Depression in Parkinson's disease.
The prevalence of major and minor depression in Parkinson's disease is around 30-40% but, unfortunately, depression remains frequently underrecognized and often undertreated. However, recognition and appropriate treatment of depression in patients with Parkinson's disease is essential for improving the cross-sectional picture and longitudinal course. This review focuses on the epidemiology, pathophysiology and different treatment modalities of depression in Parkinson's disease.


Symbiotic Interplay of Fungi, Algae, and Bacteria within the Lung Lichen Lobaria pulmonaria L. Hoffm. as Assessed by State-of-the-Art Metaproteomics.
Lichens are recognized by macroscopic structures formed by a heterotrophic fungus, the mycobiont, which hosts internal autotrophic photosynthetic algal and/or cyanobacterial partners, referred to as the photobiont. We analyzed the structure and functionality of the entire lung lichen Lobaria pulmonaria L. Hoffm. collected from two different sites by state-of-the-art metaproteomics. In addition to the green algae and the ascomycetous fungus, a lichenicolous fungus as well as a complex prokaryotic community (different from the cyanobacteria) was found, the latter dominated by methanotrophic Rhizobiales. Various partner-specific proteins could be assigned to the different lichen symbionts, for example, fungal proteins involved in vesicle transport, algal proteins functioning in photosynthesis, cyanobacterial nitrogenase and GOGAT involved in nitrogen fixation, and bacterial enzymes responsible for methanol/C1-compound metabolism as well as CO-detoxification. Structural and functional information on proteins expressed by the lichen community complemented and extended our recent symbiosis model depicting the functional multiplayer network of single holobiont partners.1 Our new metaproteome analysis strongly supports the hypothesis (i) that interactions within the self-supporting association are multifaceted and (ii) that the strategy of functional diversification within the single lichen partners may support the longevity of L. pulmonaria under certain ecological conditions.


Current treatment approaches to surgery for brain metastases.
The role for surgical treatment of brain metastases continues to evolve. Data have demonstrated survival and quality-of-life benefits for surgical treatment of appropriate lesions in selected patients. With improvements in surgical technique, along with therapeutic improvements in the management of systemic cancers, more patients are now eligible for surgical resection. Selection of patients for surgical treatment depends on performance status, size, location, and number of brain lesions, as well as the status of systemic disease. Although surgery has traditionally been performed for patients with a single brain metastasis, an increasing number of patients with multiple brain metastases may also be treated surgically. Surgical techniques, such as image guidance, intraoperative ultrasound, functional neuronavigation, cortical mapping, and awake craniotomies, have expanded the scope of lesions that can be removed safely to optimize outcomes. Seizures, peritumoral edema, and venous thromboembolic disease all contribute significantly to surgical morbidity and mortality and thus require aggressive treatment around the time of the surgical procedure to improve the quality of life and maximize survival time.


Suspected endothelial pencil graphite deposition.
A 14-year-old male patient had an ocular trauma with a pencil. Biomicroscopic examination revealed a broken part of pencil into the cornea. Foreign body removal and corneal wound closure were performed in the same day. After corneal repair, there was a grade 4+ anterior chamber reaction just like in preoperative examination. Dilated examination showed a very small piece broken tip of pencil on the upper nasal quadrant of the lens. A small and linear deposition was also seen on endothelial surface. Endothelial deposition and foreign body disappeared with intensive topical steroid treatment.


Construction and validation of safe care theory for older inpatients from the perspective of socio-ecological model: a study protocol.
In an ageing society, older adults are the main users of healthcare services, and Chinese healthcare systems have been struggling to meet the care demand of older adults. Due to the illness, many older inpatients cannot finish daily activities independently and require healthcare from caregivers. Evaluating the care needs of older adults and exploring the factors affecting safe care at multiple levels are conducive to providing systematic care services for older inpatients. This study aims to examine which and how factors impact safe care for older inpatients and propose a safe care theory to provide directions on improving the safe care system in the hospital. A mixed-methods study with three interrelated research streams will be designed. (1) A safe care concept model: we will conduct a scoping review to extract the facilitators and barriers influencing the safe care of older inpatients and construct a concept model based on the socio-ecological model and the Yorkshire Contributory Factors Framework. (2) A safe care theory model: we will conduct a qualitative study with thematic analysis (aimed at older inpatients, caregivers and nurses) to define the concept connotations and propose a theory model. (3) A safe care theory: we will use the scales related to the theory model to test the concepts and statements. We will revise the theory model and derive a safe care theory based on the mixed-methods study results. This study will start in October 2023 and end in October 2025. This study was approved by the ethics committee (No. 20221598). All participants will be provided with consent forms prior to data collection. The study will be disseminated via peer-reviewed manuscripts and conferences. ChiCTR2300067421.


The effects of hypercortisolism on the frequency and magnitude of sleep EEG waves in patients with Cushing syndrome: A spectral analysis study.
Our aim was to investigate the effects of endogenous chronic hypercortisolism on sleep electroencephalogram (EEG) and differences between the adrenocorticotropic hormone (ACTH)-dependent and independent Cushing Syndrome (CS) patients through a sleep spectral analysis program. A total of 32 patients diagnosed as having endogenous CS (12 ACTH-dependent and 20 ACTH-independent) and a control group comprising 16 healthy individuals were included in the study. Polysomnographic analysis was performed. Blood samples were collected at 08:00 AM for analysis of ACTH and basal cortisol, and at 00:00 AM for midnight cortisol levels. The frequency and power of the slow wave activity (SWA), theta, alpha, and beta waves of the first and last non-rapid eye movement (NREM) cycles were measured with a spectral analysis program. The CS patient group had higher SWA power, especially in the first NREM cycle. In the ACTH-dependent group, SWA maximum and mean power values were higher in the frontal channels in the first NREM, compared to the last NREM sleep stage (p<0.05). Cortisol has been found to be associated with SWA waves, making these waves higher in power, especially in the first NREM phase. This difference was much less pronounced in the final NREM sleep stage. The difference between the first and last NREM sleep stages with respect to the power of SWA in the frontal channel in the ACTH-dependent group suggests that not only cortisol but also high levels of ACTH affect the power of slow waves during sleep.


Spectral engineering of ultrathin germanium solar cells for combined photovoltaic and photosynthesis.
In densely populated areas, ground mounted photovoltaic power plants compete with agriculture for cultivable land. Agrivoltaic systems allow the combination of these two forms of land use by deliberately designed light sharing. In this contribution, we present a spectrally selective solar cell, for use in agrivoltaic systems, greenhouses, and photo-bioreactors. Our concept benefits from a solar cell with a transmission spectrum which can be easily tuned for the specific absorption requirements of algae and plants. This is achieved by a Fabry-Perot-type multilayer resonator as a back reflector, which determines the transmission and absorption spectrum of the solar cell. We demonstrate the extent of how this transmission spectrum can be engineered by varying the layer thicknesses of the reflector and we show how the reflecting metal layers in the back reflector influence the transmission and photocurrent generation of the spectrally selective solar cell. Finally, we analyze the optical loss mechanisms of the solar cell layer stack to address further optimization potential. Our work offers a spectrally selective solar cell which can be easily adjusted for the requirements of combining photovoltaic and photosynthesis.


Surgery for Neck Recurrence of Differentiated Thyroid Cancer: Outcomes and Risk Factors.
Persistent/recurrent disease in the neck is frequent in patients with differentiated thyroid cancer (DTC). Assess efficacy, safety, and prognostic factors of first neck reoperation in DTC. Retrospective study of consecutive patients undergoing neck reoperation for recurrent/persistent DTC in a referral cancer center. Response after reoperation was defined according to the 2015 American Thyroid Association guidelines. One hundred sixty-one DTC patients were enrolled (64% females, median age 35 years, 96% papillary DTC). Initial stage was pT3 in 43% and pT4 in 10%, pN1 in 74%. Aggressive histology was present in 25% of the patients, in both primary and persistent/recurrent tumor. Four patients had no malignancy in the reoperative specimen, and 1 patient died due to postoperative hematoma and was excluded from further analysis. Following reoperation, 15 patients (10%) had persistent structural disease, 16 (10%) had biochemical incomplete response, 26 (17%) had indeterminate response, and 99 (63%) had complete response (CR), among whom 24 relapsed later. After a median follow-up of 5 years, only 83 patients (53%) had CR without the need for further treatments. The rate of permanent complications was: hypoparathyroidism 2%, laryngeal nerve palsy 0.6%, other 6%. Age ≥45 years, aggressive histology, and lymph node ratio ≥0.6 at initial surgery were independent risk factors for incomplete response after reoperation. Male sex, aggressive histology, and ≥10 metastases at reoperation were independent risk factors of secondary relapse following CR achieved with reoperation. A careful risk-benefit analysis should guide surgical decision, particularly in patients with risk factors for incomplete response.


Efficacy of Bezlotoxumab Against Clostridioides difficile Infection: A Case-Series Study at a University Hospital in Japan and Literature Review.
Background Clostridioides difficile infection (CDI) recurrence is a public health concern as well as a health economic burden. Bezlotoxumab treatment is one way to prevent recurrence; however, its clinical results have not been reported in Japan. Therefore, we investigated the efficacy and safety of bezlotoxumab in patients with CDI at a university hospital in Japan and compared them with previously reported findings. Methodology We retrospectively examined all patients with some risk factors for recurrent CDI who received bezlotoxumab at the discretion of physicians at the Aichi Medical University Hospital, Aichi, Japan, between July 2018 and July 2022. The primary outcome was the three-month CDI recurrence rate. The secondary outcomes were an initial clinical cure and the six-month CDI recurrence rate. The safety of the administration was also assessed. Results A total of nine patients who received bezlotoxumab were included during the study period. The rate of CDI recurrence within three months was 28.5% (2/9). Two patients died due to other causes before their diarrhea improved. None of the patients experienced CDI recurrence between three and six months after the initial clinical cure of the baseline episode. Patients showed good tolerability to bezlotoxumab with no adverse effects. Two patients with a single episode of CDI recurrence before bezlotoxumab administration showed no recurrence. Conclusions In this Japanese case-series study, the efficacy of bezlotoxumab in preventing CDI recurrence in elderly patients with CDI and multiple underlying diseases was inferior to that reported in previous studies that analyzed real-world data. It is possible that bezlotoxumab may not be fully effective in elderly patients with CDI.


Increased Risk of Second Primary Malignancy and Mortality at ten Years After Stem Cell Transplant for Multiple Myeloma: An Analysis of 14,532 Patients.
Background The landscape for patients with multiple myeloma has improved dramatically over the last 15 years. Immunomodulatory imide drugs (IMiDs) have shown great efficacy in both the setting of initial therapy and as maintenance after autologous stem cell transplant (ASCT). Concern has arisen, however, regarding the risk of second primary malignancies (SPMs) that appear to be associated with the use of IMiD agents. SPMs are a known sequela of multiple myeloma treatment, particularly as a consequence of maintenance lenalidomide status-post stem cell transplant (SCT). The benefit of SCT has become less clear with the utilization of newer, more effective initial therapies. Objectives To determine the effect of SCT on SPM risk and overall survival in multiple myeloma patients at 5 and 10 years after treatment initiation. Methods We used TriNetX, a global federated health research network providing access to electronic medical records (diagnoses, procedures, medications, laboratory values, genomic information) from approximately 58 million patients in 49 large healthcare organizations. We created two patient cohorts who had all received treatment with thalidomide, lenalidomide, or pomalidomide. One cohort had received SCT while the other had not. Both cohorts were then analyzed for the development of all non-myeloma malignancies which occurred at least one year after initiation of treatment. Results At 5 years, SPMs were 5.8% more likely in patients who received stem cell transplant (22.4% vs 16.6%, RR 0.741, p value <0.0001) but 5-year survival favored transplanted patients by 2.38% (64.85% vs 62.474%, p value 0.0044). 10-year survival favored patients who did not receive transplant by 1.44% (42.279% vs 40.838%, p value 0.0279). The Kaplan-Meier curves cross at year 6. Conclusions It has previously been shown that the use of alkylating agents in myeloma patients significantly increases the risk of SPM, but that difference had curiously not been shown to have a negative impact on survival. Our analysis shows that this negative survival impact does exist but requires six or more years of follow up to become evident. Recent analyses from studies using older regimens show no overall survival benefit from the use of stem cell transplant. As non-transplant regimens become more effective at producing minimal residual disease (MRD) negativity, it seems that transplantation for myeloma patients will soon be regarded as unnecessary or even detrimental.


Complement-dependent histamine release from rat peritoneal mast cells, induced by lipopolysaccharides from Bacteroides oralis, Fusobacterium nucleatum and Veillonella parvula.
The capacity of phenol/water extracted lipopolysaccharides (LPS) from Bacteroides, Fusobacterium and Veillonella to induce histamine release from rat peritoneal mast cells has been evaluated by means of a bioassay using atropinized guinea pig ileum and a fluorescence assay. Histamine release was found to be completely complement dependent. It was also found that LPS of Veillonella have the greatest capacity to induce histamine release and Bacteroides have the weakest.


Conjunctival flap with auricular cartilage grafting: a modified Hughes procedure for large full thickness upper and lower eyelid defect reconstruction.
To investigate the suitability of a modified Hughes procedure, which consists of conjunctival flap with auricular cartilage grafting in reconstructing large full thickness upper and lower eyelid defect. Patients with full thickness eyelid carcinoma involving more than 50% margin length who underwent surgical resection were retrospectively reviewed in the study. The defects were reconstructed using conjunctival flap with auricular cartilage grafting, covered with myocutaneous flap above. Followed-up time ranged from 12 to 24mo. Outcomes were classified as "good", "fair", and "poor" by evaluating the margin appearance, eyelid appearance, and complications. A total of 42 patients were enrolled in the study (26 males, 16 females, mean age, 68.6±7.7y, range: 53 to 82y). The mean defect widths measured 23.2±2.9 mm (range, 17 to 28 mm). The mean posterior lamellar defect height was 5.5±1.3 mm (4 to 8 mm). Thirty-seven patients had a "good" outcome (88.1%), 5 patients had a "fair" outcome (11.9%), and no one had a "poor" outcome. Conjunctival flap with auricular cartilage grafting and myocutaneous flap grafting is an effective procedure in reconstructing large full thickness upper and lower eyelid defect. It can not only achieve satisfied reconstruction, but also preserve intact tarsal plate of the opposite eyelid, avoiding retraction or entropion.


Intensive Blood Pressure Lowering in Patients with Moderate to Severe Grade Acute Cerebral Hemorrhage: Post Hoc Analysis of Antihypertensive Treatment of Acute Cerebral Hemorrhage (ATACH)-2 Trial.
To study the effect of intensive blood pressure reduction in patients with moderate to severe intracerebral hemorrhage (ICH) within the subjects recruited in Antihypertensive Treatment of Acute Cerebral Hemorrhage 2 trial. Randomized, multicenter, 2 group, open-label clinical trial. A total of 110 sites in the USA, Japan, China, Taiwan, South Korea, and Germany. A total of 1,000 patients underwent randomization from May 2011 till September 2015. We analyzed the effect of intensive (goal 110-139 mm Hg) over standard (goal 140-179 mm Hg) systolic blood pressure (SBP) reduction using intravenous nicardipine within 4.5 h of symptom onset in moderate to severe grade subjects with ICH in a non-prespecified analysis. Moderate to severe grade was defined by Glasgow Coma Scale score <13 or baseline National Institutes of Health Stroke Scale score ≥10 or baseline intraparenchymal hemorrhage volume ≥30 mL or presence of intraventricular hemorrhage. The primary outcome was death or disability (score 4-6 on the modified Rankin scale) at 3 months after randomization ascertained by a blinded investigator. Of a total of 682 subjects who met the definition of moderate to severe grade (mean age 61.9 ± 13.1 years, 62.5% men) with a mean baseline SBP of 174.7 ± 24.8 mm Hg, the frequency of hematoma expansion was significantly lower among subjects randomized to intensive SBP reduction than among subjects randomized to standard SBP reduction (20.4 vs. 27.9%, relative risk [RR]: 0.7; 95% confidence interval [CI]: 0.55-0.96). The primary endpoint of death or disability was observed in 52.5% (170/324) of subjects receiving intensive SBP reduction and 48.9% (163/333) of subjects receiving standard SBP reduction (RR: 1.1; 95% CI: 0.9-1.2). Intensive SBP lowering reduced the frequency of hematoma expansion but did not reduce the rate of death or disability in patients with moderate to severe grade ICH.


Cast thin film biosensor design based on a Nafion backbone, a multiwalled carbon nanotube conduit, and a glucose oxidase function.
Novel electroanalytical sensing nanobiocomposite materials are reported. These materials are prepared by mixing multiwalled carbon nanotubes (MWNTs), a Nafion cation exchanger, and glucose oxidase (GOD) in appropriate amounts. The MWNTs are cylindrical with a diameter in the range 40-60 nm and with a length of up to several micrometers, and they provide electrical conductivity. Nafion acts as a polymer backbone to give stable and homogeneous cast thin films. Both MWNTs and Nafion provide negative functionalities to bind to positively charged redox enzymes such as glucose oxidase. The resulting biosensing composite material is inexpensive, reliable, and easy to use. The homogeneity of the MWNT-Nafion-GOD nanobiocomposite films was characterized by atomic force microscopy (AFM). Amperometric transducers fabricated with these materials were characterized electrochemically using cyclic voltammetry and amperometry in the presence of hydrogen peroxide and in the presence of glucose. Their linear response to hydrogen peroxide was demonstrated. The glucose biosensor sensitivity was strongly influenced by the glucose oxidase concentration within the nanobiocomposite film. The optimized glucose biosensor (2.5 mg/mL GOD) displayed a sensitivity of 330 nA/mM, a linear range of up to 2 mM, a detection limit of 4 microM, and a response time of <3 s.


Decision analysis approach to risk/benefit evaluation in the ethical review of controlled human infection studies.
Risks and benefit evaluation for controlled human infection studies, where healthy volunteers are deliberately exposed to infectious agents to evaluate vaccine efficacy, should be explicit, systematic, thorough, and non-arbitrary. Decision analysis promotes these qualities using four steps: (1) determining explicit criteria and measures for evaluation, (2) identifying alternatives to the study, (3) defining the models used to estimate the measures for each alternative, and (4) running the models to produce the estimates and compare the alternatives. In this paper, we describe how decision analysis might be applied by funders and regulators, as well as by others contemplating the use of novel controlled human infection studies for vaccine development and evaluation.


Cutaneous Toxicity Associated With Enfortumab Vedotin: A Real-Word Study Leveraging U.S. Food and Drug Administration Adverse Event Reporting System.
Enfortumab vedotin (EV) has been demonstrated to have a significant response rate in early phase trials and is known for its tolerable side-effect profile. Emerging case reports have raised awareness of cutaneous toxicities, which may be a potentially fatal complication. To assess the potential relevance between EV and cutaneous toxicities reports through data mining of the U.S. Food and Drug Administration (FDA) adverse event reporting system (FAERS). Data from January 1, 2019, to November 4, 2021, in the FAERS database were retrieved. Information component (IC) and reporting odds ratio (ROR) were used to evaluate the association between EV and cutaneous toxicities events. EV was significantly associated with cutaneous toxicities in the database compared with both all other drugs (ROR 12.90 [10.62-15.66], IC 2.76 [2.52-3.01], middle signal) and platinum-based therapy (ROR 15.11 [12.43-18.37], IC 2.91 [2.66-3.15], middle signal) in the FAERS database. A significant association was detected between EV and all the cutaneous adverse effects (AEs) except erythema, palmar-plantar erythrodysesthesia syndrome, and dermatitis allergic. Both Stevens-Johnson syndrome and toxic epidermal necrolysis occurred 15 times as frequently for EV compared with all other drugs (ROR = 15.20; ROR = 15.52), while Stevens-Johnson syndrome occurred 18 times and toxic epidermal necrolysis occurred 7 times as frequently for EV compared with platinum-based therapy in the database (ROR = 18.74; ROR = 7.80). All groups that limited the gender and age showed a significant association between EV and cutaneous toxicities. A significant signal was detected between EV use and cutaneous toxicities. It is worth noting that Stevens-Johnson syndrome and toxic epidermal necrolysis were significantly associated with EV use.


Parenteral nourishment of patients undergoing surgical or traumatic stress.
Severe surgical or other traumatic stress initiates an integrated central nervous system and metabolic response characterized by catabolism which selectively preserves vital organs, drawing on peripheral tissue proteins for required amino acids. When oral intake is prohibited adequate intravenous nutritional support hastens convalescence and may be life-saving. Intravenous nutrients routinely consist of amino acids for replacement of lost protein, a nonprotein calorie source--usually glucose, and vitamins and minerals. Lipid, infrequently used in routine surgery as part of the calorie source, supplies essential fatty acids and prevents side effects resulting with large amounts of intravenous glucose. Lipid has other benefits. Stress-induced hormones stimulate lipid catabolism. When lipid is used for part of the calorie requirement in intravenous feedings, the plasma insulin level is reduced and peripheral amino acids become available for synthesis of critically needed visceral proteins. Recent work has shown that the branched chain amino acids carnitine and some species of lipid added to intravenous nutrient formulations postoperatively affect the nitrogen retention and may hasten convalescence. Further work should be directed at understanding the unique biochemical changes occurring after injury, devising objective assay procedures to measure the severity of the response and improving intravenous formulations for the acutely ill surgical patient.


Influence of Cu Content on the Microstructure and Mechanical Properties of Cr-Cu-N Coatings.
The Cr-Cu-N coatings with various Cu contents (0-25.18 (±0.17) at.%) were deposited on Si wafer and stainless steel (SUS 304) substrates in reactive Ar+N2 gas mixture by a hybrid coating system combining pulsed DC and RF magnetron sputtering techniques. The influence of Cu content on the coating composition, microstructure, and mechanical properties was investigated. The microstructure of the coatings was significantly altered by the introduction of Cu. The deposited coatings exhibit solid solution structure with different compositions in all of the samples. Addition of Cu is intensively favored for preferred orientation growth along (200) direction by restricting in (111) direction. With increasing Cu content, the surface and cross-sectional morphology of coatings were changed from triangle cone-shaped, columnar feature to broccoli-like and compact glassy microstructure, respectively. The mechanical properties including the residual stress, nanohardness, and toughness of the coatings were explored on the basis of Cu content. The highest hardness was obtained at the Cu content of 1.49 (±0.10) at.%.


Takotsubo cardiomyopathy: an overlooked cause of chest pain.
Takotsubo cardiomyopathy (TTC), also known as apical ballooning syndrome, broken heart syndrome, or stress-induced cardiomyopathy, is defined as a transient disturbance of the left ventricle, which is quite often associated with electrocardiographic abnormalities that may mimic acute myocardial infarction. The syndrome is also characterized by a mild alteration of cardiac biomarkers in absence of coronary blood flow obstruction on the coronariography. Clinical presentation is often manifested by angina, dyspnea, syncope, and arrhythmias. Peculiarly, the left ventricle takes the form of "tako-tsubo" (a Japanese word for "octopus trap") on the imaging workup. The authors report the case of a post-menopausal, hypertensive, dyslipidemic and type-II diabetic woman admitted at the emergency service with acute chest pain post physical exertion. Electrocardiogram showed signs of ischemia and myocardial necrosis markers were mildly increased. Echocardiography and ventriculography showed apical and mid-ventricular akinesia, with mild atherosclerotic coronary lesions. Thus diagnostic workup and the outcome followed the diagnostic criteria for TTC. The authors called attention to the potential of overlooking this diagnosis, since this syndrome is still not widely recognized.


Freshwater fishes of Patagonia: conservation and fisheries.
The absence of much literature on the Patagonian fish fauna in comparison with that of the neotropics, has previously been blamed on its poor species diversity. Knowledge of the fishes of Patagonia, however, rose sharply at the beginning of the present century, allowing for an understanding of the complex biogeographical history that has led to the present diversity and distribution patterns. There are several new and potential threats to biodiversity and conservation of Patagonian fishes, such as the introduction of exotic species, damming, climate change and changes geared to safeguard economic interests, often acting synergistically. A great amount of new information is now available and the aim of the present review is to articulate this knowledge in a comprehensive way in order to aid in the development of tools to face the increasing challenges posed by environmental change and human activity. Knowledge about fishes of Patagonia has grown at the same time as human actions, and presence.


Colectomy induces an aldosterone-mediated increase in jejunal glucose uptake in rats.
The main function of the colon is water and electrolyte absorption. Total colectomy eliminates this colonic function and may alter the absorptive capacity of the small intestine for nutrients. This study examines the effect of total colectomy on jejunal glucose absorption and investigates the potential role of aldosterone in mediating the alterations in glucose uptake post-colectomy using the aldosterone antagonist spironolactone. Total colectomy with ileo-rectal anastomosis was performed on anesthetized rats. Sham rats were identically handled without colon resection. Two days post-surgery, groups of colectomized rats were injected with either a daily subcutaneous dose of spironolactone or sesame oil for 12days. Body weight changes and food and water intake were measured in all experimental groups. Glucose absorption was measured by in-vivo single pass perfusion in the rat jejunum of control, sham, colectomized, colectomized with spironolactone, and colectomized with sesame oil treatment. Na/K ATPase, SGK1, SGLT1 and GLUT2 expressions were determined in jejunal mucosa in control, colectomized and colectomized/spironolactone injected rats by Western blot analysis. Histological assessment was performed on jejunal sections in control and colectomized groups. Glucose absorption significantly increased in colectomized rats with an observed increase in Na/K ATPase and SGK1 expression. No significant expression change in SGLT1 and GLUT2 was detected in the jejunum in colectomized rats. Spironolactone, however, significantly decreased the glucose uptake post-colectomy and normalized Na/K ATPase and SGK1 expression. Our results suggest that jejunal glucose uptake increases post-colectomy as a possible consequence of an aldosterone-mediated function.


Syntheses, structures, spectroscopy, and chromotropism of new complexes arising from the reaction of nickel(II) nitrate with diphenyl(dipyrazolyl)methane.
The complexes [(dpdpm)Ni(2-NO3)2] (1), [(dpdpm)Ni(2-NO3)(1-NO3)(CH3CN)] (2), [(dpdpm)2Ni(1-NO3)(H2O)]NO3 (3), and [(dpdpm)2Ni(H2O)2][NO3]2 (4) (dpdpm = diphenyl(dipyrazolyl)methane, Ph2C(C3N2H3)2), have been prepared and characterized by IR and UV-vis-NIR spectroscopy and X-ray diffraction studies. X-ray studies have confirmed that complexes 1-4 all adopt variously distorted octahedral structures in the solid state, the largest distortions arising from the small bite-angle of the bidentate nitrate ligand in 1 and 2. Magnetic moment measurements indicate that these solids are paramagnetic with two unpaired electrons. The solution 1H NMR data show that the paramagnetism is maintained in solution. Absorption spectra of 1-4 show three main bands in the region of 350-1000 nm representing spin allowed (d-d) transitions from the ground state 3A2g to the excited states 3T2g, 3T1g(3F), and 3T1g(3P). A weak shoulder was also detected at about 700-800 nm in most spectra, representing spin-forbidden transitions 3A2g 1Eg. A comparison of the crystal field parameters 10Dq and B for 1-4 to the corresponding values for related complexes indicated that these parameters are fairly insensitive to structural variations within this family of complexes. The 10Dq/B ratios show greater variations, but no clear correlations are apparent between 10Dq/B and such structural features as the nature of ligator atoms (N:O ratio), the bonding mode of the nitrate ligand, or the overall charge. Complexes 1 (green) and 2 (blue) interconvert as a function of temperature (solutions and solid samples), concentration of CH3CN (solutions), or CH3CN vapor pressure (solid samples).


Fine needle aspirative biopsy of the liver in HBsAG-positive patients with end-stage renal failure.
HBsAg-positive patients with end-stage renal failure have a high prevalence of asymptomatic chronic hepatitis. In order to determine the usefulness of hepatic cytology in the diagnosis of liver disease, the findings of hepatic needle core biopsy (NCB) and fine needle aspirative biopsy (FNAB) were compared in 15 HBsAg-positive uremic patients. The patients, aged 42 +/- 12 years, 14 males, were on hemodialysis for periods ranging from 13 to 105 months. The NCB was processed by standard histologic and immunohistochemical techniques and FNAB by the conventional technique, using the total corrected increment score (TCI). Plasma samples were collected for evaluation of hepatic function and for viral serologic tests. In 15 patients a diagnosis was made by NCB: normal, 7 cases; chronic persistent hepatitis, 4 cases; and chronic active hepatitis, 4 cases. When the patients were allocated into two groups according to the severity of the liver histologic findings [group I--minor changes (normal+chronic persistent hepatitis), 11 patients; group II--major changes (chronic active hepatitis), 4 patients], statistically higher values were found in the major changes group for alanine aminotransferase (49 +/- 33 vs. 24 +/- 11, p = 0.04), gamma-glutamyl transpeptidase [148 +/- 53 vs. 38 +/- 28, p < (minor) 0.02] and TCI (3.7 +/- 1.2 vs. 2.5 +/- 0.8, p = 0.04). In conclusion, liver FNAB can be useful as a screening procedure for the identification of liver histologic changes (minor or major) in uremic HBsAG-positive patients.


Efficacy and Safety of Metronidazole Monotherapy versus Vancomycin Monotherapy or Combination Therapy in Patients with Clostridium difficile Infection: A Systematic Review and Meta-Analysis.
Clostridium difficile infection (CDI) has become a global epidemiological problem for both hospitalized patients and outpatients. The most commonly used drugs to treat CDI are metronidazole and vancomycin. The aim of this study was to compare the efficacy and safety of metronidazole monotherapy with vancomycin monotherapy and combination therapy in CDI patients. A comprehensive search without publication status or other restrictions was conducted. Studies comparing metronidazole monotherapy with vancomycin monotherapy or combination therapy in patients with CDI were considered eligible. Meta-analysis was performed using the Mantel-Haenszel fixed-effects model, and odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated and reported. Of the 1910 records identified, seventeen studies from thirteen articles (n = 2501 patients) were included. No statistically significant difference in the rate of clinical cure was found between metronidazole and vancomycin for mild CDI (OR = 0.67, 95% CI (0.45, 1.00), p = 0.05) or between either monotherapy and combination therapy for CDI (OR = 1.07, 95% CI (0.58, 1.96), p = 0.83); however, the rate of clinical cure was lower for metronidazole than for vancomycin for severe CDI (OR = 0.46, 95% CI (0.26, 0.80), p = 0.006). No statistically significant difference in the rate of CDI recurrence was found between metronidazole and vancomycin for mild CDI (OR = 0.99, 95% CI (0.40, 2.45), p = 0.98) or severe CDI (OR = 0.98, 95% CI (0.63, 1.53), p = 0.94) or between either monotherapy and combination therapy for CDI (OR = 0.91, 95% CI (0.66, 1.26), p = 0.56). In addition, there was no significant difference in the rate of adverse events (AEs) between metronidazole and vancomycin (OR = 1.18, 95% CI (0.80, 1.74), p = 0.41). In contrast, the rate of AEs was significantly lower for either monotherapy than for combination therapy (OR = 0.30, 95% CI (0.17, 0.51), p < 0.0001). Metronidazole and vancomycin are equally effective for the treatment of mild CDI, but vancomycin is superior for the treatment of severe CDI. Combination therapy is not superior to monotherapy because it appears to be associated with an increase in the rate of AEs.


Is atelectasis following aortocoronary bypass related to temperature?
To determine the frequency of acute postoperative atelectasis in patients undergoing aortocoronary bypass with either normothermic (warm) or hypothermic (cold) technique. Prospective, randomized study comparing two groups. University-affiliated hospital. Three hundred thirty-one patients (166 cold and 165 warm) undergoing isolated aortocoronary bypass. Chest radiographs were obtained preoperatively, on the day of surgery, and subsequently as clinically indicated until discharge from the hospital. Radiologist (blinded to the patient allocation into warm or cold group) scored the atelectasis from 0 to 3 based on its severity. Regression analysis was used to determine if there was any difference in the atelectasis scores between the two groups. Mean daily postoperative atelectasis scores were not different between the cold and warm groups. The number of patients requiring chest radiographs was similar in both groups. The percent of patients with abnormal chest radiographs was similar in both groups. The temperature of cardioplegia has no effect on the development of atelectasis following aortocoronary bypass, and therefore temperature-related cold injury is not a major cause of atelectasis following this type of surgery.


Unusual segregation of t(11;22) resulting from crossing-over followed by 3:1 disjunction at meiosis I.
Reciprocal translocation t(11;22)(q23;q11) is of particular interest because the unbalanced offspring of the translocation carriers usually present with a supernumerary derivative chromosome 22. This common unbalanced karyotype is the result of 3:1 chromosome segregation during meiosis. We report the third case of a rare segregation pattern of a paternal 11;22 translocation. The proband's karyotype revealed the presence of a der(11) and two copies of a der(22), i.e. 47,XX,t(11;22)(q23;q11),+der(22) t(11;22)pat. The karyotype is the result of paternal 3:1 segregation after crossing-over involving the derived and the normal chromosome 22, as revealed by chromosome polymorphism analysis. Contrary to the preferential maternal, transmission of this common unbalanced translocation, the data from the literature, including our case, may suggest preferential paternal transmission of this rare type of unbalanced translocation.


Different intravitreal properties of three triamcinolone formulations and their possible impact on retina practice.
We sought to better characterize the intravitreal profile of different triamcinolone formulations. The study was performed in vitro and in vivo. Kenalog-40, Triesence, and Transton were characterized for ocular pharmacokinetics, particle size, crystallinity, and dissolving kinetics in vitreous following an intravitreal injection into 12 rabbit eyes. The relationship of free drug levels in the aqueous and vitreous was investigated through a dual-probe microdialysis and liquid chromatography tandem mass spectrometry. Triesence had the most uniform particle size distribution (mean 11.51 μm) and Kenalog-40 had the largest particle sizes (mean 18.86 μm). Triesence and Kenalog-40 had 100% crystallinity, while Transton had 89% crystallinity. Triesence had a slower dissolution in vitreous than that of Kenalog-40, and Transton had the fastest dissolution, though their solubility was very similar. Following a 1.2 mg intravitreal injection in the rabbit eye, Triesence had a significantly lower ocular free drug level than Kenolog-40 (P = 0.025) and Transton (P = 0.007). Quantitative dual-probe microdialysis revealed that the aqueous free triamcinolone (Kenolog-40) was less than 1% of the vitreous free triamcinolone during the first few hours, and this percentage increased to 26.8% at 2 weeks and was 11.7% at 3 weeks following an intravitreal injection. Triesence demonstrated a significantly slower dissolution profile and lower free drug level in the vitreous than the other preserved triamcinolone, which may translate into a longer therapeutic duration and lower rate of drug-associated complications.


[The differential diagnosis of indolent ulcers upon return from the Tropics: frambesia].
A 26-year-old patient was referred for investigation of chronic skin ulcerations which had appeared 2 months after a one-week stay in the Ivory Coast. The diagnosis was established clinically and serologically and the patient was successfully treated with penicillin. Even if yaws is a rare imported disease in Switzerland, it should always be considered in differential diagnosis of painless skin ulcerations in travellers returning from tropical countries, bearing in mind that the number of cases of yaws has increased in several tropical countries.


Nutrient and Mineral Profile of Chosen Fresh and Smoked Fish.
In the present study, were determined the basic nutrients (dry matter, crude ash, crude protein, ether extract, and energy) and mineral elements content in chosen species of raw and smoked freshwater and sea fish. The content of dry matter, and basic nutrients and Na+, K+, Ca+2, Mg+2, P+2, Zn+2, and Cu+2 in the fish samples was determined. The dietary intake of several macro- and microconstituents per one serving (150 g fresh or smoked fish) was calculated. The fresh fish contained on average 220.2 to 283.7 g·kg-1 of dry matter, 12.4 to 10.7 g·kg-1 of crude ash, 176.2 to 173.5 g·kg-1 of crude protein, 32.6 to 78.6 g·kg-1 of ether extract, and 104.6 to 119.1 kcal (freshwater and sea fish, respectively). Thermal treatment reduces the water and fat content in fish meat. Reduction of the K, Ca, Mg, P, Zn, and Cu levels was observed most frequently. The one serving of fish covers approximately 23% and 12% of the recommended dietary amount of K, 7.5-5.0% of Ca, ~12% of Mg, 6.8 to 12.5% of Zn, and about covered 6.7% of Cu. The smoking process increased the concentration of some basic nutrients and reduced the fat and mineral content. Whitefish, trout, halibut, mackerel, and herring had the highest levels of the analyzed minerals.


Embodiment and enculturation: the future of architectural design.
A half-century ago the Dutch architect Aldo van Eyck encouraged designers to think about "space and time" not as abstractions in themselves but rather as cultural events better approached through the medium of "place and occasion." Van Eyck made this point on the basis of his own travels and through his extensive readings in cultural anthropology, and his prescience is only now acquiring the credibility that it deserves through the work of a multitude of interdisciplinary researchers. Phenomenologists argue that we are embodied organisms-acting-within-environments, and these inhabiting abodes are constructed of both material and cultural dimensions. We are thus preeminently social in our range of self-consciousness, and intensely ceremonial in every facet of our being. Evolutionary psychologists and anthropologists are currently locating the origin and development of our most basic social behaviors far in our pre-human past; neuroscientists are today modeling our social circuits in the deepest reaches of our brains. Architecture would gain much from an updated cultural theory grounded in these new models of human existence.


Knowledge of the endpoint: effect on perceptual values.
The main purpose of this study was to examine the influence of knowledge of running length (i.e., duration or distance), or the lack of it (unknown endpoint) on the ratings of perceived exertion and estimated time to exhaustion. Fourteen men were recruited for this study. Participants performed 3 tests of a similar intensity (90 % maximal aerobic velocity) and length (100 % Tlim/Dlim). However, the exercise length was differently expressed. This was either unknown or defined in terms of duration or distance. The tests with a known length were performed in a counterbalanced order. During the tests, ratings of perceived exertion, estimated time to exhaustion, and heart rate were measured then compared by using 2-way analysis of variance for repeated measures. The results show that the ratings of perceived exertion, estimated time to exhaustion, and heart rate increased significantly with exercise duration (p < .001). Moreover, the ratings of perceived exertion were significantly different between the test with an unknown running endpoint and that with a known running distance at 40, 60 and 80 % Tlim (p < .05). Therefore, athletes perceived the run as being easier during the test with an unknown running endpoint compared to the test with a known running distance. Consequently, knowledge of running length influenced the ratings of perceived exertion probably due to teleoanticipation.


A vision of quality in health care delivery.
Empirical evidence is thin, so one must reply on informed judgment, common sense, and theory when describing a high-quality health plan. Using this approach, a high-quality health plan would be characterized by excellence in the following areas: physician selection and development; health improvement; information systems; continuous quality improvement; cooperation with health care purchasers; alignment of financial incentives and appropriate capitation; and patient involvement. High-quality health plans would be nurtured by a national context in which medical education recognizes managed care and quality measurement, risk-adjusted premiums are the norm, competition is managed, and government has a limited role.


Parental Discipline During Emerging Adulthood: A Person-Centered Approach.
Although most parental discipline research examines the effects of discipline in children and adolescents, recent research has demonstrated that emerging adults continue to receive parental discipline. Importantly, a newly validated instrument for assessing discipline specifically during emerging adulthood has been created. Scales from this instrument include maternal and paternal approval, disappointment, and abuse, and these scales were associated with other parenting behaviors and psychological outcomes during emerging adulthood. However, a person-centered approach has not been conducted with this instrument. Given that discipline occurs at an idiographic level and that group norms inform such behaviors, a person-centered approach would identify highly informative emerging adult profiles based on patterns of discipline they receive from their parents. Thus, the current study utilized latent profile analysis (LPA) of 1110 participants attending a Southern United States university to identify emerging adult discipline profiles. These groups were then associated with parental and emerging adult psychological problems to gain an understanding of how these factors relate to different patterns of discipline across gender. Results best supported four profiles labeled as approving, distant, disappointed, and abusive. These groups reported increasingly higher parental and personal psychological problems across approving, distant, disappointed, and abusive profiles. Gender moderated some of these effects. Implications and future directions are discussed.


Analysis of the use of MEDLARS in Mexico.
A statistical analysis of MEDLARS usage by Mexico's National Health Information and Documentation Center (CENIDS) is described. A total of 13,029 connect hours was registered during the period 1977-1986. MEDLINE was the MEDLARS database most frequently used, representing 82.83% of total use. Some 41,563 online searches, requested by 30,775 users, were performed by CENIDS' headquarters staff during this period. Findings from this study will be used to further research on information services in order to maximize the effectiveness of existing resources.


Toward defining the anatomo-proteomic puzzle of the human brain: An integrative analysis.
The human brain is exceedingly complex, constituted by billions of neurons and trillions of synaptic connections that, in turn, define ∼900 neuroanatomical subdivisions in the adult brain (Hawrylycz et al. An anatomically comprehensive atlas of the human brain transcriptome. Nature 2012, 489, 391-399). The human brain transcriptome has revealed specific regional transcriptional signatures that are regulated in a spatiotemporal manner, increasing the complexity of the structural and molecular organization of this organ (Kang et al. Spatio-temporal transcriptome of the human brain. Nature 2011, 478, 483-489). During the last decade, neuroproteomics has emerged as a powerful approach to profile neural proteomes using shotgun-based MS, providing complementary information about protein content and function at a global level. Here, we revise recent proteome profiling studies performed in human brain, with special emphasis on proteome mapping of anatomical macrostructures, specific subcellular compartments, and cerebrospinal fluid. Moreover, we have performed an integrative functional analysis of the protein compilation derived from these large-scale human brain proteomic studies in order to obtain a comprehensive view of human brain biology. Finally, we also discuss the potential contribution of our meta-analysis to the Chromosome-centric Human Proteome Project initiative.


Hemophilic Arthropathy: Barriers to Early Diagnosis and Management.
Hemophilia is a congenital coagulopathy characterized by a deficiency of one of the clotting factors. It is characterized by the development of hematomas and hemarthrosis, either spontaneously or after minor trauma. The recurrence of hemarthroses leads to progressive and degenerative joint damage from childhood (hemophilic arthropathy). This arthropathy is characterized by disabling physical effects that limit the functionality and quality of life of these patients. Medical progress achieved over the last decade in the drug treatment of hemophilia has improved the medium and long-term prospects of patients with more effective and long-lasting drugs. The universal use of safer, more effective and prolonged prophylactic treatments may promote the prevention of bleeding, and also therefore, of the development of hemarthrosis and joint damage. A number of imaging instruments have been developed for the assessment of hemarthrosis and hemophilic arthropathy, using ultrasound, magnetic resonance imaging and simple radiology. Different physical examination scores and questionnaires allow the assessment of joint health, self-perceived activity and functionality of patients with hemophilia. The approach to these patients should be interdisciplinary. Assessment of the processes that affect pain in these patients and the development of pain education models should be implemented. Expert advice and information to patients with hemophilia should be based on individual functional prevention diagnoses, advice on available therapies and sports practice, as well as health recommendations.


Mutations of toluene-4-monooxygenase that alter regiospecificity of indole oxidation and lead to production of novel indigoid pigments.
Broad-substrate-range monooygenase enzymes, including toluene-4-monooxygenase (T4MO), can catalyze the oxidation of indole. The indole oxidation products can then condense to form the industrially important dye indigo. Site-directed mutagenesis of T4MO resulted in the creation of T4MO isoforms with altered pigment production phenotypes. High-pressure liquid chromatography, thin-layer chromatography, and nuclear magnetic resonance analysis of the indole oxidation products generated by the mutant T4MO isoforms revealed that the phenotypic differences were primarily due to changes in the regiospecificity of indole oxidation. Most of the mutations described in this study changed the ratio of the primary indole oxidation products formed (indoxyl, 2-oxindole, and isatin), but some mutations, particularly those involving amino acid G103 of tmoA, allowed for the formation of additional products, including 7-hydroxyindole and novel indigoid pigments. For example, mutant G103L converted 17% of added indole to 7-hydroxyindole and 29% to indigoid pigments including indigo and indirubin and two other structurally related pigments. The double mutant G103L:A107G converted 47% of indole to 7-hydroxyindole, but no detectable indigoid pigments were formed, similar to the product distribution observed with the toluene-2-monooxygenase (T2MO) of Burkholderia cepacia G4. These results demonstrate that modification of the tmoA active site can change the products produced by the enzyme and lead to the production of novel pigments and other indole oxidation products with potential commercial and medicinal utility.


The prevalence of ankylosing hyperostosis in a Jerusalem population--with description of a method of grading the extent of the disease.
The prevalence of ankylosing hyperostosis in a Jewish hospital population is presented. In individuals over the age of 40 years the overall prevalence was 22.4% in males and 13.4% in females. The prevalence increased with age to a maximum of 46% in males and 30% in females over the age of 80 years. A method of grading the disease according to extent is described. The most extensive grade III is seen almost exclusively in males.


Baicalin ameliorates renal fibrosis via inhibition of transforming growth factor β1 production and downstream signal transduction.
Previous studies have demonstrated the potential antifibrotic effects of baicalin in vitro, via examination of 21 compounds isolated from plants. However, its biological activity and underlying mechanisms of action in vivo remain to be elucidated. The present study aimed to evaluate the effect of baicalin on renal fibrosis in vivo, and the potential signaling pathways involved. A unilateral ureteral obstruction (UUO)‑induced renal fibrosis model was established using Sprague‑Dawley rats. Baicalin was administrated intraperitoneally every 2 days for 10 days. The degree of renal damage and fibrosis was investigated by histological assessment, and detection of fibronectin and collagen I mRNA expression levels. Epithelial‑mesenchymal transition (EMT) markers, transforming growth factor-β1 (TGF-β1) levels and downstream phosphorylation of mothers against decapentaplegic 2/3 (Smad2/3) were examined in vivo and in an NRK‑52E rat renal tubular cell line in vitro. Baicalin was demonstrated to markedly ameliorate renal fibrosis and suppress EMT, as evidenced by reduced interstitial collagen accumulation, decreased fibronectin and collagen I mRNA expression levels, upregulation of N‑ and E‑cadherin expression levels, and downregulation of α‑smooth muscle actin and vimentin expression. Furthermore, baicalin decreased TGF‑β1 expression levels in serum and kidney tissue following UUO, and suppressed Smad2/3 phosphorylation in rat kidney tissue. In vitro studies identified that baicalin may inhibit the phosphorylation of Smad2/3 under the same TGF‑β1 concentration. In conclusion, baicalin may protect against renal fibrosis, potentially via inhibition of TGF‑β1 production and its downstream signal transduction.


Genomic and molecular evidence reveals novel pathways associated with cell surface polysaccharides in bacteria.
Amino acid (acyl carrier protein) ligases (AALs) are a relatively new family of bacterial amino acid adenylating enzymes with unknown function(s). Here, genomic enzymology tools that employ sequence similarity networks and genome context analyses were used to hypothesize the metabolic function(s) of AALs. In over 50% of species, aal and its cognate acyl carrier protein (acp) genes, along with three more genes, formed a highly conserved AAL cassette. AAL cassettes were strongly associated with surface polysaccharide gene clusters in Proteobacteria and Actinobacteria, yet were prevalent among soil and rhizosphere-associated α- and β-Proteobacteria, including symbiotic α- and β-rhizobia and some Mycolata. Based on these associations, AAL cassettes were proposed to encode a noncanonical Acp-dependent polysaccharide modification route. Genomic-inferred predictions were substantiated by published experimental evidence, revealing a role for AAL cassettes in biosynthesis of biofilm-forming exopolysaccharide in pathogenic Burkholderia and expression of aal and acp genes in nitrogen-fixing Rhizobium bacteroids. Aal and acp genes were associated with dltBD-like homologs that modify cell wall teichoic acids with d-alanine, including in Paenibacillus and certain other bacteria. Characterization of pathways that involve AAL and Acp may lead to developing new plant and human disease-controlling agents as well as strains with improved nitrogen fixation capacity.


Inflammation in rat pregnancy inhibits spiral artery remodeling leading to fetal growth restriction and features of preeclampsia.
Fetal growth restriction (FGR) and preeclampsia (PE) are often associated with abnormal maternal inflammation, deficient spiral artery (SA) remodeling, and altered uteroplacental perfusion. Here, we provide evidence of a novel mechanistic link between abnormal maternal inflammation and the development of FGR with features of PE. Using a model in which pregnant rats are administered low-dose lipopolysaccharide (LPS) on gestational days 13.5-16.5, we show that abnormal inflammation resulted in FGR mediated by tumor necrosis factor-α (TNF). Inflammation was also associated with deficient trophoblast invasion and SA remodeling, as well as with altered uteroplacental hemodynamics and placental nitrosative stress. Moreover, inflammation increased maternal mean arterial pressure (MAP) and was associated with renal structural alterations and proteinuria characteristic of PE. Finally, transdermal administration of the nitric oxide (NO) mimetic glyceryl trinitrate prevented altered uteroplacental perfusion, LPS-induced inflammation, placental nitrosative stress, renal structural and functional alterations, increase in MAP, and FGR. These findings demonstrate that maternal inflammation can lead to severe pregnancy complications via a mechanism that involves increased maternal levels of TNF. Our study provides a rationale for the use of antiinflammatory agents or NO-mimetics in the treatment and/or prevention of inflammation-associated pregnancy complications.


Selective Enzymatic Demethylation of N2 ,N2 -Dimethylguanosine in RNA and Its Application in High-Throughput tRNA Sequencing.
The abundant Watson-Crick face methylations in biological RNAs such as N1 -methyladenosine (m1 A), N1 -methylguanosine (m1 G), N3 -methylcytosine (m3 C), and N2 ,N2 -dimethylguanosine (m22 G) cause significant obstacles for high-throughput RNA sequencing by impairing cDNA synthesis. One strategy to overcome this obstacle is to remove the methyl group on these modified bases prior to cDNA synthesis using enzymes. The wild-type E. coli AlkB and its D135S mutant can remove most of m1 A, m1 G, m3 C modifications in transfer RNA (tRNA), but they work poorly on m22 G. Here we report the design and evaluation of a series of AlkB mutants against m22 G-containing model RNA substrates that we synthesize using an improved synthetic method. We show that the AlkB D135S/L118V mutant efficiently and selectively converts m22 G modification to N2 -methylguanosine (m2 G). We also show that this new enzyme improves the efficiency of tRNA sequencing.


Analyses of degradation products from lipid and protein hydrolyses in the small intestine of broiler chickens fed on maize-based diets containing guar gum, or wheat-based diets.
1. Three maize diets containing graded levels (0, 0.1, 0.3%) of guar gum and two wheat diets differing in their in vitro viscosities were fed to male broiler chickens (7 to 23 d) for measurements of growth performance and analyses of degradation products from lipid and protein hydrolyses in the small intestine of broiler chickens. Analyses of degradation products were conducted to define which step (hydrolysis or absorption) was most involved in the negative effects of the digesta viscosity on lipid and protein digestibilities. The experiment was also carried out to examine whether effects of wheats could be explained in terms of intestinal viscosity alone. 2. The intestinal viscosities with wheat diets were within the range of those observed with the three maize diets. The correlations between in vivo and in vitro viscosities were higher with real than with potential applied viscosity of diets, both in jejunum and ileum. 3. The mean gain:food ratio observed with wheat diets was lower (P<0.05) than with maize diets despite lower (P<0.05) mean intestinal viscosities in birds given the wheat than given the maize diets. This shows that factors different from intestinal viscosity were also involved in the negative effects of wheats. 4. Distributions of nitrogen compounds in digesta were characterised by low proportions of compounds with high molecular weight (>12,000). For all classes of nitrogen compounds, the contents measured in digesta dry matter did not differ between chickens fed with or without guar gum. 5. Distributions of lipid classes in both jejunum and ileum were characterised by a large proportion of free fatty acids (FFA) and very few triglycerides (TG). In the ileum, FFA and TG contents were both positively correlated with supernatant viscosity, but the slope for FFA content was 35 times higher than for TG. In these relationships, there was no difference between maize and wheat diets. 6. It is concluded that absorption was the main step involved in the lipid digestibility reduction due to intestinal viscosity. For proteins, the most important step (hydrolysis or absorption) involved in decreased digestibility due to intestinal viscosity was not clearly identified.


Neuropeptides in cerebrospinal fluid in normal-pressure hydrocephalus and dementia.
Delta-sleep-inducing peptide (DSIP), vasoactive intestinal peptide (VIP), peptide YY (PYY) and somatostatin (SOM) were assayed with specific radioimmunological methods in cerebrospinal fluid (CSF) of healthy volunteers, 12 patients with Alzheimer's disease (AD), 11 patients with multi-infarct dementia (MID) and 10 patients with normal-pressure hydrocephalus (NPH). Patients with NPH were reinvestigated 3 months after a ventriculoperitoneal shunt operation. DSIP, PYY and SOM levels in CSF were decreased in patients with NPH compared to controls. The CSF concentration of SOM was also significantly reduced in patients with AD. No correlations were found between the degree of dementia in any of the illnesses and the CSF concentrations of the peptides. The concentration of DSIP, VIP and SOM increased significantly in parallel to the clinical improvement after the shunt operation in NPH patients.


Risks and rewards of using prepaid vs. postpaid incentive checks on a survey of physicians.
Survey researchers use monetary incentives as a strategy to motivate physicians' survey participation. Experiments from general population surveys demonstrate that prepaid incentives increase response rates and lower survey administration costs relative to postpaid incentives. Experiments comparing these two incentive strategies have rarely been attempted with physician samples. A nationally representative sample of oncologists was recruited to participate in the National Survey of Precision Medicine in Cancer Treatment. To determine the optimal strategy for survey incentives, sample members were randomly assigned to receive a $50 prepaid incentive check or a $50 promised (postpaid) incentive check. Outcome measures for this incentives experiment include cooperation rates, speed of response, check-cashing behavior, and comparison of hypothetical costs for different incentive strategies. Cooperation rates were considerably higher for sample members in the prepaid condition (41%) than in the postpaid condition (29%). Similar differences in cooperation rates were seen for physicians when stratified by region, size of the physician's metropolitan statistical area, specialty, and gender by age. Survey responders in the prepaid condition responded earlier in the field period than those in the postpaid condition, thus requiring fewer contacts. In the prepaid group, 84% of sample members who responded with a completed survey cashed the incentive check and only 6% of nonresponders cashed the check. In the postpaid condition, 72% of survey responders cashed the check; nonresponders were not given a check. The relatively higher cooperation rates and earlier response of the responders in the prepaid condition was associated with a 30% cost savings for the prepaid condition compared to the postpaid incentive condition. The results of this study suggest that the rewards of offering physicians a prepaid incentive check outweigh the possible risks of nonresponders cashing the check. The relative cost benefit of this strategy is likely to vary depending on the amount of the incentive relative to the costs of additional contact attempts to nonresponders.


Nitrogenase switch-off by ammonium ions in Azospirillum brasilense requires the GlnB nitrogen signal-transducing protein.
Nitrogenase activity in several diazotrophs is switched off by ammonium and reactivated after consumption. The signaling pathway to this system in Azospirillum brasilense is not understood. We show that ammonium-dependent switch-off through ADP-ribosylation of Fe protein was partial in a glnB mutant of A. brasilense but absent in a glnB glnZ double mutant. Triggering of inactivation by anaerobic conditions was not affected in either mutant. The results suggest that glnB is necessary for full ammonium-dependent nitrogenase switch-off in A. brasilense.


Type 2 diabetes model TSOD mouse is exposed to oxidative stress at young age.
Tsumura Suzuki Obese Diabetes (TSOD) mouse, a model of obese type 2 diabetes, older than around 11 weeks of age develops diabetic phenotypes. Previous studies have indicated that the development of diabetes is partly due to three loci associated with body weight and glucose homeostasis. However, little is known about the initial events triggering the development of the diabetic phenotypes in TSOD mouse. Here, we investigated the alteration of diabetes-related parameters, including the levels of blood glucose and inflammatory cytokines, and the oxidative stress status, in young TSOD mice. TSOD mice at 5 weeks of age showed increases in body weight and plasma total cholesterol level, but not hyperglycemia or impaired glucose tolerance, compared with age-matched control Tsumura Suzuki Non-Obese (TSNO) mice. Plasma tumor necrosis factor (TNF)-α and interleukin (IL)-6 were not detected in TSOD mice at 5 weeks of age. However, plasma total hydroxyoctadecadienoic acid (tHODE), a biomarker of oxidative stress, was increased in TSOD mice relative to TSNO mice at same age. The results demonstrated that young TSOD mice are exposed to oxidative stress before developing the diabetic phenotypes, and suggested that oxidative stress is an initial event triggering the development of diabetes in TSOD mice.


Grasp-reflex strength from right and left hands in relation to serum cortisol level and fetal position in human neonates.
The grasp-reflex strengths from right (R) and left (L) hands were studied in human neonates in relation to serum cortisol levels and fetal position. In males with right-ear out, there was no correlation between grasp-reflex strength from right hand and cortisol. The grasp-reflex strength from left hand significantly decreased as cortisol increased linearly in these subjects. In males with left-ear out, the grasp-reflex strengths from right and left hands were found to be negatively linearly correlated with serum cortisol level. In females with right-ear out, the grasp-reflex strength from right hand was not significantly correlated with cortisol, but grasp reflex from left hand linearly decreased as cortisol increased. In females with left-ear out, only the grasp reflex from right hand linearly increased with cortisol. Only in males with right-ear out, the R-L grasp-reflex strength linearly increased from left dominance toward right dominance. It was concluded that the stress hormone cortisol may be disadvantageous and/or advantageous for the prenatal development of the right and left brain according to fetal position; cortisol may also affect the emergence of cerebral lateralization.


[The most common form of dizziness in middle age: phobic postural vertigo].
Up to now, there have been only a few valid epidemiological investigations of dizziness or vertigo as key symptoms. According to an analysis of 4,214 patients examined between 1989 and 2002 in an outpatient dizziness unit, benign peripheral paroxysmal positional vertigo (BPPV) and phobic postural vertigo (PPV) constitute the two most frequent syndromes. In this study, the relative age and sex distribution of both disorders was analysed. In the age group from 20 to 50 years, PPV was comparatively the most frequent form of dizziness, with a share of 22% to 26%. When left untreated, PPV becomes chronic in most cases and leads to considerable impairments, also at work. However, when diagnosed correctly, it can be treated successfully in more than 70% of cases. Thus, it takes on considerable medical and socioeconomic significance and should be part of the diagnostic repertoire of every doctor.


Interferon Alfa-2b for Pigmented Ocular Surface Squamous Neoplasia: A Report of 8 Lesions.
To study the efficacy of interferon alfa-2b (IFN-a2b) on pigmented ocular surface squamous neoplasia (p-OSSN) and assess the resolution of the pigment to the treatment. A retrospective case series of 8 tumors in 7 patients. The mean age at diagnosis of p-OSSN was 65 years (median, 61 years; range, 51-84 years), and all patients were men. The mean duration of symptoms was 2 months (median, 1 month; range, 1-4 months). One patient had 2 distinct lesions in the same eye. Tumor epicenter was located at the limbus (n = 5) or bulbar conjunctiva (n = 2). Complexion-associated melanosis was noted in all eyes. The mean basal dimension of the tumor was 8 mm (median, 7 mm; range, 5-12 mm). The mean % of tumor pigmentation was 47% (median, 30%; range, 10%-100%). The treatment details included topical IFN-a2b (n = 1) or a combination of topical and subconjunctival injection of IFN-a2b (n = 7). All patients with p-OSSN showed excellent response to IFN-a2b with complete tumor regression and resolution of tumor-associated pigment with a mean number of 2 subconjunctival IFN-a2b injections (median, 2; range, 0-3) and topical IFN-a2b for an average of 2 months (median, 2 months; range, 1-3 months). There was no change in the complexion-associated melanosis with IFN-a2b. IFN-a2b is very effective in the management of p-OSSN. There is a complete resolution of the pigment along with the tumor.


Alcohol abuse in sickle cell disease: the Pisces Project.
Alcohol abuse is common in patients with chronic painful medical disorders, but it has not been studied in sickle cell disease (SCD). In a prospective cohort study of SCD adults, 31.4% were identified as abusing alcohol. There were no significant differences between alcohol abusers and nonabusers on demographics, biological variables, depression, anxiety, measures of crisis and noncrisis pain, or opioid use, but abusers reported more pain relief from opioids than nonabusers did. Alcohol abusers had fewer unscheduled clinic visits, emergency room visits, hospital days, and any health care utilization for SCD, but this was only significant for emergency room visits. Quality of life was similar between both groups, except that alcohol abusers unexpectedly had better overall physical summary scores. Alcohol abusers were more likely to report coping by ignoring pain, diverting attention, and using particular self-statements.


Reward prediction error in learning-related behaviors.
Learning is a complex process, during which our opinions and decisions are easily changed due to unexpected information. But the neural mechanism underlying revision and correction during the learning process remains unclear. For decades, prediction error has been regarded as the core of changes to perception in learning, even driving the learning progress. In this article, we reviewed the concept of reward prediction error, and the encoding mechanism of dopaminergic neurons and the related neural circuities. We also discussed the relationship between reward prediction error and learning-related behaviors, including reversal learning. We then demonstrated the evidence of reward prediction error signals in several neurological diseases, including Parkinson's disease and addiction. These observations may help to better understand the regulatory mechanism of reward prediction error in learning-related behaviors.


Echoguided drug infiltration in chronic prostatitis: results of a multi-centre study.
In chronic prostatitis there are many causes that may provoke a therapeutical failure of a systemic antibiotic treatment. At the moment a consensus has not been reached on the efficacy of the many therapeutical options that are available with not one of these approaches being efficacious in all patients. In our view the main causes of treatment failure are the well-known hurdle to antibiotic diffusion inside the glandular parenchyma associated with the so-called intraprostatic bacterial biofilms and the possible presence of local auto-immune reactions. Given this background, we tested ultrasound guided intraprostate infiltration of a cocktail of antibiotics and betamethasone, for a therapeutical options. 320 patients, referred to us because of symptoms indicative of chronic prostatitis, were enrolled in this study. The inclusion criteria were the severity of the symptoms and the failure of repeated cycles of antibiotics in the previous 12 months. At the initial consultation patients completed the NIH Prostatitis Symptoms Index (NIH-CPSI). All underwent: a) digital rectal examination (DRE), b) transrectal prostatic ultrasound scan (TRUS), c) uroflowmetry, d) cultures of first voiding and after prostatic massage urine and cultures of sperm for saprophytic and pathogen germs, yeasts and protozoa, e) DNA amplification with polymerase chain reaction (PCR) on urine and sperm, for Chlamydia trachomatis, Mycoplasmas (Ureaplasma urealyticum and Mycoplasma hominis), Gonococcus, HPV and HCV Patients on the basis of laboratory results received a cocktail of antibiotics associated with betamethasone. The cocktail was administered as prostate infiltration. Administration was repeated after 7 and 14 days. Final assessment of the efficacy of therapy included not only the NIH-CPSI scores but also the patient's subjective judgement expressed as a "percentage overall improvement". The percentage judgements were arbitrarily divided into 4 classes: 0-30% no improvement (Class I); 30-50% satisfactory improvement (Class II); 50-80% good improvement (Class III; 80-100% cured (Class IV). Statistical analysis of the results showed 68% of patients were included in the Class IV and 13% were no responders (Class I). In our opinion this is one of the more valid therapeutical approaches to chronic bacterial or abacterial prostatitis also if it requires more studies.


Achieving control over the branched/linear selectivity in palladium-catalyzed allylic amination.
Palladium-catalyzed reaction of unsymmetrical allylic electrophiles with amines gives rise to regioisomeric allylic amines. We have found that linear products result from the thermodynamically controlled isomerization of the initially formed branched products. The isomerization is promoted by protic acid and active palladium catalyst. The use of base shuts down the isomerization pathway and allows for the preparation and isolation of branched allylic amines. Solvent plays a key role in achieving high kinetic regioselectivity and in controlling the rate of isomerization. The isomerization can be combined with ring-closing metathesis to afford the synthesis of exocyclic allylic amines from their endocyclic precursors.


Potential of Biological Processes to Eliminate Antibiotics in Livestock Manure: An Overview.
Degrading antibiotics discharged in the livestock manure in a well-controlled bioprocess contributes to a more sustainable and environment-friendly livestock breeding. Although most antibiotics remain stable during manure storage, anaerobic digestion can degrade and remove them to various extents depending on the concentration and class of antibiotic, bioreactor operating conditions, type of feedstock and inoculum sources. Generally, antibiotics are degraded during composting > anaerobic digestion > manure storage > soil. Manure matrix variation influences extraction, quantification, and degradation of antibiotics, but it has not been well investigated. Fractioning of manure-laden antibiotics into liquid and solid phases and its effects on their anaerobic degradation and the contribution of abiotic (physical and chemical) versus biotic degradation mechanisms need to be quantified for various manures, antibiotics types, reactor designs and temperature of operations. More research is required to determine the kinetics of antibiotics' metabolites degradation during anaerobic digestion. Further investigations are required to assess the degradation of antibiotics during psychrophilic anaerobic digestion.


Glycerol Monolaurate Contributes to the Antimicrobial and Anti-inflammatory Activity of Human Milk.
Human milk has antimicrobial compounds and immunomodulatory activities. We investigated glycerol monolaurate (GML) in human milk versus bovine milk and infant formula for antimicrobial and anti-inflammatory activities. Human milk contained approximately 3000 µg/ml of GML, compared to 150 μg/ml in bovine milk and none in infant formula. For bacteria tested (Staphylococcus aureus, Bacillus subtilis, Clostridium perfringens, Escherichia coli), except Enterococcus faecalis, human milk was more antimicrobial than bovine milk and formula. The Enterococcus faecalis strain, which was not inhibited, produced reutericyclin, which is an analogue of GML and functions as a growth stimulant in bacteria that produce it. Removal of GML and other lipophilic molecules from human milk by ethanol extraction resulted in a loss of antibacterial activity, which was restored by re-addition of GML. GML addition caused bovine milk to become antimicrobial. Human milk but not bovine milk or formula inhibited superantigen and bacterial-induced IL-8 production by model human epithelial cells. GML may contribute beneficially to human milk compared to bovine milk or infant formula.


Development and use of a portable paediatric resuscitation card.
Inaccuracy and delay in decision making in paediatric resuscitation has been previously demonstrated and may result in preventable death. We assessed several domains of paediatric resuscitation knowledge amongst a sample of tertiary hospital paediatric doctors, developed a portable aide-memoire reference card containing reference normal values, including an algorithm for recognition and management of the seriously ill/arrested child, and assessed the ability of medical staff to use this card to obtain accurate information. A convenience sample of 46 members of the Royal Children's Hospital medical staff completed a questionnaire. Knowledge deficits identified were used to create a 9 x 6 cm, name tag sized, laminated card providing physiological parameters and information required for paediatric resuscitation. The card was then distributed to all medical staff. A sample of 18 doctors completed an identical questionnaire 4 months after introduction of the card. Pre- and post-card results were analysed across a range of knowledge domains. Basic calculations were incorrect in over 40% of all pre-card responses. Seniority did not predict more correct answers. The post-card group obtained significantly more correct answers than the pre-card group. Medical staff wore, and were able to use the card to provide the correct values for paediatric resuscitation parameters. The use of a card significantly improved knowledge of the correct values for resuscitation data. This project has resulted in the card being issued to all medical and nursing staff and is now accessible via the Royal Children's Hospital internet at http://perseus.rch.unimelb.edu.au/genmed/resuscardontheweb.htm


Comparison of the clinic microscopy laboratory with the cytopathology laboratory in the detection of malignant cells in body fluids.
The clinical microscopy (fluids) laboratory evaluates almost every body fluid that is obtained in the hospital. Because the fluids laboratory functions at all hours, it is often the first laboratory to receive a body fluid. In addition to its primary purpose of quantitating categories of cells, the medical technologist in this laboratory has an opportunity to identify malignant cells. To our knowledge, no formal study has ever been undertaken to evaluate the performance of the fluids laboratory in detecting malignancy. The authors therefore retrospectively identified 928 body fluids (pleural, peritoneal, cerebrospinal, and miscellaneous) over a 2-year period that had undergone simultaneous cytologic examination in our cytopathology laboratory and body fluid analysis in our fluids laboratory. Of these, a cytologic diagnosis of malignancy was made by the cytopathology laboratory in 107 cases; 821 were considered to be benign. No false-positive results were rendered by the fluids laboratory (100% specificity), but only 26 of the 107 malignant cases were identified (24% sensitivity); the overall accuracy was 93%. Factors contributing to the inability of the fluids laboratory to identify malignant cells included (1) too few cells to warrant a cytocentrifuge preparation, especially in cerebrospinal fluid specimens; (2) differences in the processing of specimens; (3) differences in staining procedures; and (4) differences in the training of personnel. The authors conclude that although the fluids laboratory correctly identifies neoplastic cells in approximately one fourth of the cases in which they are present, it should not be expected to detect malignant cells in every cytologically malignant case.(ABSTRACT TRUNCATED AT 250 WORDS)


Novel recurrent chromosomal aberrations detected in clonal plasma cells of light chain amyloidosis patients show potential adverse prognostic effect: first results from a genome-wide copy number array analysis.
Immunoglobulin light chain (AL) amyloidosis is a rare plasma cell dyscrasia characterized by the deposition of abnormal amyloid fibrils in multiple organs, thus impairing their function. In the largest cohort studied up to now of 118 CD138-purified plasma cell samples from previously untreated immunoglobulin light chain amyloidosis patients, we assessed in parallel copy number alterations using high-density copy number arrays and interphase fluorescence in situ hybridization (iFISH). We used fluorescence in situ hybridization probes for the IgH translocations t(11;14), t(4;14), and t(14;16) or any other IgH rearrangement as well as numerical aberrations of the chromosome loci 1q21, 8p21, 5p15/5q35, 11q22.3 or 11q23, 13q14, 15q22, 17p13, and 19q13. Recurrent gains included chromosomes 1q (36%), 9 (24%), 11q (24%), as well as 19 (15%). Recurrent losses affected chromosome 13 (29% monosomy) and partial losses of 14q (19%), 16q (14%) and 13q (12%), respectively. In 88% of patients with translocation t(11;14), the hallmark chromosomal aberration in AL amyloidosis, a concomitant gain of 11q22.3/11q23 detected by iFISH was part of the unbalanced translocation der(14)t(11;14)(q13;q32) with the breakpoint in the CCND1/MYEOV gene region. Partial loss of chromosome regions 14q and 16q were significantly associated to gain 1q. Gain 1q21 detected by iFISH almost always resulted from a gain of the long arm of chromosome 1 and not from trisomy 1, whereas deletions on chromosome 1p were rarely found. Overall and event-free survival analysis found a potential adverse prognostic effect of concomitant gain 1q and deletion 14q as well as of deletion 1p. In conclusion, in the first whole genome report of clonal plasma cells in AL amyloidosis, novel aberrations and hitherto unknown potential adverse prognostic effects were uncovered.


Metabarcoding reveals massive species diversity of Diptera in a subtropical ecosystem.
Diptera is often considered to be the richest insect group due to its great species diversity and broad ecological versatility. However, data on dipteran diversity from subtropical ecosystems have hitherto been scarce, due to the lack of studies conducted at an appropriate large scale. We investigated the diversity and composition of Diptera communities on Tianmu Mountain, Zhejiang, China, using DNA metabarcoding technology, and evaluated their dynamic responses to the effects of slope aspect, season, and altitudinal zone. A total of 5,092 operational taxonomic units (OTUs) were discovered and tentatively assigned to 72 dipteran families, including 2 family records new for China and 30 family records new for the locality. Cecidomyiidae, Sciaridae, and Phoridae were the predominant families, representing 53.6% of total OTUs, while 52 families include >95% unidentified and presumed undescribed species. We found that the community structure of Diptera was significantly affected by aspect, seasonality (month) and elevation, with richer diversity harbored in north-facing than south-facing slopes, and seasonality a more profound driver of community structure and diversity than elevation. Overall, massive species diversity of Diptera communities was discovered in this subtropical ecosystem of east China. The huge diversity of potentially undescribed species only revealed by metabarcoding now requires more detailed taxonomic study, as a step toward an evolutionary integration that accumulates information on species' geographic ranges, ecological traits, functional roles, and species interactions, and thus places the local communities in the context of the growing knowledge base of global biodiversity and its response to environmental change.


Multiplexed hybridization detection with multicolor colocalization of quantum dot nanoprobes.
We demonstrate a hybridization detection method using multicolor oligonucleotide-functionalized quantum dots as nanoprobes. In the presence of various target sequences, combinatorial self-assembly of the nanoprobes via independent hybridization reactions leads to the generation of discernible sequence-specific spectral codings. Detection of single-molecule hybridization is achieved by measuring colocalization of individual nanoprobes. Genetic analysis for anthrax pathogenicity through simultaneous detection of multiple relevant sequences is demonstrated using this novel biosensing method as proof-of-concept.


Development and validation of a questionnaire for the assessment of bowel and lower urinary tract symptoms in women.
To develop a simple but sensitive instrument to evaluate and document symptoms of both bowel and urinary dysfunction in women. A 22-item questionnaire covering a range of bowel and urinary symptoms was developed and underwent rigorous psychometric testing. The gynaecology departments of three hospitals, a urogynaecology clinic, a functional bowel clinic and a general practice. Six hundred and thirty women, comprising four groups: 1. women awaiting hysterectomy (n = 379), 2. women following hysterectomy (n = 45), 3. women referred with functional bowel and/or urinary symptoms (n = 65), 4. asymptomatic controls (n = 141). The content, construct and criterion validity, internal consistency, reliability and responsiveness of the questionnaire were measured. RESULTS Peer and patient reports and missing data patterns supported face and content validity. Factor analysis showed a clinically relevant four-factor structure with low content replication able to distinguish between patient groups, indicating good internal structure. Comparison with clinical, anorectal physiological, videoproctographic, transit time and urodynamic test results provide provisional indication of criterion validity. Key domain question analysis and Cronbach's alphas showed internal consistency. Kappa values demonstrated good test-retest reliability and key question correlation over time proved responsiveness. Our findings support the suitability, clinical validity, reliability and responsiveness of a simple questionnaire, which is sensitive to the constraints of clinical practice. The authors recommend its use in health care evaluation research assessing the effects of pelvic surgery and as a useful tool in comparing treatment efficacy.


Evaluation and treatment of sleep complaints: patients' subjective responses.
This study set out to evaluate whether patients' expectations affected their responses to treatment of a sleep disorder. Fifty consecutive patients attending a sleep clinic for the first time and who had different diagnoses of sleep disorders were included in this study. The patients completed a set of 6 questionnaires on 7 occasions as they progressed through the process of a sleep clinic referral, assessment and treatment. Self-report questionnaires were used to assess their sleepiness, fatigue and alertness. Predictor measures included mental health and individual items assessing expectation regarding the seriousness of the sleep problem. A battery of questions dealt with mental health issues, patients' expectation and their commitment to the sleep investigation and treatment process. Each patient's responses were examined over a period of 6 months. Immediately following their interview with the sleep consultant, the patients' concern regarding their sleep problem was higher than the first measures obtained at baseline. Compared to prior to their first consultation with a sleep specialist, while on treatment they directed more attention to their sleep problem when problems associated with fatigue were reduced. Although there was a lessening in fatigue with treatment, subjectively rated sleepiness (Epworth Sleepiness Scale) did not vary over the study. Contact with a sleep center and the diagnosis and treatment of individual sleep problems also resulted in improved satisfaction with life. Contact with and treatment at a sleep clinic was found to be beneficial. The fatigue levels were reduced and the patients had greater life satisfaction regardless of the diagnosis and treatment of their sleep disorder, although subjective sleepiness did not change. Patient expectations were not critical in determining the outcome of the sleep clinic assessment.


Structure of product-bound Bacillus caldolyticus uracil phosphoribosyltransferase confirms ordered sequential substrate binding.
Uracil phosphoribosyltransferase (UPRTase) is part of the salvage pathway that leads to the biosynthesis of UMP. It catalyzes the formation of UMP and pyrophosphate from uracil and alpha-D-5-phosphoribosyl-1-pyrophosphate. Unlike enzymes in the de novo synthesis of UMP, UPRTases have only been found in lower organisms and are therefore potential targets for the development of new antibiotics. UPRTase from Bacillus caldolyticus has been crystallized and the structure has been determined by isomorphous replacement and refined to 3.0 A resolution. UPRTase from B. caldolyticus forms a dimer with the active sites pointing away from each other. A long arm from each subunit wraps around the other subunit, contributing half of the dimer interface. The monomer adopts the phosphoribosyltransferase type I fold, with a small C-terminal hood defining the uracil-binding site. The structure contains a well defined UMP molecule in the active site. The binding of UMP involves two sequence segments that are highly conserved among UPRTases. The first segment, Asp131-Ser139, contains the PRPP-binding consensus sequence motif known from other type I phosphoribosyltransferases and binds the ribose-5'-phosphate part of UMP. The second segment, Tyr193-Ala201, which is specific for uracil phosphoribosyltransferases, binds the uracil part of UMP through backbone contacts, partly mediated by a water molecule. Modelling of a PRPP-enzyme complex reveals that uracil can be activated to its tautomeric enol form by the complex. This is consistent with kinetic data, which display ordered sequential binding of substrates, with PRPP binding first. Based on this observation, a reaction mechanism is proposed.


Characterization of hepatic glutathione S-transferases in coho salmon (Oncorhynchus kisutch).
The glutathione S-transferases (GSTs) are a family of phase II detoxification enzymes which protect against chemical injury. In contrast to mammals, GST expression in fish has not been extensively characterized, especially in the context of detoxifying waterborne pollutants. In the Northwestern United States, coho salmon (Oncorhynchus kisutch) are an important species of Pacific salmon with complex life histories that can include exposure to a variety of compounds including GST substrates. In the present study we characterized the expression of coho hepatic GST to better understand the ability of coho to detoxify chemicals of environmental relevance. Western blotting of coho hepatic GST revealed the presence of multiple GST-like proteins of approximately 24-26kDa. Reverse phase HPLC subunit analysis of GSH affinity-purified hepatic GST demonstrated six major and at least two minor potential GST isoforms which were characterized by liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI MS-MS) and Fourier transform-ion cyclotron resonance (FT-ICR) MS analyses. The major hepatic coho GST isoforms consisted of a pi and a rho-class GST, whereas GSTs representing the alpha and mu classes constituted minor isoforms. Catalytic studies demonstrated that coho cytosolic GSTs were active towards the prototypical GST substrate 1-chloro-2,4-dinitrobenzene, as well as towards ethacrynic acid and nitrobutyl chloride. However, there was no observable cytosolic GST activity towards the pesticides methyl parathion or atrazine, or products of oxidative stress, such as cumene hydroperoxide and 4-hydroxynonenal. Interestingly, coho hepatic cytosolic fractions had a limited ability to bind bilirubin, reflecting a potential role in the sequestering of metabolic by-products. In summary, coho salmon exhibit a complex hepatic GST isoform expression profile consisting of several GST classes, but may have a limited a capacity to conjugate substrates of toxicological significance such as pesticides and endogenous compounds associated with cellular oxidative stress.


AN EIGENVECTOR METHOD FOR ESTIMATING PHYLOGENETIC INERTIA.
We propose a new method to estimate and correct for phylogenetic inertia in comparative data analysis. The method, called phylogenetic eigenvector regression (PVR) starts by performing a principal coordinate analysis on a pairwise phylogenetic distance matrix between species. Traits under analysis are regressed on eigenvectors retained by a broken-stick model in such a way that estimated values express phylogenetic trends in data and residuals express independent evolution of each species. This partitioning is similar to that realized by the spatial autoregressive method, but the method proposed here overcomes the problem of low statistical performance that occurs with autoregressive method when phylogenetic correlation is low or when sample size is too small to detect it. Also, PVR is easier to perform with large samples because it is based on well-known techniques of multivariate and regression analyses. We evaluated the performance of PVR and compared it with the autoregressive method using real datasets and simulations. A detailed worked example using body size evolution of Carnivora mammals indicated that phylogenetic inertia in this trait is elevated and similarly estimated by both methods. In this example, Type I error at α = 0.05 of PVR was equal to 0.048, but an increase in the number of eigenvectors used in the regression increases the error. Also, similarity between PVR and the autoregressive method, defined by correlation between their residuals, decreased by overestimating the number of eigenvalues necessary to express the phylogenetic distance matrix. To evaluate the influence of cladogram topology on the distribution of eigenvalues extracted from the double-centered phylogenetic distance matrix, we analyzed 100 randomly generated cladograms (up to 100 species). Multiple linear regression of log transformed variables indicated that the number of eigenvalues extracted by the broken-stick model can be fully explained by cladogram topology. Therefore, the broken-stick model is an adequate criterion for determining the correct number of eigenvectors to be used by PVR. We also simulated distinct levels of phylogenetic inertia by producing a trend across 10, 25, and 50 species arranged in "comblike" cladograms and then adding random vectors with increased residual variances around this trend. In doing so, we provide an evaluation of the performance of both methods with data generated under different evolutionary models than tested previously. The results showed that both PVR and autoregressive method are efficient in detecting inertia in data when sample size is relatively high (more than 25 species) and when phylogenetic inertia is high. However, PVR is more efficient at smaller sample sizes and when level of phylogenetic inertia is low. These conclusions were also supported by the analysis of 10 real datasets regarding body size evolution in different animal clades. We concluded that PVR can be a useful alternative to an autoregressive method in comparative data analysis.