A highly selective "turn-on" electroanalysis strategy with reduced copper metal-organic frameworks for sensing histamine and histidine.
A highly selective and sensitive electroanalysis strategy has been developed for sensing histamine (HTA) and histidine (His) with "turn-on" signal outputs using copper nanocomposites (Cu NCs) of reduced copper metal-organic frameworks (Cu MOFs). It was discovered that the Cu NC-modified electrodes could display the sharp and stable oxidation peaks of solid-state CuCl electrochemistry at a low potential (about -0.10 V). More interestingly, once HTA or His was introduced, the peaking currents of the electrodes would increase due to the specific interaction between Cu2+ and imidazole groups of HTA or His. A highly selective electroanalysis method was thereby developed for the detection of both HTA and His in the concentration range of 0.010-100 μM. Besides, the application feasibility of the developed electroanalysis strategy was demonstrated for the evaluation of HTA and His separately in red wine and urine samples. Such an electroanalysis candidate for HTA and His holds great potential for wide applications in the fields of food analysis and clinical disease diagnosis.


Electroencephalographic and epileptic patterns in X chromosome anomalies.
Although epilepsy and mental retardation are commonly observed in individuals with chromosomal aberrations, the identification of EEG/epileptic profiles in those with specific chromosome anomalies remains difficult. A few syndromes seem to show peculiar clinical and EEG associations. The authors report an electroclinical investigation on a group of patients carrying X chromosome anomalies: 16 patients with Turner's syndrome, 17 with Klinefelter's syndrome, 1 with an X-autosomal rearrangement, 2 with Xq isochromosome [Xq(i)], and 7 with triple X syndrome. Epilepsy and/or EEG anomalies were found in three of the patients with Klinefelter's syndrome, in one patient with an X-autosomal rearrangement, and in five of those with triple X syndrome. No epilepsy or EEG anomalies were detected in the other patients. Epilepsy may be associated with Klinefelter's syndrome. In addition, the authors found that an electroclinical pattern, represented by paroxysmal activity in the posterior regions (temporo-parieto-occipital areas) with complex partial seizures and easily controlled by antiepileptic drugs, may be present in patients with triple X syndrome. In contrast, gross X-autosomal rearrangements are associated with polymorphic EEG/epileptic findings. Although further studies are needed to validate these observations, they clearly confirm the strict relationship between X chromosome anomalies and epilepsy.


Hemostasis in spontaneous subarachnoid hemorrhage.
To comprehensively examine changes in the hemostatic systems early after spontaneous subarachnoid hemorrhage (SAH) and to assess the relationships between those changes and neurological findings, computed tomographic findings, and clinical outcomes, we reviewed 167 patients who were admitted within 24 hours of the onset of SAH. Blood was taken from all of the patients at admission for detailed examinations of the hemostatic systems. The following results were obtained: 1) the levels of the thrombin-antithrombin complex (elevation indicating the activation fo the blood coagulation system), plasmin-antiplasmin complex, and D-dimer (elevation indicating the activation of the fibrinolytic system) significantly increased with the neurological severity, amount of subarachnoid clot, and severity of clinical outcome; 2) the levels of the thrombin-antithrombin complexes and plasmin-antiplasmin complexes were significantly higher in patients with intracerebral or intraventricular hematomas than in patients without those hematomas; 3) in each of almost all the neurological and computed tomographic grades, the levels of the thrombin-antithrombin complexes were significantly higher in the patients with poor outcomes than in those with good outcomes; 4) the poor outcome rate significantly increased with neurological severity and the amount of subarachnoid clot. These data suggest that the activation of the blood coagulation system as well as of the fibrinolytic system occurred early in the course of SAH and that these systems were activated to a greater extent with the severity of neurological grades, computed tomographic findings, and clinical outcome.(ABSTRACT TRUNCATED AT 250 WORDS)


Prolonged fasting with fluid therapy is related to poorer outcomes in medical patients.
An inadequate fluid therapy can worsen the outcomes of surgical patients, but there are no data in medical patients. The aim of this study was to determine the adequacy of fluid therapy in hospitalised patients of medical wards, and its influence on outcomes. Cross-sectional study including nil-per-os patients admitted in medical wards of the Complejo Asistencial Universitario de León. The administered fluid therapy was compared with the standardised requirements. Nutritional status was evaluated with Subjective Global Assessment. Fasting was considered inappropriate if it lasted > 7 days in well-nourished, and >5 days in malnourished patients if nutritional support had not been provided. Fluid therapy lasted 4 (IQR = 2) days, and fasting was inadequately maintained in 27% of patients. Fluid requirements were correctly fulfilled, but patients received an excess of sodium (+58.4%) and chloride (+62.2%), and potassium administration was insufficient (-35.1%). Glucose supply was 68.8 (29.2) g/d, and 99% received < 130 g/d. Patients with an inadequate duration of fasting had a longer hospital stay after adjusting for sex, age, nutritional status, infused volume, electrolytes, glucose and diseases. Only malnutrition predicted mortality during hospitalisation (OR 10.5; 95%CI 1.3 to 83.2), when multivariate analysis was performed. Fasting medical patients receive an inadequate supply of glucose and electrolytes. Prolonged fluid therapy and malnutrition may worsen the outcomes of these patients, independently of other conditions like age or diseases.


Mononuclear infiltrates in human intracranial tumors as a prognostic factor. Influence of preoperative steroid treatment. I. Glioblastoma.
One hundred ninety-nine glioblastomas were investigated for the presence of mononuclear infiltrates in the light of preoperative steroid treatment and in regard to their prognostic influence. Preoperative steroid treatment does not seem to severely influence the frequency of lymphocytic infiltration in the doses routinely administered by us. The presence of infiltrates corresponds with a better prognosis for the disease, and with a mean postoperative survival time of 8.1 months as compared to 5.6 months in the group without infiltrates, irrespective of adjuvant treatment. As a prognostic factor, infiltrates may be of relevance for a statistical evaluation, but not a reliable indicator in the individual case.


[A possibility of using some pyrethroids to prevent plague in the Siberian natural foci of the souslik type].
Experiments have established that the pyrethroids deltamethrin and cypermethrin (decis and cimbush) may be used in the Siberian natural plague foci for not only emergency, but also early prevention of plague. This substantially expands and simplifies the possibility of organizing disinfection actions and reduces the cost of treatments. The findings are determined by the specific features of the biology and ecology of fleas inhabiting in the natural plague foci of the souslik type in a continental climate area. The specific features include the coincidence of preimago stages and the larger proportion of an adults to rodent nests; the low migration of imagoes from the inhabiting nests to the ground surface, only one insect generation that can develop within a comparatively short (4-5-month) warm period of a year.


Stroke in users of low-dose oral contraceptives.
Previous studies have linked the use of oral contraceptive agents to an increased risk of stroke, but those studies have been limited to oral contraceptives containing more estrogen than is now generally used. In a population-based, case-control study, we identified fatal and nonfatal strokes in female members of the California Kaiser Permanente Medical Care Program and who were 15 through 44 years of age. Matched controls were randomly selected from female members who had not had strokes. Information about the use of oral contraceptives (essentially limited to low-estrogen preparations) was obtained in interviews. A total of 408 confirmed strokes occurred in a total of 1.1 million women during 3.6 million woman-years of observation. The incidence of stroke was thus 11.3 per 100,000 woman-years. On the basis of data from 295 women with stroke who were interviewed and their controls, the odds ratio for ischemic stroke among current users of oral contraceptives, as compared with former users and women who had never used such drugs, was 1.18 (95 percent confidence interval, 0.54 to 2.59) after adjustment for other risk factors for stroke. The adjusted odds ratio for hemorrhagic stroke was 1.14 (95 percent confidence interval, 0.60 to 2.16). With respect to the risk of hemorrhagic stroke, there was a positive interaction between the current use of oral contraceptives and smoking (odds ratio for women with both these factors, 3.64; 95 percent confidence interval, 0.95 to 13.87). Stroke is rare among women of childbearing age. Low-estrogen oral-contraceptive preparations do not appear to increase the risk of stroke.


Experiential learning strategies for promoting positive staff attitudes toward the elderly.
It is generally acknowledged that American society devalues its elderly. Young people incorporate pervasive attitudes at an early age. These attitudes are later reflected in the views of health professionals. An essential component of effective care for the elderly is the attitude of the caregivers. Staff attitudes are considered important because of their presumed influence on staff behavior and the quality of care delivered. Attitude change is very difficult to achieve unless the individual is exposed to an experience that places the learning situation on a very personal level. Experiential learning activities can be tailored to provide that personal experience. If attitudes can be changed at the same time that factual information is being presented, experiential activities offer the educator a potent tool for learning. This paper suggests several such activities aimed at enhancing positive attitudes toward the elderly.


Emergency department management of acute asthma exacerbations.
Asthma is a disease of the airways characterized by inflammation, hyperresponsiveness, and bronchoconstriction. The diagnosis is primarily a clinical one, based on a focused history and physical examination, to differentiate from other entities such as heart failure, pneumonia, and pulmonary embolism. Radiographs, laboratory studies, and blood gases are not routinely recommended, except in atypical or refractory cases, or if there is diagnostic uncertainty. The cornerstone of acute asthma treatment includes short-acting beta agonists, anticholinergics, and systemic corticosteroids. This issue reviews the latest evidence in diagnostic and treatment strategies, including other pharmacologic treatments and newer management strategies to avoid intubation.


Design, synthesis, and preliminary biological evaluation of new isoform-selective f-current blockers.
New I(f) blockers have been designed and tested on HEK293 cells stably expressing the HCN1, HCN2, and HCN4 channels to find compounds able to discriminate among the channel isoforms. Among the synthesized compounds, the cis-butene derivative (R)-5 shows some preference for HCN2 while the pseudodimeric product (R)-6 shows selectivity for HCN1. These compounds can be important pharmacological tools to study the channels in native tissues and may be useful to design safe drugs.


HSP27 Alleviates Cardiac Aging in Mice via a Mechanism Involving Antioxidation and Mitophagy Activation.
Aging-induced cardiac dysfunction is a prominent feature of cardiac aging. Heat shock protein 27 (HSP27) protects cardiac function against ischemia or chemical challenge. We hypothesized that HSP27 attenuates cardiac aging. Transgenic (Tg) mice with cardiac-specific expression of the HSP27 gene and wild-type (WT) littermates were employed in the experiments. Echocardiography revealed a significant decline in the cardiac function of old WT mice compared with young WT mice. In striking contrast, the aging-induced impairment of cardiac function was attenuated in old Tg mice compared with old WT mice. Levels of cardiac aging markers were lower in old Tg mouse hearts than in old WT mouse hearts. Less interstitial fibrosis and lower contents of reactive oxygen species and ubiquitin-conjugated proteins were detected in old Tg hearts than in old WT hearts. Furthermore, old Tg hearts demonstrated lower accumulation of LC3-II and p62 than old WT hearts. Levels of Atg13, Vps34, and Rab7 were also higher in old Tg hearts than in old WT hearts. Additionally, old Tg hearts had higher levels of PINK1 and Parkin than old WT hearts, suggesting that mitophagy was activated in old Tg hearts. Taken together, HSP27 alleviated cardiac aging and this action involved antioxidation and mitophagy activation.


Inhibition of hepatitis B virus DNA replication by imino sugars without the inhibition of the DNA polymerase: therapeutic implications.
Previously we have shown that the imino sugar inhibitor of N-linked glycan processing, N-nonyl-deoxynojirimycin (N-nonyl-DNJ), had antiviral activity in the woodchuck model of chronic hepatitis B virus (HBV) infection. In studying the mechanism of action of this compound, it was discovered that imino sugars could inhibit HBV secretion without inhibiting N-linked glycoprocessing. Although N-nonyl-DNJ is an inhibitor of the endoplasmic reticulum (ER) glucosidase, here it is shown that N-nonyl-DNJ retained antiviral activity at concentrations that had no significant impact on ER glucosidase function. Taken together, these results suggested that N-nonyl-DNJ possessed an antiviral activity attributable to a function other than an impact on glycoprocessing. This hypothesis was confirmed by experiments showing that N-nonyl-deoxygalactojirimycin (N-nonyl-DGJ), an alkyl derivative of galactose with no impact on glycoprocessing, retains anti-HBV activity. The data suggest that N-nonyl-DGJ exerts its antiviral action at a point before viral envelopment and may prevent the proper encapsidation of the HBV pregenomic RNA.


Supraphysiological Levels of Testosterone Induce Vascular Dysfunction via Activation of the NLRP3 Inflammasome.
Background: Both supraphysiological and subphysiological testosterone levels are associated with increased cardiovascular risk. Testosterone consumption at supraphysiological doses has been linked to increased blood pressure, left ventricular hypertrophy, vascular dysfunction, and increased levels of inflammatory markers. Activation of the NLRP3 inflammasome contributes to the production of proinflammatory cytokines, leading to cardiovascular dysfunction. We hypothesized that supraphysiological levels of testosterone, via generation of mitochondrial reactive oxygen species (mROS), activates the NLRP3 inflammasome and promotes vascular dysfunction. Methods: Male, 12 week-old C57Bl/6J (WT) and NLRP3 knockout (NLRP3-/-) mice were used. Mice were treated with testosterone propionate [TP (10 mg/kg) in vivo] or vehicle for 30 days. In addition, vessels were incubated with testosterone [Testo (10-6 M, 2 h) in vitro]. Testosterone levels, blood pressure, vascular function (thoracic aortic rings), pro-caspase-1/caspase-1 and interleukin-1β (IL-1β) expression, and generation of reactive oxygen species were determined. Results: Testosterone increased contractile responses and reduced endothelium-dependent vasodilation, both in vivo and in vitro. These effects were not observed in arteries from NLRP3-/- mice. Aortas of TP-treated WT mice (in vivo), as well as aortas from WT mice incubated with testo (in vitro), exhibited increased mROS levels and increased caspase-1 and IL-1β expression. These effects were not observed in arteries from NLRP3-/- mice. Flutamide [Flu, 10-5 M, androgen receptor (AR) antagonist], carbonyl cyanide m-chlorophenyl hydrazone (CCCP, 10-6 M, mitochondrial uncoupler) and MCC950 (MCC950, 10-6 M, a NLRP3 receptor inhibitor) prevented testosterone-induced mROS generation. Conclusion: Supraphysiological levels of testosterone induce vascular dysfunction via mROS generation and NLRP3 inflammasome activation. These events may contribute to increased cardiovascular risk.


A Novel Orthotopic Mouse Model of Lung Metastasis Using Fluorescent Patient-derived Osteosarcoma Cells.
A mouse model of metastatic osteosarcoma is imperative to identify effective agents for metastatic osteosarcoma, which is a recalcitrant disease. In the present study, we established osteosarcoma patient-derived cells (OS-PDCs) and transfected them with green fluorescent protein (GFP). The OS-PDCs were transfected with GFP-lentivirus. GFP-expressing OS-PDCs (2.0×105) were then injected into the tibia of nude mice to establish the patient-derived orthotopic cell (PDOC) model (n=3). Six weeks after injection, the primary tumor and each organ were resected and imaged. Primary orthotopic tumors were established in two out of three mice. The GFP-expressing OS-PDCs in the PDOC model were visualized. Multiple GFP-expressing lung metastases were detected in one of the two mice with primary tumor. The present study proves the concept that a GFP-expressing PDOC model can mimic clinical lung-metastatic osteosarcoma. This model can serve as a paradigm to screen for effective drugs for osteosarcoma lung metastasis.


Federal court rules on Hyde Amendment in Michigan case.
In a ruling issued on July 18 (1994), the US District Court for the Western District of Michigan found that the state's near ban on abortion coverage under Medicaid violates federal law because it is more restrictive than the current version of the federal Hyde Amendment. Chief Judge Benjamin F. Gibson ordered Michigan to cover abortions in cases of rape and incest, even though a 1988 law adopted by a voter initiative and upheld in 1992 by the state Supreme Court prohibits public funding except in cases of life endangerment. Last October, Congress approved the fiscal year 1994 Medicaid budget and slightly expanded abortion coverage to include funding for abortions in cases of rape and incest, as well as life endangerment. Summit Medical Center v. Smith, a CRLP lawsuit that was consolidated with Planned Parenthood v. Engler, was the second case this year in which a federal court ruled on state obligations under current Medicaid law. In early May, in a similar CRLP case, US District Court Judge Edward Nottingham enjoined enforcement of an amendment to the Colorado Constitution on the same grounds (see RFN III/9). On June 1, a trial court judge ordered Montana to comply with the Hyde Amendment in an CRLP suit; a federal district court in Montana came to the same conclusion on June 20 in a case filed by Planned Parenthood. CRLP suits in federal court against states for non-compliance are still pending in Arkansas, Louisiana, North Dakota, Oklahoma, and Pennsylvania.


Pathologic role and temporal appearance of newly emerging autoepitopes in relapsing experimental autoimmune encephalomyelitis.
Relapsing experimental autoimmune encephalomyelitis (R-EAE) is a CD4+ T cell-mediated demyelinating disease model for multiple sclerosis. Myelin destruction during the initial relapsing phase of R-EAE in SJL mice initiated by immunization with the proteolipid protein (PLP) epitope PLP139-151 is associated with activation of T cells specific for the endogenous, non-cross-reactive PLP178-191 epitope (intramolecular epitope spreading), while relapses in R-EAE induced with the myelin basic protein (MBP) epitope MBP84-104 are associated with PLP139-151-specific responses (intermolecular epitope spreading). Here, we demonstrate that T cells specific for endogenous myelin epitopes play the major pathologic role in mediating clinical relapses. T cells specific for relapse-associated epitopes can serially transfer disease to naive recipients and are demonstrable in the CNS of mice with chronic R-EAE. More importantly, induction of myelin-specific tolerance to relapse-associated epitopes, by i.v. injection of ethylene carbodiimide-fixed peptide-pulsed APCs, either before disease initiation or during remission from acute disease effectively blocks the expression of the initial disease relapse. Further, blockade of B7-1-mediated costimulation with anti-B7-1 F(ab) during disease remission from acute PLP139-151-induced disease prevents clinical relapses by inhibiting activation of PLP178-191-specific T cells. The protective effects of anti-B7-1 F(ab) treatment are long-lasting and highly effective even when administered following the initial relapsing episode wherein spreading to a MBP epitope (MBP84-104) is inhibited. Collectively, these data indicate that epitope spreading is B7-1 dependent, plays a major pathologic role in disease progression, and follows a hierarchical order associated with the relative encephalitogenic dominance of the myelin epitopes (PLP139-151 > PLP178-191 > MBP84-104).


Surfactant improves gas mixing and alveolar ventilation in preterm lambs.
Prophylactic treatment with ovine surfactant was evaluated in preterm lambs at risk for development of hyaline membrane disease. Eight mechanically ventilated newborn lambs were treated before delivery and 10 served as controls (gestational age 129-131 d). Lung mechanics, functional residual capacity, alveolar ventilation, efficiency of ventilation, and distribution of ventilation were tested using pressure, flow, and nitrogen elimination (nitrogen washout during 100% oxygen breathing) measurements in the endotracheal tube. The surfactant-treated animals showed significantly improved gas mixing efficiency in the lung with improved alveolar ventilation. Single exponential washout pattern dominated in both groups. Adequate functional residual capacity was established earlier after birth in the treated lambs than in the control animals. Lung mechanics in the treated group showed significant improvement in dynamic lung compliance. Surfactant treatment also improved gas exchange and reduced respirator pressure requirement. We speculate that the main functional effect of surfactant treatment in preterm lambs at risk to develop hyaline membrane disease is to maintain the patency of the peripheral airways in the lung, which improves diffusive gas mixing, alveolar ventilation, and gas exchange. The techniques used in this study should also be useful to evaluate lung function in preterm human infants after specific adaptation of the equipment size.


The nature of puerperal psychosis at Muhimbili National Hospital: its physical co-morbidity, associated main obstetric and social factors.
Eighty six in-patients suffering from puerperal psychosis within six weeks after childbirth were prospectively investigated in Muhimbili National Hospital during two years. Formal psychiatric history, mental status evaluation, research and diagnostic criteria including ICD 10 and clinical progression were employed for diagnosis. Using a structured questionnaire, the socio-demographic characteristics, concomitant physical disorders, major obstetric events, period of onset of puerperal psychosis following delivery and social support given were established. Mean age was found to be 23.6 years; the majority was primiparous women with parity of between one and three children. Main physical co-morbidities included anaemia in 51.4% of cases, infections in 44.2% and EPH-gestosis in 17.4%. Most mothers received social support from their extended families. Organic psychosis was found in four fifths of the mothers and schizophrenia in 8.1%. A high rate of early onset puerperal psychosis (3.2/1000 (births), predominantly in young primiparous women, was found.


In-vitro susceptibility of Haemophilus influenzae to loracarbef (LY 163892) and other oral antibiotics. Collaborative Study Group on Pediatric Infectious Disease in Lombardy.
Data on susceptibility of Haemophilus influenzae are scanty in Italy. We compared the activity of loracarbef (Ly 163892), a new carbacephem, with that of 4 other agents against 265 strains of H. influenzae (46 type b, 219 nontypable) isolated from adults and children at Istituti Clinici di Perfezionamento of Milano, between 1/1/84 and 1/1/89, and also from 7 children at pediatric departments in Lombardy during 1988. In adults 72 strains were all isolated from sputum of patients with pneumonia or chronic bronchitis; in children 199 strains were isolated from conjunctiva (53% of the patients had also a concomitant respiratory infection), 24 from middle ear, 18 from sputum and 32 from blood or cerebrospinal fluid. Minimal inhibiting concentrations (MIC) were determined by the broth microdilution technique. The incidence of resistance of H. influenzae to ampicillin was 3.8%; the lowest percentage of resistance was found for loracarbef (0%) and the highest for erythromycin (94% for strains isolated from children and 97% for strains isolated from adults).


Modeling uptake of nanoparticles in multiple human cells using structure-activity relationships and intercellular uptake correlations.
Biomedical applications of nanoparticles (NPs) are largely dependent on their cellular uptake potential that enables them to reach the specific targets in the body. Experimental determination of cellular uptake of diverse functionalized NPs in different human cell types is tedious, expensive and time intensive, hence compelling for alternative methods. We developed quantitative structure-activity relationship (QSAR) models for predicting uptake of functionalized NPs in multiple cell types in accordance with the OECD guidelines. The decision treeboost QSAR models precisely predicted uptake of 104 NPs in five different cell types yielding high R2 between experimental and model predicted values in the respective training (>0.966) and test (>0.914) sets. The cross-validation Q2 values ranged between 0.627 and 0.926. Low RMSE (<0.11) and MAE (<0.09) in test data emphasized for the usefulness of developed models for predicting new NPs, which outperformed the previous reports. Relevant structural features of NPs (modifier) that were responsible and influence the cellular permeability were identified. Here, we also attempted to develop intercellular uptake correlations based quantitative activity-activity relationship (QAAR) models for predicting cellular viability of NPs for all the cell types. The performances of all the 20 developed QAAR models were highly comparable with the QSAR models. The applicability domains of the developed models were defined using leverage method. The proposed QAAR models can be employed for extrapolating activity endpoints of NPs to either of the five cell types when the data for the other cell type are available. The developed models can be used as tools for screening new functionalized NPs for their cell-specific affinities prior to their biomedical applications.


The molecular defences against reactive oxygen species in yeast.
There is rapidly expanding interest into the protective systems against reactive oxygen species (ROS) in the eukaryotic cell, now that the links between oxidative damage, various disease states, and ageing, are firmly established in higher organisms. Yeast molecular genetics should be able to provide powerful insight into these mechanisms; this potential is now starting to be exploited. A number of primary antioxidant activities and systems of metal-ion homeostasis or detoxification have now been demonstrated to contribute to oxidative-stress protection in yeast. Also, evidence is emerging that the oxidative-stress response of this organism is complex, involving separate transcription-factor responses to peroxide, superoxide anion and metal ions.


NFAT pulls the strings during CD4+ T helper cell effector functions.
The Ca(2+) dependent transcription factor family known as nuclear factor of activated T cells (NFAT) has been shown to be important in T-cell immune responses. Because NFAT proteins have a weak DNA-binding capacity, they cooperate with other transcription factors at composite sites within the promoters of target genes. Recently, NFAT was shown to also be important for the induction of specific genetic programs that guide the differentiation and effector or regulatory activities of CD4(+) T helper subsets via the transcriptional regulation of their lineage-specific transcription factors, specifically T-bet (Th1), Gata3 (Th2), RORgammat (Th17), and Foxp3 (iTregs). In addition, the NFAT family governs the transcription of several signature cytokines, including their cytokine receptors. Subsequently, the integration of these complex intracellular signal transduction cascades is considered to critically determine the crosstalk between the T-cell receptor and receptors that are activated by both the adaptive and innate immune systems to determine pathways of T helper cell differentiation and function. Here, we carefully review the critical role of the established transcriptional partners and functional outcomes of these NFAT interactions in regard to the effector responses of these clinically relevant CD4(+) T helper subsets.


Structural basis of the tight binding of pyridoxal 5'-phosphate to a low molecular weight protein tyrosine phosphatase.
Pyridoxal 5'-phosphate (PLP) binds tightly to bovine low Mr protein tyrosine phosphatase (BPTP), but it is a very poor substrate for the enzyme. The structural basis of this tight binding of PLP is examined here by a variety of methods. Binding constants of a number of PLP analogues were measured with wild-type BPTP, and PLP binding constants of some site-specific mutants of BPTP were determined at pH 5.0 through the use of several independent methods. The tight binding of PLP (Ki = 7.6 microM) causes a downfield shift of the His-72 Cepsilon1H resonance in the 1H NMR spectrum of the protein, consistent with a structural alteration in the phosphate binding loop transmitted through a complex hydrogen bond network that exists between His-72 and Asn-15, which is a residue in the phosphate binding loop. 1H NMR spectroscopy with an MLEV-17 spectral editing scheme was used to monitor the aldehyde resonance of PLP during titration of a catalytically inactive C12A mutant of BPTP. The aldehydic proton resonance of PLP shifted from 10.43 to 10.26 ppm upon complex formation with the C12A mutant. This resonance occurs far from the region where a hemithioacetal hydrogen would be expected to appear, consistent with the conclusion that the Cys-17 side chain of BPTP does not add to the aldehyde group of PLP. UV-visible spectrophotometric titration also supported this conclusion. The binding constant of PLP to a C17A mutant was similar to that exhibited with wild-type protein. These results show that Cys-17 makes virtually no contribution to the tight binding of PLP by BPTP, in contrast to a published report that it is "essential" for binding PLP. On the other hand, Asp-129 of BPTP was found to be very important for binding PLP. It is concluded that Asp-129 binds to the pyridinium nitrogen of PLP and that this renders Asp-129 effectively unavailable to serve its essential catalytic role as a general acid. The interactions described here should be useful in the design of specific inhibitors of this and related phosphotyrosyl protein phosphatases.


A multi-species occupancy modeling approach to access the impacts of land use and land cover on terrestrial vertebrates in the Mumbai Metropolitan Region (MMR), Western Ghats, India.
Urbanization is one of the main drivers in the conversion of natural habitats into different land use and land cover types (LULC) which threaten the local as well as global biodiversity. This impact is particularly alarming in tropical countries like India, where ~18% of the world's population live, and its ever-growing economy (i.e., industrial development) expanded urban areas by several folds. We undertook this study to examine the impacts of urbanization (i.e., LULC) on terrestrial vertebrates (mammals, birds, reptiles, and amphibians) in the Mumbai Metropolitan Region (MMR), Western Ghats, India. We sampled different habitats ranged from highly disturbed urban areas to less disturbed forested areas. Multiple sampling methods such as quadrat sampling, line transect, point count, and camera trapping were used to quantify the target taxa. We used multi-species occupancy modeling in the Bayesian framework to estimate detection probability and occupancy and to assess the effect of various LULC on different species. All four groups showed a significant negative impact of increasing anthropogenic habitat cover on occupancy. Out of 213 species detected in this study, 96% of mammals, 85% of birds, 93.75% of amphibians, and 69.43% of reptiles showed a negative effect of anthropogenic habitat cover. Evidence suggests that historical and recent human disturbances could have played an important role in transforming this area from semi-evergreen and moist deciduous forest to open, scrubby, dry deciduous, and fire-prone landscape. This might be the reason for the high occupancy of open and degraded forest habitat preferring species in our study area. We recommend species-rich areas in the MMR, e.g., Karnala Bird Sanctuary (KBS) and Prabalgad-Matheran-Malanggad Hill Range (PMMHR), must be conserved through habitat restoration, ecotourism, public awareness, and policymaking.


High-density ear-EEG.
Ear-EEG enables recording of EEG in real-life environments in an unprecedented discreet and minimal obtrusive way. As ear-EEG are recorded from electrodes placed in or around the ear, the spatial coverage of the potential field on the scalp is inherently limited. Despite the limited spatial coverage, the potential field in-the-ear can still be measured in multiple points and thereby provide spatial information. We present a method to perform and visualize high-density ear-EEG recordings, and illustrate the method through recordings of auditory and visually evoked steady-state responses, for a single subject. The auditory and visually evoked responses showed distinctive differences in the response field in the ear, reflecting the very different locations of the underlying cortical sources. In conclusion, high-density ear-EEG can be used to investigate how different cortical sources maps to the ear, and provides a way to select optimal electrode positions for given brain phenomena.


Discovery and Mechanism of Small Molecule Inhibitors Selective for the Chromatin-Binding Domains of Oncogenic UHRF1.
Chromatin abnormalities are common hallmarks of cancer cells, which exhibit alterations in DNA methylation profiles that can silence tumor suppressor genes. These epigenetic patterns are partly established and maintained by UHRF1 (ubiquitin-like PHD and RING finger domain-containing protein 1), which senses existing methylation states through multiple reader domains, and reinforces the modifications through recruitment of DNA methyltransferases. Small molecule inhibitors of UHRF1 would be important tools to illuminate molecular functions, yet no compounds capable of blocking UHRF1-histone binding in the context of the full-length protein exist. Here, we report the discovery and mechanism of action of compounds that selectively inhibit the UHRF1-histone interaction with low micromolar potency. Biochemical analyses reveal that these molecules are the first inhibitors to target the PHD finger of UHRF1, specifically disrupting histone H3 arginine 2 interactions with the PHD finger. Importantly, this unique inhibition mechanism is sufficient to displace binding of full-length UHRF1 with histones in vitro and in cells. Together, our study provides insight into the critical role of the PHD finger in driving histone interactions, and demonstrates that targeting this domain through a specific binding pocket is a tractable strategy for UHRF1-histone inhibition.


ERK6, a mitogen-activated protein kinase involved in C2C12 myoblast differentiation.
ERK6, a mitogen-activated protein (MAP) kinase-related serine/threonine kinase, is highly expressed in human skeletal muscle and appears to function as a signal transducer during differentiation of myoblasts to myotubes. In transfected 293 cells, activation of the 45-kDa enzyme results in tyrosine-phosphorylated 46- and 56-kDa forms, which phosphorylate myelin basic protein. Overexpression of wild-type ERK6 or the inactive mutant Y185F has no effect on fibroblast and myoblast proliferation, but it enhances or inhibits C2C12 cell differentiation to myotubes, respectively. Our findings suggest ERK6 to be a tissue-specific, differentiation signal-transducing factor that is connected to phosphotyrosine-mediated signaling pathways distinct from those activating other members of the MAP kinase family such as LRK1 and ERK2.


Serum levels of CD8 antigen and soluble interleukin 2 receptors in patients with B cell chronic lymphocytic leukemia.
We assayed the plasma levels of CD8 antigen (CD8Ag) and soluble interleukin 2 receptor (sIL-2R) in 34 subjects with B cell chronic lymphocytic leukemia (B-CLL) and in 15 controls using an immunoenzymatic method. The results showed higher average levels of soluble CD8 (sCD8) and sIL-2R in the leukemic patients compared to the controls (sCD8 = 860 vs. 306 U/ml; sIL-2R = 4,131 vs. 311 U/ml). The two antigen levels were significantly higher in patients with progressive disease than in those with indolent disease, and they also correlated with Rai's stage. sIL-2R levels correlated with lymphocyte count (p less than 0.001), while there was no correlation between sCD8 levels and total number of lymphocytes. These results seem to show that the measurement of serum levels of CD8Ag and sIL-2R may be a useful tool in the prognostic evaluation of patients with B-CLL.


Effect of substituents of alloxazine derivatives on the selectivity and affinity for adenine in AP-site-containing DNA duplexes.
Using the DNA duplex containing an AP site (5'-TCC AGX GCA AC-3'/3'-AGG TCN CGT TG-5', X = AP site, N = A, T, C, or G), we have found that 2-amino-4-hydroxypteridine (pterin) selectively binds to guanine (G), and that the enhanced binding affinity for G is obtained by its methylated derivative 2-amino-6,7-dimethyl-4-hydroxypteridine (diMe pteridine). Similarly, among the cytosine (C)-selective ligands, i.e. derivatives of 2-amino-1,8-naphthyridine, a trimethyl-substituted derivative (2-amino-5,6,7-trimethyl-1,8-naphthyridine) selectively binds to C with a strong binding affinity of 1.9 × 10(7) M(-1). In the case of lumazine derivatives, pteridine-2,4(1H,3H)-dione (lumazine) binds to adenine (A), and its methylated derivative, 6,7-dimethylpteridine-2,4(1H,3H)-dione (diMe lumazine) strongly binds to A with enhanced binding affinity, keeping the same base-selectivity. On the other hand, the benzo-annelated (with phenyl ring, 2.4 Å) derivative of lumazine, benzo[g]pteridine-2,4(1H,3H)-dione (alloxazine), can bind to A selectively, whereas its methylated ligand, 7,8-dimethylbenzo[g]pteridine-2,4(1H,3H)-dione (lumichrome) selectively binds to thymine (T) over A, C and G. Methyl-substituted lumichrome derivatives show moderate binding affinities for target nucleobases. The changes in the base-selectivity and binding affinities are discussed in detail with respect to the substituents of these ligands, considering hydrogen-bonding patterns, size of AP site and stacking interactions.


Time-resolved scattering investigations of brome mosaic virus microcrystals appearance.
The behavior of brome mosaic virus in solution as a function of physico-chemical conditions has already been characterized by Small Angle X-ray Scattering studies. The most striking result was that the precipitates induced by the addition of polyethylene glycol were in fact made of microcrystals. This result was reinvestigated on the ID2 beamline at ESRF (Grenoble, France) to determine whether there was an amorphous state before the organized one, and measure the necessary period of latency for the microcrystals to form. The stopped-flow device associated to the high brilliance of the beamline enabled us to characterize the growth of the diffraction peaks as a function of time.


Gain and fidelity of transmission patterns at cortical excitatory unitary synapses improve spike encoding.
Neuronal spike encoding and synaptic transmission in the brain need be precise and reliable for well-organized behavior and cognition. Little is known about how a unitary synapse reliably transmits presynaptic sequential spikes and how multiple unitary synapses precisely drive their postsynaptic neurons to encode spikes. To address these questions, we investigated the dynamics of glutamatergic unitary synapses as well as their role in driving the encoding of cortical fast-spiking neurons. Synaptic transmission patterns randomly fluctuate among facilitation, depression and parallel over time. The postsynaptic calmodulin-signaling pathway enhances initial responses and converts this fluctuation to a synaptic depression. We integrated current pulses mathematically based on synaptic plasticity and found that they improve spike capacity and timing precision by shortening the spike refractory period at postsynaptic neurons. Our results indicate that the gain and fidelity of synaptic patterns enable reliable transmission of presynaptic signals by the synapse and precise encoding of spikes by postsynaptic neurons. These reproducible neural codes may be involved in controlling well-organized behavior.


Intergenerational transmission of aggression in romantic relationships: the moderating role of attachment security.
This prospective study used longitudinal, multi-reporter data to examine the influence of parents' marital relationship functioning on subsequent adolescent romantic relationships. Consistent with Bryant and Conger's (2002) model for the Development of Early Adult Romantic Relationships (DEARR), we found that interactional styles, more specifically paternal aggression and satisfaction, exhibited in parents' marital relationship when their adolescents were age 13 were predictive of qualities of the adolescent's romantic relationships 5 years later. Continuities were domain specific: paternal satisfaction predicted adolescent satisfaction and paternal aggression predicted adolescent aggression. Attachment security moderated the link between paternal aggression and subsequent adolescent aggression, with continuities between negative conflictual styles across relationships reduced for secure adolescents. Results are interpreted as suggesting that attachment may help attenuated the transmission of destructive conflict strategies across generations.


[Cloning, eukaryotic expressing and function analysis of Schistosoma japonicum apoptosis gene Sjcaspase3].
For further research of the apoptosis mechanism of Schistosoma japonicum (S. japonicum). The cDNA encoding Sjcaspase3 of Schistosoma japonicum was amplified by polymerase chain reaction (PCR) technique, which contained 900 nucleotides and encoded 299 amino acids. The theory molecular weight and isoelectric point (PI) of the deduced protein is 33.5 kDa and 6.39, respectively. Real-time PCR was used to analyze the transcription profiles of Sjcaspase3 at different development stages of S. japonicum. The results showed that this gene was expressed in all stages of S. japonicum with the highest expression in 21d worms, and the level of gene transcription in 42 d female worms was higher than that of male worms. The recombinant plasmid pXJ40-FLAG-Sjcaspase3 was constructed and transfection into Hela cells successfully. Real-time PCR and Western blotting analysis showed Sjcaspase3 was successfully expressed in Hela cells. Enzyme activity analysis revealed that recombinant Sjcaspase3 possessed the activity to cut substrate DEVD. Flow cytometry proved that Sjcaspase3 could induce early apoptosis of Hela cells. The results provide the basis for proceeding further study on the biological function of Sjcaspase3 and better understand the apoptosis mechanism of S. japonicum.


Suppression of plant-generated reactive oxygen species is required for successful infection by the rice blast fungus.
Magnaporthe oryzae is a filamentous ascomycete that continuously threatens global rice production. The infection cycle of this pathogen commences with the attachment of conidia to rice plants, followed by the formation and maturation of a specialized infection structure-the appressorium. Melanized appressoria generate immense turgor pressure, which allows the fungus to break through the plant cuticle and cell wall by means of a penetration peg. These stages occur within the first twenty-four hours after which time the penetration peg gives rise to and subsequent primary and secondary infection hyphae. Upon infection, the plant recognizes the pathogen, triggering a series of defense responses and signaling events including the secretion of reactive oxygen species (ROS). In a recent paper, we showed that barley plants generate ROS and cell wall appositions (CWAs) around infection sites and that a fungal gene we termed MoHYR1 is necessary for ameliorating these defense reactions and ensuring successful infection and colonization. When this gene is deleted from the M. oryzae genome, the plant oxidative responses are stronger and disease is reduced.


A rapid High Performance Liquid Chromatographic (HPLC) method for the simultaneous determination of seven UV filters found in sunscreen and cosmetics.
A rapid High Performance Liquid Chromatographic (HPLC) method was developed for the simultaneous determination of seven Ultra Violet (UV) filters most commonly found in cosmetics and sunscreen. The object of the method development was to provide a reliable rapid method, that would simultaneously separate a combination of the UV Filters, most commonly found in cosmetics and sunscreen products, utilizing a minimum of environmentally friendly solvents. The compounds separated were: benzophenone 3 (BZ3), methylbenzildene camphor (MBC), octyl dimethyl PABA (ODP), octocrylene (OCR), octyl methoxycinnamate (OMC), butyl - methoxydibenzoylmethane (BDM) and octyl salicylate (OS). An adjusted mobile phase consisting of ethanol and 1% acetic acid, combined with a Thermo Hypersil C(18) BDS 3 micron column resulted in a method, which allowed the analysis of the seven compounds in seven minutes. The proposed method was validated utilising the International Congress on Harmonisation (ICH) and the Food and Drug Administration (FDA) guidelines. All parameters examined were found to be well within the stated guidelines.


Traditional effects of medicinal plants in the treatment of respiratory diseases and disorders: an ethnobotanical study in the Urmia.
To identify, present and review the respiratoty medicinal plants which used by Urmian herbalists. The list of traditional healers of West Azarbaijan Province was prepared and data were obtained by direct observation, interviews and the questionnaires After that, herbarium samples were collected from the desired area and deposited in herbarium unit of the Faculty of Agriculture, Urmia University, Urmia, Iran. Our results demonstrated that 20 medicinal plants from 10 plant families are used to treat respiratory disorders. Also, the most plant part that used for treating of respiratory disorders was seed (27%) and the most traditional form prescribed by herbalists was boiled (54%). Forty three percentage of Urmia herbalists have used herbs for the treatment of cough. People in this area have a strong belief that plants have a positive impact in the treatment of respiratory disorders and they have used medicinal plants since ancient times to treat these disorders. Our study revealed the importance of herbal medicines and traditional medicine in this area as medicinal resource for drug discovery in future.


Molecular simulation of gas adsorption, diffusion, and permeation in hydrated Nafion membranes.
Molecular simulations were performed to characterize hydrated Nafion membranes in terms of gas adsorption, diffusion, and permeation. The experimental results validate the molecular model of Nafion with respect to material density, morphology, free volume, and water diffusivity. Nafion's adsorption property is examined in terms of the solubility and adsorption isotherms for gases, including H(2), O(2), and N(2). The adsorption capacity of hydrated Nafion is shown to be strong for O(2) and N(2) but not for H(2). Due to the dilution effect, N(2) is able to suppress the loading of O(2) and protect the fuel cell from fuel crossover. The dynamic behaviors of H(2) and O(2) are represented by self-diffusion coefficients, with the results showing that H(2) diffusion in Nafion membranes is nearly 1 order of magnitude faster than O(2) diffusion. The effects of water content and the concentration of adsorbed gases were verified, and a close correlation of Nafion free volume to gas transport properties was revealed. On the basis of the solution-diffusion mechanism, the permeabilities of H(2) and O(2) in hydrated Nafion membranes are calculated and compared with corresponding experiments, and the permeability of H(2) is found to be approximately twice that of O(2).


Tropical spastic paraparesis/HTLV-I-associated myelopathy in Brazil.
Brazil, the largest Latin American country, is highly heterogeneous, both demographically and socioeconomically. The overall human T-cell lymphotropic virus type I (HTLV-I) seroprevalence among blood donors is approximately 0.45%. These rates are highly variable, from 0 to 1.8%. Since 1989, many series of tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM) cases have appeared in the literature, with high variation in the prevalence of HTLV-I among TSP patients (14.7-57%). The main clinical features of Brazilian TSP/HAM are similar to those in other endemic countries, but sensory signs are more frequent. Recently, the presence of peripheral nerve and muscular involvement has been characterized. The first nationwide study on the disease has been recently completed: it enrolled 163 patients and concluded that TSP/HAM is common in Brazil, mainly in the northeast and southeast regions; it predominates among women and whites; the most important risk factors for infection are sexual promiscuity and blood transfusion; and, although a remarkably uniform disease throughout the country, some statistically significant differences were detected, such as a higher proportion of females over males in the northeast region, a higher proportion of whites the southeast and the south and mulattos in the northeast, and, finally, a high rate of venereal diseases in the southeast region and of intravenous drug use in the south. Brazil seems to be a perfect setting for future epidemiologic, clinical, basic, and therapeutic studies on TSP/HAM.


Increasing antigenic and genetic diversity of the V3 variable domain of the human immunodeficiency virus envelope protein in the course of the AIDS epidemic.
Population-wide variation in genomic RNA of human immunodeficiency virus type 1 (HIV-1) encompassing the V3 loop of the envelope protein was studied in serum samples of 74 newly infected individuals from three Dutch cohorts: 30 homosexual men, 32 drug users, and 12 hemophiliacs. During acute infection, HIV-1 RNA sequences present in serum are relatively homogeneous, which makes direct sequencing feasible. This offered an opportunity to study the infecting virus variants before mutations had accumulated in the new host. The sampling dates ranged from 1980 to 1991, thus spanning the entire AIDS epidemic in The Netherlands. The diversity in the sequenced region increased over time in both the homosexual and the drug-user risk groups. Furthermore, this increase was associated with an increase in antigenic variation, as witnessed by serum reactivity to a V3 peptide panel. Despite this diversification, some 1990 sequences still closely resembled the earliest 1980 sequence, making ancestral inferences problematic. No evidence was found of a change in the master sequence of the virus quasi-species over time. At the amino acid level, no risk-group-associated variation was found, but at the nucleotide level, the drug-user and homosexual/hemophiliac sequences could be distinguished on the basis of a single silent nucleotide change in the sequence encoding the tip of the V3 loop. Hemophiliac sequences could not be distinguished from those of homosexuals. In spite of the large and increasing genetic variability, all sequences were more similar to the European/American HIV consensus sequence than to that of non-Western strains.


Blind nasotracheal intubation in awaken patient scheduled for hemimandibulectomy. Case report.
Several resources can be used for the approach of the airways. Maintaining a patient awake when control of ventilation/oxygenation is uncertain is an option when intubation is doubtful. Blind nasotracheal intubation (NTI) is an alternative to fiberoptic endoscopy. A 75-year old patient, weighing 56 kg, was scheduled for hemimandibulectomy; she presented cervical immobility secondary to arthrodesis, mouth opening of 2.2 cm, moderate retrognatism, voluntary protrusion of the mandible was absent, mentostemal distance of 11 cm and mento-thyroid distance of 6 cm, therefore receiving a score of 5 on the Wilson scale. The patient signed an informed consent after being informed about the procedure. After monitoring and oxygenation, continuous infusion of dexmedetomidine was initiated. Superior and inferior laryngeal nerve block was performed with 2.0% lidocaine without vasoconstrictor and the hypopharinx was anesthetized with a lidocaine spray. Before NTI, ondansetron, midazolam, fentanyl, and droperidol were administered and the patient remained awake and cooperative. Nasal insertion of the tracheal tube was oriented by its opacification and respiratory sounds and the placement was confirmed by pulmonary auscultation and capnography. Continuous infusion of propofol and remifentanil was instituted, vecuronium was administered and controlled ventilation was initiated. The surgery lasted 60 minutes without intercurrences. At the end, the patient was breathing spontaneously, so she was extubated and transferred to the recovery room from where she was discharged without any complaints. Nasotracheal intubation is an alternative to fiberoptic endoscopy when safety and control of the airways is uncertain. Informing the patient about the procedure was essential. Safety was assured and respiratory depression and hemodynamic instability was not observed.


Rigid gas permeable lens binding: significance and contributing factors.
A retrospective analysis of lens binding was performed using records from 279 cases of overnight wear of rigid gas permeable (RGP) lenses in a variety of materials and designs. The overall incidence of lens binding on eye opening was 22%. Typically, the lens was bound nasally, became mobile spontaneously in less than 1 h, and produced staining of the central cornea and inferior conjunctiva. A corneal indentation ring was noted in 53% of eyes that experienced a bound lens. A statistical analysis was performed to determine whether RGP lens binding was associated with particular lens parameters, patient characteristics, or lens fitting factors. Overnight lens binding was found to occur more frequently with lenses of large diameter, flat base curve and minimal axial edge lift, fitted "on-K" or flat relative to central corneal curvature, and exhibiting less than optimal on-eye lens movement before eye closure.


[Multiple lymphomatous polyposis--rare case of gastrointestinal hemorrhage].
The authors report a case of a 57 years old male patient, who was admitted to gastroenterology department with upper gastrointestinal haemorrhage. The urgent upper gastrointestinal endoscopy revealed an ulcerated polypoid tumor in the region of angulus of the stomach, and multiple polypoid lesions in the bulbar part of the duodenum. Upon this endoscopic appearance colonoscopy was performed, which revealed a polyposis syndrome in the colorectum. Computer tomography detected mesenterial, retroperitoneal and mediastinal lymph node involvement as well. In this case the primary or secondary origin of the gastrointestinal lymphoma was not verifiable. According to literature data this histological type of the gastrointestinal lymphoma has poor response to chemotherapy, the prognosis is unfavourable. In this particular case the administered chemotherapy resulted in total remission at the lymphoma patient clinically staging III Ae. In the proper follow-up examinations of the patient upper and lower endoscopy, histology samples, laboratory parameters, computer tomography, and physical examination in every 3 months are the methods.


Dose-Related Reference Range as a Tool in Therapeutic Drug Monitoring.
Therapeutic drug monitoring (TDM) aims to individualize drug therapy. This systematic review provides a state-of-the-art overview of the benefits of adding the dose-related reference range (DRR) as a second reference range to the set of tools used by TDM for measurement and evaluation. It discusses alternative pharmacokinetic approaches for individualization of drug therapy. Literature was searched in PubMed. Textbooks provided Bateman transformations for calculating expected drug concentrations at various times after drug application in "normal patients," that is, the population of phase II clinical trials. The review compiles conditions and prerequisites for these transformations to be valid. Relating a measured drug concentration to the orienting therapeutic reference range provides pharmacodynamic information for improving the benefit-to-risk ratio of desired drug effects versus adverse drug effects. The discriminating DRR considers a patient's individual pharmacokinetic situation. DRR is statistically based on the pharmacokinetic parameters total clearance, time to reach maximal concentrations, and elimination half-life. Relating the measured drug concentration to a range rather than a particular value, DRR determines if individual patients do or do not belong to the population of "normal patients." Once a patient is identified to be outside the population of "normal patients," the clinical-pharmacological TDM report elaborates the cause. It consists of the measured value, the TDM 9-field-board, the elimination pathways table, and a medication recommendation taking into account clinical information. The internet-based platform KONBEST supports editing of the clinical-pharmacological TDM report. It is personally signed and send to the therapist. The DRR embedded into a clinical-pharmacological TDM report allows adjusting a patient's medication to the patient's individual needs (individualization of drug therapy).


Retrospective confidence judgements made by adults with traumatic brain injury: relative and absolute accuracy.
Eighteen adult survivors of moderate or severe traumatic brain injury (TBI) and 18 controls studied and were tested on two lists of noun-pairs, and made item-by-item retrospective confidence judgements (RCJs) of their answers using a Likert scale. For both groups, correlations between RCJ ratings and recall were extremely high, indicating that survivors of TBI were as accurate as non-injured controls when comparing their confidence in one answer to another. However, as groups, survivors of TBI were over-confident and control participants were under-confident, but only when uncertain as to the accuracy of their answer. Recall errors of 'interference' were analysed post-hoc. Survivors of TBI displayed higher confidence in interference errors than in non-interference errors, while control participants did not. These results are discussed within the context of self-monitoring by clinical and non-clinical populations. The importance of both relative and absolute measures of metamemory accuracy is highlighted.


Characterization of the bactericidal activity of the natural diterpene kaurenoic acid.
Kaurenoic acid is a diterpene with selective antibacterial activity against Gram-positive bacteria. The compound is bacteriolytic for Bacillus cereus. This activity was only partially affected by the composition and pH of the culture medium. Loss of the ability to retain the Gram stain and morphological alterations were produced in B. cereus cells exposed to kaurenoic acid. On the other hand, LPS mutants of Salmonella typhi were resistant to the compound, but spheroplasts of Escherichia coli became more sensitive to kaurenoic acid.


Physiologic distribution and differentiation of melanocytes in human fetal and neonatal skin equivalents.
There is evidence that epidermal keratinocytes play a critical role in melanocyte position and differentiation in the epidermis, although little is known about the molecular mechanisms involved. We have used an in vitro skin equivalent as a model system in which to study keratinocyte/melanocyte interactions in both fetal and neonatal skin. Because the skin equivalent model has been shown to closely simulate the morphologic and biochemical features of differentiated epidermis we hypothesized that the factors that influence melanocyte position and differnetiation would also function in this system. Localization of melanocytes in skin equivalents, using the monoclonal antibody HMB-45, established that melanocytes in fetal skin equivalents are grouped and distributed both basally and suprabasally, whereas melanocytes in neonatal skin equivalents are singly distributed among basal epidermal keratinocytes, similar to the distributions of fetal and neonatal melanocytes, respectively, in vivo. Similarly, in fetal and neonatal skin equivalents the patterns of expression of a number of melanoma/melanocyte-associated antigens closely parallels that seen in vivo. These results suggest that the skin equivalent model is an excellent system in which to study the dynamic factors that regulate melanocyte migration, proliferation, and differentiation during ontogeny and post-natal differentiation of the skin.


Frailty and survival.
Using data for selected developed countries, the factors affecting an individual's susceptibility to morbidity and mortality are analyzed. "On the basis of empirical data the author concludes that frailty is not unchangeable throughout a person's lifetime but subject to period effects,...which tend to overwhelm the genetic element.... Current external conditions...exert a pervasive influence on the frailty of an individual and the mortality of the population making them responsive to health-related policies and personal choice." (SUMMARY IN FRE AND ITA)


Cost-effectiveness and budget impact analysis of PPV23 vaccination for the Malaysian Hajj pilgrims.
The potential occurrence of disease outbreaks during the hajj season is of great concern due to extreme congestion in a confined space. This promotes the acquisition, spread and transmission of pathogenic microorganisms and pneumococcal disease are one of the most frequent infections among Hajj pilgrims. This study aimed to assess the cost-effectiveness and budget impact of introducing the PPV23 to Malaysian Hajj pilgrims. A decision tree framework with a 1-year cycle length was adapted to evaluate the cost-effectiveness of a PPV23 vaccination program with no vaccination. The cost information was retrieved from the Lembaga Tabung Haji Malaysia (LTH) database. Vaccine effectiveness was based on the locally published data and the disease incidence specifically related to Streptococcus pneumoniae was based on a literature search. Analyses were conducted from the perspective of the provider: Ministry of Health and LTH Malaysia. The incremental cost-effectiveness ratios (ICER), cases averted, and net cost savings were estimated. Findings from this study showed that PPV23 vaccination for Malaysian Hajj pilgrims was cost-effective. The PPV23 vaccination programme has an ICER of MYR -449.3 (US$-110.95) per case averted. Based on the national threshold value of US$6,200-US$8,900 per capita, the base-case result shows that introduction of the PPV23 vaccine for Malaysian Hajj pilgrims is very cost-effective. Sensitivity analysis revealed parameters related to annual incidence and hospitalised cost of septicemia and disease without vaccination as the key drivers of the model outputs. Compared with no vaccination, the inclusion of PPV23 vaccination for Malaysian Hajj pilgrims was projected to result in a net cost saving of MYR59.6 million and 109,996 cases averted over 5 years period. The PPV23 vaccination program could substantially offer additional benefits in reducing the pneumococcal disease burden and healthcare cost. This could be of help for policymakers to consider the implementation of PPV23 vaccination for Malaysian performing hajj.


EGCG-rich green tea extract stimulates sRAGE secretion to inhibit S100A12-RAGE axis through ADAM10-mediated ectodomain shedding of extracellular RAGE in type 2 diabetes.
The receptor for advanced glycation of end products (RAGE) plays a critical role in the progression of type 2 diabetes (T2D). Soluble RAGE (sRAGE) is one of the RAGE variants, which acts as a decoy domain receptor and competes with RAGE, thus contributing to prevention of T2D. In this study, we conducted clinical trials of (-)-epigallocatechin-3-gallate (EGCG) rich green tea extract (300-900 mg/day) to investigate the effect of EGCG on relationship between S100A12 RAGE ligand and diverse sRAGE in T2D. Moreover, mechanism of sRAGE production also confirmed in vitro. Our data indicated that EGCG could stimulate sRAGE circulation but inhibited RAGE ligand in T2D, and ADAM10-mediated ectodomain shedding of extracellular RAGE was mainly involved in EGCG-stimulated sRAGE circulation. The present evidence indicates that EGCG has a potential to block S100A12-RAGE axis by stimulating sRAGE production through ADAM10-mediated ectodomain shedding of extracellular RAGE. Therefore, EGCG contributes to nutritional strategies for diabetes, not only because of its efficient antioxidant activity to scavenge free radicals, but also because of its ability stimulating sRAGE release in the circulation. Additionally, ADAM10-induced ectodomain shedding of extracellular RAGE leading to sRAGE circulation should be a potential of passive mechanism of sRAGE production to block S100A12-RAGE axis-related pathogenesis of proinflammation and diabetes.


On the quenching of the fluorescence yield in photosynthetic systems.
A modified matrix model describing transfer of excitation energy in the photosynthetic pigment system is discussed. In addition to the antenna pigments and reaction centers of the simple matrix model, a coupling complex is postulated mediating energy transfer between antenna and reaction centers. The values of the parameters describing the transfer properties of the coupling complex can be chosen in such a way that a number of recent unexplained measurements of fluorescence properties of various purple bacteria can be described. If such coupling complexes are present in oxygen evolving organisms, some of their properties must be different from those of purple bacteria.


Evaluation of AnaeroGen system for growth of anaerobic bacteria.
The Oxoid AnaeroGen system was compared with the BBL GasPak for the production of an anaerobic atmosphere and was evaluated for its ability to support the growth of 135 clinically significant anaerobic bacteria. An anaerobe chamber was used as the "gold standard" for supporting the growth of anaerobes. The AnaeroGen requires no catalyst, produces no hydrogen, requires no water, and reduces preparation time to a minimum. The water-activated BBL GasPak generates hydrogen. For 132 of the 135 strains tested, better initial growth at 48 h was noted for the jar methods than for the anaerobe chamber. At 72 h, 113 of the 135 strains showed equal growth, and at 7 days, only marginal differences in growth patterns were noted. The AnaeroGen never failed to reduce the anaerobic indicator, while the BBL GasPak occasionally failed to do so. The AnaeroGen performed at least as well as, and sometimes better than, the established methods. The AnaeroGen is a good alternative for use in anaerobic jars.


Downregulation of Cell Surface Major Histocompatibility Complex Class I Expression Is Mediated by the Left-End Transcription Unit of Fowl Adenovirus 9.
Major histocompatibility complex class I (MHC-I) molecules play a critical role in the host's antiviral response by presenting virus-derived antigenic peptides to cytotoxic T lymphocytes (CTLs), enabling the clearance of virus-infected cells. Human adenoviruses evade CTL-mediated cell lysis, in part, by interfering directly with the MHC-I antigen presentation pathway through the expression of E3-19K, which binds both MHC-I and the transporter associated with antigen processing protein and sequestering MHC-I within the endoplasmic reticulum. Fowl adenoviruses have no homologues of E3-19K. Here, we show that representative virus isolates of the species Fowl aviadenovirus C, Fowl aviadenovirus D, and Fowl aviadenovirus E downregulate the cell surface expression of MHC-I in chicken hepatoma cells, resulting in 71%, 11%, and 14% of the baseline expression level, respectively, at 12 h post-infection. Furthermore, this work reports that FAdV-9 downregulates cell surface MHC-I through a minimum of two separate mechanisms-a lysosomal-independent mechanism that requires the presence of the fowl adenovirus early 1 (FE1) transcription unit located within the left terminal genomic region between nts 1 and 6131 and a lysosomal-dependent mechanism that does not require the presence of FE1. These results establish a new functional role for the FE1 transcription unit in immune evasion. These studies provide important new information about the immune evasion of FAdVs and will enhance our understanding of the pathogenesis of inclusion body hepatitis and advance the progress made in next-generation FAdV-based vectors.


Arbuscular mycorrhizal fungi serve as keystone taxa for revegetation on the Tibetan Plateau.
Revegetation is widely used to enhance degraded topsoil recovery with the enhancements of soil nutrient accumulation and soil structure stabilization. Arbuscular mycorrhizal fungi (AMF) are important for the allocation of carbon into the soil and the formation of soil aggregates. Thus, we hypothesized that AMF could construct more niches for other microbes during revegetation, making AMF keystone taxa of soil. Soil fungal and bacterial communities were investigated under a revegetation experiment and correlation networks between soil fungi and bacteria were constructed. Simultaneously, the plant growth level, soil properties and structure, and soil microbial carbon decomposition abilities were measured. The results revealed that AMF were the most central fungi at the phylum (degree = 3), class (degree = 11), and family (degree = 15) levels. The reads number of AMF were positively correlated with both fungal (R2 = 0.431, P < 0.001) and bacterial (R2 = 0.106, P = 0.044) richness. Higher colonization of AMF in roots and/or more AMF extraradical mycelium and spores in soil indicated a better plant growth, more stable soil aggregates, and a higher carbon decomposition ratio. Our results highlight that AMF are keystone taxa in revegetation, as they play significant roles in enhancing the recovery of the belowground microbiome diversity, soil structure stability, and nutrients cycling. The positive roles of AMF in revegetation support the application of AMF in ecosystem recovery.


Extraskeletal osteosarcoma with pulmonary metastasis in a female f344 rat.
A subcutaneous mass in the right femoral region of a female F344 Slc/N rat was examined histopathologically. At 83 weeks of age, the animal showed symptoms of severe anemia and nasal bleeding. Necropsy revealed that the mass had invaded the skeletal muscles but did not affect the bones. Multicentric nodules were also observed in the lung. Histopathology revealed a sheet-like growth pattern of polygonal tumor cells with round or comma-shaped nuclei and pale eosinophilic cytoplasm. Osteoid tissue was observed in not only the original lesion but also the metastatic foci in the lung. Each tumor cell was surrounded by argentophil fibers and few collagen fibers. Immunohistochemically, the tumor cells were positive for proliferating cell nuclear antigen (PCNA), vimentin, osterix and osteocalcin, but negative for keratin, S-100, von Willebrand factor, CD-31, CD-34, desmin, α-smooth muscle actin, lysozyme, α1-antitrypsin and rat malignant fibrous histiocytoma (MFH) antigen. CD-68-positive cells were considered to be infiltrated macrophages because they were negative for PCNA. On the basis of these findings, we diagnosed the present case as extraskeletal osteosarcoma.


Mangiferin ameliorates insulin resistance by inhibiting inflammation and regulatiing adipokine expression in adipocytes under hypoxic condition.
Adipose tissue hypoxia has been recognized as the initiation of insulin resistance syndromes. The aim of the present study was to investigate the effects of mangiferin on the insulin signaling pathway and explore whether mangiferin could ameliorate insulin resistance caused by hypoxia in adipose tissue. Differentiated 3T3-L1 adipocytes were incubated under normal and hypoxic conditions, respectively. Protein expressions were analyzed by Western blotting. Inflammatory cytokines and HIF-1-dependent genes were tested by ELISA and q-PCR, respectively. The glucose uptake was detected by fluorescence microscopy. HIF-1α was abundantly expressed during 8 h of hypoxic incubation. Inflammatory reaction was activated by up-regulated NF-κB phosphorylation and released cytokines like IL-6 and TNF-α. Glucose uptake was inhibited and insulin signaling pathway was damaged as well. Mangiferin substantially inhibited the expression of HIF-1α. Lactate acid and lipolysis, products released by glycometabolism and lipolysis, were also inhibited. The expression of inflammatory cytokines was significantly reduced and the damaged insulin signaling pathway was restored to proper functional level. The glucose uptake of hypoxic adipocytes was promoted and the dysfunction of adipocytes was relieved. These results showed that mangiferin could not only improve the damaged insulin signaling pathway in hypoxic adipocytes, but also ameliorate inflammatory reaction and insulin resistance caused by hypoxia.


[The renal involvement of primary vasculitis: clinical and pathological analysis of 5 cases].
Primary vasculitis, include microscopic polyarteritis (MPA) and Wegener's granulomatosis (WG), is one of the causes of Glomerulonephritis and renal failure. Recently antineutrophil cytoplasmic autoantibodies (ANCA) is considered to be a very important tool for the diagnosis of MPA and WG. The management of ANCA was performed in 42 patients with variant primary glomerulonephritis with crescents formation or sclerotic glomerulonephritis, 5 of them show positive, appeared as a pattern of P-ANCA. Most of the patients were old male, with fever, malaise, weight loss, anemia, muscle and joint pain, some of them have chronic cough, even hemoptysis, opacities in middle-lower fields of both lungs, which didn't response to antibiotics therapy. This is the first report about renal involvement of primary vasculitis from China. Our result suggest that primary vasculitis is not a rare course of renal failure in China.


Relational-Level Factors Influencing Suicidal Behaviors Among Korean Adolescents.
To identify relational-level risk and protective factors for suicidal ideation, suicide plan, and suicide attempt in a nationally representative sample of Korean adolescents. This study is a secondary data analysis of cross-sectional national data on Youth Health Behavior collected in June 2017. The final sample (n = 62,276), collected from 2,400 classes in 800 schools, reflects stratification, clustering, and weight. It is representative of the population (n = 3,027,488). This study used relational factor variables, including experiences of assault, living with family or not, and adolescents' confidants. Dependent variables included suicidal ideation, suicide plan, and suicide attempt. This study used logistic regression analyses on the complex sample to examine relational-level risk and protective factors for suicidal ideation, plan, and attempt. The adjusted logistic regression models found that experiences of assault, living with family or not, and adolescents' confidants were all significantly associated with suicidal ideation, plan, and attempt. In particular, 35.3% of victims had thought about suicide seriously, and victims of assault were approximately eight times more likely to attempt suicide compared to nonvictims. The experience of assault by others was found to be a strongly associated risk factor for suicidal behaviors in adolescents. Living with family and the presence of confidants to talk with were found to be protective factors against suicidal behaviors. To be specific, talking with parents about personal worries and troubles was more protective against suicidal behaviors than talking with a sibling, friend, or teacher. Nurses should provide crisis intervention for symptoms of trauma and suicidal behaviors among assault victims. Suicide prevention efforts should focus more on adolescents not living with family. They should also aim to enhance adolescents' family interactions. Encouraging adolescents to talk with their parents may mitigate the effects of risk factors on suicidal behaviors.


Empowering the disempowered: harm reduction with racial/ethnic minority clients.
Harm-reduction principles, such as empowerment of clients and goals for moderation, align well with the cultural worldviews of many clients of color. Empirically supported harm-reduction strategies often work well with ethnic minority clients. However, clients of color require special clinical considerations. A case study illustrates the use of the community participatory model, which combines harm reduction, cultural sensitivity, and community support. Treatment services can be provided under one roof to eliminate barriers to seeking and receiving services. Harm-reduction therapists can carefully assess and diagnose clients of color to minimize the potential shortcomings and cultural biases in assessment tools. Therapy will include the family and incorporate traditional practices as desired by clients. Use of these methods will empower and support clients of color as they seek their treatment goals.


Non-muscle myosins 2A and 2B drive changes in cell morphology that occur as myoblasts align and fuse.
The interaction of non-muscle myosins 2A and 2B with actin may drive changes in cell movement, shape and adhesion. To investigate this, we used cultured myoblasts as a model system. These cells characteristically change shape from triangular to bipolar when they form groups of aligned cells. Antisense oligonucleotide knockdown of non-muscle myosin 2A, but not non-muscle myosin 2B, inhibited this shape change, interfered with cell-cell adhesion, had a minor effect on tail retraction and prevented myoblast fusion. By contrast, non-muscle myosin 2B knockdown markedly inhibited tail retraction, increasing cell length by over 200% by 72 hours compared with controls. In addition it interfered with nuclei redistribution in myotubes. Non-muscle myosin 2C is not involved as western analysis showed that it is not expressed in myoblasts, but only in myotubes. To understand why non-muscle myosins 2A and 2B have such different roles, we analysed their distributions by immuno-electron microscopy, and found that non-muscle myosin 2A was more tightly associated with the plasma membrane than non-muscle myosin 2B. This suggests that non-muscle myosin 2A is more important for bipolar shape formation and adhesion owing to its preferential interaction with membrane-associated actin, whereas the role of non-muscle myosin 2B in retraction prevents over-elongation of myoblasts.


Cultural Factors, Migrant Status, and Vulnerability to Increasing Temperatures among Hispanic/Latino Farmworkers: A Systematic Review.
Cultural factors and acculturative stressors affect the health and safety behaviors of Hispanic/Latino farmworkers. Cultural factors and stressors also increase their risk of heat-related illnesses (HRIs). Interventions targeting HRIs in this population should account for cultural factors. Hispanic/Latino farmworkers have been widely recognized as a particularly vulnerable population in the U.S., with among the lowest levels of income and education in the country. Existing research has identified and explored factors, including cultural and demographic characteristics, that increase the vulnerability of these workers to adverse occupational health and safety outcomes. This review assesses Hispanic/Latino farmworkers' vulnerability to increasing temperatures and intense heat events, focusing on the role of demographic and cultural factors in heat-related health outcomes. A systematic literature search was conducted using the search terms "heat" and "(Hispanic or Latino) farmworkers" and "health" over the years 2000 to 2020. A total of 348 articles were screened through a title review. The articles included in this review focused on heat-related illnesses (HRIs) and related symptoms among the population of interest. Hispanic/Latino workers were at heightened risk of HRI symptoms as a result of their work environments, working conditions, acculturative stressors, and other cultural factors.


A case of pachydermodactyly in a seventeen year old associated with repetitive minor trauma.
A boy presented initially to a Rheumatology clinic with a three year history of asymptomatic swelling of the third to fourth proximal interphalangeal (PIP) joints bilaterally. A presumptive diagnosis of seronegative arthritis was made. Sulfasalazine was commenced without improvement and resulted in mood disturbance. Blood tests including ESR, lupus anticoagulant, rheumatoid factor and CCP antibodies were unremarkable. Hand radiographs were normal. MRI showed oedema within soft tissues around PIP joints. His care was transferred to the Rheumatology unit in our hospital and the rheumatological diagnosis was revised; sulfasalazine was stopped and skin biopsy organised. Onward referral to Dermatology was made. Examination revealed symmetrical swelling and thickening of soft tissues on PIP joints with no evidence of joint synovitis. He denied habitual behaviour but was noted to rub his fingers subconsciously. With this as a cause of repetitive minor trauma, a clinical diagnosis of pachydermodactyly was made. Skin biopsy was supportive showing a dermis with coarse collagen. Pachydermodactyly is rare. This case highlights the importance of prompt recognition to avoid invasive and excessive diagnostic procedures as well as unnecessary immunosuppression.


16S ribosomal RNA gene-based phylogenetic analysis of abundant bacteria in river, canal and potable water in Bangkok, Thailand.
In Southeast Asian countries, industrialization and urbanization is occurring rapidly, and water pollution in rivers and canals poses serious problems in some areas, especially in cities. Excess inflow of domestic, agricultural, and industrial wastewater to freshwater environments disturbs the aquatic microbial ecosystem, which can further pollute water by inhibiting biodegradation of pollutants. Therefore, monitoring of microbes in freshwater environment is important to identify changes in indigenous microbial populations and to estimate the influence of wastewater inflows on them. Polymerase chain reaction (PCR)-denaturing gradient gel electrophoresis (DGGE) analysis is suitable for monitoring changes in microbial communities caused by human activities, but this method can be difficult in eutrophic freshwater samples that contain PCR inhibitors. In this study, we optimized DNA extraction procedures and PCR conditions for DGGE analysis of bacterial populations in freshwater samples (canal, river, and tap water) collected in Bangkok, Thailand. A simple freeze-thaw procedure was effective for extracting DNA from bacterial cells in the samples, and LA Taq with added bovine serum albumin provided the best PCR amplification. The PCR-DGGE approach revealed that the most common bacteria in freshwater samples belonged to Gammaproteobacteria, while a Gram-positive bacterium was present at Bangkok Noi Canal. Temporally and spatially continuous analyses of bacterial populations in Bangkok canals and rivers by PCR-DGGE approach should be useful to recognize disturbances of microbial ecosystems caused by excess inflows of wastewater.


Immunization and vaccine-preventable illness, United States, 1992 to 1997.
In contrast to the 1980s, immunization rates increased dramatically in the United States in the mid-1990s. Three-quarters of all 2-year-olds had received all recommended immunizations in 1997 as compared to just over one-half in 1992. Immunization rates for individual vaccines have reached 90 percent for three of the vaccines--measles, mumps, rubella; pollo; and Haemophilus influenzae type b (Hib). The vaccine for diphtheria, tetanus and pertussis, however, and the newer vaccine for hepatitis B have not yet reached 90 percent of 2-year-olds. The rising immunization levels in young children have resulted in declining incidence of almost all of the vaccine-preventable illnesses. Cases of measles and Hib have declined 95 percent and the incidence of rubella and congenital rubella, hepatitis B and mumps has also declined. Pertussis (whooping cough), however, continued its pattern of periodic increases and decreases. This lack of improvement is probably due to a combination of lower immunization levels for pertussis and waning immunity in previously immunized adolescents and young adults. Federal efforts such as the President's Childhood Immunization Initiative along with its Vaccines for Children program have been credited for a great deal of this improvement. These programs increased public awareness of the need for and access to immunizations, better tracking of immunizations and vaccine-preventable illnesses and have also removed cost barriers to receipt of such protection. At the same time, new vaccines (against chickenpox and rotavirus) and safer versions of older vaccines (pertussis) have been brought into widespread use. Children can now be vaccinated against increasing varieties of childhood diseases. While progress in immunization has been good, areas in need of improvement remain. Pertussis continues to be a problem both in terms of incidence and immunization levels. Also, immunization levels differ significantly by poverty level and race and ethnicity. Black, Hisparic, American Indian and Asian children are less likely to be fully immunized than non-Hispanic white children and poor children are less likely to be fully immunized than nonpoor children.


Subjective satisfaction in long-term orthokeratology patients.
To evaluate the subjective satisfaction in visual stability, night vision complains, and light distortion phenomena, and also the number of hours and days per week of lens wear, in patients with myopia undergoing orthokeratology (OK) treatment for at least 1 year. A visual analog scale (VAS) questionnaire containing 18 items was administered to 44 patients, 29 women and 15 men (mean age, 24.39 ± 9.11 years), with a baseline spherical equivalent refractive error of -2.40 ± 0.94 diopters and astigmatism up to -0.5 diopters. Average treatment period by the time of data collection was 19 ± 7 months. Patients rated their satisfaction with the correction, with complaints of visual distortion being graded on a scale of 0 to 10, where 0 indicated no discomfort at all. More than 50% of patients skipped lens wear at least 1 night per week. The most common wearing pattern was 6-8 hours a day for 72.7% with 54.5% of patients wearing lenses every 2-3 nights only. Subjective vision scores after lens removal was 9.1 ± 1.1 after having worn the lenses and 8.1 ± 1.4 after skipping lens wear for 1 night. Subjective vision scores before lens insertion at the end of the day was 6.9 ± 2.0 and 5.8 ± 2.4, respectively. The number of hours until noticeable blur reduced with increased level of baseline myopia (r = 0.396; P < 0.001). Orthokeratology patients show an irregular wearing pattern after 1 year of treatment that has significant effects on the subjective visual performance over the next day of skipping lens wear. Light distortion under low-light conditions seems to be a transient complication of the treatment and most of the patients report an improvement after the first weeks of treatment.


Alterations of gut fungal microbiota in patients with rheumatoid arthritis.
Rheumatoid arthritis (RA) is a systemic autoimmune disease, in addition, gut microbiota plays an important role in the etiology of RA. However, our understanding of alterations to the gut fungal microbiota in Chinese population with RA is still limited. Serum samples were obtained from 62 patients with RA, and 39 age- and gender-matched healthy controls (HCs). Fecal samples were obtained from 42 RA patients and 39 HCs. Fecal fungal microbiota targeting internal transcribed spacer region 2 (ITS2) rRNA genes was investigated using MiSeq sequencing, as well as their associations with some diagnostic biomarkers for RA. Our results showed that the fungal diversity did not alter in RA patients but taxonomic composition of the fecal fungal microbiota did. The gut mycobiota of RA patients was characterized by decreased abundance of Pholiota, Scedosporium, and Trichosporon. The linear discriminant analysis (LDA) effect size analysis (LEfSe) analysis identified several RA-enriched fungal genera, which were positively correlated with most RA biomarkers. Furthermore, since RA is an age- and gende-related disease, we classified RA patients into subgroups with age and gender and analyzed the sequencing results. Our data demonstrated that Wallemia and Irpex were the most discriminatory against RA patients over 60 years old, while Pseudeurotiaceae was the most discriminatory against female RA patients. The case-control study presented here confirmed the alterations of gut fungal microbiota in Chinese patients with RA, and we speculated that the fungal dysbiosis may contribute to RA development.


Psychodermatology knowledge and awareness: A cross-sectional Egyptian perspective.
The merging of psychiatry and dermatology has resulted in a relatively newer emerging field known as psychodermatology (PD). The aim of this cross sectional study was to assess knowledge, attitudes, and practice patterns of Egyptian dermatologists towards psychodermatology. A cross sectional study was designed and data were collected using structured self-administered online questionnaires. A total of 212 dermatologists completed the full questionnaire. Those with incomplete or partially answered responses were excluded. 171 (81.1%) were females and 40 (18.9%) were males. The majority (n = 109;51.4%) of dermatologists completing the survey were between 30 and 40 years age group while those between 40 and 50 years of age accounted for 48 (22.6%). The vast majority of respondent dermatologists never referred (n = 87; 41%) or very rarely referred (n = 58; 27.5%) any psychocutaneous patients to a psychiatrist. Almost 75% of responding dermatologists were not aware of available community or educational resources for PD and 157 (74.1%) expressed interest in receiving continuing medical education (CME) programs. In conclusion, psychodermatology training among dermatologists shall enhance and improve their approach to psychocutaneous conditions.


Self-assembly of supramolecular fullerene ribbons via hydrogen-bonding interactions and their impact on fullerene electronic interactions and charge carrier mobility.
The anisotropy of the electronic interactions between fullerenes in crystalline solids was examined using a confocal fluorescence microscope by probing the polarization of the fluorescence emission arising from fullerene excimer-like emitting states. Crystals of C(60) obtained by vacuum-sublimation or from chloroform solution exhibited no or little polarization (p = 0 or 0.11, respectively), as expected from the high symmetry of the C(60) fcc lattice or the low degree of anisotropy induced by included solvent molecules. The use of hydrogen-bonding to supramolecularly control interfullerene electronic interactions was explored using a fullerene derivative (1) combining a solubilizing 3,4-di-tert-butylbenzene group and a barbituric acid hydrogen-bonding (H-B) moiety. The crystal structure of 1 establishes the existence of fullerene H-B tapes along which interfullerene electronic interactions are expected to be large. In agreement with this, we observe very strong polarization of the fullerene excimer-like emission (p = 0.78), indicative of a high degree of anisotropy in the fullerene interactions. The charge-carrier mobility of 1 as determined from OFET devices was found to be lower than that of C(60) (1.2 x 10(-4) vs 1.2 x 10(-2) cm(2)/s V), which is rationalized on the basis of the reduced dimensionality of 1 as a wire-like semiconductor and variations in the morphology of the device active layer revealed by AFM measurements.


Factors influencing health practitioners' cognitive processing and decision-making style.
Successful interventions, healthcare planning, and patient-centered care require explanation, justification, and collaboration through interprofessional clinical decision-making (CDM). Understanding health practitioners' decision-making styles and influencing factors can enhance CDM capabilities. Health professionals and students (N = 229) completed an online survey on their decision-making styles, interprofessional education, interprofessional practice, discipline education, clinical experience, processing styles, personality, interpersonal motivational factors, and age. To assess the influence of task structure, participants answered CDM questions on a high- and a low-structured case study. Age demonstrated an effect on the level of clinical experience, while clinical experience also mediated the effect of age on rational processing styles. While personality results were mixed, consistent with previous findings, conscientiousness predicted rational processing style. Effects of interpersonal motivation on personality were also mixed, insofar as results indicated an association between conscientiousness and both experiential and rational processing styles. Interpersonal motivation also predicted rational processing styles. The complexity of CDM and factors influencing healthcare practitioners' processing and decision-making styles was highlighted. To optimize CDM processes by addressing errors and biases, CDM, and practice complexity, healthcare practitioner education should include theory-driven CDM orientation frameworks.


Differential expression of the apurinic / apyrimidinic endonuclease (APE/ref-1) multifunctional DNA base excision repair gene during fetal development and in adult rat brain and testis.
The multifunctional mammalian apurinic/apyrimidinic (AP) endonuclease is responsible for the repair of AP sites in DNA. In addition, this enzyme has been shown to function as a redox factor facilitating the DNA binding capability of Jun-Jun homodimers and Fos-Jun heterodimers by altering their redox state and to be involved in calcium mediated transcriptional repression of the parathyroid hormone gene. Previous studies examining the tissue specific distribution of the AP endonuclease (APE) transcript and protein by Northern analysis and enzymatic assays, respectively, have shown that this gene is expressed in all tissues at relatively similar levels. In the current study, adult and fetal rat tissue sections were examined for the expression of the APE transcript in specific subpopulations of cells and during development by in situ hybridization. In the adult brain, the APE transcript showed a widespread, but heterogeneous pattern of expression. Predominant levels of transcript were detected in the suprachiasmatic nuclei, the supraoptic and paraventricular nuclei, the hippocampus and the cerebellum. During fetal development, transcript was detected in all somatic sites examined with very high levels in the thymus, liver and developing brain. Examination of the adult testis indicated that the expression of the transcript varies with the stage of spermatogenesis with the highest levels being present over round spermatids. These results provide evidence that the APE gene is not homogeneously expressed, but rather is found in subpopulations of cells in the brain and testes and during development.


Integration host factor amplifies the induction of the aceBAK operon of Escherichia coli by relieving IclR repression.
A binding site for integration host factor (IHF) was identified upstream of the aceBAK promoter. Under inducing conditions, IHF activates aceB::lacZ expression by opposing IclR repression. In contrast, IHF has little effect on aceB::lacZ expression under repressing conditions. The ability of IHF to relieve repression under inducing but not repressing conditions allows this protein to amplify the induction of aceBAK.


Exposure to hospital roommates as a risk factor for health care-associated infection.
Numerous patient- and hospital-level characteristics have been established as risk factors for the transmission of health care-associated infections (HAIs). Few studies have quantitatively assessed the impact of exposure to hospital roommates on the acquisition of infections. This study evaluated the association between roommate exposures and the risk of HAIs. A retrospective cohort of adult patients admitted to a Canadian teaching hospital between June 30, 2001, and December 31, 2005, was studied. Exposures were characterized as total daily roommate exposures and daily unique roommate exposures. Outcomes examined were methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), and Clostridium difficile. The number of roommate exposures per day was significantly associated with MRSA and VRE infection or colonization (MRSA: hazard ratio [HR] = 1.10, 95% confidence interval [CI] = 1.05 to 1.15; VRE: HR = 1.11, 95% CI = 1.02 to 1.21), and with C difficile infection (HR = 1.11, 95% CI = 1.03 to 1.19). A significant association also was found for number of unique roommate exposures per day and VRE (HR = 1.15, 95% CI = 1.02 to 1.28). The significant associations found between daily roommate exposures and the infection outcomes suggest a possible role for limiting patient-to-patient contact in an infection prevention and control program in this facility. These findings have implications for the deployment and design of acute care hospitals.