A unique coordination environment for an ion: EXAFS studies and bond valence model approach of the encapsulated cation in the Preyssler anion.
X-Ray absorption spectroscopy was used to probe the coordination of different encrypted cations in the Preyssler anions [M(n+)P5W(30)O(110)]((15-n)-)(M(n+)= Sr2+, Am3+, Eu3+, Sm3+, Y3+, Th4+, U4+ in decreasing order of ionic radius, IR), hereafter abbreviated [M(n+)PA](15-n)-. The increase of the M-W distance and the decrease of the M-P distance with increasing M ionic radius reveal that the M cation is displaced along the C5 axis within the Preyssler cavity. The slight change (0.07 A) of the M-O distance that does not correspond to the IR difference of 0.27 A confirms that the cavity retains its rigidity upon cation substitution. Geometric modeling of the encapsulated cation in the channel was performed for comparison to the EXAFS results. The position of the cation in the cavity was calculated as well as the M-O10, -W5 and -P5 distances. This modeling confirms the cation displacement toward the center of the Preyssler anion as the cation size increases, which is understood in terms of the non-homogenous electrostatic potential present within the cavity. The bond valence model approach was applied to obtain experimental bond valences. Only the bond valence sum (BVS) of Am3+ is close to its actual charge. Sums smaller than the actual valences of the +3 and +4 ions (2.39-2.63 for +3 cations, Y, Sm, Eu; 3.17 and 3.38 for +4 cations, U and Th, respectively) were obtained, and a larger sum (2.89) was obtained for Sr2+. The deviations from the formal M sums of the encapsulated ions are attributed to the rigidity of the Preyssler framework. The tendency toward coordinative unsaturation for electroactive cations, such as Eu3+, is thought to be the driving force for facile reduction. Unlike other inorganic chelating ligands, the Preyssler anion provides a unique redox system to stabilize an electroactive cation in a low oxidation state.


The politics of birth control.
By the time Senate subcommittee hearings on the "population crisis" ended in 1968, a sizeable consensus had begun to emerge favoring government support of voluntary family planning programs at home and abroad. The goal to develop a national family planning program was easier to set than to accomplish, however, and there have been no lack of difficult questions to haggle over in the past 20 years. Beginning with the Johnson administration, the executive branch of government has tended to favor block-grant funding of family planning services, while Congress has insisted on categorical funding. Conflict has also existed over financial eligibility for government-supported services, over whether teenagers and unmarried women should be served in publicly supported clinics and over which services should be included in the definition of family planning. The Reagan administration has exacerbated the conflicts with attempts to redefine family planning by placing primary emphasis on natural methods and abstinence for those who wish to prevent pregnancy and attempts to deny funding to both domestic and foreign programs that support access to abortion. While future government support for family planning programs does not seem seriously threatened, funding has not grown in 15 years, once the effects of inflation are taken into account, and most programs have had to limit eligibility to survive. The Bush administration is unlikely to be as confrontational as the Reagan administration on the subject of family planning, but the political reality is that conflict can be expected to continue.


Cerebral and myocardial infarction induced by nonbacterial thrombotic endocarditis in a patient with ovarian cancer: report of a case.
A 40-year-old woman was admitted to our hospital because of left hemiplegia. She was affected with myocardial infarction and cerebral infarction. Echocardiogram revealed that the aortic and mitral valves had thick and uneven echoes suggesting vegetations. Judging from the finding that repeated blood cultures were negative, we had considered in her lifetime that myocardial and cerebral infarctions were due to embolization associated with nonbacterial thrombotic endocarditis (NBTE). At autopsy, histological diagnosis was made as ovarian cancer with disseminated intravascular coagulation. From the clinical course and the histological findings, we diagnosed this patient as NBTE.


TMEM230: How does it fit in the etiology and pathogenesis of Parkinson's disease?
Mutations in the transmembrane protein 230 (TMEM230) gene were recently identified in a large Canadian pedigree and 7 smaller Chinese families, nominating TMEM230 as the third gene causing a Mendelian form of late onset Parkinson's disease (PD) with typical Lewy-body pathology (after synuclein alpha (SNCA) and leucine rich repeat kinase 2 (LRRK2)). The protein encoded by TMEM230 remains largely uncharacterized, but initial evidence points to roles in the trafficking of recycling vesicles, retromers, and endosomes, suggesting intriguing links to the pathways targeted by other PD-causing genes. The focus on family-based studies is gaining new momentum in the next-generation sequencing era, for the discovery of further, high-penetrance (medically relevant) genetic variants in PD. However, at this junction, important aspects of the TMEM230 story remain unclear, such as the prevalence of these mutations in the Chinese and other populations of the world, the penetrance of the mutations, and even their mode of inheritance. The first replication studies among Chinese and White PD patients have been largely negative. Furthermore, much more work remains ahead to elucidate the mechanisms by which these mutations might lead to neuronal cell death, alpha-synuclein pathology, and parkinsonism. © 2017 International Parkinson and Movement Disorder Society.


Is it true that treatment in patients with Subaxial Cervical Spine Injury Classification System (SLICS) 4 is the surgeon's choice?
The Subaxial Cervical Spine Injury Classification System (SLICS) is a commonly used algorithm for diagnosing and managing subaxial cervical spine trauma. A SLIC score 4 suggests either surgery or non-surgically treatment depending on the surgeon's experience and patient's conditions. Prognosis and treatment results were analyzed in patients with SLIC score 4. The patients with SLIC score 4 were retrospectively reviewed from 2012 to 2019. Forty-one patients were included and divided into two groups: non-surgically treated and surgically treated. Demographic data and radiographs were analyzed. Statistical analysis was performed to determine the difference between the two clinical groups. Twenty-two patients were non-surgically treated, and nineteen patients were surgically treated. There was no neurological deterioration in both groups. However, there was no statistically significant difference in the last follow-up AISA and Nurick grade (p> 0.05). There was no significant difference in the number of patients who showed improvement when comparing the initial and the last follow-up neurological status (p> 0.05). Regardless of the treatment method, the spinal cord injury patients with SLICS point 4 showed a relatively good prognosis. Patients with SLIC score 4 could be treated non-surgically or surgically based on the surgeon's experience and factors associated with the patient's acute health status and chronic comorbidities.


Studies on Agrobacterium tumefaciens. VIII. Avirulence induced by temperature and ethidium bromide.
When tumorigenic strains of Agrobacterium tumefaciens were subcultured at temperatures between 31.5 and 37 degrees C or in broth containing ethidium bromide, they lost their capacity to induce tumors in tomato plants. The sensitivities of curing virulence (tumorigenicity) depended on the density of the population of cells, fewer cells (100/ml) being more sensitive to curing than higher densities (10(6)/ml). The loss of virulence need not require the total loss of the virulence-specifying plasmid, but may result from a loss of a small segment of that plasmid. Virulent strains made avirulent by temperature or ethidium bromide treatment still harbor a large plasmid of 70-80 megadaltons size compared with the 100- to 120-megadalton plasmid in the untreated strains.


[Mandibular unilateral free-end missing reconstructed by implant prosthesis].
A 58-year-old woman presented with a chief complaint of masticatory dysfunction caused by the missing of lower right molars and the detachment of fixed partial denture at the upper right molar region. For this case, implant-retained fixed partial denture with hybrid ceramics facing cast crowns for lower right molar region and conventional fixed partial denture for upper right molar region, considering both the secondary caries and the extrusion of upper right second molar, were fabricated. The patient was followed for >4 years after treatment, and separation between mandibular implant prosthesis and the lower right second premolar was observed during the follow-up period. The interdental separation was treated by refabrication of the prosthesis of the second premolar. Physical teeth movement may cause separation between natural tooth and implant-retained prosthesis. Functional problems caused by the loss of occlusal support were successfully rehabilitated using implant-retained fixed partial denture.


Form and contour: breeding and genetics of organ shape from wild relatives to modern vegetable crops.
Shape is a primary determinant of consumer preference for many horticultural crops and it is also associated with many aspects of marketing, harvest mechanics, and postharvest handling. Perceptions of quality and preference often map to specific shapes of fruits, tubers, leaves, flowers, roots, and other plant organs. As a result, humans have greatly expanded the palette of shapes available for horticultural crops, in many cases creating a series of market classes where particular shapes predominate. Crop wild relatives possess organs shaped by natural selection, while domesticated species possess organs shaped by human desires. Selection for visually-pleasing shapes in vegetable crops resulted from a number of opportunistic factors, including modification of supernumerary cambia, allelic variation at loci that control fundamental processes such as cell division, cell elongation, transposon-mediated variation, and partitioning of photosynthate. Genes that control cell division patterning may be universal shape regulators in horticultural crops, influencing the form of fruits, tubers, and grains in disparate species. Crop wild relatives are often considered less relevant for modern breeding efforts when it comes to characteristics such as shape, however this view may be unnecessarily limiting. Useful allelic variation in wild species may not have been examined or exploited with respect to shape modifications, and newly emergent information on key genes and proteins may provide additional opportunities to regulate the form and contour of vegetable crops.


A comparative study of prokaryotic diversity and physicochemical characteristics of Devils Hole and the Ash Meadows Fish Conservation Facility, a constructed analog.
Devils Hole is the sole natural habitat of the critically endangered Devils Hole pupfish (Cyprinodon diabolis). To establish a backup population, the Ash Meadows Fish Conservation Facility (AMFCF), a full-scale replica of the uppermost 6.7 m of Devils Hole, was constructed by management agencies in the mid-2010s. Despite rigorous efforts to mimic the bathymetric and physical details of the Devils Hole environment, the biogeochemistry and microbiology of the AMFCF refuge tank remain largely unaddressed. We evaluated water physicochemistry and employed Illumina DNA sequencing of 16S rRNA gene libraries to evaluate planktonic and benthic bacterial and archaeal community composition within their respective physicochemical contexts in Devils Hole and AMFCF on the same day. Major ion concentrations were consistent between the two systems, but water temperature and dissolved oxygen dynamics differed. Bioavailable nitrogen (primarily nitrate) was 5x lower in AMFCF. Devils Hole and AMFCF nitrogen:phosphorus molar ratios were 107:1 and 22:1, indicative of different nutrient control mechanisms. Both sites are microbiologically diverse, with over 40 prokaryotic phyla represented at each, with 37 shared between them and nearly than half deriving from candidate divisions. The abundance and composition of predicted photosynthetic primary producers (Cyanobacteria) was markedly different between sites: Devils Hole planktonic and sediment communities were dominated by Oscillatoria spp. (13.2% mean relative abundance), which proved virtually undetectable in AMFCF. Conversely, AMFCF was dominated by a predicted heterotroph from the Verrucomicrobiaceae family (31.7%); which was comparatively rare (<2.4%) in Devils Hole. We propose that the paucity of bioavailable nitrogen in AMFCF, perhaps resulting from physical isolation from allochthonous environmental inputs, is reflected in the microbial assemblage disparity, influences biogeochemical cycling of other dissolved constituents, and may ultimately impact survivorship and recruitment of refuge populations of the Devils Hole pupfish.


Ichthyosis fetalis in a cross-bred lamb.
Ichthyosis is a dermatological disease characterized by varying degrees of generalized hyperkeratosis and alopecia. Two congenital forms of ichthyosis are recognized in animals: fetalis (IF) and congenita. The disease occurs rarely in cattle, swine, dogs, chickens and a goat; it has not been reported in sheep. To provide clinical, laboratory and pathological assessments of a case of IF in a cross-bred lamb. A male cross-bred lamb. Physical examination revealed apathy, fever, ectropion and eclabium. Generalized thickening and scaling of the skin was noted; this was most severe on the face, ears, inner thighs, limbs and perineum. Deep fissures and wounds were present on the hind limbs and forelimbs. The lamb was monitored for 75 days. During this period, lesions progressed and occasionally obstructed the nostrils and increasingly made it difficult for the lamb to flex major limb joints. Postmortem findings included severe epidermal thickening, multiple subcutaneous abscesses, ectropion and corneal scars. Histological findings revealed diffuse orthokeratotic hyperkeratosis, follicular keratosis, irregular epidermal hyperplasia and atrophy of the sebaceous glands. Serum vitamin A concentration was within the normal range for the species. This case report describes a case of presumptive ichthyosis fetalis in a lamb. Greater awareness by practitioners is required for this disease to be included in the differential diagnosis of dermatopathies in this species.


Carbazole Annulation via Cascade Nucleophilic Addition-Cyclization Involving 2-(Silyloxy)pentadienyl Cation.
We report a new strategy toward the synthesis of highly functionalized carbazoles via 2-(silyloxy)pentadienyl cation intermediates, which were generated upon ionization of vinyl-substituted α-hydroxy silyl enol ethers under Brønsted acid catalysis. These electrophilic species were found to readily undergo cascade reactions with substituted indoles to generate carbazole molecular scaffolds in good yields via a sequence of regioselective nucleophilic addition, followed by intramolecular dehydrative cyclization.


House Dust Mite-Specific Sublingual Immunotherapy Prevents the Development of Allergic Inflammation in a Mouse Model of Experimental Asthma.
Evidence regarding sublingual immunotherapy (SLIT) efficacy and its good safety profile has been demonstrated with pollen and house dust mite (HDM) allergens in the treatment of airway allergies. In addition, the use of grass pollen presents a SLIT disease-modifying treatment for respiratory allergies. The aim of this study was to demonstrate the efficacy of HDM-based SLIT in mouse models of allergic airway inflammation and to gain insights into the involved local immunological mechanisms. Balb/c mice were sensitized/challenged with Dermatophagoides farinae (Der f) extract and underwent Der f-SLIT in prophylactic and therapeutic settings. The SLIT efficacy was assessed using lung function measurements, analysis of local inflammatory responses by bronchoalveolar lavage cell differentiation and lung histology. Humoral and cellular responses were monitored by ELISA, cytokine bead array and flow cytometry analyses. In a prophylactic setting, Der f-SLIT with 12 development units per dose reduced the eosinophil-dominated inflammatory response in the lung paralleled by a marked reduction in airway hyperresponsiveness. Local Th2 responses were prevented as demonstrated by significantly lower levels of IL-5 and IL-13. Additionally, SLIT-treated mice revealed a lower proportion of CD4-CD8- x03B3;δ cells and a higher frequency of CD8+CD25+IFNx03B3;+ T cells in the lungs compared to sham-treated mice. In a therapeutic setting, Der f-SLIT also resulted in reduced inflammatory responses in the lung. The efficacy of Der f-SLIT was demonstrated in prophylactic and therapeutic conditions using experimental mouse models of HDM-induced airway inflammation. A potential role of a so far underestimated lymphocyte subpopulation was also indicated.


E-referrals: improving the routine interspecialty inpatient referral system.
Interspecialty referrals are an essential part of most inpatient stays. With over 130 referrals occurring per week at the Royal Devon and Exeter Hospital, the process must be efficient and safe. The current paper-based 'white card' system was felt to be inefficient, and a Trust incident highlighted patient safety concerns. Questionnaires reinforced the need for improvement, with concerns such as a lack of referral traceability and delays in the referral delivery due to workload. The aims of the project were to improve patient safety and junior doctor efficiency in the referral process. Through appreciative enquiry and the PDSA (Plan-Do-Study-Act) model, an electronic referral system was developed, piloted within two specialties and later expanded to others with improvements made along the way based on user feedback. The system includes novel features including specialties 'acknowledging' a referral to allow referral progress to be tracked. The system stores all referrals, creating a fully auditable inpatient referral pathway. Qualitative data indicated improvement to patient safety and user experience (n=31). Timings for referrals were measured over a 6-month period; referrals became faster with the electronic system, with average time from decision to refer to referral submission improving from 2.1 hours to 1.9 hours, with a noted statistically significant improvement in timings on a statistical process control chart. An unexpected benefit was that patients were also reviewed faster by specialties. Measuring these changes presented a significant challenge due to the complexity of the referral process, and this was a big limitation. Overall, the re-design of a paper-based referral system into an electronic system has been proven to be more efficient and felt to be safer for patients. This is a sustainable change which is being rolled out Trust-wide. We hope that the reporting of this project will help others considering reviewing their inpatient referral pathways.


Iodine-131 MIBG scintigraphy of neuroendocrine tumors other than pheochromocytoma and neuroblastoma.
Metaiodobenzylguanidine (MIBG) locates most pheochromocytomas and neuroblastomas. The tracer is concentrated in intracellular storage vesicles by an active process. Many other neuroendocrine tumors of the amine precursor uptake and decarboxylation (APUD) series have hormonal storage vesicles and, thus, the potential to take up [131I]MIBG. A variety of neuroendocrine tumors in 57 patients were studied 1, 2, and 3 days after 0.5 mCi [131I]MIBG. Views from skull to pelvis were obtained. Results of MIBG scans were compared with all available imaging modalities (including plain radiography, liver scan, ultrasound, computed tomography, and angiography) and surgical exploration. The neuroendocrine nature of the tumor was determined by histology, immunohistochemistry, electron microscopy, and the assay of appropriate biogenic amines and peptide hormones. Results were (positive/total cases): carcinoids (four of ten), nonsecreting paragangliomas (three of three), sporadic medullary carcinomas of the thyroid (MCT) (one of five), familial MCT (one of 26), chemodectomas (two of five), oat cell carcinomas (zero of four), choriocarcinoma (one of one), atypical schwannoma (with storage granules) (one of one), Merkel cell skin cancer (one of one), islet cell carcinoma (zero of one). We conclude that a wide range of neuroendocrine tumors show [131I]MIBG uptake; tumors other than pheochromocytomas and neuroblastomas are less often seen scintigraphically, but in certain cases (e.g., carcinoid and nonsecreting paragangliomas) scintigraphy may be useful in depicting the extent and location of disease and may indicate therapeutic potential. Iodine-131 MIBG shows promise in the diagnosis and staging of tumors of varied types.


Inhibitory effects of 1,25(OH)2D3 on the proliferation of hepatocellular carcinoma cells through the downregulation of HDAC2.
The inhibitory effects of 1,25(OH)2D3 on the proliferation of a variety of cancer cell lines have been extensively reported. However, the underlying mechanisms remain largely unknown. In the present study, the effects of 1,25(OH)2D3 on the in vitro proliferation of human hepatocellular carcinoma HepG2 cells and the mechanism involved were investigated. Flow cytometry and MTT assay revealed that 1,25(OH)2D3 inhibited cell proliferation in vitro. Western blotting and real-time PCR indicated that 1,25(OH)2D3 upregulated the expression of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) and attenuated that of histone deacetylase 2 (HDAC2). Knockdown of HDAC2 completely mimicked the effects of 1,25(OH)2D3 on PTEN gene expression. The influence of 1,25(OH)2D3 on PTEN expression was reversed in the cells treated with a recombinant pEGFP-LV2-HDAC2 plasmid. Akt phosphorylation, which was downregulated by 1,25(OH)2D3 treatment, was promoted by HDAC2 overexpression. These findings revealed that 1,25(OH)2D3 inhibited cell growth possibly by HDAC2-mediated PTEN upregulation, Akt deactivation, and inhibition of the PI3K/Akt signaling pathway.


Cex1p is a novel cytoplasmic component of the Saccharomyces cerevisiae nuclear tRNA export machinery.
The Saccharomyces cerevisiae Yor112wp, which we named Cex1p, was identified using a yeast tRNA three-hybrid interaction approach and an in vivo nuclear tRNA export assay as a cytoplasmic component of the nuclear tRNA export machinery. Cex1p binds tRNA saturably, and associates with the nuclear pore complex by interacting directly with Nup116p. Cex1p co-purifies with the nuclear tRNA export receptors Los1p and Msn5p, the eukaryotic elongation factor eEF-1A, which delivers aminoacylated tRNAs to the ribosome, and the RanGTPase Gsp1p, but not with Cca1p, a tRNA maturation enzyme that facilitates translocation of non-aminoacylated tRNAs across the nuclear pore complex. Depletion of Cex1p and eEF-1A or Los1p significantly reduced the efficiency of nuclear tRNA export. Cex1p interacts with Los1p but not with eEF-1A in vitro. These findings suggest that Cex1p is a component of the nuclear aminoacylation-dependent tRNA export pathway in S. cerevisiae. They also suggest that Cex1p collects aminoacyl-tRNAs from the nuclear export receptors at the cytoplasmic side of the nuclear pore complex, and transfers them to eEF-1A using a channelling mechanism.


Student Team Achievement Division as a tool for peer assisted co-operative learning in neuroanatomy.
Student Team Achievement Division (STAD) is a co-operative learning approach premised on a group learning activity that emphazises learning as a social exchange of knowledge between students, in which each student is accountable for his or her own learning and is also encouraged to assist others in achieving their goals. It promotes the cognitive, psychomotor, and emotional growth of students involved in the team. By random sequencing, 60 participants were allocated to interventional group (n=30) and control group (n=30). The participants of the interventional group were subjected to STAD strategy and participants of the control group were instructed to do a conventional self learning on the ventricles of brain. The outcomes were statistically analysed. It was found that the performance of the students is far better with STAD approach than conventional self learning. Our study has shown that Students team Achievement Division can be used as an effective tool for Peer assisted Co-operative Learning in Anatomy. Further studies can be done to investigate the contribution of STAD to teaching other disciplines of Anatomy and other basic medical sciences.


Catalytic asymmetric enyne addition to aldehdyes and Rh(I)-catalyzed stereoselective domino Pauson-Khand/[4 + 2] cycloaddition.
The 1,1'-bi-2-naphthol-ZnEt2-Ti(O(i)Pr)4-Cy2NH system is found to catalyze the 1,3-enyne addition to aliphatic aldehydes as well as other aldehydes at room temperature with 75-96% yield and 82-97% ee. This system is also broadly applicable for the highly enantioselective reaction of other alkyl-, aryl-, and silylalkynes with structurally diverse aldehydes. The propargylic alcohols prepared from the catalytic asymmetric enyne addition to aliphatic aldehydes are used to prepare a series of optically active trienynes. In the presence of a catalytic amount of [RhCl(CO)2]2 and 1 atm of CO, the optically active trienynes undergo highly stereoselective domino Pauson-Khand/[4 + 2] cycloaddition to generate optically active multicyclic products. The Rh(I) catalyst is also found to catalyze the coupling of a diyne with CO followed by [4 + 2] cycloaddition to generate an optically active multicyclic product. These transformations are potentially useful for the asymmetric synthesis of polyquinanes containing a quaternary chiral carbon center.


[The Vaccination Program of Andalucía: the identification of evaluation indicators in the framework of quality assurance].
Quality assurance constitutes a major element in the evaluation of health services and has recently been introduced into our field. From this perspective, we intend to identify indicators for the evaluation the Andalusian Vaccination Programme, following the scheme proposed by Donabedian. A group of experts with different training backgrounds agreed upon the techniques on which the methodology used was based. Panels of experts were formed and the nominal group technique was used to identify criteria and standards. Mail surveys were made in order to select the most relevant standards from a multiple perspective: importance, ease of measurement and intervention capability. The aspects to be evaluated were defined about structure process and result. A total of 175 criteria and standards were identified, 42 related to structure, 68 related to process and 65 to results. The aspects to be evaluated, selected according to the priority technique used, are proposed to be employed systematically. The possibility of using them in the different structural levels of the health services is discussed.


Transient hepatic intensity differences: part 2, Those not associated with focal lesions.
The purpose of our study was to evaluate and to show the range of appearance of transient hepatic signal intensity differences when not associated with focal lesions, and to correlate morphology, cause, and pathogenesis. Hepatic arterial phenomena, visualized on MRI and CT, must be considered important signs of underlying liver disorders, which these phenomena contribute to evaluate. Accordingly, the hepatic arterial phase must always be performed on MRI as well as on CT, even if no focal lesion is expected.


[Confocal laser endomicroscopy principles and performing algorithm in gastric mucosa examination].
Accuracy of endoscopic examination in early gastric cancer and precancerous conditions diagnostics for many years depended only on quality of biopsy. That's why, risk of overlooking gastric focal carcinoma, particularly-- multiple, was relatively high. Last couple of years new endoscopic method--confocal laser endomicroscopy (CLE) was released for commercial use. This approach provides real-time information about morphology of gastric mucosa during endoscopic examination. CLE is a variation of confocal microscopy--morphologic technique, providing examination of thick specimens or live tissue. CLE system is a single-channel fluorescence microscope, used in endoscopy, where confocal probe incorporated into endoscope or mounted into accessory channel. For proper results of CLE intravenous administration of fluorescence agent is needed. In our study in P.A. Herzen Moscow Cancer Research Institute we have used 10% fluorescein sodium, due to acriflavine use is prohibited in Russian Federation. In 157 patients with suspected early gastric cancer mean time of CLE was 24 ± 3.5 min. In all cases descriptive images were acquired. Mean amount of endomicrosocpic images in one patient was as high as 162 ± 8.3.


Lower cytotoxicity, high stability, and long-term antibacterial activity of a poly(methacrylic acid)/isoniazid/rifampin nanogel against multidrug-resistant intestinal Mycobacterium tuberculosis.
To overcome the undesirable side effects and reduce the cytotoxicity of isoniazid (INH) and rifampin (RMP) in the digestive tract, a poly(methacrylic acid) (PMAA) nanogel was developed as a carrier of INH and RMP. This PMAA/INH/RMP nanogel was prepared as a treatment for intestinal tuberculosis caused by multidrug-resistant Mycobacterium tuberculosis (MTB). The morphology, size, and in vitro release properties were evaluated in a simulated gastrointestinal medium, and long-term antibacterial performance, cytotoxicity, stability, and activity of this novel PMAA/INH/RMP nanogel against multidrug-resistant MTB in the intestine were investigated. Our results indicate that the PMAA/INH/RMP nanogel exhibited extended antibacterial activity by virtue of its long-term release of INH and RMP in the simulated gastrointestinal medium. Further, this PMAA/INH/RMP nanogel exhibited lower cytotoxicity than did INH or RMP alone, suggesting that this PMAA/INH/RMP nanogel could be a more useful dosage form than separate doses of INH and RMP for intestinal MTB. The novel aspects of this study include the cytotoxicity study and the three-phase release profile study, which might be useful for other researchers in this field.


Heterogeneous rate constants for indium mediated allylations: cinnamyl chloride in ethanol/water mixtures.
Indium mediated allylation (IMA) offers a powerful tool to synthetic chemists for creating carbon-carbon bonds. However, its rate limiting step, the heterogeneous reaction of allyl halides at solid indium surfaces, is still poorly understood. For example, solvent effects, especially the presence of water, on IMA are dramatic. We report for the first time rate constants for the heterogeneous rate limiting step of IMA. The rate constant for reaction of cinnamyl chloride on indium decreases from 5.5 × 10(-4) cm/s in 80% ethanol/20% water to 1 × 10(-4) cm/s in 99.8% ethanol/0.2% water. In addition, the percent water has a dramatic effect on induction time. This study further establishes photomicroscopy as a powerful tool for the determination of heterogeneous rate constants.


Multicentre analytical evaluation of a new point-of-care system for the determination of cardiac and thromboembolic markers.
The cobas h 232 point-of-care analyzer by Roche is the instrument successor of the Cardiac reader allowing the quantitative determination of troponin T, creatine kinase MB, myoglobin, NT-proBNP and D-dimer. In this study 1329 patients with acute coronary syndromes, heart failure, thromboembolic or other diseases and 945 healthy donors were assessed. Comparisons versus central laboratory methods were carried out with 2379 samples from these individuals; out of these, 1591 samples gave quantitative results within the measuring range and were included in the evaluation. The point-of-care assays for creatine kinase MB, myoglobin, NT-proBNP and D-dimer were within a relative bias range of -5.9 to +6.9% compared to the laboratory assay. The troponin T assay showed a bias of -11.0% and after change of the calibration procedure of +1.9%. None of the five point-of-care assays had a relative difference between the new system and the precursor device that was higher than +5.0%. Within-series coefficients of variation of patient samples were found in a range from 4.8 to 14.8%. No significant interference was observed with lipemic, hemolytic and icteric blood or at different hematocrit values. Due to its good analytical agreement with the laboratory methods and with its precursor device, the cobas h 232 system can be reliably used to support on-site decision making for cardiovascular patients in acute and non-acute settings.


Radiosurgery for unruptured cerebral arteriovenous malformations in pediatric patients.
Unruptured cerebral arteriovenous malformations (AVMs) in pediatric patients (age <18 years) were excluded from A Randomized Trial of Unruptured AVMs (ARUBA). Therefore, the efficacy of radiosurgery for unruptured pediatric AVMs is poorly understood. The goal of this study is to determine the outcomes and define the predictors of obliteration following radiosurgery for unruptured AVMs in pediatric patients. We evaluated a prospective database, from 1989 to 2013, of AVM patients treated with radiosurgery at our institution. Patients with age less than 18 years at the time of radiosurgery, unruptured nidi, and at least 2 years of radiologic follow-up or AVM obliteration were selected for analysis. Statistical analyses were performed to determine actuarial obliteration rates and identify factors associated with obliteration. In the 51 unruptured pediatric AVM patients included for analysis, the median age was 13 years, and the most common presentation was seizure in 53 %. The median nidus volume and radiosurgical margin dose were 3.2 cm(3) and 21.5 Gy, respectively. The median radiologic follow-up was 45 months. The actuarial AVM obliteration rates at 3, 5, and 10 years were 29 %, 54 %, and 72 %, respectively. In the multivariate Cox proportional hazards regression analysis, higher margin dose (P = 0.002), fewer draining veins (P = 0.038), and lower Virginia Radiosurgery AVM Scale (P = 0.003) were independent predictors of obliteration. Obliteration rates were significantly higher with a margin dose of at least 22 Gy (P = 0.003) and for nidi with 2 or fewer draining veins (P = 0.001). The incidences of radiologically evident, symptomatic, and permanent radiation-induced changes were 55 %, 16 %, and 2 %, respectively. The annual post-radiosurgery hemorrhage rate was 1.3 %, and the incidence of post-radiosurgery cyst formation was 2 %. Radiosurgery affords a favorable risk to benefit profile for unruptured pediatric AVMs. Pediatric patients with unruptured AVMs merit further study to define an optimal management approach.


Surgical Excision of Heterotopic Ossification Leads to Re-Emergence of Mesenchymal Stem Cell Populations Responsible for Recurrence.
Trauma-induced heterotopic ossification (HO) occurs after severe musculoskeletal injuries and burns, and presents a significant barrier to patient rehabilitation. Interestingly, the incidence of HO significantly increases with repeated operations and after resection of previous HO. Treatment of established heterotopic ossification is challenging because surgical excision is often incomplete, with evidence of persistent heterotopic bone. As a result, patients may continue to report the signs or symptoms of HO, including chronic pain, nonhealing wounds, and joint restriction. In this study, we designed a model of recurrent HO that occurs after surgical excision of mature HO in a mouse model of hind-limb Achilles' tendon transection with dorsal burn injury. We first demonstrated that key signaling mediators of HO, including bone morphogenetic protein signaling, are diminished in mature bone. However, upon surgical excision, we have noted upregulation of downstream mediators of osteogenic differentiation, including pSMAD 1/5. Additionally, surgical excision resulted in re-emergence of a mesenchymal cell population marked by expression of platelet-derived growth factor receptor-α (PDGFRα) and present in the initial developing HO lesion but absent in mature HO. In the recurrent lesion, these PDGFRα+ mesenchymal cells are also highly proliferative, similar to the initial developing HO lesion. These findings indicate that surgical excision of HO results in recurrence through similar mesenchymal cell populations and signaling mechanisms that are present in the initial developing HO lesion. These results are consistent with findings in patients that new foci of ectopic bone can develop in excision sites and are likely related to de novo formation rather than extension of unresected bone. Stem Cells Translational Medicine 2017;6:799-806.


Limitations on environmental control of multiple fixed-ratio behavior.
Eight white rats were trained to make fixed numbers of responses on each of two bars alternately in the presence of different exteroceptive stimuli. Three types of error were observed: alternating-bar switching before response requirements for reinforcement were met; perseverating-responding on the wrong bar after reinforcement; and overshooting-responding on a bar after reinforcement became available. Alternating and perseverating errors occurred mainly on the bar requiring the smaller ratio. When the ratios on the bars were changed, alternating errors were most common, but they diminished rapidly. Perseverating and overshooting errors did not diminish.


[Primary amenorrhea by transverse vaginal septum: a case report and review of the literature].
The transverse vaginal septum is one of the rarest anomalies of the reproductive tract classified depending on location. It is manifested by primary amenorrhea, cyclic pain and progressive mass growth at abdominopelvic level, ultrasound and magnetic resonance imaging provides the diagnosis, location and thickness of a transverse vaginal septum, treatment is surgical. We present a case of a teenage patient with primary amenorrhea due to lower transverse vaginal septum with surgical resection and satisfactory follow-up with successful vaginal patency.


Lack of awareness of treatment failure among HIV-1-infected patients in Guinea-Bissau - a retrospective cohort study.
With more people receiving antiretroviral treatment (ART), the need to detect treatment failure and switch to second-line ART has also increased. We assessed CD4 cell counts (as a marker of treatment failure), determined the rate of switching to second-line treatment and evaluated mortality related to treatment failure among HIV-infected patients in Guinea-Bissau. In this retrospective cohort study, adult patients infected with HIV-1 receiving ≥6 months of ART at an HIV clinic in Bissau were included from June 2005 to July 2014 and followed until January 2015. Treatment failure was defined as 1) a fall in CD4 count to baseline (or below) or 2) CD4 levels persistently below 100 cells/µL after ≥6 months of ART. Cox hazard models, with time since six months of ART as the time-varying coefficient, were used to estimate the hazard ratio for death and loss to follow-up. We assessed 1,591 HIV-1-infected patients for immunological treatment failure. Treatment failure could not be determined in 594 patients (37.3%) because of missing CD4 cell counts. Among the remaining 997 patients, 393 (39.4%) experienced failure. Only 39 patients (9.9%) with failure were switched from first- to second-line ART. The overall switching rate was 3.1 per 100 person-years. Mortality rate was higher in patients with than without treatment failure, with adjusted hazard rate ratios (HRRs) 10.0 (95% CI: 0.9-107.8), 7.6 (95% CI: 1.6-35.5) and 3.1 (95% CI: 1.5-6.3) in the first, second and following years, respectively. During the first year of follow-up, patients experiencing treatment failure had a higher risk of being lost to follow-up than patients not experiencing treatment failure (adjusted HRR 4.4; 95% CI: 1.7-11.8). We found a high rate of treatment failure, an alarmingly high number of patients for whom treatment failure could not be assessed, and a low rate of switching to a second-line therapy. These factors could lead to an increased risk of resistance development and excess mortality.


Factors increasing the risk for hearing loss in 'pop' musicians.
Hearing thresholds were determined in 83 'pop' musicians with an average age of 26 years, average exposure time of 9 years and average weekly exposure time of 18 hours. The following factors had a statistically significant influence (p 95) on hearing: ageing, brief exposure per session, long exposure time in years (2 kHz), participation in military service (250 Hz), listening to pop music with head phones (2 kHz).


Minimum ten-year follow-up of cemented total hip replacement in patients with osteonecrosis of the femoral head.
Between November 1970 and September 1984 the senior author performed fifty-three consecutive total hip arthroplasties with cement in forty-one patients with the diagnosis of osteonecrosis of the femoral head. Five hips in three patients with failed renal transplants requiring chronic hemodialysis were excluded. At the time of final review, a minimum of ten years after the procedure, twenty-one patients (twenty-eight hips) were living, fifteen patients (eighteen hips) had died, and two patients (two hips) were lost to follow-up. A minimum ten-year follow-up radiograph was obtained on twenty-two (79%) of the hips in surviving patients. During the follow-up period 17.4% of hips (eight hips) required revision: 13.0% (six hips) for aseptic loosening, 2.2% (one hip) for sepsis, and 2.2% (one hip) for recurrent dislocation. All eight revisions occurred in patients living at time of final review, giving a revision prevalence of 22.9% (17.1% for aseptic loosening, 2.9% for sepsis, and 2.9% for recurrent dislocation) in patients surviving ten years. The prevalence of revision of the femoral component for aseptic loosening was 6.5% (three hips) for all hips and 9.1% (three hips) in patients surviving at least ten years. The prevalence of femoral aseptic loosening, defined as those components revised for aseptic loosening and those that demonstrated definite or probable radiographic loosening, was 13.0% (six hips) for all hips and 28.6% (six hips) for hips with at least ten-year radiographic follow-up. The prevalence of revision of the acetabular component for aseptic loosening was 13.0% (six hips) for all hips and 18.2% (six hips) in patients surviving at least ten years. The prevalence of acetabular aseptic loosening was 15.2% (seven hips) for all hips and 29.2% (seven hips) for hips with at least ten-year radiographic follow-up. In patients with osteonecrosis of the femoral head survivorship was significantly inferior to that in the senior author's overall patient population with regard to revision for aseptic loosening (p=0.019), revision for acetabular loosening (p=0.01), revision for femoral loosening (p=0.008), and aseptic femoral loosening (p=0.004). Survivorship to aseptic acetabular loosening was not significantly different (p=0.32). Young age at the time of surgery significantly increased the risk of subsequent component loosening (p<0.008) and revision due to aseptic loosening (p<0.002). These findings demonstrate the relatively poor durability of cemented total hip arthroplasty in patients with osteonecrosis of the femoral head as compared to patients with other diagnoses and suggest that the younger age in this patient population compromises results.


An infantile autistic syndrome characterised by the presence of succinylpurines in body fluids.
Succinyladenosine and succinylaminoimidazole carboxamide riboside were found in body fluids from 3 children, including a brother and sister, with severe psychomotor delay and autism. Both succinylpurines were identified by acid hydrolysis, anion-exchange chromatography, and ultraviolet spectrophotometry. Concentrations of both compounds were around 100 mumol/l in cerebrospinal fluid, between 5 and 10 mumol/l in plasma, and in the mmol/l range in urine. Succinylpurines were undetectable in cerebrospinal fluid and plasma from controls but there might be trace amounts in normal urine. The compounds are dephosphorylated derivatives of the intracellular metabolites adenylosuccinate and succinylaminoimidazole carboxamide ribotide, the two substrates of adenylosuccinase (adenylosuccinate lyase, EC 184.108.40.206). Their presence indicates a deficiency of this enzyme, which is involved in both de novo synthesis of purines and the formation of adenosine monophosphate from inosine monophosphate. Assays in one patient revealed markedly decreased adenylosuccinase activity in the liver and absence of activity in the kidney. The accumulation of both succinylpurines in the cerebrospinal fluid suggests that there is also a deficiency of this enzyme in the brain and that it may be the basic defect in a subgroup of children with genetically determined autism.


Recognition of core binding sites by bacteriophage integrases.
Bacteriophage integrases promote recombination between DNA molecules that carry attachment sites. They are members of a large and widely distributed family of site-specific recombinases with diverse biological roles. The integrases of phages lambda and HK022 are closely related members of this family, but neither protein efficiently recombines the attachment sites of the other phage. The nucleotides responsible for this specificity difference are located close to the points of recombinational strand exchange, within an integrase binding motif called the extended core binding site. There are four imperfectly repeated copies of this motif in each set of phage attachment sites, but only two, B' and C, contain major specificity determinants. When these specificity determinants were replaced by the corresponding nucleotides from a site with the alternative specificity, the resulting mutant was recombined by both integrases. Thus, the determinants act by impeding recombination promoted by the non-cognate integrase. We found that identical nucleotide substitutions within different core site copies had different effects on recombination, suggesting that integrase does not recognize each of the extended core binding sites in the same way. Finally, substitution at several positions in lambda integrase with the corresponding HK022-specific amino acids prevents recombination of lambda attachment sites, and this defect can be suppressed in an allele-specific manner by appropriate substitutions of HK022-specific nucleotides in the extended core binding sites.


Toxicity of tannins towards the free-living nematode Caenorhabditis elegans and the brine shrimp Artemia salina.
Toxicities of gallo- and condensed tannins towards the free-living nematode Caenorhabditis elegans is dependent on the tannins' molecular sizes. In the present paper we investigate the toxicity of ellagitannins to C elegans and the toxicity of ellagi-, gallo-, and condensed tannins to the brine shrimpArtemia salina. Ellagitannins 1 and 2 were isolated from Euphorbia supina and identified as tellimagrandin I and rugosin A methyl ester, respectively. An ellagitannin preparation from Cornus officinalis was chromatographically fractionated into ellagitannins A through H, having different molecular weights and specific rotations. Three of the ten ellagitannins, 2, G, and H produced significant toxicity towards C. elegans, showing the presence of an activity-structure relationship, as opposed to the results from tests of gallo- and condensed tannins. Ellagi-, gallo-, and condensed tannins also produced toxicity in A. salina.


Measurement properties of selected patient-reported outcome measures for use in randomised controlled trials in patients with systemic lupus erythematosus: a systematic review.
The heterogeneous multisystem manifestations of SLE include fatigue, pain, depression, sleep disturbance and cognitive dysfunction, and underscore the importance of a multidimensional approach when assessing health-related quality of life. The US Food and Drug Administration has emphasised the importance of patient-reported outcomes (PROs) for approval of new medications and Outcome Measures in Rheumatology has mandated demonstration of appropriate measurement properties of selected PRO instruments. Published information regarding psychometric properties of the Medical Outcomes Survey Short Form 36 (SF-36), Lupus Quality of Life Questionnaire (LupusQoL) and Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F), and their suitability as end points in randomised controlled trials (RCTs) and longitudinal observational studies (LOS) were assessed. A search of English-language literature using MEDLINE and EMBASE identified studies related to development and validation of these instruments. Evidence addressed content validity, reliability (internal consistency and test-retest reliability), construct validity (convergent and divergent) and longitudinal responsiveness, including thresholds of meaning and discrimination. All instruments demonstrated strong internal consistency, reliability and appropriate face/content validity, indicating items within each instrument that measure the intended concept. SF-36 and LupusQoL demonstrated test-retest reliability; although not published with FACIT-F in SLE supported by evidence from other rheumatic diseases. All instruments demonstrated convergent validity with other comparable PROs and responsivity to treatment. The measurement properties of PRO instruments with published data from RCTs including: SF-36, LupusQoL and FACIT-F indicate their value as secondary end points to support labelling claims in RCTs and LOS evaluating the efficacy of SLE treatments.


Development and evaluation of a booklet to promote ealthy lifestyle in people with HIV.
To develop and evaluate an educational primer to promote healthy lifestyles in people with HIV. Study of technological development in three stages: Development of the booklet, with bibliographical review, illustrations, layout, diagramming, adopting as reference the trans-theoretical model of behavior change; Analysis of content and appearance by 22 judges; Semantic analysis by 22 people with HIV. The proportion of positive evaluations of the items was measured, considering a percentage equal to or greater than 85%. My motivational booklet for change! Practices for promoting a healthy lifestyle" had six areas: Body weight control; Healthy eating; Exercise practice; Smoking, alcohol and other drugs; Stress control; and Drug treatment. Most of the items evaluated agreed with an overall average of 92.4% by the judges and 98.9% by the target audience. The booklet had evidence of adequate validity to be used by people with HIV.


Use of chemical coagulants to control fouling potential for wastewater membrane bioreactor processes.
Chemical coagulation with ferric chloride, alum, and an organic polymer were used to control the fouling potential of mixed liquors for submerged membrane bioreactor (MBR) processes in treating municipal wastewater. Their filterability was evaluated using a submerged hollow fiber ultrafiltration apparatus operated in constant permeate flux mode. The collected transmembrane pressures over filtration time were used to calculate the membrane fouling rates. The results showed that coagulation pretreatment can reduce fouling rates when MBRs were operated above the critical flux. Even though coagulation with the organic polymer formed larger mixed liquor suspended solids particles and had shorter time-to-filtration than those with ferric chloride and alum, the filterability for membrane filtration were similar, indicating that the membrane fouling in MBR systems was mainly controlled by the concentration of smaller colloidal particles.


The need for an interdisciplinary approach in forensic sciences: perspectives from a peculiar case of mummification.
The finding of a mummified body raises many problems, also because of the limits of the medico-legal investigations in case of mummification. Psychological autopsy and behavioral analysis have demonstrated a significant impact in case of equivocal death. The mummified corpse of a woman was found sealed in a wardrobe during the death investigation of a 36-year-old man, later discovered to be the woman's son. The woman's corpse was well preserved and no external injuries were found. Autopsy could not ascertain the cause of death. The state of the premises and the writings on the walls offered an opportunity to investigate the man's psychological profile and to better understand how the events might have taken place. The role of an accurate investigative analysis of the crime scene is a cornerstone of forensic pathology and the case presented underlies the importance of an interdisciplinary approach in forensic sciences.


Effects of water model and simulation box size on protein diffusional motions.
We performed molecular dynamics simulations of ubiquitin with the distinct water models, TIP3P, SPC, SPC/E, and SPC/Fw, in different system sizes with different box shapes. The translational diffusion constants of pure water linearly depend on the effective box length, which is known as finite size effect, whereas the first and second rotational times of pure water are nearly constant. We then observed that both the overall translation and rotational motions of the protein are linearly correlated to the viscosity of pure water. As expected from the finite size effect in pure water, the translational diffusion of the protein is significantly affected by the system size, and rotational diffusion is nearly size-independent. After correction for the finite size effect, the SPC/E and SPC/Fw models reproduce both the translational and rotational motion of the protein relatively well. Thus, water models that reproduce the experimentally derived diffusional properties of pure water accurately are expected to also be suitable for simulating protein diffusion quantitatively.


[Cervico-facial and otorhinolaryngoiatrical paleoanatomy and paleopathology in ancient Egypt].
The present article illustrates the history of the Aegyptian otorhinolaryngiatry and cervico-facial surgery, on the basis of the existing funerary, cultural, archaeological documentation, and in relation to their influence on the medical tradition of the following periods.


Biocompatible astaxanthin as a novel marine-oriented agent for dual chemo-photothermal therapy.
The photothermal effect of a marine-oriented xanthophyll carotenoid, astaxanthin (AXT), was characterized based on its potential absorption of visible laser light and conversion of optical light energy into heat for thermal treatment. As an antioxidant and anticancer agent, AXT extracted from marine material can be utilized for photothermal therapy due to its strong light absorption. The current study investigated the feasibility of the marine-based material AXT to increase the therapeutic efficacy of chemo-photothermal therapy (PTT) by assessing photothermal sessions in both cells and tumor tissues. A quasi-cw Q-switched 80 W 532 nm laser system was utilized to induce thermal necrosis in in vitro and in vivo models. An in vitro cytotoxicity study of AXT was implemented using squamous cell carcinoma (VX2) and macrophage (246.7) cell lines. In vivo PTT experiments were performed on 17 rabbits bearing VX2 tumors on their eyes that were treated with or without intratumoral injection of AXT at a dose of 100 μl (300 μg/ml) followed by laser irradiation at a low irradiance of 0.11 W/cm2. Fluorescence microscopy images revealed cellular death via apoptosis and necrosis owing to the dual chemo-photothermal effects induced by AXT. In vivo experimental results demonstrated that the AXT-assisted irradiation entailed a temperature increase by 30.4°C after tumor treatment for 4 min. The relative variations in tumor volume confirmed that the tumors treated with both AXT and laser irradiation completely disappeared 14 days after treatment, but the tumors treated under other conditions gradually grew. Due to selective light absorption, AXT-assisted laser treatment could be an effective thermal therapy for various drug-resistant cancers.


Neck muscle activity in fighter pilots wearing night-vision equipment during simulated flight.
Night-vision goggles (NVG) in jet fighter aircraft appear to increase the risk of neck strain due to increased neck loading. The present aim was, therefore, to evaluate the effect on neck-muscle activity and subjective ratings of head-worn night-vision (NV) equipment in controlled simulated flights. Five experienced fighter pilots twice flew a standardized 2.5-h program in a dynamic flight simulator; one session with NVG and one with standard helmet mockup (control session). Each session commenced with a 1-h simulation at 1 Gz followed by a 1.5-h dynamic flight with repeated Gz profiles varying between 3 and 7 Gz and including aerial combat maneuvers (ACM) at 3-5 Gz. Large head-and-neck movements under high G conditions were avoided. Surface electromyographic (EMG) data was simultaneously measured bilaterally from anterior neck, upper and lower posterior neck, and upper shoulder muscles. EMG activity was normalized as the percentage of pretest maximal voluntary contraction (%MVC). Head-worn equipment (helmet comfort, balance, neck mobility, and discomfort) was rated subjectively immediately after flight. A trend emerged toward greater overall neck muscle activity in NV flight during sustained ACM episodes (10% vs. 8% MVC for the control session), but with no such effects for temporary 3-7 Gz profiles. Postflight ratings for NV sessions emerged as "unsatisfactory" for helmet comfort/neck discomfort. However, this was not significant compared to the control session. Helmet mounted NV equipment caused greater neck muscle activity during sustained combat maneuvers, indicating increased muscle strain due to increased neck loading. In addition, postflight ratings indicated neck discomfort after NV sessions, although not clearly increased compared to flying with standard helmet mockup.


[A case of clivus chordoma showing hemorrhage in the posterior fossa].
We are reporting a rare case of clivus chordoma with fatal hemorrhage in the posterior fossa. A 38-year-old woman afflicted with sudden onset of severe headache and vomiting. On neurological examination, she was mildly lethargic. She had slight dysarthria and nystagmus, but no cranial nerve abnormalities. Craniogram revealed erosive changes in the right petrous bone. CT scan showed a massive intracerebellar hemorrhage and isodense mass in the sphenoid sinus, which were not enhanced by contrast medium. She became comatose and died 3 days later. No operation was performed. Autopsy revealed massive hemorrhage in the posterior fossa and yellowish, gelatinous tumor extending from the right clivus to the sphenoid sinus. Histological examination showed a chordoma. This case demonstrates that the hemorrhage associated with brain tumor, especially in posterior fossa, produces a significant sudden elevation of intracranial pressure and leads clinically to a rapid loss of consciousness and death soon after the onset.


Spirocurcasone, a diterpenoid with a novel carbon skeleton from Jatropha curcas.
Spirocurcasone (14), a diterpenoid possessing the unprecedented "spirorhamnofolane" skeleton, was isolated from the root barks of Jatropha curcas, a plant extensively cultivated throughout the world, along with 11 known and two other new diterpenoids. The stereostructure of spirocurcasone was established using HRESIMS, NMR, and quantum mechanical calculation of the electronic circular dichroic (ECD) spectrum. Some of the isolated diterpenoids showed a potent activity against L5178Y, a mouse lymphoma cell line.


Bilateral optic nerve hypoplasia.
In the past 10 years, 15 children with bilateral optic nerve hypoplasia have been studied at the Royal Alexandra Hospital for Children. There were 5 boys and 10 girls. Nine were first-born and they presented at a mean age of 5 months (range: 4 days to 25 months). Five presented with suspected blindness and 7 with abnormal eye movements (nystagmus or less commonly squint). The other 3 presented because of fits or developmental delay. Eight showed evidence of neural damage--microcephaly, seizures and/or abnormalities of tone. Four appeared to be of normal or near normal intelligence, 6 were mildly retarded and 5 severely so. Two patients had already died, one suddenly. Six of the 7 cases investigated in detail had evidence of hypothalamic pituitary dysfunction. Another one had a minimal hypothalamic abnormality. Four were severely growth retarded and 2 were receiving growth hormone replacement. Two males had micropenis and a girl had precocious puberty with partial diabetes insipidus. Neuroradiological investigations showed an absent septum pellucidum in only 5 cases. Five patients had other major CNS malformations. Five patients had normal CT scans; 3 of these 5 appeared of normal intelligence and all 5 had normal neurological examinations. Bilateral optic nerve hypoplasia is frequently associated with serious brain and endocrine abnormalities.


Upregulation of NF-E2-related factor-2-dependent glutathione by carnosol provokes a cytoprotective response and enhances cell survival.
To explore whether glutathione (GSH) increased through Nrf-2 activation is involved in the cytoprotective effects of carnosol in HepG2 cells. Human hepatoma cell line HepG2 were exposed to rosemarry essential oil or carnosol. Cell viability was measured using an Alamar blue assay. The production of intracellular GSH was determined using monochlorobimane. The level of protein or mRNA was examined by Western blotting or RT-PCR, respectively. Rosemarry essential oil (0.005%-0.02%) and carnosol (5 and 10 mol/L) increased the intracellular GSH levels and GSH synthesis enzyme subunit GCLC/GCLM expression. Rosemary essential oil and carnosol increased nuclear accumulation of Nrf2 and enhanced Nrf2-antioxidant responsive element (ARE)-reporter activity. Transfection of the treated cells with an Nrf2 siRNA construct blocks GCLC/GCLM induction. Furthermore, pretreatment of the HepG2 cells with essential oil and carnosol exerted significant cytoprotective effects against H(2)O(2) or alcohol. In TNFα-treated cells, the nuclear translocation and transcriptional activity of NF-κB was abolished for 12 h following carnosol pretreatment. Cotreatment with GSH also suppressed NF-κB nuclear translocation, whereas cotreatment with BSO, a GSH synthesis blocker, blocked the inhibitory effects of carnosol. This study demonstrated that Nrf2 is involved in the cytoprotective effects by carnasol, which were at least partially mediated through increased GSH biosynthesis.


The pharmacokinetics of subcutaneously injected Bimosiamose disodium in healthy male volunteers.
Bimosiamose is a novel synthetic pan-selectin antagonist developed for the treatment of acute and chronic inflammatory disorders. Therefore the pharmacokinetics of Bimosiamose disodium were studied in healthy male volunteers after single and multiple subcutaneous injections. A randomized, double-blind, placebo-controlled dose escalation trial was carried out. The subjects received subcutaneous injections of placebo or 100, 200 or 300 mg Bimosiamose disodium into the abdomen. Plasma and urine concentrations of Bimosiamose were determined. The maximum plasma concentration was 2.17+/-0.70 microg/ml and the AUC(0-infinity) 11.1+/-2.9 h microg/ml after the highest dose on day 1 (mean+/-SD). For the apparent clearance CL/f 28.7+/-7.3 l/h and the terminal half life t(1/2) 3.7+/-0.6 h were calculated. The mean residence time MRT(infinity) of 5.5 to 6.3 h for s.c. injection exceeded that after i.v. infusion due to an extended absorption time. For multiple dosing, constant pre-dose concentrations of about 20 ng/ml may be reached after two subsequent doses of 200 or 300 mg Bimosiamose disodium once daily. Almost 15% of the administered drug was excreted unchanged in urine. Moreover, Bimosiamose was well tolerated.


The role of epidermal growth factor-containing topical products on recovery and post-inflammatory hyperpigmentation prevention after laser surgeries: A systematic review and meta-analysis.
Post-inflammatory hyperpigmentation (PIH) is a common complication after laser surgeries. Recent studies applied epidermal growth factor (EGF) on the lasered area after laser surgery to decrease the incidence of PIH with controversial results. Therefore, a comprehensive literature review of randomized controlled trials (RCTs) was conducted to investigate the issue. Two reviewers independently searched the literatures, extracted, and analyzed the data. A total of seven RCTs involving 169 patients were included to evaluate the efficacy of EGF on recovery and PIH prevention after laser surgery. The results show that the incidence of PIH in the EGF group was relatively lower than that in the control group, although the difference was not statistically significant (OR 0.64, 95% CI 0.33 ~ 1.25, p = 0.19). However, the EGF groups had a significant decrease in melanin index (MI) scores at the 1st month after the laser surgery when compared to the control groups (SMD -1.57, 95% CI -2.83 ~ -0.31, p = 0.01). In addition, the patients on the EGF side rated significantly higher satisfactory scores (SMD 0.49, 95% CI 0.22 ~ 0.76, p = 0.0004). There was no significant difference as regard to changes in MI at the 2nd week and 2nd month, erythema index (EI), and trans-epidermal water loss (TEWL) at days 3 and 7 after laser therapy, respectively. The current meta-analysis found a limited temporary inhibitory effect of EGF-containing topical products on PIH with no significant effect on reducing post-laser erythema or promoting epidermal barrier repair. More studies are needed in the future due to the small sample size and marked intergroup heterogeneities.


Enteric nervous system α-synuclein immunoreactivity in idiopathic REM sleep behavior disorder.
To investigate the expression of α-synuclein in colonic biopsies of patients with idiopathic REM sleep behavior disorder (iRBD) and address if α-synuclein immunostaining of tissue obtained via colonic biopsies holds promise as a diagnostic biomarker for prodromal Parkinson disease (PD). Patients with iRBD, patients with PD, and healthy controls were prospectively recruited to undergo colonic biopsies for comparison of α-synuclein immunoreactivity patterns between the groups by using 2 different antibodies. There was no difference in colonic mucosal and submucosal immunostaining between groups using the 15G7 α-synuclein antibody, which was found in almost all participants enrolled in this study. By contrast, immunostaining for serine 129-phosphorylated α-synuclein (pSyn) in submucosal nerve fibers or ganglia was found in none of 14 controls but was observed in 4 of 17 participants with iRBD and 1 out of 19 patients with PD. The present findings of pSyn immunostaining of colonic biopsies in a substantial proportion of iRBD participants raise the possibility that this tissue marker may be a suitable candidate to study further as a prodromal PD marker in at-risk cohorts.


The natural tiling approach to cation conductivity in KAlO2 polymorphs.
A detailed analysis of correlations between structural features and cation conductivity is performed for KAlO(2) polymorphs in a wide temperature range of 300-1023 K. To explore the migration maps of K(+) cations we have used neutron diffraction data for low- and high-temperature KAlO(2) polymorphs and applied for the first time a novel algorithm based on the natural tiling concept and implemented it into the program package TOPOS. Five independent elementary channels for the K(+) cation migration have been revealed whose cross-sections were found to be essentially different in the low-temperature form, indicating a high anisotropy of the cation conductivity. During the transition to the cubic high-temperature phase all five channels become equivalent with sharply increased cross-sections that account for the jump-like increase of the cation conductivity and gives rise to its three-dimensional character.


Reliability of EEG Interactions Differs between Measures and Is Specific for Neurological Diseases.
Alterations of interaction (connectivity) of the EEG reflect pathological processes in patients with neurologic disorders. Nevertheless, it is questionable whether these patterns are reliable over time in different measures of interaction and whether this reliability of the measures is the same across different patient populations. In order to address this topic we examined 22 patients with mild cognitive impairment, five patients with subjective cognitive complaints, six patients with right-lateralized temporal lobe epilepsy, seven patients with left lateralized temporal lobe epilepsy, and 20 healthy controls. We calculated 14 measures of interaction from two EEG-recordings separated by 2 weeks. In order to characterize test-retest reliability, we correlated these measures for each group and compared the correlations between measures and between groups. We found that both measures of interaction as well as groups differed from each other in terms of reliability. The strongest correlation coefficients were found for spectrum, coherence, and full frequency directed transfer function (average rho > 0.9). In the delta (2-4 Hz) range, reliability was lower for mild cognitive impairment compared to healthy controls and left lateralized temporal lobe epilepsy. In the beta (13-30 Hz), gamma (31-80 Hz), and high gamma (81-125 Hz) frequency ranges we found decreased reliability in subjective cognitive complaints compared to mild cognitive impairment. In the gamma and high gamma range we found increased reliability in left lateralized temporal lobe epilepsy patients compared to healthy controls. Our results emphasize the importance of documenting reliability of measures of interaction, which may vary considerably between measures, but also between patient populations. We suggest that studies claiming clinical usefulness of measures of interaction should provide information on the reliability of the results. In addition, differences between patient groups in reliability of interactions in the EEG indicate the potential of reliability to serve as a new biomarker for pathological memory decline as well as for epilepsy. While the brain concert of information flow is generally variable, high reliability, and thus, low variability may reflect abnormal firing patterns.


Mechanisms operative in the antitumor activity of temozolomide in glioblastoma multiforme.
Glioblastoma multiforme (GBM) is the most frequent and incurable brain tumor in adults. Although temozolomide (TMZ) does not cure GBM, it has demonstrated anti-GBM activity and has improved survival (8-14 months) and quality of life. We studied the mechanisms by which TMZ affects 2 human GBM cell lines; U251-MG and U87-MG, aiming to unravel the drug-activated cascades to enable the development of combination therapies that will improve the efficacy of TMZ. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium assay was used to assess cell viability. Modulation of gene expression by TMZ therapy was assayed by gene profiling and verified by quantitative real-time polymerase chain reaction. Protein levels influenced by the treatment were studied by Western blots and immunocytochemistry. Increasing concentrations of TMZ decreased cell viability in a concentration-dependent manner. The expression of 1,886 genes was altered >2-fold after TMZ treatment. We focused on the 81 genes similarly altered by TMZ treatment in both cell lines to neutralize tissue-specific characteristics. Fourteen target genes of hypoxia-inducible factor (HIF-1), were found to be up-regulated after TMZ treatment including vascular endothelial growth factor (VEGF). HIF-1alpha expression was constant at the mRNA level; however, its post-treatment protein levels increased compared with those of untreated control cells. The genetic analyses suggest that treatment with TMZ activates stress mechanisms in GBM cells that include the angiogenesis-inducing proteins HIF-1alpha and VEGF. We propose that treatment with TMZ be supplemented with either an antibody to VEGF or down-regulators of HIF-1alpha to improve clinical results of TMZ in the treatment of GBM.


Conversion of a silencer into an enhancer: evidence for a co-repressor in dorsal-mediated repression in Drosophila.
The dorsal (dl) protein gradient determines patterns of gene expression along the dorsal-ventral axis of the Drosophila embryo. dl protein is at peak levels in ventral nuclei of the embryo where it activates some genes (twist and snail) and represses others [zerknullt (zen), decapentaplegic and tolloid]. It is a member of the rel family of transcription factors and interacts with specific DNA sequences in the regulatory regions of its target genes. These sequences (dl binding sites), when taken from the context of either an activated or repressed promoter, mediate transcriptional activation of a heterologous promoter, but not repression. We found that T-rich sequences close to the dl binding sites in the silencer region of the zen promoter are conserved between three Drosophila species. Using this sequence information we defined a minimal element that can mediate repression of a heterologous promoter. This element interacts with at least two factors present in embryonic extracts, one of which is dl protein. The other factor binds to the T-rich site. Point mutations in either site abolish ventral repression in vivo. In addition, mutations in the T-rich site cause ectopic expression in ventral regions indicating that the minimal silencer was converted into an enhancer.


Comparison of clinical course of polymyositis and dermatomyositis: a follow-up study in Tokushima University Hospital.
Polymyositis (PM) and dermatomyositis (DM) are systemic inflammatory disorders affecting skeletal muscles and other organs, and are associated with high morbidity and mortality rates. In this study, we studied the prevalence, clinical features and its comparative outcome of PM/DM, comparing PM and DM. Twenty-three PM/DM patients (9 PM and 14 DM) were included in this study. The complication of interstitial pneumonia (IP) was found in 17 patients (74%). HRCT showed that non-specific interstitial pneumonia pattern was the most common in patterns of lung involvement. Twenty-one patients (91%) with PM/DM received high dose of prednisolone therapy. The percentage of patients who received methylprednisolone (mPSL) pulse and cyclosporin A was higher in DM patients than in PM patients. The percentage of patients who received mPSL pulse and cyclosporin A was higher in later (after Apr 2004) patients than in former (before Mar 2004) patients. Malignant diseases appeared in 3 patients with DM which consisted of breast cancer, epipharyngeal cancer and gastric cancer. We observed 2 deaths in DM patients during the course of therapy; one was due to IP, and the other due to miliary tuberculosis. This study showed that a poorer prognosis was observed in patients with DM when compared with those with PM, and immunosuppressive medications may be implicated at least partially in increased risk of infections and malignancies in PM/DM patients especially DM patients, indicating that patients with PM/DM may require careful monitoring during the clinical course.


Generation and characterization of antibody against paf1 complex in Drosophila melanogaster.
Paf1 complex was identified in yeast and characterized to function in transcription and its related events. We identified the Drosophila homological components of paf1, CDC73 and RTF1 of paf1 complex. The genes encoding Drosophila paf1, CDC73 and RTF1 were cloned and expressed. With the purified recombinant proteins of truncated components of paf1 complex, antibodies against the Drosophila paf1, CDC73 and RTF1 were generated. These antibodies have been shown to be able to detect the endogenous paf1 subunits as well as their human counterparts in the HeLa extract. On Drosophila polytene chromosomes, these antibodies have been demonstrated to locate the paf1 complex at actively transcribing sites, which co-localized with phosphorylated RNA polymerase II, indicating that paf1 complex in Drosophila is involved in transcription or the events coupling with transcription.


Polypeptide N-acetylgalactosaminyltransferase-6 expression in gastric cancer.
Gastric cancer (GC) is one of the leading causes of cancer-related deaths, with limited improvement in its clinical outcome worldwide. Aberrant mucin-type O-glycosylation is a critical event widespread in the development of GC. Polypeptide N-acetylgalactosaminyltransferases (GALNTs) regulate the initial step and determine the sites of mucin-type O-glycoprotein bio-synthesis. GALNT6 has considerable potential as a biomarker in various cancers. The roles of GALNT6 in GC were analyzed, and the results showed that GALNT6 expression markedly increased in GC tissues compared with those in adjacent gastric tissues. High intratumoral GALNT6 density was associated with the clinicopathological parameters of TNM stage and distant metastasis. GALNT6 was identified as an independent prognosticator for the poor prognosis of GC patients. Moreover, the high expression level of GALNT6 was significantly associated with the low expression levels of E-cadherin and β-catenin and the high expression levels of MMP9. These findings indicated that GALNT6 could provide new insights into the characterization of GC as well as contribute to the development of an efficient prognostic indicator and novel therapeutic modalities for GC.


The MADS-box gene Agamous-like 11 is essential for seed morphogenesis in grapevine.
Despite the wide appreciation of seedless grapes, little is known about the molecular mechanisms that drive the stenospermocarpic seedless-type phenotype in grapevine. In order to address the molecular mechanisms that control seedlessness in grapevine, our study aimed to characterize VviAGL11, a class D MADS-box transcription factor gene that has been proposed as the major candidate gene involved in Vitis vinifera seed morphogenesis. VviAGL11 allelic variations in seeded and seedless grapevine cultivars were determined, and its correlations with allele-specific steady-state mRNA levels were investigated. VviAGL11 relative expression was significantly higher in seeds at 2, 4, and 6 weeks after fruit set, whereas in the seedless grape its transcript levels were extremely low in all stages analyzed. In situ hybridization revealed transcript accumulation specifically in the dual endotesta layer of the seeds, which is responsible for elongation and an increase of cell number, a necessary step to determine the lignification and the final seed size. No hybridization signals were visible in the seedless grapevine tissues, and a morphoanatomical analysis showed an apparent loss of identity of the endotesta layer of the seed traces. Ectopic expression of VviAGL11 in the Arabidopsis SEEDSTICK mutant background restored the wild-type phenotype and confirmed the direct role of VviAGL11 in seed morphogenesis, suggesting that depletion of its expression is responsible for the erroneous development of a highly essential seed layer, therefore culminating in the typical apirenic phenotype.


Chondroprotective effects of pulsed shortwave therapy in rabbits with experimental osteoarthritis.
Osteoarthritis (OA) represents a public health challenge since the pathogenic treatment, able to induce cartilage regeneration, still remains unknown. Ageing of the population and increasing OA prevalence have led to a lot of research, aiming to identify treatments acting on chondrocytes that play a determinant role in cartilage degeneration÷regeneration balance. Pulsed shortwave therapy (with the classical application form - Diapulse) is a physiotherapy method with anabolic effects demonstrated on nervous, conjunctive and vascular tissues, but its effects on OA cartilage are not known. Our aim was to demonstrate the effects of Diapulse on the cartilage in experimental induced OA. Experimental OA was induced in 10 mature female rabbits by anterior cruciate ligament transection (ACLT). Ten weeks after ACLT, rabbits were randomized in a treatment group and a control group. Treatment group was exposed to Diapulse at a frequency of 27.12 MHz, pulse length of 65 μs, pulse frequency of 300 pulses÷s (300 Hz) for 10 minutes÷day. Control group was exposed to sham therapy. After treatment, rabbits were sacrificed and the cartilage was evaluated by histopathological examinations with Hematoxylin-Eosin (HE) staining and transmission electron microscopy (TEM). OA characteristic changes were found in both groups. In the treatment group, we found that Diapulse influenced the degenerative process in the OA cartilage by improving the chondrocyte viability and the capacity to maintain cellular matrix integrity and structure. Diapulse can be considered a disease modifying therapeutic procedure and could be a reliable option for treatment of OA patients.


Insomnia in Older Adults: Relations to Depression and Anxiety.
The authors examine the relations between insomnia and depression using the Beck Depression Inventory and between insomnia and anxiety using the State-Trait Anxiety Inventory and the Neuroticism Extroversion Openness-Personality Inventory (NEO) in a sample of 27 community-dwelling older patients with insomnia (mean age = 70.1 years). Sleep parameters were measured using both subjective (daily sleep logs) and objective (wrist actigraph) methods. Results varied according to the method used to measure sleep: with sleep logs, longer wake after sleep onset was related to both greater depression and anxiety (NEO), and longer time in bed was related to greater anxiety (NEO); with the actigraph, longer total sleep time was related to both greater depression and anxiety, and shorter sleep onset was related to greater depression.


Structure and sequence conservation of hao cluster genes of autotrophic ammonia-oxidizing bacteria: evidence for their evolutionary history.
Comparison of the organization and sequence of the hao (hydroxylamine oxidoreductase) gene clusters from the gammaproteobacterial autotrophic ammonia-oxidizing bacterium (aAOB) Nitrosococcus oceani and the betaproteobacterial aAOB Nitrosospira multiformis and Nitrosomonas europaea revealed a highly conserved gene cluster encoding the following proteins: hao, hydroxylamine oxidoreductase; orf2, a putative protein; cycA, cytochrome c(554); and cycB, cytochrome c(m)(552). The deduced protein sequences of HAO, c(554), and c(m)(552) were highly similar in all aAOB despite their differences in species evolution and codon usage. Phylogenetic inference revealed a broad family of multi-c-heme proteins, including HAO, the pentaheme nitrite reductase, and tetrathionate reductase. The c-hemes of this group also have a nearly identical geometry of heme orientation, which has remained conserved during divergent evolution of function. High sequence similarity is also seen within a protein family, including cytochromes c(m)(552), NrfH/B, and NapC/NirT. It is proposed that the hydroxylamine oxidation pathway evolved from a nitrite reduction pathway involved in anaerobic respiration (denitrification) during the radiation of the Proteobacteria. Conservation of the hydroxylamine oxidation module was maintained by functional pressure, and the module expanded into two separate narrow taxa after a lateral gene transfer event between gamma- and betaproteobacterial ancestors of extant aAOB. HAO-encoding genes were also found in six non-aAOB, either singly or tandemly arranged with an orf2 gene, whereas a c(554) gene was lacking. The conservation of the hao gene cluster in general and the uniqueness of the c(554) gene in particular make it a suitable target for the design of primers and probes useful for molecular ecology approaches to detect aAOB.


Examination of contraction-induced muscle pain as a behavioral correlate of physical activity in women with and without fibromyalgia.
This study aimed to compare muscle pain intensity during a sustained isometric contraction in women with and without fibromyalgia (FM), and examine the association between muscle pain and self-reported levels of physical activity. Fourteen women with FM and 14 healthy women completed the study, where muscle pain ratings (MPRs) were obtained every 30 s during a 3 min isometric handgrip task at 25% maximal strength, and self-reported physical activity was quantified using the Baecke Physical Activity Questionnaire. Women with FM were less physically active than healthy controls. During the isometric contraction, MPR progressively increased in both groups at a comparable rate, but women with FM generally reported a greater intensity of muscle pain than healthy controls. Among all women, average MPR scores were inversely associated with self-reported physical activity levels. Women with FM exhibit augmented muscle pain during isometric contractions and reduced physical activity than healthy controls. Furthermore, contraction-induced muscle pain is inversely associated with physical activity levels. These observations suggest that augmented muscle pain may serve as a behavioral correlate of reduced physical activity in women with FM. Implications for Rehabilitation Women with fibromyalgia experience a greater intensity of localized muscle pain in a contracting muscle compared to healthy women. The intensity of pain during muscle contraction is inversely associated with the amount of physical activity in women with and without fibromyalgia. Future studies should determine whether exercise adherence can be improved by considering the relationship between contraction-induced muscle pain and participation in routine physical activity.


[Prostatitis in China: research and clinical practice].
In recent years, significant progress has been achieved in the epidemiological, basic and clinical researches on prostatitis in China. From the perspective of clinical practice, Chinese Urological Association (CUA) Guidelines on Prostatitis has been applied nationwide and promoted the standardization of the diagnosis and management of prostatitis in China.


Risk score for peri-interventional complications of carotid artery stenting.
Routinely available independent risk factors for the peri-interventional outcome of patients undergoing elective carotid artery stenting (CAS) are lacking. The rationale of the study was to create a risk score identifying high-risk patients. We prospectively enrolled 606 consecutive patients assigned to CAS at a secondary care hospital. Various biochemical, clinical, and lesion-related risk factors were prospectively defined. The primary end point reflecting periprocedural complications encompassed minor and major stroke, nonfatal myocardial infarction and all-cause mortality within 30 days. Three percent of patients (n=18) experienced a nonfatal minor (n=13) or major (n=5) stroke. 1.3% of patients (n=8) died from fatal stroke (n=4) or other causes (n=4). No myocardial infarction was observed within 30 days after stenting. Multivariable analysis revealed diabetes mellitus with inadequate glycemic control (HbA1c > 7%), age > or = 80 years, ulceration of the carotid artery stenosis, and a contralateral stenosis > or = 50% as independent risk factors. A risk score formed with these variables showed a superior predictive value (C-statistic = 0.73) compared with single risk factors. The presence of 2 or more of these risk factors identified patients with a risk of 11% for a periprocedural complication compared with 2% in patients with a score of 0 or 1. In patients undergoing elective CAS, a risk score based on routinely accessible variables was able to identify patients at high-risk for atherothrombotic events and all-cause death within 30 days after the intervention.


A hypoperfusion context may aid to interpret hyperlactatemia in sepsis-3 septic shock patients: a proof-of-concept study.
Persistent hyperlactatemia is particularly difficult to interpret in septic shock. Besides hypoperfusion, adrenergic-driven lactate production and impaired lactate clearance are important contributors. However, clinical recognition of different sources of hyperlactatemia is unfortunately not a common practice and patients are treated with the same strategy despite the risk of over-resuscitation in some. Indeed, pursuing additional resuscitation in non-hypoperfusion-related cases might lead to the toxicity of fluid overload and vasoactive drugs. We hypothesized that two different clinical patterns can be recognized in septic shock patients through a multimodal perfusion monitoring. Hyperlactatemic patients with a hypoperfusion context probably represent a more severe acute circulatory dysfunction, and the absence of a hypoperfusion context is eventually associated with a good outcome. We performed a retrospective analysis of a database of septic shock patients with persistent hyperlactatemia after initial resuscitation. We defined hypoperfusion context by the presence of a ScvO2 < 70%, or a P(cv-a)CO2 ≥6 mmHg, or a CRT ≥4 s together with hyperlactatemia. Ninety patients were included, of whom seventy exhibited a hypoperfusion-related pattern and 20 did not. Although lactate values were comparable at baseline (4.8 ± 2.8 vs. 4.7 ± 3.7 mmol/L), patients with a hypoperfusion context exhibited a more severe circulatory dysfunction with higher vasopressor requirements, and a trend to longer mechanical ventilation days, ICU stay, and more rescue therapies. Only one of the 20 hyperlactatemic patients without a hypoperfusion context died (5%) compared to 11 of the 70 with hypoperfusion-related hyperlactatemia (16%). Two different clinical patterns among hyperlactatemic septic shock patients may be identified according to hypoperfusion context. Patients with hyperlactatemia plus low ScvO2, or high P(cv-a)CO2, or high CRT values exhibited a more severe circulatory dysfunction. This provides a starting point to launch further prospective studies to confirm if this approach can lead to a more selective resuscitation strategy.


Enhanced electricity production from microbial fuel cells with plasma-modified carbon paper anode.
Microbial fuel cells (MFC) provide a new opportunity for simultaneous electricity generation and waste treatment. An improvement in the anode capacity of MFCs is essential for their scale-up and commercialization. In this work we demonstrate, for the first time, that plasma-based ion implantation could be used as an effective approach to modify carbon paper as an anode for MFC to improve its electricity-generating capacity. After the N(+) ion implantation, a decreased charge-transfer resistance is achieved, which is attributed to the increased C-N bonds after N(+) ion implantation. In addition, the surface roughness and hydrophobicity are also changed, which favor microbial adhesion on the anode surface. The cyclic voltammetry results show that both the electrochemical activity and the electron transfer are enhanced remarkably, leading to better MFC performance compared to the control. Such a plasma surface modification technique provides an effective way to modify the electrode for enhancing MFC performance for power generation.


Comparative inhibition of hepatic hydroxymethylbilane synthase by both hard and soft metal cations.
The in vitro inhibition of hydroxymethylbilane synthase (EC 188.8.131.52, uroporphyrinogen I synthetase) obtained from livers of Sprague-Dawley rats has been studied with a wide range of di- and tri-valent metal ions. After purification by cell lysis, heat treatment, and centrifugation, the stable, soluble enzyme yielded sigmoidal inhibition curves with increasing concentrations of each of the 16 test ions. Using the negative logarithm of metal concentration for 50% inhibition (the pM50 value), the metal ions could be classified according to their Klopman hardness values. Very soft ions including Hg2+, intermediate ions including Cr3+, and very hard ions including Al3+ all yielded large pM50 values indicating strong inhibition. In comparison to known metal-ion chemical behaviour, these three ions could indicate three different types of inhibitory binding sites at or near the active site: Hg2+ corresponding to sulfur in cysteine, Cr3+ corresponding to nitrogen in histidine, and Al3+ corresponding to oxygen in carboxyl groups. The presence of the first two sites is also indicated by the pH dependence of activity.


Profile and quality of life of women in pelvic floor rehabilitation.
Describe the sociodemographic, clinical, and sexual profile, identify profile variables that affect the Health-Related Quality of Life (HRQoL), and evaluate the correlation between two HRQoL questionnaires used in a pelvic floor rehabilitation program. This is an observational, analytical, and cross-sectional study, based on patient records and two questionnaires for HRQoL evaluation. Women presented a mean age of 55.4 years; were married; white; had stress, urge, or mixed urinary incontinence (UI) of moderate to large urine release; and daily or diurnal UI. Only 50.5% had an active sex life and most had sexual complaints. The change in sexual activity and some types of UI affected the HRQoL. The two questionnaires presented a correlation. The profile and correlation between the questionnaires are consistent with the literature. The type of UI and changes in sexual activity affect the HRQoL.


An Integrated Experimental and Computational Approach for Characterizing the Kinetics and Mechanism of Triadimefon Racemization.
Enantiomers of chiral molecules commonly exhibit differing pharmacokinetics and toxicities, which can introduce significant uncertainty when evaluating biological and environmental fates and potential risks to humans and the environment. However, racemization (the irreversible transformation of one enantiomer into the racemic mixture) and enantiomerization (the reversible conversion of one enantiomer into the other) are poorly understood. To better understand these processes, we investigated the chiral fungicide, triadimefon, which undergoes racemization in soils, water, and organic solvents. Nuclear magnetic resonance (NMR) and gas chromatography / mass spectrometry (GC/MS) techniques were used to measure the rates of enantiomerization and racemization, deuterium isotope effects, and activation energies for triadimefon in H2 O and D2 O. From these results we were able to determine that: 1) the alpha-carbonyl carbon of triadimefon is the reaction site; 2) cleavage of the C-H (C-D) bond is the rate-determining step; 3) the reaction is base-catalyzed; and 4) the reaction likely involves a symmetrical intermediate. The B3LYP/6-311 + G** level of theory was used to compute optimized geometries, harmonic vibrational frequencies, nature population analysis, and intrinsic reaction coordinates for triadimefon in water and three racemization pathways were hypothesized. This work provides an initial step in developing predictive, structure-based models that are needed to identify compounds of concern that may undergo racemization. Chirality 28:633-641, 2016. © 2016 Wiley Periodicals, Inc.


Placebo-induced improvements: how therapeutic rituals affect the patient's brain.
The placebo effect has evolved from being thought of as a nuisance in clinical research to a biological phenomenon worthy of scientific investigation. The study of the placebo effect and of its evil twin, the nocebo effect, is basically the study of the therapeutic ritual around the patient, and it plays a crucial role in the therapeutic outcome. In recent years, different types of placebo responses have been analyzed with sophisticated biological tools that have uncovered specific mechanisms at the neuroanatomical, neurophysiological, biochemical, and cellular levels. Most of our knowledge about the neurobiological mechanisms of the placebo response comes from pain and Parkinson's disease, whereby the neuronal networks involved in placebo responsiveness have been identified. In the first case, opioid, cannabinoid, and cholecystokinin circuits have been found to be involved. In the second case, dopaminergic activation in the striatum and neuronal changes in basal ganglia have been described. This recent research has revealed that these placebo-induced biochemical and cellular changes in a patient's brain are very similar to those induced by drugs. This new way of thinking may have profound implications in clinical trials and medical practice both for pharmacological interventions and for nonpharmacological treatments such as acupuncture.


Developmental and Reproductive Effects of Iron Oxide Nanoparticles in Arabidopsis thaliana.
Increasing use of iron oxide nanoparticles in medicine and environmental remediation has led to concerns regarding exposure of these nanoparticles to the public. However, limited studies are available to evaluate their effects on the environment, in particular on plants and food crops. Here, we investigated the effects of positive (PC) and negative (NC) charged iron oxide (Fe₂O₃) nanoparticles (IONPs) on the physiology and reproductive capacity of Arabidopsis thaliana at concentrations of 3 and 25 mg/L. The 3 mg/L treated plants did not show evident effects on seeding and root length. However, the 25 mg/L treatment resulted in reduced seedling (positive-20% and negative-3.6%) and root (positive-48% and negative-negligible) length. Interestingly, treatment with polyethylenimine (PEI; IONP-PC coating) also resulted in reduced root length (39%) but no change was observed with polyacrylic acid (PAA; IONP-NC coating) treatment alone. However, treatment with IONPs at 3 mg/L did lead to an almost 5% increase in aborted pollen, a 2%-6% reduction in pollen viability and up to an 11% reduction in seed yield depending on the number of treatments. Interestingly, the treated plants did not show any observable phenotypic changes in overall size or general plant structure, indicating that environmental nanoparticle contamination could go dangerously unnoticed.