The effect of pentoxifylline on erythrocyte deformability and on phosphatide fatty acid distribution in the erythrocyte membrane.
Ten maturity-onset diabetics with chronic vascular disease were treated with 400 mg pentoxifylline 3-times daily for 14 days. Erythrocyte deformability (using a filtration technique for whole blood) and phosphatide fatty acid distribution in the erythrocyte membrane were measured before and after the treatment period. Statistical analysis of the data showed that the erythrocyte filtration rate had increased significantly by the end of treatment (2alpha = 0.02), and that there were only slight changes in erythrocyte membrane phosphatide fatty acid levels. The drug was well tolerated, and there were no adverse laboratory findings in the parameters measured. On the basis of results described by other investigators, theimprovement in erythrocyte deformability was attributed to an increase in erythrocyte ATP levels. The authors discuss the importance of red cell fluidity for capillary perfusion.


The correlation between peri-operative hyperglycemia and mortality in cardiac surgery patients: a systematic review.
Hyperglycemia occurs frequently in patients undergoing cardiac surgery. It has been identified as a risk factor for increased peri-operative morbidity and mortality. To review the evidence of the correlation of peri-operative hyperglycemia with mortality in cardiac surgery patients and to discuss the main results in order to provide evidence-based knowledge for the appropriate glycemic control. We searched the electronic databases MEDLINE, CINAHL and EMBASE in June 2010. The material of our study was articles published between 1 January 1990 and 31 May 2010, which investigated the correlation between peri-operative hyperglycemia and in-hospital and/or 30-day cardiac surgery mortality. Out of the 16 reviewed articles in our study, 12 (75%) significantly associated hyperglycemia and inadequate blood glucose control with increased mortality. In addition, four of the reviewed articles were controlled randomized trials and among them only one demonstrated strong correlation between poor glycemic control and mortality. No study was multi-centre and the reviewed articles were characterized by different definitions of peri-operative hyperglycemia, different intensity and duration of the applied therapy and heterogeneity of the population. It is clear that peri-operative hyperglycemia is harmful for cardiac surgery patients. The significant shortage of randomized controlled trials, the absence of multicentre studies, the different definitions of peri-operative hyperglycemia, the different intensity and duration of the applied insulin therapy protocol and the heterogeneity of the studied population (diabetics and non-diabetics) are significant limitations, which could explain the inconsistent findings of the literature. These limitations indicate the need for further research.


Early caffeine therapy and clinical outcomes in extremely preterm infants.
To determine if early caffeine (EC) therapy is associated with decreased bronchopulmonary dysplasia (BPD) or death, decreased treatment of patent ductus arteriosus (PDA), or shortened duration of ventilation. In a retrospective cohort of 140 neonates ≤1250 g at birth, infants receiving EC (initiation <3 days of life) were compared with those receiving late caffeine (LC, initiation ≥3 days of life) using logistic regression. Of infants receiving EC, 25% (21/83) died or developed BPD compared with 53% (30/57) of infants receiving LC (adjusted odds ratio (aOR) 0.26, 95% confidence interval (CI) 0.09 to 0.70; P<0.01). PDA required treatment in 10% of EC infants versus 36% of LC infants (aOR 0.28, 95%CI 0.10 to 0.73; P=0.01). Duration of mechanical ventilation was shorter in infants receiving EC (EC, 6 days; LC, 22 days; P<0.01). Infants receiving EC therapy had improved neonatal outcomes. Further studies are needed to determine if caffeine prophylaxis should be recommended for preterm infants.


Cerebellopontine angle paraganglioma - report of a case and review of literature.
Majority of the cerebellopontine angle (CPA) tumors are acoustic neuromas, while bulk of the non-acoustic tumors are formed by meningiomas and epidermoid cysts. Primary paraganglioma is a rare tumor in this location, with only two such cases having been reported in the literature, till date. Recently, a case has been described wherein a paraganglioma was apparently arising as a primary lesion in the cerebellar hemisphere. We report another case of an intracranial paraganglioma of the CPA in a 40-year-old female, which did not have any vascular attachment but had focal cerebellar extension.


Induction of GFAP production in human glioma lines grafted into the anterior chamber of the rat eye.
Three established glial fibrillary acidic protein (GFAP)-negative cell lines from human gliomas were transplanted to the anterior chamber of the rat eye. Short-term survival was seen with all transplants. The cells expressed GFAP following transplantation. For comparison, 4 GFAP-positive cell lines were transplanted. With grafting of 5000 cells of any of 6 bipolar cell lines, the transplanted cells could be seen to develop multiple, slender processes reminiscent of mature astrocytes. When 50,000 cells were grafted, vascularized cell mats covering the corneae were seen. The induction of GFAP production and the phenotypic changes were interpreted as signs of differentiation induced by the new environment. All transplanted cells were rejected after 8 weeks.


Timing and distribution of flash-evoked activity in the lateral geniculate nucleus of the alert monkey.
Simultaneous recording of activity from multiple cortical laminae in alert monkeys, using multichannel electrodes, has been used to identify the intracranial generators of surface-recorded, visually evoked potentials (VEP) to stroboscopic flash. Beyond their clinical implications, these results offer an unique view of the timing and sequence of cortical visual processing in the alert monkey, including the somewhat surprising findings of an extremely short-latency response in lamina IVA, a contra- over ipsilateral latency advantage throughout lamina IV, and the lack of a consistent flash-evoked response in the major cortical recipient of the magnocellular system, lamina IVCa. The present study used similar techniques to examine flash-evoked activity in LGN and in optic tract, both to elucidate the role of the subcortical pathways in establishing this pattern, and to provide a parallel, detailed view of the timing of visual activity in LGN and optic tract in the alert monkey. Flash-evoked responses are robust in both parvo- and magnocellular laminae, but these responses differ along several dimensions: (1) parvocellular multiunit activity (MUA) is 1/4 to 1/2 the amplitude of magnocellular MUA; (2) oscillatory activity is higher in frequency and shorter in duration in parvo- than in magnocellular responses; (3) inhibitory processes appear less prominent and diverse in parvo- than in magnocellular activity; (4) mean onset latencies of MUA are longer in parvo- than in magnocellular laminae, but there is extensive overlap in these distributions. Latencies encountered in ipsilateral lamina 3, and at laminar borders dorsal to 3, group more clearly with those of the magnocellular laminae than with those of the other parvocellular laminae. As a result, in the parvocellular division as a whole, the average latency to ipsilateral stimulation is shorter than that to contralateral stimulation. The optic tract exhibits a dorsal-to-ventral progression of onset latency and oscillation frequency consistent with a dorsal/ventral segregation of the inputs to parvo- and magnocellular layers. Comparison of optic tract and LGN data reveals that while many LGN response characteristics are initiated in the retina, significant modification of retinal output occurs at LGN. The techniques used here permit a particularly sensitive and reliable assessment of the timing and distribution of visual responses in the optic tract and LGN of alert monkeys. Our data support the view that in the alert monkey, the surface-VEP to passive, binocular flash primarily reflects activation of parvocellular thalamorecipient laminae of Area 17.(ABSTRACT TRUNCATED AT 400 WORDS)


Nuclear stabilization of p53 requires a functional nucleolar surveillance pathway.
The nucleolar surveillance pathway monitors nucleolar integrity and responds to nucleolar stress by mediating binding of ribosomal proteins to MDM2, resulting in p53 accumulation. Inappropriate pathway activation is implicated in the pathogenesis of ribosomopathies, while drugs selectively activating the pathway are in trials for cancer. Despite this, the molecular mechanism(s) regulating this process are poorly understood. Using genome-wide loss-of-function screens, we demonstrate the ribosome biogenesis axis as the most potent class of genes whose disruption stabilizes p53. Mechanistically, we identify genes critical for regulation of this pathway, including HEATR3. By selectively disabling the nucleolar surveillance pathway, we demonstrate that it is essential for the ability of all nuclear-acting stresses, including DNA damage, to induce p53 accumulation. Our data support a paradigm whereby the nucleolar surveillance pathway is the central integrator of stresses that regulate nuclear p53 abundance, ensuring that ribosome biogenesis is hardwired to cellular proliferative capacity.


Exceptional point protected robust on-chip optical logic gates.
Optical logic gates are crucial components for information processing and communication using photons. Current optical logic gates typically rely on the light interference principle which requires an accurate manipulation of the dynamical phase of light, making the device quite sensitive to system disturbances such as fabrication errors. Here we introduce non-Hermitian principles into the design of optical logic gates that work in the signal transmission process. We propose an exclusive-or gate for silicon-on-insulator platform by employing the physics in the exceptional point (EP) encirclement process. The EP induced mode switching behavior is applied to manipulate the phase of light which is topologically protected by the energy surface around the EP. As a result, the performance of the device is found to be extremely robust to structural parameter disturbances. The proposed non-Hermitian principle is expected to find applications for other on-chip photonic devices toward high robust performance.


Evaluation of five rapid systems for the identification of Neisseria gonorrhoeae.
Five commercial kit systems for the rapid identification of Neisseria gonorrhoeae were evaluated. The systems were tested with various pathogenic and saprophytic Neisseria and Branhamella strains having reactions typical for their individual species. Three systems (RIM-N, quadFERM, and RapID NH) were found to be 100% sensitive and specific.


Subarachnoid Hemorrhage-Triggered Acute Hypotension Is Associated with Left Ventricular Cardiomyocyte Apoptosis in a Rat Model.
Whether hypotension that occurs due to neurogenic stunned myocardium after subarachnoid hemorrhage (SAH) is associated with cardiomyocyte apoptotic cell death remains unknown. In this study, 18 male rats were subjected to sham or the endovascular perforation model of SAH surgery. Based on the mean arterial pressure (MAP) after SAH, rats were separated into SAH with hypotension (SAH hypotension) or SAH with blood pressure preservation (SAH BP preservation) groups. All animals were euthanized 2 h after the surgical procedure. Hearts were removed and separated transversely into base and apex parts, then Western blot analyses and immunohistochemistry were performed only in the apex part. One rat died as a result of severe SAH and two rats with mild SAH were excluded. We analyzed data from 15 rats that were divided into three groups: sham, SAH hypotension, and SAH BP preservation (n = 5, each). There was a significantly higher cleaved caspase-3/caspase-3 ratio in the SAH hypotension group compared with sham and the SAH BP preservation group. Cardiomyocyte apoptosis was demonstrated in the SAH rats. This is the first experimental report that describes SAH-induced neurogenic stunned myocardium with ensuing hypotension may result from the acute apoptotic cardiomyocyte cell death in the left ventricle.


Final HIV status outcome for HIV-exposed infants at 18 months of age in nine states and the Federal Capital Territory, Nigeria.
While antiretroviral therapy (ART) coverage for pregnant women has undergone steady scale-up, Nigeria's final mother- to-child transmission of HIV (MTCT) rate remains unacceptably high at 10%. This study aimed to determine final outcomes (MTCT rates) and their correlates among HIV-exposed infants (HEI) in nine states and the Federal Capital Territory, Nigeria. This retrospective, cross-sectional study was conducted at 96 primary, secondary and tertiary health facilities supported by the Institute of Human Virology Nigeria. Data was abstracted for a birth cohort of HEI born between October 30, 2014 and April 30, 2015 whose 18-24 month final outcome was assessed by October 30, 2016. Only infants with a six-week first DNA PCR result, and a rapid HIV antibody test result at age 18 to 24 months were included. Multivariate logistic regression (adjusted odds ratios [aORs]) evaluated for predictors of HIV positivity at ≥18 months. After testing at ≥18 months, 68 (2.8%) of the 2,405 exposed infants in the birth cohort were HIV-positive. After a minimum of 18 months of follow-up, 51 (75%) HIV-positive infants were alive on ART; 7 (10%) had died, 5 (7.3%) were lost to follow-up and 5 (7.3%) were transferred out. Rural maternal residence, lack of maternal ART/ARV prophylaxis, mixed infant feeding and infant birth weight less than 2.5 kg correlated with an HIV-positive status for infant final outcomes. The final HIV positivity rate of 2.8% is encouraging, but is not population-based. Nevertheless, supported by our findings, we recommend continued programmatic focus on early access to quality prenatal care and maternal ART for pregnant women, especially for women living with HIV in rural areas. Furthermore, implementation of nationwide sensitization and education on six-months' exclusive infant breastfeeding with concurrent maternal ART should be strengthened and sustained to reduce MTCT rates.


[Determination of anticonvulsive preparations in the blood serum of patients by high-performance liquid chromatography].
A method for simultaneous measurement of hexamydine, phenobarbital, diphenin and carbamazepine concentrations in serum using high performance liquid chromatography is described. The procedure employs acetonitrile extraction of anticonvulsants and chromatography of the extract under the following conditions: a column containing lichrosorb RP-8 10 microns (250 x 4 mm), mobile phase consisting of 30 vol.% ethanol solution in 0.01 M KH2PO4 pH 5.3, flow rate 0.5 ml/min, column temperature 30 degrees C, injection volume 20 microliters, detector wavelength 220 nm. Hexenal is used as an internal standard. The concentration range is 5-50 mg/l for phenobarbital, diphenin and carbamazepine and 5-30 mg/l for hexamydine. The relative standard deviation varies between 0.018 and 0.057 for therapeutic and toxic concentrations.


Default mode network differences between rigidity- and tremor-predominant Parkinson's disease.
Parkinson's disease (PD) traditionally is characterized by tremor, rigidity, and bradykinesia, although cognitive impairment also is a common symptom. The clinical presentation of PD is heterogeneous and associated with different risk factors for developing cognitive impairment. PD patients with primary akinetic/rigidity (PDAR) are more likely to develop cognitive deficits compared to those with tremor-predominant symptoms (PDT). Because cognitive impairment in PD appears to be related to changes in the default mode network (DMN), this study tested the hypothesis that DMN integrity is different between PDAR and PDT subtypes. Resting state fMRI (rs-fMRI) and whole brain volumetric data were obtained from 17 PDAR, 15 PDT and 24 healthy controls (HCs) using a 3T scanner. PD patients were matched closely to HCs for demographic and cognitive variables, and showed no symptoms of dementia. Voxel-based morphometry (VBM) was used to examine brain gray matter (GM) volume changes between groups. Independent component analysis (ICA) interrogated differences in the DMN among PDAR, PDT, and HC. There was decreased activity in the left inferior parietal cortex (IPC) and the left posterior cingulate cortex (PCC) within the DMN between PDAR and both HC and PDT subjects, even after controlling for multiple comparisons, but not between PDT and HC. GM volume differences between groups were detected at a lower threshold (p < 0.001, uncorrected). Resting state activity in IPC and PCC were correlated with some measures of cognitive performance in PD but not in HC. This is the first study to demonstrate DMN differences between cognitively comparable PDAR and PDT subtypes. The DMN differences between PD and HC appear to be driven by the PDAR subtype. Further studies are warranted to understand the underlying neural mechanisms and their relevance to clinical and cognitive outcomes in PDAR and PDT subtypes.


Increased density of the thalamus on CT scans in patients with GM2 gangliosidoses.
In 13 patients, the GM2 gangliosidoses, Sandhoff disease and Tay-Sachs disease, were found to be constantly associated with homogeneously and symmetrically increased CT attenuation within the thalami. In the only patient examined with MR imaging, a T2-weighted sequence showed hypointense thalami. It is suggested that this finding is caused by an accumulation of calcium, associated with the intracellular storage of GM2 ganglioside. The finding of dense thalami may be useful as a specific diagnostic criterion for GM2 gangliosidoses. In a few patients with blocks in adjacent steps in the sphingolipid metabolism, this finding was not present.


Outcome of hysteroscopic resection of submucous myomas for infertility.
To examine the reproductive outcome after operative hysteroscopic resection of submucous myomas in women for whom no other infertility factor was identified. Fifteen infertile women with submucous myomas underwent an intensive workup to exclude other causes of infertility. Operative hysteroscopy for resection of the submucous myomas was performed using a rigid 26 French resectoscope (Karl Storz GmbH & Co., Tuttlingen, Germany). Academic tertiary referral center. The mean +/- SD duration of the procedure was 25.5 +/- 5.6 minutes. No operative or postoperative complications occurred and all patients were discharged within 6 hours. The follow-up period was 12.0 +/- 4.2 months (mean +/- SD). Seven women conceived (pregnancy rate of 47%) and six of them subsequently delivered at term. The results of this study indicate that operative hysteroscopy achieved a pregnancy rate comparable to myomectomy via laparotomy. These results suggest that operative hysteroscopy is the procedure of choice for the resection of submucous myomas in infertile women.


Determination of noradrenaline and dopamine in Chinese herbal extracts from Portulaca oleracea L. by high-performance liquid chromatography.
A simple, rapid and accurate high-performance liquid chromatographic (HPLC) technique coupled with photodiode array (PDA) detection was developed for the simultaneous determination of noradrenaline (NA) and dopamine (DA) in Chinese herbal plant extracts from the different parts of Portulaca oleracea L. The effects of various parameters, such as sodium dodecyl sulfate (SDS) concentration, pH value and proportion of methanol on chromatographic behavior of the analytes (NA and DA) were investigated. Separation of NA and DA was achieved within 10 min by a mobile phase consisting of 70% (v/v) methanol and 0.02 M potassium dihydrogen phosphate solution, which contained 30 mM SDS and was adjusted to pH 3.0 with H3PO4. NA and DA showed good linear relationships in the range of 0.004-6.00 microg and 0.011-8.25 microg respectively. The correlation coefficients of the calibration curve for the analytes exceeded 0.999. The detection limits for NA and DA were 0.40 ng and 0.55 ng, at a signal-to-noise ratio of 3, respectively. Moreover, the optimized HPLC method was employed to analyze three different parts of Portulaca oleracea L.


Liver transplantation in malignant primary hepatic neoplasms.
Between April 1986 and August 1990, 151 liver transplantations were performed at our institution, 16 (11%) of them in 14 patients with primary hepatic tumors. There were 12 hepatocellular carcinomas, 1 angiosarcoma, and 1 Klatskin tumor. None of the tumors was resectable, and there was no preoperative evidence of extrahepatic tumoral extension. Exploratory laparotomy was performed prior to transplantation in three patients and selective embolization of the tumor in six patients. There was no difference in the intraoperative requirements for blood or plasma in the patients with hepatic tumors when compared with other transplant recipients (28.6 +/- 23.6 units packed red blood cells [PRBC] versus 20.1 +/- 17.8 units PRBC, and 17.9 +/- 12.2 units plasma versus 17.1 +/- 10.5 units plasma, respectively). Extracorporeal venovenous bypass was used in all but one patient. There was no significant differences in the incidence of acute rejection or in the length of hospitalization in these patients when compared with other transplant recipients. All patients received triple immunosuppressive therapy (corticosteroids, azathioprine, and cyclosporin A). Intraoperative mortality was zero. At a mean of 13.3 months' follow-up (range: 1 to 47 months), 2 of 14 patients had died of sepsis and 1 of terminal cirrhosis (autopsies revealed no evidence of tumor recurrence); 3 patients (21%) had recurrences of the tumor (1 in the central nervous system and liver, and the other 2 in the lung). One of the three patients with a recurrent tumor is still alive after 16 months. The remaining nine patients (64%) are still alive.


A case report of anorectal malignant melanoma with mucosal skipped lesion.
We report our experience involving a case of relatively rare anorectal malignant melanoma with skipped lesion. The patient was a 72-year-old man who had visited a local clinic complaining of a mass in the anal region, whereupon he was referred to our hospital on suspicion of a malignant melanoma. Close examination revealed a 25-mm black type 1 tumor one-third the size of the circumference of the anal canal and located externally to it. We performed transanal resection of the tumor and confirmed a diagnosis of malignant melanoma. Notably, multiple macular black lesions spaced away from the main lesion were observed during surgery in half of the circumference of the anal canal, from the tumor to the pectinate line. A biopsy of the area also revealed malignant melanoma; therefore, we performed abdominoperineal resection. Pathological diagnosis indicated a submucosal depth; the patient was thus diagnosed with T4 N2c M0 stage IIIb malignant melanoma and was followed on an outpatient basis. Patients with anorectal malignant melanoma have very poor prognoses owing to early lymph node metastasis and hematogenous metastasis. Our case illustrates that small anorectal malignant melanoma lesions can spread from the main lesion and invade the mucosa; examinations may sometimes miss such skipped lesions. Skipped lesions can occur in anorectal melanomas; thus, careful scrutiny of such lesions is required. Moreover, lesion resection is critical for anorectal malignant melanomas.


Adjustments of cognitive control in younger and older adults.
The effects of aging on behavioral and electrophysiological indices of adjustments of cognitive control were examined in two experiments. Specifically, we considered the effects of aging of patterns of response time and modulations of the event-related brain potentials (ERPs) on sequential trial effects, error-related slowing, and local switch costs in two modified Stroop tasks. The behavioral data reveal that sequential trial effects were observed when color, but not word, identification was required and that these effects were similar in younger and older adults; that the degree of error-related slowing was similar for younger and older adults in Experiment 1 and greater in older than younger adults in Experiment 2; that local switch costs in response time were similar in younger and older adults and that the requirement to switch between color and word identification resulted in a dramatic increase in the number of color intrusion errors in older adults in Experiment 2. The ERP data revealed that endogenously generated adjustments of cognitive control were associated with a parietal slow wave that mirrored the behavioral data and was similar in amplitude in younger and older adults and an anterior frontal slow wave that was absent in older adults. The ERP data also revealed that an enhancement of the P3 component and a frontal slow wave that differentiated color switch trials from color non-switch and word trials in younger adults were attenuated in older adults.


A simple and inexpensive external fixator.
A simple and inexpensive external fixator has been designed. It is constructed of galvanized iron pipe and mild steel bolts and nuts. It can easily be manufactured in a hospital workshop with a minimum of tools.


The current state of sexual fluidity research.
Sexual fluidity research (i.e., change over time in one or more sexual orientation dimensions) has grown exponentially, with advancements in conceptual models, measurement, and understanding of sexual orientation as a construct and developmental process that accommodates potential for change. Sexual fluidity research has also moved beyond samples of white cisgender women to consider the experiences of individuals with other sociodemographic characteristics and has examined change across multiple dimensions of sexual orientation, mechanisms of change, and associations with health outcomes. This review provides a brief narrative of historical conceptualizations of sexual orientation and fluidity and the current state of research on sexual fluidity. Finally, we identify opportunities for future research, policy, and clinical practice.


2,2'-[2,4-Bis(naphthalen-1-yl)cyclo-butane-1,3-di-yl]bis-(1-methyl-pyridinium) diiodide: thermal-induced [2 + 2] cyclo-addition reaction of a heterostilbene.
The asymmetric unit of the title compound, C(36)H(32)N(2) (2+)·2I(-), consists of one half-mol-ecule of the cation and one I(-) anion. The cation is located on an inversion centre. The dihedral angle between the pyridinium ring and the naphthalene ring system in the asymmetric unit is 19.01 (14)°. In the crystal, the cations and the anions are linked by C-H⋯I inter-actions into a layer parallel to the bc plane. Intra- and inter-molecular π-π inter-actions with centroid-centroid distances of 3.533 (2)-3.807 (2) Å are also observed.


Bacteria associated with Zn-hyperaccumulators Arabidopsis halleri and Arabidopsis arenosa from Zn-Pb-Cd waste heaps in Poland as promising tools for bioremediation.
To identify metal adapted bacteria equipped with traits positively influencing the growth of two hyperaccumulator plant species Arabidopsis arenosa and Arabidopsis halleri, we isolated bacteria inhabiting rhizosphere and vegetative tissues (roots, basal and stem leaves) of plants growing on two old Zn-Pb-Cd waste heaps in Bolesław and Bukowno (S. Poland), and characterized their potential plant growth promoting (PGP) traits as well as determined metal concentrations in rhizosphere and plant tissues. To determine taxonomic position of 144 bacterial isolates, 16S rDNA Sanger sequencing was used. A metabolic characterization of isolated strains was performed in vitro using PGP tests. A. arenosa and A. halleri accumulate high amounts of Zn in their tissues, especially in stem leaves. Among in total 22 identified bacterial taxa, the highest level of the taxonomical diversity (H' = 2.01) was revealed in A. halleri basal leaf endophytes originating from Bukowno waste heap area. The 96, 98, 99, and 98% of investigated strains showed tolerant to Cd, Zn, Pb and Cu, respectively. Generally, higher percentages of bacteria could synthesize auxins, siderophores, and acetoin as well as could solubilize phosphate. Nine of waste heap origin bacterial strains were tolerant to toxic metals, showed in vitro PGP traits and are potential candidates for bioremediation.


Genome-wide identification of RUB activating enzyme and conjugating enzyme gene families and their expression analysis under abiotic stresses in Capsicum annuum.
NEDD8/RUB, as a ubiquitin-like protein, participates in the post-translational modification of protein and requires unique E1, E2, and E3 enzymes to bind to its substrate. The RUB E1 activating enzyme and E2 conjugating enzyme play a significant role in the neddylation. However, it is unknown whether RUB E1 and E2 exist in pepper and what its function is. In this study, a total of three putative RUB E1 and five RUB E2 genes have been identified in the pepper genome. Subsequently, their physical and chemical properties, gene structure, conserved domains and motifs, phylogenetic relationship, and cis-acting elements were analyzed. The structure and conserved domain of RUB E1 and E2 are similar to that of Arabidopsis and tomato. The RUB E1 and E2 genes were randomly distributed on seven chromosomes, and there were two pairs of collinearity between pepper and Arabidopsis and eight pairs of collinearity between pepper and tomato. Phylogenetic analysis reveals that RUB E1 and E2 genes of pepper have a closer relationship with that of tomato, potato, and Nicotiana attenuate. The cis-elements of RUB E1 and E2 genes contained hormone response and stress response. RUB E1 and E2 genes were expressed in at least one tissue and CaRCE1.3 and CaRCE2.1 were exclusively expressed in flowers and anthers. Moreover, the expression of RUB E1 genes (CaECR1, CaAXR1.1, and CaAXR1.2) and RUB E2 genes (CaRCE1.1, CaRCE1.2, and CaRCE2.1) was increased to varying degrees under low-temperature, drought, salt, ABA, and IAA treatments, while CaRCE1.3 and CaRCE2.2 were down-regulated under low-temperature treatment. In addition, these genes were hardly expressed under MeJA treatment. In summary, this study provides a theoretical foundation to explore the role of RUB E1 and E2 in the response of plants to stress.


In vivo incorporation of [32P]orthophosphate into myelin basic protein of developing rabbit brain: its location in components 3 and 5 and in a new protein tentatively identified as basic protein component 7.
Myelin was isolated from the brains of 16-day-old rabbits that had received intracerebral injections of [32P]orthophosphate 24 h earlier. The basic protein was extracted and examined by polyacrylamide gel electrophoresis both at low and at high pH. At low pH a single band corresponding to the basic protein contained all of the covalently bound protein radioactivity. At high pH, three bands of radioactivity corresponding to basic protein components 3, 5, and 7 were observed. Estimation of the specific radioactivities of the components in conjunction with their high pH electrophoretic mobilities indicated that components 3, 5, and 7 contained one, two, and three phosphate groups per molecule of protein, respectively.


Associations of prognostic-awareness-transition patterns with end-of-life care in cancer patients' last month.
Cancer patients heterogeneously develop prognostic awareness, and end-of-life cancer care has become increasingly aggressive to the detriment of patients and healthcare sustainability. We aimed to explore the never-before-examined associations of prognostic-awareness-transition patterns with end-of-life care. Prognostic awareness was categorized into four states: (1) unknown and not wanting to know; (2) unknown but wanting to know; (3) inaccurate awareness; and (4) accurate awareness. We examined associations of our previously identified three prognostic-awareness-transition patterns during 334 cancer patients' last 6 months (maintaining accurate prognostic awareness, gaining accurate prognostic awareness, and maintaining inaccurate/unknown prognostic awareness) and end-of-life care (cardiopulmonary resuscitation, intensive care unit care, mechanical ventilation, chemotherapy/immunotherapy, and hospice care) in cancer patients' last month by multivariate logistic regressions. Cancer patients in the maintaining-accurate-prognostic-awareness and gaining-accurate-prognostic-awareness groups had significantly lower odds of cardiopulmonary resuscitation (adjusted odds ratio [95% confidence interval]: 0.22 [0.06-0.78]; and 0.10 [0.01-0.97], respectively) but higher odds of hospice care (3.44 [1.64-7.24]; and 3.28 [1.32-8.13], respectively) in the last month than those in the maintaining inaccurate/unknown prognostic awareness. The maintaining-accurate-prognostic-awareness group had marginally lower odds of chemotherapy or immunotherapy received than the gaining-accurate-prognostic-awareness group (0.58 [0.31-1.10], p = .096]). No differences in intensive care unit care and mechanical ventilation among cancer patients in different prognostic-awareness-transition patterns were observed. End-of-life care received in cancer patients' last month was associated with the three distinct prognostic-awareness-transition patterns. Cancer patients' accurate prognostic awareness should be facilitated earlier to reduce their risk of receiving aggressive end-of-life care, especially for avoiding chemotherapy/immunotherapy close to death. ClinicalTrials.gov:NCT01912846.


Maximum allowable exposure to different heat radiation levels in three types of heat protective clothing.
To determine safe working conditions in emergency situations at petro-chemical plants in the Netherlands a study was performed on three protective clothing combinations (operator's, firefighter's and aluminized). The clothing was evaluated at four different heat radiation levels (3.0, 4.6, 6.3 and 10.0 k∙W∙m-2) in standing and walking posture with a thermal manikin RadMan™. Time till pain threshold (43°C) is set as a cut-off criterion for regular activities. Operator's clothing did not fulfil requirements to serve as protective clothing for necessary activities at heat radiation levels above 1.5 k∙W∙m-2 as was stated earlier by Den Hartog and Heus1). With firefighter's clothing it was possible to work almost three min up to 4.6 k∙W∙m-2. At higher heat radiation levels firefighter's clothing gave insufficient protection and aluminized clothing should be used. Maximum working times in aluminized clothing at 6.3 k∙W∙m-2 was about five min. At levels of 10.0 k∙W∙m-2 (emergency conditions) emergency responders should move immediately to lower heat radiation levels.


Interaction of plasma glutathione redox and folate deficiency on arsenic methylation capacity in Bangladeshi adults.
Inorganic arsenic(As) is metabolized through a series of methylation reactions catalyzed by arsenic(III)-methyltransferase (AS3MT), resulting in the generation of monomethylarsonic (MMAs) and dimethylarsinic acids (DMAs). AS3MT activity requires the presence of the methyl donor S-adenosylmethionine, a product of folate-dependent one-carbon metabolism, and a reductant. Although glutathione (GSH), the primary endogenous antioxidant, is not required for As methylation, GSH stimulates As methylation rates in vitro. However, the relationship between GSH redox and As methylation capacity in humans is unknown. We wished to test the hypothesis that a more oxidized plasma GSH redox status is associated with decreased As methylation capacity and examine whether these associations are modified by folate nutritional status. Concentrations of plasma GSH and GSSG, plasma folate, total blood As (bAs), total urinary As (uAs), and uAs metabolites were assessed in a cross-sectional study of n=376 Bangladeshi adults who were chronically exposed to As in drinking water. We observed that a decreased plasma GSH/GSSG ratio (reflecting a more oxidized redox state) was significantly associated with increased urinary %MMA, decreased urinary %DMA, and increased total bAs in folate-deficient individuals (plasma folate ≤ 9.0 nmol/L). Concentrations of plasma GSH and GSSG were independently associated with increased and decreased As methylation capacity, respectively. No significant associations were observed in folate-sufficient individuals, and interactions by folate status were statistically significant. Our findings suggest that GSH/GSSG redox regulation might contribute to the large interindividual variation in As methylation capacity observed in human populations.


Personalized radiation therapy and biomarker-driven treatment strategies: a systematic review.
Radiosensitivity varies to a great extent across tumor types and also between patients bearing the same type of tumor. Radiation oncology pioneered the field of biomarkers with attempts to correlate tumor response to clonogenic survival, tumor potential doubling time (Tpot), and PaO₂. Biomarkers predicting the clinical outcome after radiotherapy are already available, but their levels of evidence are heterogeneous. In light of these molecular factors, the issue of personalized radiation therapy in combination or as a standalone modality is addressed. Known molecular prognostic and predictive biomarkers and their present or potential respective therapeutic implications are described for six tumor types where radiotherapy is considered to be part of the mainstay: chemoradiation (e.g., gliomas, head and neck, cervical cancer), radiotherapy with or without androgen deprivation (e.g., prostate), neo-adjuvant chemoradiation (e.g., rectum), or adjuvant radiotherapy (e.g., breast).


Increased circulating levels of irisin are associated with cardiovascular risk factors in subjects with acromegaly.
Irisin, a peptide secreted from muscle and adipose tissues, is associated with insulin resistance as well as metabolic and cardiovascular diseases. Acromegaly is a rare disorder caused by overproduction of growth hormone (GH) and is associated with functional and structural differentiation of adipose and muscle tissues. Acromegalic subjects are also at risk of vascular diseases and metabolic dysfunctions. We aimed to determine the altered levels of irisin in subjects with active acromegaly and controlled acromegaly and in controls, and to ascertain whether there is an association between irisin and hormonal and cardiometabolic parameters. We enrolled 40 subjects with active acromegaly, 30 subjects with controlled acromegaly, and 40 control subjects of matched age, gender, BMI, and occurrence of hypertension, diabetes, and metabolic syndrome distribution in the present cross-sectional study. Hormonal and metabolic parameters, carotid intima media thickness (cIMT), and epicardial fat thickness (EFT) of the subjects were evaluated. Irisin levels were measured using ELISA. Circulating levels of irisin were significantly higher in acromegalic subjects compared to both controlled acromegalic subjects and controls. Moreover, irisin levels were elevated in controlled acromegalic subjects compared to controls. Irisin displayed a positive correlation with insulin resistance, cIMT, EFT, BMI, GH, and insulin-like growth factor (IGF-1) in acromegalic subjects. Irisin levels were independently associated with cIMT and EFT according to multiple regression analyses. There was an independent relationship between irisin and IGF-1. Elevated irisin levels in acromegalic subjects were associated with cIMT and EFT, suggesting that irisin is a surrogate marker for cardiovascular risk in acromegalic subjects.


Synthesis and biological evaluation of deoxy-hematoxylin derivatives as a novel class of anti-HIV-1 agents.
SAR studies for the exploration a novel class of anti-human immunodeficiency virus type 1 (HIV-1) agents based on the hematoxylin structure (1) are described. The systematic deoxygenations of 1 including asymmetric synthesis were conducted to obtain a compound showing high potencies for inhibiting the nuclear import and viral replication as anti-HIV-1 agent. Among all, C-3-deoxygenated analog 16 exhibited most promising biological activities as anti-HIV-1 agent such as lower cytotoxicity (16:1; >80:40 μM), stronger inhibition of nuclear import (0.5:1.3 μM), and viral replication in HIV-1-infected TZM-bl cells (24.6:100 μM), human peripheral blood mononuclear cells (PMBCs) (30.1 μM: toxic). Different spectra of inhibitory activities against infected three healthy humans macrophages with high (donor A) and low (donor B and C) amounts of virus were also observed. Thus 16 showed 10-times stronger activity than 1 (16:1; 0.1:<1.0 μM) in the case of A, while 16 and 1 showed comparable activities in the cases of B and C (>0.01 and >0.00 1μM). The comparison of the inhibition of viral p24 antigen production was clearly indicated that compound 16 is at least twofold more potent anti-viral activity than 1. Thus, structures and actions of deoxy analogs particularly 16 could provide valuable information for the development of a novel class of anti-HIV-1 agents.


Higher-order topological insulator in cubic semiconductor quantum wells.
The search for exotic new topological states of matter in widely accessible materials, for which the manufacturing process is mastered, is one of the major challenges of the current topological physics. Here we predict higher order topological insulator state in quantum wells based on the most common semiconducting materials. By successively deriving the bulk and boundary Hamiltonians, we theoretically prove the existence of topological corner states due to cubic symmetry in quantum wells with double band inversion. We show that the appearance of corner states does not depend solely on the crystallographic orientation of the meeting edges, but also on the growth orientation of the quantum well. Our theoretical results significantly extend the application potential of topological quantum wells based on IV, II-VI and III-V semiconductors with diamond or zinc-blende structures.


HDL, its enzymes and its potential to influence lipid peroxidation.
In seeking an explanation of the inverse relationship between serum high density lipoprotein (HDL) concentration and coronary heart disease (CHD) incidence, most investigations have been directed at its role in reverse cholesterol transport. However, recently it has become clear that HDL has the potential to limit oxidative modification of low density lipoprotein (LDL) whether induced by transition metals or by cells in tissue culture. In view of the current theory that oxidative modification of LDL is an important element in atherogenesis, this suggests another potential mechanism by which HDL might impede the development of CHD. HDL is the major carrier of cholesteryl ester hydroperoxides, but more than this it appears to have the prolonged capacity to decrease the total amount of lipid peroxides generated on LDL during oxidation while the quantity accumulating on HDL itself reaches an early plateau. These effects are not explained by chain-breaking antioxidants present in HDL and are likely to involve an enzymic mechanism. Several enzymes are present on HDL: paraoxonase, lecithin:cholesterol acyl transferase, platelet activating factor acetylhydrolase, phospholipase D and protease. Apolipoproteins, such as apolipoprotein AI, could also have enzymic activity. Evidence that some of these might act to metabolise lipid peroxidation products, such as oxidised phospholipids and lyso-phosphatidylcholine, is discussed in this review.


Biosynthetic Plastics as Tunable Elastic and Visible Stent with Shape-Memory to Treat Biliary Stricture.
Common biliary tract is ≈4 mm in diameter to deliver bile from liver to small intestine to help digestion. The abnormal narrowing leads to severe symptoms such as pain and nausea. Stents are an effective treatment. Compared with non-degradable stents which require repeated removal, biodegradable stents have the advantage of reducing secondary injury related to endoscopic operation and patient burden. However, current biodegradable materials may cause tissue hyperplasia and the treatment method does not target etiology of stricture. So recurrence rates after biodegradable stent implantation are still high. Here, a biodegradable helical stent fabricated from biosynthetic P(3HB-co-4HB) is reported. Tunable properties can be acquired through altering culture substrates. Stent shows shape memory in various solvents. The stent has an optimized design with helical structure and outer track. The self-expanding of helical structure and double drainage realized by outer track greatly improve drainage of bile. Importantly, stent-loading triamcinolone acetonide can inhibit proliferation of fibroblasts and reduce incidence of restricture. Therapeutic effect is also demonstrated in minipigs with biliary stricture. The results of minipig experiments show that biliary duct in treatment group is unobstructed and tissue hyperplasia is effectively inhibited.


Recognition memory and introspective remember/know judgments: evidence for the influence of distractor plausibility on "remembering" and a caution about purportedly nonparametric measures.
One popular technique in the study of human recognition memory involves the elicitation of remember and know judgments and the attribution of those judgments to qualitative states of memory retrieval. An alternative view, reviewed here, implicates quantitative, but not qualitative, differences in evidence as the basis for those two judgments. That theory makes two clear and testable predictions: that of criterion shifts in "remembering" and that of isodiscriminability across different response sets. In this experiment, the makeup of the distractor set in a recognition test is shown to influence overall recognition criterion and also rates of "remember" responses. The second portion of the article demonstrates how A' is a poor choice of a measure to test the prediction of isodiscriminability. When this measure is corrected (Equation 7) to make it more consistent with current knowledge about the receiver-operating characteristic in recognition memory, it reveals that there is no difference in discriminability between "remember" and all positive responses.


Detection of amyloid beta protein in the urine of Alzheimer's disease patients and healthy individuals.
To seek for a new valid biomarker using non-invasive specimens for the diagnosis of Alzheimer's disease (AD) and mild cognitive impairment (MCI), we carried out the detection of amyloid beta (Abeta) protein in urine. Ten-millilitre urine samples were first sedimented with trichloroacetic acid, and the pellets were resuspended for further analysis by Western blotting with anti-Abeta antibody. The detection sensitivity of the method was 40pg/ml. Rates of subjects positive for monomeric Abeta according to their clinical dementia rating (CDR) were 11.1% for CDR 0, 62.5% for CDR 0.5, 83.3% for CDR 1, 54.5% for CDR 2 and 0% for CDR 3. A single Abeta band relative to the CDR score reflects an alteration in the production, solubility and clearance of Abeta in the brain. Thus, the method could be used as both a diagnostic and monitoring tool in assessing AD and MCI patients during disease-modifying therapies.


Mediation of multiple pathways regulating cell proliferation, migration, and apoptosis in the human malignant glioma cell line U87MG via unphosphorylated STAT1: laboratory investigation.
Signal transducer and activator of transcription 1 (STAT1) is thought to be a tumor suppressor protein. The authors investigated the expression and role of STAT1 in glioblastoma. Immunohistochemistry was used to detect the expression of STAT1 in glioblastoma and normal brain tissues. Reverse transcription-polymerase chain reaction and Western blot analysis were used to detect mRNA and protein expression levels of STAT1. Cell growth, proliferation, migration, apoptosis, and the expression of related genes and proteins (Bcl-2, Bax, cleaved caspase-3, caspase-9, p21, and proliferating cell nuclear antigen) were examined in vitro via cell counting kit-8, wound-healing, flow cytometry, Rhodamine B, TUNEL, and Western blot assays. Human glioblastoma had decreased expression of STAT1 proteins. Transfection of the U87MG cells with STAT1 plasmid in vitro demonstrated significant inhibition of cell growth and an increase in apoptotic cell death compared with cells transfected with vector or mock plasmids. These effects were associated with the upregulation of cleaved caspase-3, Bax, and p21 and the downregulation of Bcl-2 expression. The results of this study suggest that increased expression of STAT1 by transfection with STAT1 plasmid synergistically inhibits human U87MG glioblastoma cell growth in vitro.


Attenuation of cardioprotective effect by postconditioning in coronary stenosed rat heart and its restoration by carvedilol.
The aim of this study was to assess whether and how infarct size (IS) reduction by postconditioning is modified in the heart with coronary stenosis (CS), and how beta-blocker treatment affects it. The IS was assessed by 30-min acute coronary occlusion and 24-h reperfusion in rat hearts in which CS had been induced. Modification of IS by postconditioning and the effects of daily carvedilol treatment were measured, together with reperfusion injury - salvage kinase activities. Four weeks after CS induction, any reduction of IS by postconditioning was lost, whereas it reduced IS in rats without CS. In the hearts without CS, postconditioning activated both the ERK and Akt pathway. However, in the hearts with CS, postconditioning failed to do so. In hearts with CS plus daily carvedilol treatment, postconditioning reduced IS compared with the hearts without carvedilol, although postconditioning did not activate the Akt and ERK pathways. CS impaired Akt and ERK activation, resulting in a failure to reduce IS by postconditioning. Carvedilol treatment restored the IS reduction by postconditioning, possibly via other mechanism(s) of the ERK and Akt pathways.


Identification and characterization of sequence signatures in the Bacillus subtilis promoter Pylb for tuning promoter strength.
To thoroughly characterize the Pylb promoter and identify the elements that affect the promoter activity. The sequences flanking the - 35 and - 10 box of the Pylb promoter were divided into six segments, and six random-scanning mutant promoter libraries fused to an enhanced green fluorescent protein EGFP were made and analyzed by flow cytometry. Our results showed that the four nucleotides flanking the - 35 box could mostly influence the promoter activity, and this influence was related to the GC content. The promoters mutated in these regions were successfully used for expressing the gene ophc2 encoding organophosphorus hydrolase (OPHC2) and the gene katA encoding catalase (KatA). Our work identified and characterized the sequence signatures of the Pylb promoter that could tune the promoter strength, providing further information for the potential application of this promoter. Meanwhile, the sequence signatures have the potential to be used for tuning gene expression in enzyme production, metabolic engineering, and synthetic biology.


Experimentally derived viscoelastic properties of human skin and muscle in vitro.
Measurement of the mechanical properties of human skin in vivo is challenging. Moreover, those with regard to excitation frequency have been rarely reported thus far. In this study, a vibration-based experimental method was employed to measure the viscoelastic properties with regard to the excitation frequency. Pieces of human skin and skeletal muscle excised from cadavers immediately post mortem were stored in a sealed container. As the experiment began, they were removed from the container and used to measure the viscoelastic properties as time elapsed. Young's moduli of the samples of human skin tissue that were immediately removed from the container were found to be similar to those obtained with in-vivo indentation methods. They were also found to be approximately one-third of those of human skeletal muscles. The viscoelastic properties of human skin were found to remain almost constant within the frequency range up to 120 Hz and are similar to those of porcine tissue. Young's moduli of the human skin and skeletal muscle were also found to reach the maximum values approximately five days post mortem. However, the loss factor of the human skin did not vary significantly as time elapses.


Intrinsic and extrinsic causes of spatial variability across scales in a metacommunity.
The relative importance of extrinsic and intrinsic causes of variability is among the oldest unresolved problems in ecology. However, the interaction between large-scale intrinsic variability in species abundance and environmental heterogeneity is still unknown. We use a metacommunity model with disturbance-recovery dynamics to resolve the interaction between scales of environmental heterogeneity, biotic processes and of intrinsic variability. We explain how population density increases with environmental variability only when its scale matches that of intrinsic patterns of abundance, through their ability to develop in heterogeneous environments. Succession dynamics reveals how the strength of local species interactions, through its control of intrinsic variability, can in turn control the scale of metapopulation response to environmental scales. Our results show that the environment and species density might fail to show any correlation despite their strong causal association. They more generally suggest that the spatial scale of ecological processes might not be sufficient to build a predictive framework for spatially heterogeneous habitats, including marine reserve networks.


Prediction of treatment response to adalimumab: a double-blind placebo-controlled study of circulating microRNA in patients with early rheumatoid arthritis.
At least 30% of patients with rheumatoid arthritis (RA) do not respond to biologic agents, which emphasizes the need of predictive biomarkers. We aimed to identify microRNAs (miRNAs) predictive of response to adalimumab in 180 treatment-naïve RA patients enrolled in the OPtimized treatment algorithm for patients with early RA (OPERA) Study, an investigator-initiated, prospective, double-blind placebo-controlled study. Patients were randomized to adalimumab 40 mg (n=89) or placebo-adalimumab (n=91) subcutaneously in combination with methotrexate. Expressions of 377 miRNAs were determined using TaqMan Human MicroRNA LDA, A Card v2.0 (Applied Biosystems). Associations between miRNAs and treatment response were tested using interaction analyses. MiRNAs with a P-value <0.05 using three different normalizations were included in a multivariate model. After backwards elimination, the combination of low expression of miR-22 and high expression of miR-886.3p was associated with EULAR good response. Future studies to assess the utility of these miRNAs as predictive biomarkers are needed.


Bamboo: an overview on its genetic diversity and characterization.
Genetic diversity represents the heritable variation both within and among populations of organisms, and in the context of this paper, among bamboo species. Bamboo is an economically important member of the grass family Poaceae, under the subfamily Bambusoideae. India has the second largest bamboo reserve in Asia after China. It is commonly known as "poor man's timber", keeping in mind the variety of its end use from cradle to coffin. There is a wide genetic diversity of bamboo around the globe and this pool of genetic variation serves as the base for selection as well as for plant improvement. Thus, the identification, characterization and documentation of genetic diversity of bamboo are essential for this purpose. During recent years, multiple endeavors have been undertaken for characterization of bamboo species with the aid of molecular markers for sustainable utilization of genetic diversity, its conservation and future studies. Genetic diversity assessments among the identified bamboo species, carried out based on the DNA fingerprinting profiles, either independently or in combination with morphological traits by several researchers, are documented in the present review. This review will pave the way to prepare the database of prevalent bamboo species based on their molecular characterization.


Atherosclerosis precursors in Finnish children and adolescents. XIV. Zinc and copper concentrations in deciduous teeth.
Zinc and copper concentrations were analysed from cariesfree deciduous teeth of 125 Finnish children, 6-7- and 9-10-year-olds, from three cities. Enamel and dentine were separated and prepared into pills which were analysed individually with the proton induced x-ray emission spectrometry (PIXE) method. The total mean (+/- SD) zinc concentrations for enamel and dentine were 143 +/- 31 and 133 +/- 36 ppm, respectively, and are in agreement with the values reported recently. The median copper concentration for enamel was 0.54 ppm with a range from 0.0 to 4.29 and for dentine 0.27 ppm with a range from 0.0 to 3.60 being among the lowest reported. The low copper values are interesting as to the possible association with the development of atherosclerosis. Geographical differences were noted between the zinc concentrations of the three cities, the children of Helsinki having significantly higher zinc values than the children of Kuopio and Oulu. No linear correlation was found between zinc and copper concentrations at the individual level.


Effects of eight weeks of aerobic exercise and vitamin D supplementation on psychiatric comorbidities in men with migraine and vitamin D insufficiency: A randomized controlled clinical trial.
High prevalence of psychiatric comorbidities associated with migraine increases the risk of evolution from episodic migraine to chronic migraine. This study investigated the effects of eight weeks of aerobic exercise and vitamin D supplementation on psychiatric comorbidities in men with migraine and vitamin D insufficiency. Forty-eight participants took part in this randomized controlled clinical trial and were allocated into four groups: aerobic exercise and vitamin D (AE + VD), aerobic exercise and placebo (AE + Placebo), vitamin D (VD), and Placebo. AE + VD and AE + Placebo groups performed three aerobic exercise sessions per week for eight weeks and received a vitamin D supplement and placebo, respectively. The VD group received a vitamin D supplement, and the Placebo group received a placebo for eight weeks. The depression severity, quality of sleep, and physical self-concept were measured at baseline and after eight weeks. The results showed that depression severity was significantly lower in AE + VD compared to AE + Placebo, VD, and Placebo at the post-test. Our results demonstrated that in the post-test, the mean score of sleep quality in AE + VD was significantly lower than AE + Placebo, VD, and Placebo. Finally, the results revealed that after eight weeks of intervention, the physical self-concept in AE + VD was significantly higher than in VD and Placebo groups. Not having complete control of sun exposure and the diet were the limitations. The results indicated that the concomitant application of AE and VD supplementation could provoke synergistic effects leading to additional psycho-cognitive health benefits in men with migraine and vitamin D insufficiency.


Does accelerometer feedback on high-quality chest compression improve survival rate? An in-hospital cardiac arrest simulation.
We investigated whether visual feedback from an accelerometer device facilitated high-quality chest compressions during an in-hospital cardiac arrest simulation using a manikin. Thirty health care providers participated in an in-hospital cardiac arrest simulation with 1 minute of continuous chest compressions. Chest compressions were performed on a manikin lying on a bed according to visual feedback from an accelerometer feedback device. The manikin and accelerometer recorded chest compression data simultaneously. The simulated patient was deemed to have survived when the chest compression data satisfied all of the preset high-quality chest compression criteria (depth ≥51 mm, rate >100 per minute, and ≥95% full recoil). Survival rates were calculated from the feedback device and manikin data. The survival rate according to the feedback device data was 80%; however, the manikin data indicated a significantly lower survival rate (46.7%; P = .015). The difference between the accelerometer and manikin survival rates was not significant for participants with a body mass index greater than or equal to 20 kg/m(2) (93.3 vs 73.3%, respectively; P = .330); however, the difference in survival rate was significant in participants with body mass index less than 20 kg/m(2) (66.7 vs 20.0%, respectively; P = .025). The use of accelerometer feedback devices to facilitate high-quality chest compression may not be appropriate for lightweight rescuers because of the potential for compression depth overestimation. Clinical Research Information Service (KCT0001449).


The influence of freezing and freeze-drying of tissue specimens on enzyme activity.
In the presented study the influence of freezing and freeze-drying on enzyme activity is described. Attention is paid to 16 enzymes which can be used for quantitative enzyme histochemical techniques. With the exception of succinate dehydrogenase only, no significant inactivation during freezing and freeze-drying procedures could be demonstrated with lactate dehydrogenase, malate dehydrogenase (NAD+), malate dehydrogenase (decarboxylating) (NADP+), isocitrate dehydrogenase (NADP+), glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, NADH-oxydoreductase, mitochondrial glycerol-3-phosphate dehydrogenase, cytochrome c oxidase, phosphoglucomutase, glucosephosphate isomerase, glucose-6-phosphatase, acid phosphatase, beta-glucuronidase and non specific aryl esterase. Therefore, the results supply a sound foundation for those quantitative enzyme histochemical techniques in which tissue specimens are frozen or frozen-dried before enzyme estimations are performed.


[Effects of ginkgo leave concentrated oral liquor in treating asthma].
To determine the effects of Ginkgo leave concentrated oral liquor (GLC) on airway inflammation. Airway hyperreactivity and clinical symptoms and pulmonary functions of asthma patients were determined. In contrast to placebo group, GLC significantly reduced airway hyperreactivity (P < 0.05) and improved clinical symptoms (P < 0.05), pulmonary functions (P < 0.05) of the asthmatic patients. GLC is an effective drug of anti airway inflammation.


Newborn screening for cystic fibrosis is associated with reduced treatment intensity.
To determine whether the improved clinical status after newborn screening (NBS) for cystic fibrosis (CF) segregates with increased therapeutic intervention compared with presentation by clinical diagnosis (CD). In 2002, two populations (1 to 9 years of age) who presented (excluding meconium ileus) by NBS < or = 3 months of age or by CD were compared in an observational, cross-sectional design. NBS and CD populations (184 and 950 patients, respectively) were divided into 3-year age groups (1 to 3, 4 to 6, and 7 to 9 years). Therapies of duration >3 months were compared together with Pseudomonas aeruginosa infection status. NBS patients < or = 6 years of age received significantly fewer and less demanding therapies not explained by age, genotype, geography, or social deprivation. In 7- to 9-year-olds, significantly fewer NBS patients received intravenous antibiotics. NBS patients without P aeruginosa infection received significantly fewer therapies, but no differences were found between intermittently or chronically infected NBS and CD populations. Comparable results were found in deltaF508/deltaF508 subpopulations. CF populations diagnosed by NBS are associated with reduced treatment compared with age- and genotype-matched CD control subjects.


The identity status of African Americans in middle adolescence: a reexamination of Watson and Protinsky (1991).
In contrast to earlier research, Watson and Protinsky (1991) found that African American students did not experience identity foreclosure to a greater extent than did their Caucasian peers. Watson and Protinsky, however, examined only ideological identity. The purpose of the present study was to extend this line of research by examining identity development in the interpersonal domain as well as the ideological domain. Forty-eight African American students completed a revised version of the Extended Objective Measure of Ego Identity Status (EOM-EIS II). Supporting the conclusions of Watson and Protinsky, the results showed that few of the African American students were foreclosed. Instead, most of the students were in moratorium; that is, they were engaged in the identity-exploration process. Results for the interpersonal domain were similar to those for the ideological domain.


Effect of phosphorylation of phosphatidylinositol on myelin basic protein-mediated binding of actin filaments to lipid bilayers in vitro.
Myelin basic protein (MBP) binds to negatively charged lipids on the cytosolic surface of oligodendrocytes and is believed to be responsible for adhesion of these surfaces in the multilayered myelin sheath. It can also assemble actin filaments and tether them to lipid bilayers through electrostatic interactions. Here we investigate the effect of increased negative charge of the lipid bilayer due to phosphorylation of phosphatidylinositol (PI) on MBP-mediated binding of actin to the lipid bilayer, by substituting phosphatidylinositol 4-phosphate or phosphatidylinositol 4,5-bisphosphate for PI in phosphatidylcholine/phosphatidylglycerol lipid vesicles. Phosphorylation of PI caused dissociation of the MBP/actin complex from the lipid vesicles due to repulsion of the negatively charged complex from the negatively charged membrane surface. An effect of phosphorylation could be detected even if the inositol lipid was only 2mol% of the total lipid. Calcium-calmodulin dissociated actin from the MBP-lipid vesicles and phosphorylation of PI increased the amount dissociated. These results show that changes to the lipid composition of myelin, which could occur during signaling or other physiological events, could regulate the ability of MBP to act as a scaffolding protein and bind actin filaments to the lipid bilayer.


First detection of infectious spleen and kidney necrosis virus (ISKNV) associated with massive mortalities in farmed tilapia in Africa.
In late 2018, unusual patterns of very high mortality (>50% production) were reported in intensive tilapia cage culture systems across Lake Volta in Ghana. Samples of fish and fry were collected and analysed from two affected farms between October 2018 and February 2019. Affected fish showed darkening, erratic swimming and abdominal distension with associated ascites. Histopathological observations of tissues taken from moribund fish at different farms revealed lesions indicative of viral infection. These included haematopoietic cell nuclear and cytoplasmic pleomorphism with marginalization of chromatin and fine granulation. Transmission electron microscopy showed cells containing conspicuous virions with typical iridovirus morphology, that is enveloped, with icosahedral and/or polyhedral geometries and with a diameter c.160 nm. PCR confirmation and DNA sequencing identified the virions as infectious spleen and kidney necrosis virus (ISKNV). Samples of fry and older animals were all strongly positive for the presence of the virus by qPCR. All samples tested negative for TiLV and nodavirus by qPCR. All samples collected from farms prior to the mortality event were negative for ISKNV. Follow-up testing of fish and fry sampled from 5 additional sites in July 2019 showed all farms had fish that were PCR-positive for ISKNV, whether there was active disease on the farm or not, demonstrating the disease was endemic to farms all over Lake Volta by that point. The results suggest that ISKNV was the cause of disease on the investigated farms and likely had a primary role in the mortality events. A common observation of coinfections with Streptococcus agalactiae and other tilapia bacterial pathogens further suggests that these may interact to cause severe pathology, particularly in larger fish. Results demonstrate that there are a range of potential threats to the sustainability of tilapia aquaculture that need to be guarded against.


Subcutaneous or intrahepatic injection of suicide gene modified tumour cells induces a systemic antitumour response in a metastatic model of colon carcinoma in rats.
Suicide gene therapy consists of the transfer into tumour cells of a "suicide" gene that can convert a non-toxic compound into a lethal drug. Expression of the cytosine deaminase gene leads to the conversion of the non-toxic compound 5-fluorocytosine to 5-fluorouracil. We have recently shown that "suicide cell based vaccination" consisting of intrahepatic injection of cytosine deaminase expressing colon cancer cells followed by 5-fluorocytosine treatment induces regression of a distant wild-type liver tumour in rats. This study was conducted to test if (i) a distant bystander effect on a liver tumour can be induced after subcutaneous suicide cell based vaccination and (ii) suicide cell based vaccination is efficient in limiting tumour dissemination to extrahepatic compartments. An aggressive variant of rat colon carcinoma cells was selected after successive passages in vitro. Rats carrying an experimental liver "metastasis" generated by injection of these cells were vaccinated by subcapsular or subcutaneous injection of cytosine deaminase expressing cells followed by 5-fluorocytosine treatment. Subcutaneous and subcapsular vaccination induced 70% regression in the median volume of the pre-established liver tumour (p=0.001) and abolished tumour dissemination compared with control animals. This study has compared for the first time the efficiency of subcutaneous and intrahepatic suicide cell based vaccination in a metastatic colorectal carcinoma model in rats. The results indicate that both modes of vaccination are equally efficient in inducing a systemic antitumour response, suggesting that this strategy is a powerful approach against the development and dissemination of metastatic colon carcinoma.


The relevance of neutral arm positioning for true ap-view X-ray to provide true projection of the humeral head shaft angle.
Textbooks commonly recommend using the true anterior-posterior (ap)-view with the patient's arm in a sling and therefore in internal rotation (IR) for radiologic diagnostic assessment of the proximal humerus after trauma. However, IR or external rotation (ER) may affect the projection of the head shaft angle (HSA) and therefore bias the diagnostic conclusion significantly. We hypothesized that neutral rotation (NR) of the arm is mandatory for true ap-view to provide true projection of the HSA. A simplified geometrical model of the proximal humerus was used to examine the influence of different arm positions and angulations of the central ray in relation to the projection of the HSA. Both ER and IR misleadingly suggested an increased valgus angle. Simulating the true ap-view with the central ray in cranio-caudal direction, IR changed the projection of the HSA substantially. In conclusion, standard fixation of the patient's arm in a shoulder sling in IR for true ap-view may result in an oblique projection, potentially leading to incorrect surgical implications. To prevent misdiagnosed valgus or varus angulation, NR of the arm should be obeyed when performing true ap-view X-ray. We, therefore, highly recommend to overcome the traditionally arm position, ensuring the true amount of dislocation to assure correct surgical implications and comparable follow-up examinations.


Reproducibility of a semi-quantitative food frequency questionnaire in Japanese female dietitians.
To examine reproducibility of assessed intake of foods and nutrients according to a semi-quantitative food frequency questionnaire (SQFFQ) in Japanese female dietitians. An SQFFQ was self-administered to 106 (21 male and 85 female) Japanese dietitians in Aichi prefecture in autumn 1996 and the same questionnaire was repeated in autumn 1997. Reproducibility was evaluated in terms of consumption of 15 foods and energy and 30 macro- and micro-nutrients based on the SQFFQ from 84 Japanese female dietitians. For intake of foods, Pearson's correlation coefficients (CCs) with log-transformation and energy adjustment (minimum-median-maximum) ranged from 0.35 (beverages)-0.61-0.71 (dairy products). ANOVA intraclass correlation coefficients (ICCs) with log-transformation and energy adjustment ranged from 0.49 (beverages)-0.74-0.82 (dairy products). Spearman's rank CCs with energy adjustment ranged from 0.43 (confectionery)-0.57-0.76 (dairy products). Weighted kappa statistics with energy adjustment ranged from 0.34 (confectionery)-0.49-0.71 (dairy products). For consumption of nutrients, Pearson's CCs with log-transformation and energy adjustment ranged from 0.23 (zinc)-0.55-0.74 (insoluble dietary fiber). ANOVA ICCs with log-transformation and energy adjustment ranged from 0.37 (zinc)-0.70-0.84 (insoluble dietary fiber). Spearman's rank CCs with energy adjustment ranged from 0.25 (zinc)-0.56-0.74 (magnesium). Weighted kappa statistics with energy adjustment ranged from 0.25 (zinc)-0.50-0.68 (insoluble dietary fiber). Substantially high reproducibility of consumption of foods and nutrients was attained from an SOFFQ self-administered to Japanese female dietitians.


Emerging exotic compositional order on approaching low-temperature equilibrium glasses.
The ultimate fate of a glass former upon cooling has been a fundamental problem in condensed matter physics and materials science since Kauzmann. Recently, this problem has been challenged by a model with an extraordinary glass-forming ability effectively free from crystallisation and phase separation, two well-known fates of most glass formers, combined with a particle-size swap method. Thus, this system is expected to approach the ideal glass state if it exists. However, we discover exotic compositional order as the coexistence of space-spanning network-like structures formed by small-large particle connections and patches formed by medium-size particles at low temperatures. Therefore, the glass transition is accompanied unexpectedly by exotic compositional ordering inaccessible through ordinary structural or thermodynamic characterisations. Such exotic compositional ordering is found to have an unusual impact on structural relaxation dynamics. Our study thus raises fundamental questions concerning the role of unconventional structural ordering in understanding glass transition.


A novel in vitro model of sarcopenia using BubR1 hypomorphic C2C12 myoblasts.
Sarcopenia is the age-related loss of skeletal muscle mass and function with adverse outcomes that include physical disability, poor quality of life, and death. The detailed molecular mechanisms remain unknown. An in vitro muscle atrophy model is needed to enable mechanistic studies. To create such a model, we employed BubR1 insufficiency which causes premature ageing in mice. Using C2C12 cells, a recognized in vitro model of the skeletal muscle cell, we obtained the BubR1 hypomorphic C2C12 (C2C12BKD) cells by using shRNA. The resulting C2C12BKD cells displayed several characteristics of the sarcopenic muscle cell. In C2C12BKD cells, formation of myotubes, assessed by analysis of fusion index, was markedly reduced as was the expression of myogenin and MyoD, two marker genes for myogenesis. Moreover, the cells showed increased expression of the muscle-specific ubiquitin ligases Atrogin-1 and MuRF-1, indicating increased protein degradation through the ubiquitin-proteasome dependent proteolytic pathway. These results suggest that C2C12BKD cells are potentially useful as a novel in vitro model of sarcopenia.


Determination of the 4-monohydroxy metabolites of perhexiline in human plasma, urine and liver microsomes by liquid chromatography.
The use of perhexiline (PHX) is limited by hepatic and neurological toxicity associated with elevated concentrations in plasma that are the result of polymorphism of the cytochrome P450 2D6 isoform (CYP2D6). PHX is cleared by hepatic oxidation that produces three 4-monohydroxy metabolites: cis-OH-PHX, trans1-OH-PHX and trans2-OH-PHX. The current study describes an HPLC-fluorescent method utilising pre-column derivatization with dansyl chloride. Following derivatization, the metabolites were resolved on a C18 column with a gradient elution using a mobile phase composed of methanol and water. The method described is suitable for the quantification of the metabolites in human plasma and urine following clinical doses and for kinetic studies using human liver microsomes. The method demonstrates sufficient sensitivity, accuracy and precision between 5.0 and 0.01, 50.0 and 0.2 and 1.0 and 0.005 mg/l in human plasma, urine and liver microsomes, respectively, with intra-assay coefficients of variation and bias <15%, except at the lowest limit of quantification (<20%). The inter-assay coefficients of variation and bias were <15%. The application of this method to plasma and urine samples of five CYP2D6 extensive metaboliser (EM) patients at steady state with respect to PHX dosing determined that the mean (+/-S.D.) renal clearances of trans1-OH-PHX and cis-OH-PHX were 1.58+/-0.35 and 0.16+/-0.06l/h, respectively. The mean (+/-S.D.) dose recovered in urine as free and glucuronidated 4-monohydroxy PHX metabolites was 20.6+/-11.6%.


Flail chest injury-changing management and outcomes.
The purpose of this study was to assess trends in management of flail chest injuries over time and to determine impact on patient outcomes. A retrospective review of data from a prospectively collated database of all trauma patients admitted to a level 1 trauma service in Victoria was conducted. All trauma patients admitted to the hospital between July 2008 and June 2020 with an Abbreviated Injury Scale (AIS) code for flail chest injury were included. Our study included 720 patients, mean age was 59.5 ± 17.3 years old, and 76.5% of patients were male. Length of ICU stay decreased on average by 9 h each year. Regional anaesthesia use increased by 15% per year (0% in 2009 to 36% in 2020) (p < 0.001). Surgical stabilisation of rib fractures increased by 16% per year (2.9% in 2009 to 22.3% in 2020) (p = 0.006). The use of invasive ventilation decreased by 14% per year (70% in 2008 to 27% in 2020) (p < 0.001), and invasive ventilation time decreased by 8 h per year (p = 0.007). Over the past decade, we have seen increasing rates of regional anaesthesia and surgical rib fixation in the management of flail chest. This has resulted in lower requirements for and duration of invasive mechanical ventilation and intensive care unit stay but has not impacted mortality in this patient cohort.


Selenium Deficiency Influences the mRNA Expression of Selenoproteins and Cytokines in Chicken Erythrocytes.
Selenium (Se) deficiency induces hemolysis in chickens, but the molecular mechanism for this effect remains unclear. Se primarily elicits its function through the activity of selenoproteins, which contain the unique amino acid selenocysteine (Sec). In this study, we aimed to investigate the effect of Se deficiency on the expression of 24 selenoproteins and 10 cytokines. One hundred eighty chickens were randomly divided into 2 groups (90 chickens per group). During the entire experimental period, chickens were allowed ad libitum consumption of feed and water. The chickens were fed either a Se-deficient diet (0.008 mg Se/kg; produced in the Se-deficient area of Heilongjiang, China) or a Se-supplemented diet (as sodium selenite) at 0.2 mg/kg for 35 days. At the 35th day, the messenger RNA (mRNA) levels of 24 selenoproteins and 10 cytokines were examined in erythrocytes of 5 chickens per group, and the correlation was analyzed. The results showed that the expression of 24 selenoproteins and 7 cytokines (IL-2, IL-4, IL-8, IL-10, IL-12β, TGF-β4, and IFN-γ) decreased (P < 0.05), and the expression of 3 cytokines (IL-1γ, IL-6 and IL-7) was higher in the Se-deficient group. In both groups, glutathione peroxidase (GPX), thioredoxin 1 (Txnrd1), selenoprotein P1 (SELP), and selenoprotein synthetase (SPS2) were highly expressed compared to the other selenoproteins in chicken erythrocytes (P < 0.05). These data suggest that GPXs, Txnrd1, SELP, and SPS2 possibly play a more important role than the other selenoproteins. The increase of pro-inflammatory cytokines (IL-1γ, IL-6, and IL-7) suggested that the immune system of chickens was damaged by the Se deficiency. Correlation analysis suggested that although the expression of 24 selenoproteins and 7 cytokines decreased and that of 3 cytokines increased, there was a close correlation between their expression levels and a Se diet. These results suggested that Se deficiency influenced the expressions of 24 selenoproteins and 10 cytokines in chicken erythrocytes, revealing a relationship between Se and the chicken immune system. This study offers information regarding the mechanism of Se deficiency-induced hemolysis.


The alkaline transition of cytochrome c revisited: Effects of electrostatic interactions and tyrosine nitration on the reaction dynamics.
Here we investigated the effect of electrostatic interactions and of protein tyrosine nitration of mammalian cytochrome c on the dynamics of the so-called alkaline transition, a pH- and redox-triggered conformational change that implies replacement of the axial ligand Met80 by a Lys residue. Using a combination of electrochemical, time-resolved SERR spectroelectrochemical experiments and molecular dynamics simulations we showed that in all cases the reaction can be described in terms of a two steps minimal reaction mechanism consisting of deprotonation of a triggering group followed by ligand exchange. The pKaalk values of the transition are strongly modulated by these perturbations, with a drastic downshift upon nitration and an important upshift upon establishing electrostatic interactions with a negatively charged model surface. The value of pKaalk is determined by the interplay between the acidity of a triggering group and the kinetic constants for the forward and backward ligand exchange processes. Nitration of Tyr74 results in a change of the triggering group from Lys73 in WT Cyt to Tyr74 in the nitrated protein, which dominates the pKaalk downshift towards physiological values. Electrostatic interactions, on the other hand, result in strong acceleration of the backward ligand exchange reaction, which dominates the pKaalk upshift. The different physicochemical conditions found here to influence pKaalk are expected to vary depending on cellular conditions and subcellular localization of the protein, thus determining the existence of alternative conformations of Cyt in vivo.


XPB helicase regulates DNA incision by the Thermoplasma acidophilum endonuclease Bax1.
Bax1 has recently been identified as a novel binding partner for the archaeal helicase XPB. We previously characterized Bax1 from Thermoplasma acidophilum as a Mg²⁺-dependent structure-specific endonuclease. Here we directly compare the endonuclease activity of Bax1 alone or in combination with XPB. Using several biochemical and biophysical approaches, we demonstrate regulation of Bax1 endonuclease activity by XPB. Interestingly, incision assays with Bax1 and XPB/Bax1 clearly demonstrate that Bax1 produces different incision patterns depending on the presence or absence of XPB. Using atomic force microscopy (AFM), we directly visualize and compare binding of Bax1 and XPB/Bax1 to different DNA substrates. Our AFM data support enhanced DNA binding affinity of Bax1 in the presence of XPB. Taken together, the DNA incision and binding results suggest that XPB is able to load and position Bax1 on the scissile DNA substrate, thus increasing the DNA substrate range of Bax1.


C-peptide inhibitors of Ebola virus glycoprotein-mediated cell entry: effects of conjugation to cholesterol and side chain-side chain crosslinking.
We previously described potent inhibition of Ebola virus entry by a 'C-peptide' based on the GP2 C-heptad repeat region (CHR) targeted to endosomes ('Tat-Ebo'). Here, we report the synthesis and evaluation of C-peptides conjugated to cholesterol, and Tat-Ebo analogs containing covalent side chain-side chain crosslinks to promote α-helical conformation. We found that the cholesterol-conjugated C-peptides were potent inhibitors of Ebola virus glycoprotein (GP)-mediated cell entry (~10(3)-fold reduction in infection at 40 μM). However, this mechanism of inhibition is somewhat non-specific because the cholesterol-conjugated peptides also inhibited cell entry mediated by vesicular stomatitis virus glycoprotein G. One side chain-side chain crosslinked peptide had moderately higher activity than the parent compound Tat-Ebo. Circular dichroism revealed that the cholesterol-conjugated peptides unexpectedly formed a strong α-helical conformation that was independent of concentration. Side chain-side chain crosslinking enhanced α-helical stability of the Tat-Ebo variants, but only at neutral pH. These result provide insight into mechanisms of C-peptide inhibiton of Ebola virus GP-mediated cell entry.


The immunobead technique: an indicator of disturbed sperm cervical mucus interaction.
A group of 20 couples with repeatedly poor post coital tests (PCT's) where no coital disorders or cervical mucus abnormalities were present, were included in the study. The results of the Direct Immunobead (IB) and Tray-agglutination tests were compared with the results of the sperm-cervical-mucus-contact (SCMC) and post coital tests (PCT's) of each couple in order to determine the sensitivity, specificity and predictive value of the Direct IBT as a screening test for sperm antibodies. The positive predictive value of the IBT was 80%. It was also clear that a strong positive SCMC-T result correlated with agglutinating antibodies in the semen or seminal plasma. In conclusion, the IBT is a sensitive, specific and predictable test for sperm antibodies.


Studies on the leaching of fluoride in tea infusions.
In order to assess the levels of fluoride ingestion through intake of tea, studies were conducted with four different brands of tea leaves commonly available in the Indian market. Four most prevalent methods for the preparation of tea with various contact times (2,4,6,8 and 10 min) of tea leaves with water show that: (a) leaching of fluoride is least in case of leaf tea as compared to powdered tea (F levels increasing with decreasing grain size); (b) leaching of fluoride reaches a maximum after a contact of about 6 min; (c) there is no difference between levels of fluoride with or without addition of milk in the English style where tea leaves are not boiled, while for the Indian style, addition of milk and subsequent boiling resulted in reduction of fluoride levels and (d) ingestion of fluoride per cup of tea ranged from 1.55 mg/l to 3.21 mg/l amounting to an intake per day per person of fluoride between 0.3 to 1.9 mg.


Low-grade salivary duct carcinoma of the parotid gland: report of a case with immunohistochemical analysis.
Salivary duct carcinoma (SDC) is a highly aggressive malignancy of the salivary glands. However, one type of SDC, which shows minimal invasion and better prognosis, is known as low-grade SDC (LG-SDC). This report presents an additional case of LG-SDC of the parotid gland. The patient was a 38-year-old Japanese woman who noticed painless swelling of the left parotid region. Grossly, the cut surface of the tumor was cystic. Microscopically, the tumor showed a multicystic pattern, which was lined by eosinophilic to clear atypical cells with cribriform or Roman bridge patterns. An immunohistochemical examination revealed the tumor was positive for cytokeratin (CK) 7 and epithelial membrane antigen, partially positive for androgen receptor and gross cystic disease fluid protein-15, and diffusely positive for Her-2/Neu, progesterone, and estrogen receptors. The cancer cells showed focal immunopositivity for S-100 protein. Immunostaining for p63, CK14, and calponin showed an in situ pattern in most areas of this tumor, whereas the tumor showed minimal invasion. The cancer cells were diffusely positive for MUC1 and MUC6 and focally positive for MUC2 and MUC4. Finally, the tumor was diagnosed to be LG-SDC. The differential diagnosis and the mucin pattern were evaluated.


PAK1 primes MEK1 for phosphorylation by Raf-1 kinase during cross-cascade activation of the ERK pathway.
The serine/threonine kinase Raf-1 acts downstream of Ras in the MAPK pathway leading to ERK activation in response to mitogens. Raf-1 has oncogenic potential, but is normally controlled by a complex interplay of inhibitory and activating mechanisms. Although Raf-1 is phosphorylated in unstimulated cells, mitogens cause its membrane recruitment by Ras and subsequent phosphorylation on additional sites. Some of these events modulate Raf-1 kinase activity while others determine interactions with other proteins. These changes regulate the ability of Raf-1 to phosphorylate its downstream targets MEK1 and MEK2. Rho family small G proteins act synergistically with Raf-1 to stimulate the ERK pathway by a cross-cascade mechanism that enhances MEK phosphorylation by Raf-1. Here we show that both Raf-1 and MEK1 are phosphorylated by PAK1 and that mutations at PAK1 phosphorylation sites in either protein prevent cross-cascade activation. In contrast, MEK1 activation by constitutively-active Raf-1 is refractory to mutations at PAK1 phosphorylation sites. Phosphorylation of MEK1 on serine 298 does not appear to regulate the interaction between Raf-1 and MEK1, but rather the ability of Raf-1 to phosphorylate MEK1 with which it is complexed in vivo. Our findings indicate that PAK1 primes MEK1 for activation by Raf-1 and imply another level of regulation in the ERK cascade.


Whole-Cell Biotransformation of Penicillin G by a Three-Enzyme Co-expression System with Engineered Deacetoxycephalosporin C Synthase.
Deacetoxycephalosporin C synthase (DAOCS) catalyzes the transformation of penicillin G to phenylacetyl-7-aminodeacetoxycephalosporanic acid (G-7-ADCA) for which it depends on 2-oxoglutarate (2OG) as co-substrate. However, the low activity of DAOCS and the expense of 2OG restricts its practical applications in the production of G-7-ADCA. Herein, a rational design campaign was performed on a DAOCS from Streptomyces clavuligerus (scDAOCS) in the quest to construct novel expandases. The resulting mutants showed 25∼58 % increase in activity compared to the template. The dominant DAOCS variants were then embedded into a three-enzyme co-expression system, consisting of a catalase and an L-glutamic oxidase for the generation of 2OG, to convert penicillin G to G-7-ADCA in E. coli. The engineered whole-cell enzyme cascade was applied to an up-scaled reaction, exhibiting a yield of G-7-ADCA up to 39.21 mM (14.6 g ⋅ L-1 ) with a conversion of 78.42 mol %. This work highlights the potential of the integrated whole-cell system that may inspire further research on green and efficient production of 7-ADCA.


Role of central adiponectin and its interactions with NPY and GABAergic systems on food intake in neonatal layer chicken.
Adiponectin is a member of the adipokine family and contributes to regulating energy homeostasis, reproduction, and various biological functions, such as insulin receptor signaling pathway sensitivity, mitochondrial biogenesis, oxidative metabolism, neurogenesis, and suppression of inflammation. This study aimed to investigate the effects of intracerebroventricular (ICV) injection of adiponectin and its interaction with the neuropeptide Y (NPY) and GABAergic systems on central appetite regulation in neonatal layer-type chickens. In this study, 6 experiments were conducted, each of which included 4 experimental groups. In the first experiment, the chickens were injected with saline and adiponectin (20.73, 41.45, and 62.18 nmol). In the second experiment, saline, adiponectin (62.18 nmol), B5063 (NPY1 receptor antagonist, 2.12 nmol), and simultaneous injections of adiponectin and B5063 were performed. Experiments 3 to 6 were done in the same way to experiment 1, but the chickens were injected with SF22 (NPY2 receptor antagonist, 2.66 nmol), SML0891 (NPY5 receptor antagonist, 2.89 nmol), picrotoxin (GABAA receptor antagonist, 0.89 nmol), CGP54626 (GABAB receptor antagonist, 0.047 nmol) instead of B5063. Feed consumption was measured 120 min after the injection. A dose-dependent increase in appetite was observed after the injection of adiponectin (20.73, 41.45, and 62.18 nmol) (P < 0.05). The injection of B5063 + adiponectin attenuated the hyperphagic effect of adiponectin (P < 0.05). In addition, co-injection of picrotoxin and adiponectin significantly decreased adiponectin-induced hyperphagia (P < 0.05). In addition, adiponectin significantly increased the number of steps, jumps, exploratory food, pecks, and standing time, while decreasing sitting time and rest time (P < 0.05). These results suggest that the hyperphagic effects of adiponectin are probably mediated through NPY1 and GABAA receptors in neonatal layer-type chickens.


Intergroup boundaries and attitudes: the power of a single potent link.
Many prejudice reduction strategies involve linking the self to outgroup members. We tested the novel question of whether establishing a potent link with a single outgroup member can reduce explicit and implicit prejudice toward the outgroup as a whole. White participants completed a mock adoption procedure where they "adopted" a baby from another country. Three experiments showed that this single link fostered perceived overlap between the self and the ethnic outgroup. This overlap mediated the effect of the adoption manipulation on explicit prejudice, which was significantly reduced. Whereas the single link was insufficient to reduce implicit prejudice significantly when the self-outgroup member link was not practiced, repeatedly practicing this connection reduced prejudice significantly in comparison with a control group that had no connection to the outgroup member. Furthermore, unlike explicit attitudes, this effect was direct.


Elevated neutrophil function in chronic neutrophilic leukemia.
A 65-year-old man with marked leukocytosis was admitted for diagnosis and treatment. His peripheral blood leukocyte count was 37,500/microliters and the leukocytes consisted of mature neutrophil-like cells. A high neutrophil alkaline phosphatase score and a normal bone marrow cell karyotype suggested that the patient had chronic neutrophilic leukemia rather than chronic myeloid leukemia. Several neutrophil functions, such as superoxide production, nitroblue tetrazolium reduction activity, and phagocytosis, were elevated. These data and the morphological features (toxic granules and Döhle bodies) indicated that the patient's neutrophils were in an activated stage.


Comparison of whole mitochondrial genome variants between hair shafts and reference samples using massively parallel sequencing.
Hair shafts are one of the most common types of evidence at crime scenes, and mitochondrial DNA (mtDNA) has been analyzed as a valuable genetic marker for hair shafts in forensic casework. However, the mtDNA analysis strategy may vary according to the quantity and quality of DNA extracted from a forensic sample and the available massively parallel sequencing (MPS) platform in laboratories. Forensic practitioners often have to interpret mtDNA sequences exhibiting point heteroplasmy (PHP) that are analyzed using different analytical methods. In the present study, the whole mitochondrial genome (mtGenome) variants of hair shaft samples obtained from 20 donors, which were sampled in duplicate and stored at room temperature for > 1 year, were analyzed using the Precision ID mtDNA Whole Genome Panel and Ion S5 system. The whole mtGenome variants of 20 blood and 20 buccal swab samples (reference samples) from the hair shaft donors were analyzed using the Nextera XT DNA Library Prep Kit and MiSeq System. A total of 20 unique mtGenome haplotypes were observed, and 56 PHP variants were identified across the 4 sets of tissue. When the major nucleotide of PHP was considered, 16 of 20 haplotypes of the hair shaft samples matched those of the corresponding blood and buccal swab samples. In four donors, the major nucleotide of PHP was inverted at one nucleotide position between the hair shaft and reference samples. However, the data obtained on MPS, showing high PHP resolution, provided substantial information to avoid false exclusion when comparing two haplotypes containing PHP with inverted major nucleotides. In conclusion, the present study demonstrates the utility of MPS in forensic casework in the comparative analysis of mtGenome variants containing PHP.


The occurrence of killer character in yeasts of various genera.
Species of 7 of the 28 yeast genera in the National Collection of Yeast Cultures exhibited killing activity against Saccharomyces cerevisiae. The highest incidence of killer yeasts was found in the genus Hansenula (12 of the 29 strains examined). Saccharomyces, the best represented genus in the Collection, showed a low incidence of killer activity and many of the killer strains are hybrids with a common S. cerevisiae parent. The activities of culture filtrates of the 59 killer yeast isolated responded differently to pH and four types of response were recognised.


Lyt-phenotype conversion of cytotoxic T lymphocytes specific for the A and E class II major histocompatibility complex molecules.
The Lyt-1+ (high) Lyt-2+/- (low) primary cytotoxic T lymphocytes (CTL) specific for A(A alpha A beta) molecules and the Lyt-1+Lyt-2+ primary E(E alpha E beta)-specific CTL are both shown to become Lyt-1 Lyt-2+ effector cells after secondary in vitro stimulation. Thus CTL specific for class II major histocompatibility complex molecules exhibit the same Lyt-phenotype shift as class-I-specific CTL do. The data suggest that either both class-I-specific and class-II-specific CTL follow the same differentiation pathway or regulatory cellular interactions allow only Lyt-1-Lyt-2+ cells to differentiate to secondary CTL.