bore needles may result in too few cells for diagnosis. We conducted a randomized prospective study contrasting 21-gauge and 25-gauge needles in the evaluation of 50 consecutively enrolled nodules at our institution. In our investigation, 21-gauge needles more frequently provided superior biopsy specimens (50%) than did 25-gauge needles (18%). In the remaining specimens (32%), the 21-gauge and 25-gauge needles provided similar cellular material. The rate of sufficient samples was the same. We conclude that use of 21-gauge needles results in more cellular specimens but may not result in increased diagnostic accuracy.


Eating Patterns in Children with Autism Spectrum Disorder.
The purpose of this research was to analyze the eating patterns of preschool- and school-aged children with ASD, as provided by their families, in the La Araucanía Region of Chile. It involved a cross-sectional study with 72 families with children diagnosed with ASD aged between 2 and 12 years old. Food selectivity, appetite, body mass index (BMI) and frequency of food consumption were studied. The research determined that 97.67% present food selectivity, corresponding to alterations in the frequency of consumption of specific food groups. Moreover, 93.06%, 90.28%, 80.56% and 62.50% of children in the study do not meet the daily recommendations for fruit, fish, water and vegetable consumption, respectively. Therefore, it is important for these findings to be considered when designing and carrying out educational interventions regarding food in families with children with ASD for greater assertiveness and effectiveness in improving health.


Forskolin, 8-Br-3',5'-cyclic adenosine 5'-monophosphate, and catalytic protein kinase A expression in the nucleus increase radioiodide uptake and sodium/iodide symporter protein levels in RET/PTC1-expressing cells.
RET/PTC1, a thyroid-specific oncogene, has been reported to down-regulate sodium/iodide symporter (NIS) expression and function in vitro and in vivo. Recently, RET/PTC1 has been shown to interfere with TSH signaling at multiple levels in thyroid cells. The objective of this study was to investigate whether RET/PTC1-mediated NIS reduction can be rescued by activating cAMP-protein kinase A (PKA) pathways. We showed that both forskolin and 8-Br-cAMP increase radioiodide uptake and NIS protein in RET/PTC1-expressing cells to the same extent as the parental PC Cl 3 cells. We found that RET/PTC1 decreases nuclear localization of catalytic PKA, and forskolin treatment was able to counteract this RET/PTC1 effect. Furthermore, transient expression of catalytic PKA in the nucleus increased radioiodide uptake and NIS protein in RET/PTC1-expressing cells. Taken together, these studies suggest that RET/PTC1 down-regulates NIS expression by interrupting TSH/cAMP signaling, and this RET/PTC1 effect can be reversed by activating cAMP-PKA pathways.


Effect of Balloon Eustachian Tuboplasty in Adults That Only Have Symptoms of Chronic Eustachian Tube Dysfunction, With a 1-Year Follow-Up: Prospective Clinical Trial.
Balloon eustachian tuboplasty (BET) is a promising therapeutic option for eustachian tube (ET) dysfunction. However, data are lacking on the effect of BET in adults with symptoms of chronic ET dysfunction but without a contributing pathology. This study investigated the effect of BET in adult patients with only symptoms of chronic ET dysfunction. This prospective clinical trial included adult patients with aerated physiological middle ears and symptoms of ET dysfunction for more than 6 months. Compliance with follow-up was 93.3%. We evaluated the effects of BET with tympanometry, assessment of the Valsalva or Toynbee maneuver with tympanometry verification, a Eustachian Tube Dysfunction Questionnaire (ETDQ-7), and pure-tone audiometry. Data were recorded 1 day before surgery and 2, 6, and 12 months after BET. Therapy was considered successful when the patient exhibited a newly acquired ability to perform the Valsalva or Toynbee maneuver or when the ETDQ-7 score improved by 20% or more. We included 14 ears in the analysis. After 2, 6, and 12 months, therapy was successful, according to the ETDQ-7, in 11/14 (78.6%; 95% CI: 48.8-94.3), 13/14 (92.9%; 95% CI: 64.2-99.6), and 12/14 (85.7%; 95% CI: 56.2-97.5) ears, respectively. These results were statistically significant. The ETDQ-7 scores also significantly decreased at 2, 6, and 12 months after the BET, when any change was observed. All patients experienced improvement. Only 1 patient reported temporary deterioration after 2 months. Treatment was more frequently successful in patients without nasal polyps or pollinosis. Adults with only symptoms of chronic ET dysfunction benefitted more and had longer lasting results from BET, compared to patients with pathologies caused by ET dysfunction. Balloon eustachian tuboplasty could be recommended for these patients.


Analysis of sphingolipids in potatoes (Solanum tuberosum L.) and sweet potatoes (Ipomoea batatas (L.) Lam.) by reversed phase high-performance liquid chromatography electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS).
Ceramides and glucocerebrosides of potatoes (Solanum tuberosum L.) and sweet potatoes (Ipomoea batatas (L.) Lam.) were analyzed using RP-HPLC-ESI-MS/MS. Ceramides and glucocerebrosides containing the three different long-chain bases 4,8-sphingadienine (d18:2(delta4,delta8)), 4-hydroxy-8-sphingenine (t18:1(delta8)), and 8-sphingenine (d18:1(delta8)) acylated to saturated and unsaturated hydroxy- and nonhydroxy fatty acids with 16-26 carbon atoms were detected. For ceramides and glucocerebrosides 4,8-sphingadienine (d18:2(delta4,delta8)) was found as the major long-chain base, with lesser amounts of 4-hydroxy-8-sphingenine (t18:1(delta8)) and 8-sphingenine (d18:1(delta8)). 2-(Alpha-)hydroxypalmitic acid (C16:0h) was the major fatty acid, which was found to be acylated to the long-chain bases. For quantification of these compounds, an RP-HPLC-ESI-MS/MS method with an "echo-peak"-technique simulating internal standard injection was developed. The analyzed samples of potatoes and sweet potatoes showed amounts of approximately 0.1-8 microg/kg single ceramides and amounts up to 500 microg/kg glucocerebrosides, with C16:0h-glucosyl-4,8-sphingadienine as the major component.


Factors Influencing the Synthesis of Polysaccharide by Bradyrhizobium japonicum Bacteroids in Field-Grown Soybean Nodules.
Certain strains of Bradyrhizobium japonicum produce large quantities of polysaccharide in soybean (Glycine max (L.) Merr.) nodules, and nodule polysaccharide (NPS) is different from that produced in culture. A previous survey of field-grown plants showed highly variable levels of NPS among field sites. To obtain clues about the possible function of NPS, we conducted two additional surveys of field-grown plants. The amount of polysaccharide in bulk samples of nodules was not associated with soil type, texture, slope, drainage, or any of the measured soil chemical properties except pH and [Ca]. Correlations with pH and [Ca] were positive and highly significant for two independent surveys involving a total of 77 sites in two years. In a preliminary comparison of high and low levels of Ca supplied to soybean plants grown in silica sand in a greenhouse, a high level of Ca (200 mg of Ca liter) increased the NPS level and increased the Ca content of the polysaccharide fraction. B. japonicum isolates from 450 nodules collected at 10 field sites in 1993 were used to form nodules on soybean plants grown in sand culture in a greenhouse in order to examine bacterial phenotype under controlled conditions. Results showed that the NPS level in the bulk nodule sample from any given site was a function of the proportion of nodule occupants that were capable of NPS synthesis. Thus, a higher soil pH and/or [Ca] may positively influence the survival of B. japonicum capable of synthesis of the nodule-specific polysaccharide.


Synthesis and application of vinylpyridine containing ion-imprinted copolymer gel microbeads for Cu(II) solid-phase extraction.
The influence of polymer matrix on the extraction efficiency for Cu(II) and selectivity against metal ions such as Ni(II), Cd(II), Pb(II) of Cu(II) imprinted copolymer gels was described. The functional monomers investigated include the weakly basic 4-vinylpyridine (4-VP) and its mixure with the acidic and hydrogen binding methacrylic acid. Copolymer gels were prepared by dispersion cross-linking copolymerization using Cu(II)-4-(2-pyridylazo)resorcinol complex, Cu(II), or 4-(2-pyridylazo)resorcinol as templates. The chemical structure and morphology of the Cu(II)-imprinted microbeads are defined using elemental analysis, Fourier transform infrared spectroscopy, and scanning electron microscopy. Extraction efficiencies of newly synthesized sorbents were studied by batch procedure. The prepared copolymer gel with 4-VP as monomer and Cu(II)-4-(2-pyridylazo)resorcinol complex has higher capacity and selectivity toward Cu(II) than the copolymer gels prepared using the mixture of methacrylic acid and 4-VP. This new sorbent can be used as an effective SPE material for the highly selective preconcentration and separation of Cu(II) in sea water samples. It shows high mechanical and chemical stability.


Analysis of graphene TE surface plasmons in the terahertz regime.
Unlike common metals, graphene can support transverse electric (TE) surface modes when the imaginary part of its conductivity is negative. We have theoretically investigated and numerically simulated plasmonic properties of graphene TE surface plasmons (SPs) in the terahertz regime. The influence of the external magnetic field, gate voltage and temperature as the tuning schemes of the SPs have been investigated. The results show that graphene TE modes can be realized by tuning the magnetic fields or gate voltage. If the permeability of the dielectrics on both sides of the graphene layer differs enough, the graphene TE modes can still be achieved. The work presented here has the potential for application to graphene-based plasmonic devices in photonics and optoelectronics, such as sensors, polarizers and modulators.


Treatment with Depot Leuprolide Acetate in Girls with Idiopathic Precocious Puberty: What Parameter should be Used in Deciding on the Initial Dose?
Doses of gonadotropin releasing hormone (GnRH) analogues used to treat idiopathic central precocious puberty (iCPP) vary among clinicians. Study aims were to evaluate the efficacy of a monthly 3.75 mg dose of leuprolide acetate (LA) to suppress the hypothalamo-pituitary-gonadal (HPG) axis in girls with iCPP and to determine factors that may have an impact on the supressing dose. Study subjects were 220 girls receiving LA for iCPP. LA was started at a dose of 3.75 mg/28 days. Suppression was assessed using the GnRH test at the third month. To assess clinical suppression signs and symptoms of puberty were also evaluated. The dose of LA was increased to 7.5 mg/28 days in those who had a peak luteinising hormone (LH) ≥2 IU/L and in whom adequate clinical suppression of puberty was absent. Receiver operating characteristic curves were used to determine thresholds for clinical and hormonal factors affecting the suppressing dose of LA. Logistic regression analyses were used to investigate thresholds which might differentiate between those requiring high dose for suppression and those in whom lower dose LA was adequate. Peak stimulated LH <2 IU/L was achieved in 88.6% with a dose of LA of 3.75 mg (0.11±0.03 mg/kg). Significant variables for differentiating the two doses were body weight (Wt) of 36.2 kg and/or body mass index (BMI)-standard deviation scores (SDS) of 1.64 (p<0.001). Multiple logistic regressions showed that Wt and BMI-SDS values above thresholds indicated requirement of LA at a dose of 7.5 mg/28 days (p<0.001). Monthly injections of 3.75 mg LA is an effective treatment in the majority of girls with iCPP. However, a higher initial dose may be preferred in patients with a Wt ≥36 kg or BMI-SDS ≥1.6 for effective suppression of the HPG axis.


[Experience in toxicological monitoring in Moscow].
A technology for the toxicological monitoring of chemical poisoning cases in Moscow is described. Its results over 2002-2006 are presented. The distribution of poisonings by causes, gender, and age, pattern, and occurrence circumstances is analyzed. A number of difficulties arising from the filling toxicological monitoring record form No. 58-1/y are discussed. The problems facing the participants of monitoring are given.


Human P1-450 gene sequence and correlation of mRNA with genetic differences in benzo[a]pyrene metabolism.
The human P1-450 gene (6,311 base pairs), as well as the 5' (1,604 bases) and 3' (113 bases) flanking regions, have been completely sequenced. Four highly homologous boxes (61, 82, 56 and 97 base pairs) between the human and mouse P1-450 genes are found in the "TATA" box promoter region, -226, -338, and -450 upstream from the cap site, respectively. Nine genomic-DNA samples were digested with each of 23 restriction endonucleases and probed with human P1-450 cDNA fragments; restriction fragment length polymorphisms are detected, although it remains to be seen whether such a recombinant DNA test will be useful in determining individuals at increased risk for cigarette smoking-induced cancer and toxicity. We show in this report, however, that human inducible P1-450 mRNA concentrations are very highly correlated (r = 0.98; N = 6) with genetic differences in benzo[a]pyrene metabolism in mitogen-activated lymphocyte cultures.


Molecular cloning and functional characterization of BcTSA in the biosynthesis of indole alkaloids in Baphicacanthus cusia.
Baphicacanthus cusia (Nees) Bremek (B. cusia) is an essential traditional Chinese herb that is commonly used to treat colds, fever, and influenza. Indole alkaloids, such as indigo and indirubin, are the primary active constituents of B. cusia. The indole-producing reaction is crucial for regulating the flow of indole alkaloids metabolites along the pathways and coordinating primary and secondary product biosynthesis in plants. The tryptophan synthase alpha-subunit (TSA) can catalyse a process that produces indole, which is free to enter secondary metabolite pathways; however, the underlying potential mechanism of regulating indigo alkaloids synthesis remains unknown. Here, a BcTSA was cloned from the transcriptome of B. cusia. The BcTSA has a significant degree of similarity with other plant TSAs according to bioinformatics and phylogenetic analyses. Quantitative real-time PCR (RT-qPCR) research showed that BcTSA was dramatically enhanced in response to treatment with methyl jasmonate (MeJA), salicylic acid (SA), and abscisic acid (ABA), and was predominantly expressed in the stems as opposed to the leaves and rhizomes. Subcellular localization revealed that BcTSA is localized in chloroplasts, which is compatible with the fact that the conversion of indole-3-glycerol phosphate (IGP) to indole occurs in chloroplasts. The complementation assay results showed that BcTSA was functional, demonstrating that it was capable of catalyzing the conversion of IGP to indole. BcTSA was shown to stimulate the manufacture of indigo alkaloids including isatin, indigo, and indirubin when the gene was overexpressed in the hairy roots of Isatis indigotica. In conclusion, our research provides novel perspectives that might be applied to manipulating the indole alkaloid composition of B. cusia.


A postinfluenza model of Staphylococcus aureus pneumonia.
Postinfluenza Staphylococcus aureus pneumonias are increasingly recognized as a major form of life-threatening infections. A mouse model of postinfluenza S. aureus pneumonia was developed. Mice were intranasally infected with bacteria alone or bacteria plus virus. Infection was assessed by mouse survival, lung histopathology, bacterial density in the lungs, and cellular response to infection. Mice infected with both influenza virus and S. aureus showed higher mortality, greater lung parenchymal damage, and greater bacterial density at metastatic tissue sites than mice infected with only S. aureus. At 4 h, more polymorphonuclear leukocytes and fewer CD11c(+) cells were found in lung samples from mice infected with virus and bacteria than in those from mice infected with bacteria. alpha-Hemolysin and protein A were maximally expressed 4 h after infection, and Panton-Valentine leukocidin was maximally expressed 72 h after infection, with higher levels of alpha-hemolysin expression in mice infected with bacteria alone. Interferon gamma expression was higher in tissue collected from mice infected with virus plus bacteria than in those from bacteria-infected mice. The results from this model demonstrate diverse effects caused by antecedent influenza virus infection, which have a profound influence on the morbidity and mortality associated with S. aureus pneumonia.


The science of adjuvants.
Adjuvants are substances that boost the immunogenicity of vaccines. However, most successful vaccines have been derived empirically and are capable of inducing robust T- and B-cell immunity without any adjuvant additives. Emerging evidence suggests that such live vaccines induce innate immune activation via a range of stimuli, including ligands specific for Toll-like receptors, which, in effect, serve as their own adjuvants. In contrast to these live vaccines, subunit vaccines need to be supplemented with adjuvants to boost their immunogenicity. However, there is a paucity of licensed adjuvants for clinical use and, thus, there is a critical need to develop safe and effective adjuvants. In this context, recent advances in innate immunity are beginning to offer new insights into how empiric vaccines and adjuvants mediate their efficacy. In this article, we review the latest progress and emerging concepts in adjuvant development, which includes novel findings in innate immune biology and their impact on vaccinology.


Urinary Incontinence and Indwelling Urinary Catheters as Predictors of Death after New-Onset Stroke: A Report of the South London Stroke Register.
To explore the relationship between indwelling urinary catheters (IUCs), urinary incontinence (UI), and death in the poststroke period and to determine when, after the neurological event, UI has the best ability to predict 1-year mortality. In a prospective observational study, 4477 patients were followed up for 1 year after a first-ever stroke. The impact of UI or urinary catheters on time to death was adjusted in a Cox model for age, sex, Glasgow Coma Scale, prestroke and poststroke Barthel Index, swallow test, motor deficit, diabetes, and year of inclusion. The predictive values of UI assessed at the maximal deficit or 7 days after a stroke were compared using receiver-operating curves. UI at the maximal neurological deficit and urinary catheters within the first week after the stroke were present in 43.9% and 31.2% patients, respectively. They were both associated with 1-year mortality in unadjusted and adjusted analysis (hazard ratio [HR], 1.78, 95% confidence interval [CI], 1.46-2.19, and HR, 1.84, 95% CI 1.54-2.19). Patients with UI and urinary catheters had twice the mortality rate of incontinent patients without urinary catheters (HR, 10.24; 95% CI, 8.72-12.03 versus HR, 4.70; 95% CI, 3.88-5.70; P < .001). UI assessed after 1 week performed better at predicting 1-year mortality than UI assessed at the maximal neurological deficit. IUCs in the poststroke period is associated with death, especially among incontinent patients. UI assessed at 1 week after the neurological event has the best predictive ability.


Childhood Sarcoidosis mimicking Tuberculosis:A case report.
Sarcoidosis is a rare multisystem chronic inflammatory disease in children. We present a case of a five-year-old child with clinical features mimicking several diseases, including tuberculosis. After failure of treatment based on the suspected diagnosis, an axillary lymph node biopsy showed noncaseating granulomas compatible with sarcoidosis and appropriate treatment was then started.


BUMPy: A Model-Independent Tool for Constructing Lipid Bilayers of Varying Curvature and Composition.
Molecular dynamics is a powerful tool to investigate atomistic and mesoscopic phenomena in lipid bilayer systems. These studies have progressed with the advent of increased computational power, and efforts are now increasingly being directed toward investigating the role of curvature and bilayer morphology, as these are critical features of biological processes. Computational studies of lipid bilayers benefit from tools that can create starting configurations for molecular dynamics simulations, but the majority of such tools are restricted to generating flat bilayers. Generating curved bilayer configurations comes with practical complications and potential ramifications on physical properties in the simulated system if the bilayer is initiated in a high-strain state. We present a new tool for creating curved lipid bilayers that combines flexibility of shape, force field, model resolution, and bilayer composition. A key aspect of our approach is the use of the monolayer pivotal plane location to accurately estimate interleaflet area differences in a curved bilayer. Our tool is named BUMPy (Building Unique Membranes in Python), is written in Python, is fast, and has a simple command line interface.