Hysteroscopic findings in complicated and non-complicated IUD users.
The hysteroscopic findings in 100 IUD users have been evaluated. 50 women had no IUD-related problems and requested removal of the device, while the other 50 complained of either bleeding and/or pain or lost strings. Of the 29 cases with IUD-related bleeding and/or pain, hysteroscopy revealed malposition (n=6), partial expulsion (n=3), partial perforation (n=2), embedding (n=1), or disproportion (n=6). Disproportion presented as crumpling of the device in the uterine cavity or protrusion of the tip of the transverse arm inside the tubal ostia. Endometrial lesions were also more commonly seen in the study group than the control group, i.e., endometrial hyperplasia (n=8), endometrial polyps (n=8), intrauterine adhesions (n=5), and submucous fibroids (n=2). Of the 21 IUD patients with missing strings, there were previous failed trial of blind removal in 11 cases. Most lost IUDs were found inside the uterine cavity (81%) with curling and ascending strings. Partial perforation, abdominal translocation, and unnoticed complete expulsion were detected in 19% of the patients. Direct visualization of the endometrial cavity is invaluable in treating IUD users who complain of pain and/or bleeding and in locating and retrieving missing IUDs.


The E3 ubiquitin ligase MARCH3 controls the endothelial barrier.
Cell-cell contacts coordinate the endothelial barrier function in response to external cues. To identify new mediators involved in cytokine-promoted endothelial permeability, we screened a siRNA library targeting E3 ubiquitin ligases. Here, we report that silencing of the late endosome/lysosomal membrane-associated RING-CH-3 (MARCH3) enzyme protects the endothelial barrier. Furthermore, transcriptome analysis unmasked the upregulation of the tight junction-encoding gene occludin (OCLN) in MARCH3-depleted cells. Indeed, MARCH3 silencing results in the strengthening of cell-cell contacts, as evidenced by the accumulation of junctional proteins. From a molecular standpoint, the FoxO1 forkhead transcription repressor was inactivated in the absence of MARCH3. This provides a possible molecular link between MARCH3 and the signaling pathway involved in regulating the expression of junctional proteins and barrier integrity.


Tremor as a symptom of degenerative cervical myelopathy: a systematic review.
AO Spine RECODE-DCM (Research objectives and common data elements for degenerative cervical myelopathy) has highlighted that the subjective disability reported by people living with DCM is much broader than routinely considered today by most professionals. This includes a description of tremor. The objective of this review was to study the incidence and possible aetiology of tremor in degenerative cervical myelopathy (DCM). A systematic review registered in PROSPERO (CRD42020176905) was conducted in Embase and MEDLINE for papers studying tremor and DCM published on or before the 20th of July 2020. All manuscripts describing an association between tremor and DCM in humans were included. Articles relating to non-human animals, and those not available in English were excluded. An analysis was conducted in accordance with PRISMA and SWiM guidelines for systematic reviews. Out of a total of 4402 screened abstracts, we identified 7 case reports and series describing tremor in 9 DCM patients. Papers were divided into three groups for the discussion. The first group includes DCM correctly identified on presentation, with tremor as a described symptom. The second group includes cases where DCM was misdiagnosed, often as Parkinson's disease. The third group includes a single case with a previous history of DCM, presenting with an otherwise unexplained tremor. This grouping allows for the clustering of cases supporting various arguments for the association between tremor and DCM. DCM can be associated with tremor. The current evidence is restricted to case series. Further study is warranted to establish tremor prevalence, and its significance to assessment and management.


Cavity-enhanced photothermal spectroscopy: dynamics, sensitivity, and spatial resolution.
The spectrally resolved low-level absorption of thin films and of solid and liquid surfaces was measured by cavity-enhanced photothermal spectroscopy. The technique is ultrasensitive and can determine surfacespecific absorbances alpha(omega) ~ 10(-6) at a power density of 10(4)W/cm(2). Both cases of continuous wave and modulated laser light absorption were studied experimentally and are interpreted theoretically. It is shown that it is possible to achieve a spatial resolution of absorbance variations in the few-micrometer range. The thermal diffusivity can also be simultaneously measured by observing the time evolution of the surface temperature during laser irradiation.


[Dexmedetomidine suppresses the expressions of TLR4, NF-κB and ICAM-1 mRNA in the lung of rabbits during one lung ventilation].
Objective To investigate the effect of dexmedetomidine on lung injury and the expressions of Toll-like receptor 4 (TLR4), nuclear factor κB p65 (NF-κB p65) and intercellular adhesion molecular 1 (ICAM-1) mRNA during one-lung ventilation (OLV) in rabbits. Methods Thirty healthy New Zealand white rabbits were randomly divided into three groups ( n=10 in each group): two-lung ventilation (TLV) group (group T), OLV group (group O), dexmedetomidine used during OLV group (group D-O). The rabbits in group T were treated with TLV for 3.5 hours, while in group O and group D-O, the rabbits were ventilated through right lung for 3 hours following 30-minute TLV. In group D-O, dexmedetomidine (1 μg/kg) were given intravenously for 10 minutes before tracheostomy, followed by intravenous infusion at the rate of 1 μg/(kg.h). Equal volume of normal saline was given in group O and group T as controls. At the end of the experiment, rabbits were sacrificed and lung tissues were collected. The pulmonary wet/dry mass (W/D) ratio was calculated and the pathological changes of the lungs were observed using HE staining under a light microscope. The expressions of TLR4, NF-κB p65, ICAM-1 mRNA were analyzed by real-time quantitative PCR. Results W/D ratio of left lung tissues in group O and group D-O were significantly higher as compared with group T. However, W/D ratio in group D-O was obviously lower than that in group O. Compared with group T, both group O and group D-O showed much more serious morphological damage in the lung, and such lung injury was less obvious in group D-O than in group O. The expressions of TLR4, NF-κB p65, ICAM-1 mRNA increased significantly in group O as compared with group T, and such enhancement was ameliorated by dexmedetomidine as observed in group D-O. Conclusion Dexmedetomidine might inhibit inflammatory responses and attenuate OLV-induced lung injury in rabbits, possibly by suppressing the expressions of TLR4 and NF-κB p65 mRNA.


Histological study of acute vocal fold injury in a rat model.
We used an acute vocal fold injury in a rat model to characterize vocal fold wound healing by studying the expression pattern of the extracellular matrix components in the vocal fold lamina propria. Vocal fold stripping was performed unilaterally in 27 Sprague-Dawley rats. The vocal folds were harvested at 5 time points (1, 3, 5, 7, and 14 days) and histologically analyzed by Alcian blue stain, trichrome stain, and immunofluorescence with antibodies to collagen type I, collagen type III, and fibronectin. Re-epithelialization occurred by day 3 and was complete by day 14. Granulation tissue was formed by day 3. Hyaluronic acid and collagen type I appeared in injured vocal folds by day 3, peaked at day 5, and thereafter decreased. Collagen type III and fibronectin appeared by day 1 and continued to be intense at all time points after day 3. These results suggest that the expression of these extracellular matrix components peaks in the period around days 3 to 5, and that the characteristics of wound healing in the vocal fold are similar to those in the skin in the early phases, but differ during the subsequent remodeling phase.


Knowledge and attitudes of hospital staff to occupational exposure to bloodborne viruses.
In order to assess awareness of occupational risk of exposure to bloodborne viruses a questionnaire was sent to 245 health care workers, representing a 10% sample of employees with patient contact in a large teaching hospital in Scotland, stratified by occupational group. One hundred and eight questionnaires (44%) were returned. Seventy per cent of respondents in laboratory and clinical areas described themselves as having sufficient knowledge for their own area of practice, but many gave incorrect answers or expressed uncertainty about the infectivity of HIV and hepatitis B and hepatitis C viruses. Ninety-four respondents were unaware that a regimen containing more than one antiretroviral drug is now recommended for post exposure prophylaxis of HIV infection, 37 thought they had been at risk of bloodborne viral infection and had contacted the occupational health department for advice, and 68 respondents disagreed with guidelines from the United Kingdom's General Medical Council on testing of patients for bloodborne viruses. The results indicate a need for educational initiatives for new and existing staff.


Controlling for confounding variables in MS-omics protocol: why modularity matters.
As the field of bioinformatics research continues to grow, more and more novel techniques are proposed to meet new challenges and improvements upon solutions to long-standing problems. These include data processing techniques and wet lab protocol techniques. Although the literature is consistently thorough in experimental detail and variable-controlling rigor for wet lab protocol techniques, bioinformatics techniques tend to be less described and less controlled. As the validation or rejection of hypotheses rests on the experiment's ability to isolate and measure a variable of interest, we urge the importance of reducing confounding variables in bioinformatics techniques during mass spectrometry experimentation.


High-dose dexamethasone may prevent esophageal stricture after endoscopic submucosal dissection.
We report a rare case of esophageal endoscopic submucosal dissection (ESD) in a patient who underwent high-dose dexamethasone therapy for multiple myeloma shortly after ESD. A 61-year-old male was referred for treatment of esophageal superficial squamous cell carcinoma and underwent curative ESD. During his hospitalization for ESD, further examination for worsening back pain and gait disorder revealed multiple myeloma with multiple bone metastases. Consequently, high-dose dexamethasone therapy (40 mg × 4 days × 3 courses) was started on the 9th day after ESD. He was successfully treated by the subsequent peripheral blood stem cell transplantation. In the follow-up endoscopies, the artificial ulcer was shown to have re-epithelialized gradually with little or no size reduction of the ulcer bed. Minimal deformation of the lumen was observed. Histopathological assessment after surgical resection at a later date revealed thinned submucosa with minimal fibrosis of the ESD scar. This case demonstrated the effect of dexamethasone on the healing process of the artificial ulcer. Dexamethasone can be potentially useful for prevention of postoperative stricture, which is a major complication of esophageal ESD.


Autoregulation of the human N-myc oncogene is disrupted in amplified but not single-copy neuroblastoma cell lines.
Amplification of the N-myc gene is a significant adverse prognostic factor in neuroblastoma, a common childhood tumor. In non-transformed cells, myc expression is controlled through an autoregulatory circuit, through which elevated Myc protein levels lead to down-regulation of myc transcription. The precise mechanism of myc gene autoregulation is unknown. Loss of c-myc autoregulation has been documented in transformed cells from a number of different lineages, but N-myc autoregulation has not yet been investigated. In neuroblastoma, the increased N-Myc protein produced by amplified tumors would be expected to silence N-myc transcription if the autoregulatory loop were intact. To determine whether N-myc autoregulation is operative in human neuroblastoma, and to localize cis-acting elements which mediate N-myc autosuppression, we transfected a series of N-myc 5' promoter constructs into a panel of human neuroblastoma cell lines carrying one or multiple copies of N-myc. The transfected promoter was equally active in single-copy and amplified lines. Significant promoter activity in the presence of abundant Myc protein in amplified neuroblastoma lines indicates that autoregulation is disabled in this subset of tumors. To investigate whether single-copy lines produce insufficient N-Myc protein to trigger autosuppression yet retain an intact autoregulatory circuit, we transfected neuroblastoma lines with 5' promoter constructs in the presence of a c- or N-myc expression vector. Overexpression of c- or N-Myc resulted in diminution of activity of both the transfected promoter and the endogenous N-myc gene in single-copy, but not amplified lines. Using a series of 5' promoter-deletion minigenes, we localized a cis-acting element required for autoregulation close to the transcription start sites. While the precise mechanism of autosuppression remains unknown, we demonstrated that Myc is incapable of silencing the adenovirus major late promoter (AdMLP) in neuroblastoma cells, indicating that Myc suppression of its own promoter and the AdMLP involve distinct components. These studies provide the first systematic investigation of autoregulation in neuroblastoma, and indicate that single-copy neuroblastoma lines produce insufficient N-Myc protein to activate downstream effector(s) of autosuppression; the autoregulatory circuit is otherwise intact. Amplified lines, in contrast, have lost autoregulation.


Polymorphism of MTHFR C677T, serum vitamin levels and cognition in subjects with hyperhomocysteinemia in China.
Relationships between hyperhomocysteinemia (HHE) and neurodegenerative diseases have been widely studied. However, the impact of serum total homocysteine (tHcy) levels on cognitive function has not been confirmed. C677T polymorphisms in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene have impacts on tHcy level; it is suspected to influence cognitive function, but only few investigations have assessed its effects on non-dementia adults and the results have been controversial. Moreover, there is no report about Chinese subjects. In the present study, we determined C677T/MTHFR genotype, serum tHcy concentration and cognition in 182 nondemented subjects aged 55-88 years to probe the associations between MTHFRC677T mutation, increased tHcy levels and decreased cognitive function in a northern city in China. A serum tHcy level > or = 16 micromol/l was deemed HHE. Cognitive function was assessed by the Mini Mental State Examination (MMSE) and Basic Cognitive Aptitude Tests (BCAT). Results showed that: (i) subjects with the T allele had higher serum tHcy levels than those without, especially in lower folate status; (ii) T allele and CT/TT genotype frequencies in subjects with HHE were higher than in non-HHE subjects (P < 0.05); and (iii) serum tHcy level was inversely related to total BCAT score (P < 0.05) but MTHFR677 C to T polymorphism had no association with it. Our results confirmed that the MTHFR 677 C to T mutation, especially in lower serum folate concentration status, results in the increase of serum tHcy levels which is bad for cognitive function and indicates that higher serum folate level is of benefit in keeping lower serum tHcy level and better cognitive function. The results provide some valuable clues for individualized nutrition intervention of HHE and cognition decline in the middle-aged and the elderly.


Adjuvant radioactive therapy after reoperation for locoregionally recurrent papillary thyroid cancer in patients who initially underwent total thyroidectomy and high-dose remnant ablation.
Some patients have elevated stimulated thyroglobulin (sTg) concentrations after reoperation for locoregionally recurrent/persistent papillary thyroid cancer (PTC). Little is known, however, about the efficacy of adjuvant radioactive iodine (RAI) therapy in these patients. The objective of the study was to evaluate the efficacy of adjuvant RAI therapy in patients with elevated sTg after reoperation for locally recurrent/persistent PTC. This was a retrospective observational cohort study in a tertiary referral hospital. We evaluated 45 consecutive patients with sTg greater than 2 ng/ml after reoperation for locoregionally recurrent PTC, all of whom had previously undergone initial total thyroidectomy followed by high-dose RAI remnant ablation. Of these 45 patients, 23 received adjuvant RAI therapy (adjuvant group) and 22 did not (control group). Main outcome measures included changes in sTg concentration after reoperation and disease-free survival. Over time, there were no significant differences in mean sTg concentration in the adjuvant (P = 0.35) and control (P = 0.74) groups. Only 15% of patients in the adjuvant group and 33% in the control group showed a greater than 50% decrease in sTg level from baseline. There were no between-group differences in changes (P = 0.83) or percent decrease (P = 0.97) in sTg concentration and no difference in clinical recurrence-free survival (P = 0.20). In patients who still have elevated sTg after reoperation for locally recurrent/persistent PTC, adjuvant RAI therapy compared with no additional RAI therapy resulted in no significant differences in the subsequent sTg changes or the recurrence-free survival.


Association of NF-E2 Related Factor 2 (Nrf2) and inflammatory cytokines in recent onset Type 2 Diabetes Mellitus.
We investigated the association of redox regulator Nuclear factor erythroid 2-related factor 2 (Nrf2) and inflammatory cytokines as well as clinical remission in patients with recent onset type 2 diabetes (DM). Blood was collected from 180 DM patients (105 males/75 females) and 150 control subjects (86 males/64 females). Blood glucose, HbA1c, lipid profile and Nrf2 levels were determined along with circulatory cytokines in study subjects. The data were adjusted with confounding factors such as age and sex using multiple logistic regression analysis. We found that Th1/Th2 and oxidative stress markers were significantly elevated, whereas Nrf2 and its downstream targets were decreased in peripheral blood mononuclear cells (PBMCs) of DM subjects when compared with control. The circulatory levels of Nrf2 showed a positive correlation with Th2 cytokines and negative correlation to Th1 cytokines. Further, the impaired insulin secretion in pancreatic β-cells observed due to cytokine stress has been restored by activation of Nrf2 as assessed by glucose-stimulated insulin secretion (GSIS). This study identifies Nrf2 plays a central role in skewing Th1 and Th2 dominance in the progression of diabetes.


Quantitative analysis of MRI signal intensity in new variant Creutzfeldt-Jakob disease.
High signal intensity within the posterior thalamus (pulvinar nucleus) has been noted on MRI in patients with new variant Creutzfeldt-Jakob disease (nvCJD). In this study MRI examinations from three patients with proven nvCJD were compared with MRI examinations from a control group of 14 age-matched subjects with no neurological abnormalities. Mean signal intensity from seven target areas (periaqueductal tissue, posterior thalamus, dorsomedial thalamus, anterior thalamus, putamen, caudate head and frontal white matter) was calculated in each case. Absolute signal intensity measurements were not significantly different between the groups. Patients with nvCJD showed significantly higher signal intensity within dorsomedial thalamus, posterior thalamus and periaqueductal region than control patients when these measurements were normalized to the signal intensity of normal appearing white matter. Highly significant differences in posterior thalamus/putamen signal intensity ratio (PPR) and posterior thalamus/caudate ratio (PCR) were observed between the groups. For proton density images, PPR and PCR were greater than 1 for all nvCJD patients and less than 1 for all control patients. Both PPR and PCR are simple to calculate and offer a simple, non-invasive indicator of nvCJD.


AlGaAs DH pump laser for photoluminescence lifetime measurements.
The use of GaAlAs double heterostructure lasers as a pulsed excitation source for photoluminescence time-decay measurements is described. Subnanosecond laser pulses easily allow the determination of luminescence decay times >/=500 ps using a single photon counting system. In contrast to mode-locked gas or dye lasers, this new technique utilizes simple equipment (diode laser and pulse generator) and requires no special alignment or tuning procedures.


A practical implementation of de-Pake-ing via weighted Fourier transformation.
We provide an NMRPipe macro to meet an increasing need in membrane biophysics for facile de-Pake-ing of axially symmetric deuterium, and to an extent phosphorous, static lineshapes. The macro implements the development of McCabe & Wassall (1997), and is run as a simple replacement for the usual Fourier transform step in an NMRPipe processing procedure.


Metapopulation models for extinction threshold in spatially correlated landscapes.
Simple analytical models assuming homogeneous space have been used to examine the effects of habitat loss and fragmentation on metapopulation size. The models predict an extinction threshold, a critical amount of suitable habitat below which the metapopulation goes deterministically extinct. The consequences of non-random loss of habitat for species with localized dispersal have been studied mainly numerically. In this paper, we present two analytical approaches to the study of habitat loss and its metapopulation dynamic consequences incorporating spatial correlation in both metapopulation dynamics as well as in the pattern of habitat destruction. One approach is based on a measure called metapopulation capacity, given by the dominant eigenvalue of a "landscape" matrix, which encapsulates the effects of landscape structure on population extinctions and colonizations. The other approach is based on pair approximation. These models allow us to examine analytically the effects of spatial structure in habitat loss on the equilibrium metapopulation size and the threshold condition for persistence. In contrast to the pair approximation based approaches, the metapopulation capacity based approach allows us to consider species with long as well as short dispersal range and landscapes with spatial correlation at different scales. The two methods make dissimilar assumptions, but the broad conclusions concerning the consequences of spatial correlation in the landscape structure are the same. Our results show that increasing correlation in the spatial arrangement of the remaining habitat increases patch occupancy, that this increase is more evident for species with short-range than long-range dispersal, and that to be most beneficial for metapopulation size, the range of spatial correlation in landscape structure should be at least a few times greater than the dispersal range of the species.


Antithrombin III, plasminogen and alpha 2 antiplasmin in jaundice. Clinical usefulness and prognostic significance.
In this prospective study, antithrombin III, plasminogen and alpha 2 antiplasmin which are synthetised by the liver were measured and compared with the Normotest, Thrombotest and fibrinogen concentrations in 92 consecutive jaundiced patients. Antithrombin III appeared to be the most discriminant coagulation test in differentiating hepatocellular from cholestatic jaundice. A high correlation was observed between antithrombin III, plasminogen and alpha 2 antiplasmin values suggesting that the liver synthesis of these parameters was closely linked. The prognostic significance of the blood coagulation tests in patients with jaundice has been studied. In parenchymatous liver disease, antithrombin III, plasminogen and alpha 2 antiplasmin were superior to the Normotest, Thrombotest and fibrinogen concentrations in predicting the prognosis of the patients at the time of admission. In cholestatic jaundice, however, none of the blood coagulation tests studied had a prognostic significance.


ALBI/ST ratio versus FIB-4 and APRI as a predictor of posthepatectomy liver failure in hepatocellular carcinoma patients.
A precise and noninvasive method to predict posthepatectomy liver failure (PHLF) in clinical practice is still lacking. Liver fibrosis or cirrhosis accompanied with varying degrees of portal hypertension plays an important role in the occurrence of PHLF in hepatocellular carcinoma (HCC) patients. This study aims to compare the predictive ability of the albumin-bilirubin score to spleen thickness ratio (ALBI/ST) versus fibrosis-4 index (FIB-4) and aspartate aminotransferase to platelet count ratio index (ARPI) for the occurrence of PHLF. We retrospectively enrolled 932 patients who underwent liver resection for HCC between 2010 and 2017. The predictive accuracy of ALBI/ST ratio, FIB-4, and APRI for occurrence of PHLF was evaluated by receiver operating characteristic curve analysis. PHLF was diagnosed in 69 (7.4%) patients. The ALBI/ST ratio was found to be a significant predictor of PHLF. The AUC of ALBI/ST (AUC = 0.774; 95% CI, 0.731-0.817; P <.001) was larger than that of FIB-4 (AUC = 0.696; 95% CI, 0.634-0.759; P <.001) and APRI (AUC = 0.697; 95% CI, 0.629-0.764; P <.001). Multivariate analysis demonstrated that ALBI/ST ratio was a strong risk factor of PHLF in all hepatectomy subgroups. In conclusion, the ALBI/ST ratio has a superior predictive ability for PHLF compared with APRI and FIB-4.


Measurement of body fat in healthy elderly men: a comparison of methods.
Nutritional evaluation of elderly people is of great importance. Two-component methods for body composition assessment, such as anthropometry and bioelectrical impedance (BIA), are widely used in clinical practice, but their fundamental assumptions may be invalid in older people. Dual-energy X-ray absorptiometry (DXA) is a relatively new method for reliable and direct measurements of body mass in its three basic components: total body bone mineral content (TBBMC), mineral free lean tissue mass (LTM), and fat. In this study, percent body fat (%BF) estimates from anthropometry and BIA in men of various ages were compared with corresponding measurements by DXA. Body fat percentage was estimated in 67 men aged 20-95 by anthropometric measurements (skinfold thickness, body mass index, or BMI), BIA, and DXA. Age-specific equations were used for anthropometry and BIA. Limits of agreement were calculated between DXA and the other methods. The equations based on BMI and BIA systematically overestimated %BF with respect to %BF measured by DXA in people of all ages. Intermethod difference between DXA and skinfold thicknesses was less marked, but in over-80-year-olds %BF predicted by skinfold measurements underestimated %BF measured by DXA. Interindividual and age-related variation in TBBMC and in fat-free mass mineralization could partly explain the intermethod differences found between DXA and the other methods. Because of practical constraints, anthropometry and BIA are often the only available options for body composition assessment in clinical routine; therefore, further research on the validity and improvement of these methods in older people is indicated.


Medical work force changes. Implications for general practice in Victoria.
Annual surveys have supported claims that the medical work force has been increasing too rapidly and that the intake of Australian and foreign graduates should be reduced. The increase has led to changes in distribution, choice of vocation, style and work content. Female doctors have increased their working hours, are poorly represented in some specialties and are less likely than men to practice outside the metropolitan area.


Divided and focused attention in patients with lesion of the prefrontal cortex.
Despite the common claim of attention disorders in patients with frontal lobe lesion, attention has been poorly investigated and its contribution to behavioral changes has not been studied. The aim of this study was to assess divided (Experiment I) and focused attention (Experiment II) in patients with prefrontal damage. The study used simple detection tests measuring reaction times (RT) to successive stimuli of one modality and of randomly varying modalities (divided attention) and Go No-Go tests (focused attention). Experiment I showed that RT difference between patients and controls increased when stimuli modality was uncertain, a result we attributed to a deficit of divided attention. Experiment II showed that patients remained sensitive to irrelevant stimuli, demonstrating their inability to focus attention. The prominent behavioral change in patients consisted of increased distractibility which was correlated with divided and focused attention deficits. Finally, the presence on magnetic resonance imaging of a left lesion in the superior part of the prefrontal cortex and in the head of the caudate nucleus was the best predictor of attention disorders. In conclusion, this study shows that patients with a prefrontal lesion suffer from divided and focused attention deficits that correspond to behavioral changes.


Speciation analysis of both inorganic and organic 129I in seawater and its application in the study of the marine iodine cycle.
A complete protocol is presented for the speciation analysis of 129I for both inorganic and organic iodine in seawater using coprecipitation and solid-phase extraction (SPE) combined with accelerator mass spectrometry (AMS). By modifying the iodide separation process and adding a crossover removal step, the improved coprecipitation method significantly reduces the cross-contamination of iodide and iodate to less than 0.05% in the speciation analysis of inorganic 129I, with the separation efficiencies of about 95% and 93% for iodide and iodate, respectively. The SPE-DOI method for the dissolved organic 129I (DO129I) analysis was developed, whereby we report the first direct observation of DO129I/DO127I atom ratios in seawater in this paper. 129I species in seawater from Tokyo Bay were analysed. The 129I results demonstrated that our protocol for speciation analysis of 129I is reliable and provided new insights into understanding the iodine cycle.


Principles and Pitfalls: a Guide to Death Certification.
Death certificates serve the critical functions of providing documentation for legal/administrative purposes and vital statistics for epidemiologic/health policy purposes. In order to satisfy these functions, it is important that death certificates be filled out completely, accurately, and promptly. The high error rate in death certification has been documented in multiple prior studies, as has the effectiveness of educational training interventions at mitigating errors. The following guide to death certification is intended to illustrate some basic principles and common pitfalls in electronic death registration with the goal of improving death certification accuracy.


Lithium formate EPR dosimetry for verifications of planned dose distributions prior to intensity-modulated radiation therapy.
The objective of the present investigation was to evaluate lithium formate electron paramagnetic resonance (EPR) dosimetry for measurement of dose distributions in phantoms prior to intensity-modulated radiation therapy (IMRT). Lithium formate monohydrate tablets were carefully prepared, and blind tests were performed in clinically relevant situations in order to determine the precision and accuracy of the method. Further experiments confirmed that within the accuracy of the current method, the dosimeter response was independent of beam energies and dose rates used for IMRT treatments. The method was applied to IMRT treatment plans, and the dose determinations were compared to ionization chamber measurements. The experiments showed that absorbed doses above 3 Gy could be measured with an uncertainty of less than 2.5% of the dose (coverage factor kappa = 1.96). Measurement time was about 15 min using a well-calibrated dosimeter batch. The conclusion drawn from the investigation was that lithium formate EPR dosimetry is a promising new tool for absorbed dose measurements in external beam radiation therapy, especially for doses above 3 Gy.


Safety and Tolerability of Laser Hair Depilation in Pilonidal Disease: A Pilot Study.
Pilonidal disease is a common and painful disorder that can be challenging to manage. Recurrent surgical treatment is often warranted and may result in significant morbidity, with reported wound complication rates as high as 30%. Laser hair depilation of the natal cleft may decrease the incidence of recurrence. The purpose of this study was to assess the safety and tolerability of laser hair depilation in adolescents with pilonidal disease. We performed a prospective, single arm, pilot trial of laser hair depilation to the natal cleft in 13 patients with pilonidal disease. Each patient received an outpatient laser depilation treatment every four weeks with a goal of five total treatments. Follow-up tolerability was measured after each treatment by obtaining Likert scale, patient-reported, pain scores immediately after laser treatment and every six hours post-treatment, for the first 24 hours. Consistent pain scores <4 were used as a proxy for tolerability. The primary end point was tolerability and safety, defined as pain scores consistently <4 and no deep second-degree burns during the 24-hour post-treatment period. The secondary end point was disease recurrence at one year. Thirteen patients were enrolled with 12 patients completing five laser depilation treatment sessions and one patient completing only four. There was 100% tolerability of treatments with no occurrence of second-degree burns. No patient was unable to complete a treatment session because of discomfort. Significantly diminished hair growth was noted after three treatments. All 13 patients were recurrence-free at a median follow-up of 13 months post-treatment initiation. Laser hair depilation is safe and well tolerated in adolescents with pilonidal disease and may be effective at decreasing pilonidal disease recurrence. A prospective randomized controlled trial is planned to determine effectiveness of laser hair depilation compared with chemical/mechanical depilation methods in preventing pilonidal disease recurrence.


Drying of open animal joints in vivo subsequently causes cartilage degeneration.
During open orthopaedic surgery, joints may be exposed to air, potentially leading to cartilage drying and chondrocyte death, however, the long-term effects of joint drying in vivo are poorly understood. We used an animal model to investigate the subsequent effects of joint drying on cartilage and chondrocytes. The patellar groove of anaesthetised rats was exposed (sham-operated), or exposed and then subjected to laminar airflow (0.25m/s; 60 minutes) before wounds were sutured and animals recovered. Animals were monitored for up to eight weeks and then sacrificed. Cartilage and chondrocyte properties were studied by histology and confocal microscopy, respectively. Joint drying caused extensive chondrocyte death within the superficial regions of cartilage. Histology of dried cartilage demonstrated a loss of surface integrity at four weeks, fibrillations at eight weeks, and an increased modified Mankin score (p < 0.001). Cartilage thickness increased (p < 0.001), whereas chondrocyte density decreased at four weeks (p < 0.001), but then increased towards sham-operated levels (p < 0.01) at eight weeks. By week eight, chondrocyte pairing/clustering and cell volume increased (p < 0.05; p < 0.001, respectively). These in vivo results demonstrated for the first time that as a result of laminar airflow, cartilage degeneration occurred which has characteristics similar to those seen in early osteoarthritis. Maintenance of adequate cartilage hydration during open orthopaedic surgery is therefore of paramount importance.Cite this article: Dr A. Hall. Drying of open animal joints in vivo subsequently causes cartilage degeneration. Bone Joint Res 2016;5:137-144. DOI: 10.1302/2046-3758.54.2000594.


Comparing suicide attempters, suicide ideators, and nonsuicidal homeless and runaway adolescents.
This study considers variables that best distinguish among attempters, ideators, and nonsuicidal youth in a sample of 527 homeless and runaway adolescents from four Midwestern states. Univariate results indicate that attempters are significantly more likely than ideators and nonsuicidal youth to have experienced physical or sexual abuse by an adult caretaker, to have experienced sexual victimization while on their own, and to have a friend who attempted suicide. Multivariate analyses reveal five variables that best distinguish among the three groups: self-esteem, depression, physical abuse, sexual abuse, and having a friend who attempted suicide. Further analysis suggests that the accumulation of these risk factors greatly increases the chance that these youth will engage in suicidal behavior.


Primary Budd-Chiari syndrome: its significance for the choice of surgical management of a patent right inferior hepatic vein.
Budd-Chiari syndrome is still a major problem and the overall prognosis for the patients is dismal and disappointing. The case history of a patient with not only outflow obstruction of the hepatic vein but also complete obstruction of the retrohepatic inferior vena cava is presented. She had a patent right inferior hepatic vein which partially decompressed the liver via a rich network of venous collaterals. Management included an inferior vena cava to inferior vena cava shunt using a Goretex graft. The patient fared well and the postoperative course was satisfactory. The case history of this patient illustrates the importance of precise pre-operative investigations for the choice of the type of surgical management. Each patient has to be considered individually on the basis of his or her mechanical peculiarities.


Identification, expression profiling of a grass carp TLR8 and its inhibition leading to the resistance to reovirus in CIK cells.
TLR8 (toll-like receptor 8), a homolog of TLR3, TLR7 and TLR9 as prototypical intracellular members of TLR family, is generally associated with sensing single stranded RNA and plays a pivotal role in antiviral immune response. In this study, a TLR8 gene from grass carp Ctenopharyngodon idella (designated as CiTLR8) was obtained and characterized. The full-length cDNA of CiTLR8 was of 3766 bp. The open reading frame was of 3072 bp and encoded a polypeptide of 1023 amino acids, including seventeen LRR (leucine-rich repeat) motifs, one transmembrane domain and one TIR (toll/interleukin-1 receptor) domain. A single intron with the size of 839 bp was found on the neck of start codon (ATG). CiTLR8 mRNA was ubiquitously expressed in the 15 tested tissues and the expression level in gas bladder, spleen, brain, hindgut and trunk kidney tissues was high. Besides, the CiTLR8 expression in spleen and head kidney was significantly up-regulated and reached peak at 24 h post-injection of grass carp reovirus (GCRV). CiTLR8 transcription reached peak at 8 h and then declined below the normal level post-GCRV infection in the C. idella kidney (CIK) cell line; and it was rapidly and significantly down-regulated by the stimulation of the synthetic double-stranded RNA polyriboinosinic-polyribocytidylic acid sodium salt (poly I:C) in CIK cells in a dose and time-dependent manner. The inhibitor expression vectors were constructed and transfected into CIK cell line to obtain stably expressing shRNA targeting TLR8. In CiTLR8-knockdown cells, CiTLR7 transcript weakly increased, CiIFN-I mRNA was significantly down-regulated, and the expression of CiMyD88, CiIRF7 and CiMx1 scarcely changed. Post poly I:C stimulation, CiTLR8, CiTLR7 and CiMyD88 transcripts significantly increased, CiIRF7 was down-regulated after an initial phase of increase, and CiIFN-I and CiMx1 transcripts were up-regulated. After GCRV infection, the transcripts of CiTLR8, CiTLR7, CiMyD88 and CiIRF7 were up-regulated, but CiIFN-I and CiMx1 transcripts were inhibited. Nevertheless, cells transfected with pshTLR8 vectors had strong resistance against GCRV injection, suggesting CiTLR8 might play a negative role in antiviral immune response. These results collectively suggested that CiTLR8 was a novel member of TLR gene family, engaging in antiviral innate immune defense in C. idella, which laid a foundation for the further mechanism research of TLR8 in fishes.


A comprehensive approach to health promotion for the reduction of dental caries in remote Indigenous Australian children: a clustered randomised controlled trial.
To evaluate the effect of a community-oriented primary health care (CPHC) intervention on oral health behaviours of Indigenous preschool children living in remote communities of Australia's Northern Territory. The study was a community-clustered randomised controlled trial over two years, set in 30 remote Indigenous communities in the Northern Territory of Australia. Children aged 18-47 months at baseline were enrolled in the study. The intervention included fluoride varnish applications, training of primary care workers, and health promotion for oral health at an individual, family and community level. Intervention communities received six-monthly visits over two years and control communities were visited at baseline and two years later with no contact in the intervening period. The outcome measures reported in this paper are the impact of the intervention on two secondary endpoints: oral health promotion activities in the community and personal oral health practice of children. The intervention did not produce any significant change in oral health behaviours, clinical measures of oral hygiene, or community programmes promoting oral health. Dental caries can be reduced but will continue to be a problem among young remote Indigenous children while they experience major social disadvantage.


Valve surgery in congenital heart disease.
Congenital valve disease (CVD) occurs in isolated form or as part of complex malformations and presents distinct epidemiology, including: young age at onset; high prevalence of associated pathology; history of prior operations; critical clinical presentation. Therefore, multiple interventions are often needed, highlighting the palliative character of CVD surgery. At the same time, long-term survival and satisfactory quality of life expectations must be satisfied in a young, active patient population. The present study analyzes the unique aspects of surgery for CVD by reviewing clinical experience with 565 consecutive patients operated during a 7-year period. Treatment options and outcome are assessed with reference to the ability of respecting the unique demands of patients with CVD. In addition, future developments of CVD management are discussed.


ATP2B1 gene rs71454161, rs73196661 and rs73196675 polymorphisms in eclampsia.
We aimed to explore the associations of the ATP2B1 gene polymorphisms with eclampsia. A total of 150 patients with eclampsia (disease group) and 150 healthy pregnant women (control group) were taken as the subjects of study. The peripheral blood of the two groups of subjects was collected to extract deoxyribonucleic acids (DNAs), and the ATP2B1 gene rs71454161, rs73196661 and rs73196675 polymorphisms were detected by sequencing the Polymerase Chain Reaction (PCR) products, and then, analyzed combined with gene expression determined via Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR) and clinical indicators, such as 24-h urine protein, platelets, and LDH. A difference was observed in the allele distribution of ATP2B1 gene rs71454161 (p=0.000) and rs73196661 (p=0.011) between the disease group and control group. Disease group exhibited higher frequencies of allele G of rs71454161 and allele T of rs73196661 than control group. Besides, there was a difference in the genotype distribution of ATP2B1 gene rs71454161 (p=0.000), rs73196661 (p=0.000) and rs73196675 (p=0.000) between disease group and control group. Disease group exhibited higher frequencies of genotype GG of rs71454161, genotype TT of rs73196661 and genotype CG of rs73196675 than control group. Moreover, a difference in the distributions of ATP2B1 gene rs71454161 (p=0.000) and rs73196661 (p=0.014) was found between the two groups in the dominant model. Disease group exhibited lower frequencies of AA+AG of rs71454161 and CC+CT of rs73196661 than control group in the dominant model. Differences in the distributions of haplotypes ACC (p=0.000), ATC (p=0.047) and GTC (p=0.000) of ATP2B1 gene rs71454161, rs73196661 and rs73196675 were observed between disease group and control group. Furthermore, a high degree of linkage disequilibrium was detected between rs71454161 and rs73196661 (D'=0.329). The ATP2B1 gene rs73196675 polymorphism was evidently correlated with the gene expression of ATP2B1 (p<0.05), and the patients with genotype GG had a lower expression level of ATP2B1. The ATP2B1 gene rs71454161 was evidently correlated with the 24-h urinary protein in eclampsia patients (p=0.021), and the patients with genotype AG had a higher level of 24-h urinary proteins. The rs73196661 polymorphism was significantly correlated with LDH (p=0.000), and the patients with genotype CC had a higher level of LDH. The ATP2B1 gene polymorphism was significantly correlated with the occurrence and progression of eclampsia.


A Japanese familial ALS patient with autonomic failure and a p.Cys146Arg mutation in the gene for SOD1 (SOD1).
We describe a Japanese man with familial amyotrophic lateral sclerosis (ALS) associated with a p.Cys146Arg mutation in the copper/zinc superoxide dismutase gene (SOD1). The patient developed bulbar signs followed by rapidly progressive limb muscle weakness. The prominent clinical feature was orthostatic hypotension due to autonomic failure, which occurred after he underwent tracheostomy 1 year and 3 months after the onset. Thereafter, he required mechanical ventilation and progressed to communication stage V (totally locked-in state) 7 years after the onset. Neuropathology showed ALS with posterior column degeneration and multiple system degeneration. Severe neuronal loss in the intermediolateral nucleus was also observed. Two previously reported cases of ALS patients with autonomic failure showed severe neuronal loss in the intermediolateral nucleus in addition to degeneration of the motor neurons. Thus, autonomic failure due to neuronal loss in the intermediolateral nucleus could present in patients with ALS associated with certain mutations in SOD1.


Synthesis and characterization of low surface energy thermoplastic polyurethane elastomers based on polydimethylsiloxane.
Organosilicon modified polyurethane elastomers (Si-MTPUs) were synthesized in order to improve the anti-graffiti property of thermoplastic polyurethane elastomers (TPUs). Si-MTPUs were prepared from polydimethylsiloxane (PDMS) and polytetramethylene glycol (PTMG) as mixed soft segment, 1,4-butanediol (BDO) and imidazole salt ionic liquid N-glyceryl-N-methyl imidazolium chloride ([MIMl,g]Cl) used as chain extender, and 4,4'-dicyclohexylmethane diisocyanate (HMDI). The structure, thermal stability, mechanical properties and physical crosslinking density of Si-MTPUs were characterized by Fourier transform infrared spectroscopy (FTIR), thermogravimetry analysis (TGA), mechanical test and low field nuclear magnetic resonance. Surface energy and water absorption were characterized by static contact angle test and water resistance test, and anti-graffiti and self-cleaning properties were characterized with water, milk, ink, lipstick, oily markers and spray paint. It was found that the mechanical properties of Si-MTPU-10 with the content of PDMS 10 wt% were optimized, with a maximum tensile strength of 32.3 MPa and elongation at break of 656%. Surface energy reached the minimum value of 23.1 mN m-1 with the best anti-graffiti performance, which no longer decreased with the increase of PDMS contents. This work provides novel idea and strategy for the preparation of low surface energy TPUs.


Prophylactic tetracycline does not diminish the severity of epidermal growth factor receptor (EGFR) inhibitor-induced rash: results from the North Central Cancer Treatment Group (Supplementary N03CB).
Previous studies suggest tetracycline and other antibiotics lessen the severity of epidermal growth factor receptor (EGFR) inhibitor-induced rash. This study sought to confirm such findings. Patients starting an EGFR inhibitor were eligible for this randomized, double-blinded, placebo-controlled study and had to be rash-free. They were then randomly assigned to tetracycline 500 mg orally twice a day for 28 days versus a placebo. Rash development and severity (monthly physician assessment and weekly patient-reported questionnaires), quality of life (SKINDEX-16), and adverse events were monitored during the 4-week intervention and then for an additional 4 weeks. The primary objective was to compare the incidence of grade 2 or worse rash between study arms; 32 patients per group provided a 90% probability of detecting a 40% difference in incidence with a type I error rate of 0.05 (two-sided). Sixty-five patients were enrolled, and groups were balanced on baseline characteristics. During the first 4 weeks, healthcare provider-reported data found that 27 tetracycline-treated patients (82%) and 24 placebo-exposed patients (75%) developed a rash. This rash was a grade 2+ in 17 (52%) and 14 (44%), respectively (p = 0.62). Comparable grade 2+ rash rates were observed during weeks 5 through 8 as well as with patient-reported rash data throughout the study period. Quality of life was comparable across study arms, and tetracycline was well tolerated. Although previous studies suggest otherwise, this randomized, double-blinded, placebo-controlled study did not find that tetracycline lessened rash incidence or severity in patients who were taking EGFR inhibitors.


Carbon Quantum Dot Implanted Graphite Carbon Nitride Nanotubes: Excellent Charge Separation and Enhanced Photocatalytic Hydrogen Evolution.
Graphite carbon nitride (g-C3 N4 ) is a promising candidate for photocatalytic hydrogen production, but only shows moderate activity owing to sluggish photocarrier transfer and insufficient light absorption. Herein, carbon quantum dots (CQDs) implanted in the surface plane of g-C3 N4 nanotubes were synthesized by thermal polymerization of freeze-dried urea and CQDs precursor. The CQD-implanted g-C3 N4 nanotubes (CCTs) could simultaneously facilitate photoelectron transport and suppress charge recombination through their specially coupled heterogeneous interface. The electronic structure and morphology were optimized in the CCTs, contributing to greater visible light absorption and a weakened barrier of the photocarrier transfer. As a result, the CCTs exhibited efficient photocatalytic performance under light irradiation with a high H2 production rate of 3538.3 μmol g-1 h-1 and a notable quantum yield of 10.94 % at 420 nm.


Diagnostic accuracy of cone beam computed tomography and conventional multislice spiral tomography in sheep mandibular condyle fractures.
the aim of this study was to compare diagnostic accuracy of cone beam CT (CBCT) and multislice CT in artificially created fractures of the sheep mandibular condyle. 63 full-thickness sheep heads were used in this study. Two surgeons created the fractures, which were either displaced or non-displaced. CBCT images were acquired by the NewTom 3G CBCT scanner (NIM, Verona, Italy) and CT imaging was performed using the Toshiba Aquillon multislice CT scanner (Toshiba Medical Systems, Otawara, Japan). Two-dimensional (2D) cross-sectional images and three-dimensional (3D) reconstructions were evaluated by two observers who were asked to determine the presence or absence of fracture and displacement, the type of fracture, anatomical localization and type of displacement. The naked-eye inspection during surgery served as the gold standard. Inter- and intra-observer agreements were calculated with weighted kappa statistics. The receiver operating characteristics (ROC) curve analyses were used to compare statistically the area under the curve (AUC) of both imaging modalities. kappa coefficients of intra- and interobserver agreement scores varied between 0.56 - 0.98, which were classified as moderate and excellent, respectively. There was no statistically significant difference between the imaging modalities, which were both sensitive and specific for the diagnosis of sheep condylar fractures. this study confirms that CBCT is similar to CT in the diagnosis of different types of experimentally created sheep condylar fractures and can provide a cost- and dose-effective diagnostic option.


New insights into the formation of volatile compounds in mainstream cigarette smoke.
A sampling system has been set up to monitor a group of volatile smoke analytes (nitric oxide, acetaldehyde, acetone, benzene, toluene, 1,3 butadiene, isoprene and carbon dioxide) from mainstream cigarette smoke on a puff-resolved basis. The system was able to record gas evolution profiles during puffing and interpuff periods without interruption (e.g. taking clearing puffs). Gas phase smoke analytes were sampled as close to the mouth end of the cigarette filter as possible in order to minimise any dead volume effect. The results revealed that, for some volatile species, a significant fraction (e.g. up to 30% for benzene) in the cigarette mainstream smoke had been generated during the preceding smoulder period. These species were trapped or absorbed within the cigarette rod and then subsequently eluted during the puff. The identification of the two sources of the mainstream smoke, a smouldering source and a puffing source, has not been reported before. The observation contributes to the fundamental knowledge of the cigarette smoke formation and may have implications on wider smoke chemistry and associated effects.


Understanding Regium Bonds and their Competition with Hydrogen Bonds in Au2 :HX Complexes.
A theoretical study of the regium and hydrogen bonds (RB and HB, respectively) in Au2 :HX complexes has been carried out by means of CCSD(T) calculations. The theoretical study shows as overall outcome that in all cases the complexes exhibiting RB are more stable that those with HB. The binding energies for RB complexes range between -24 and -180 kJ ⋅ mol-1, whereas those of the HB complexes are between -6 and -19 kJ ⋅ mol-1 . DFT-SAPT also indicated that HB complexes are governed by electrostatics, but RB complexes present larger contribution of the induction term to the total attractive forces. 197 Au chemical shifts have been calculated using the relativistic ZORA Hamiltonian.


MicroRNA-497 suppresses proliferation and induces apoptosis in prostate cancer cells.
MicroRNAs (miRNAs) are a class of endogenously expressed small, non-coding, single-stranded RNAs that negatively regulate gene expression, mainly by binding to 3'- untranslated regions (3'UTR) of their target messenger RNAs (mRNAs), which cause blocks of translation and/or mRNA cleavage. Recently, miRNAprofiling studies demonstrated the microRNA-497 (miR-497) level to be down-regulated in all prostate carcinomas compared with BPH samples. The purpose of this study was to investigate the potential role of miR-497 in human prostate cancer. Proliferation, cell cycle and apoptosis assays were conducted to explore the potential function of miR-497 in human prostate cancer cells. Results showed that miR-497 suppressed cellular growth and initiated G0/G1 phase arrest of LNCaP and PC-3 cells. We also observed that miR-497 increased the percentage of apoptotic cells by increasing caspase-3/7 activity. Taken together, our results demonstrated that miR-497 can inhibit growth and induce apoptosis by caspase-3 activation in prostate cancer cells, which suggest its use as a potential therapeutic target in the future.


Calcium dynamics in root cells of Arabidopsis thaliana visualized with selective plane illumination microscopy.
Selective Plane Illumination Microscopy (SPIM) is an imaging technique particularly suited for long term in-vivo analysis of transparent specimens, able to visualize small organs or entire organisms, at cellular and eventually even subcellular resolution. Here we report the application of SPIM in Calcium imaging based on Förster Resonance Energy Transfer (FRET). Transgenic Arabidopsis plants expressing the genetically encoded-FRET-based Ca(2+) probe Cameleon, in the cytosol or nucleus, were used to demonstrate that SPIM enables ratiometric fluorescence imaging at high spatial and temporal resolution, both at tissue and single cell level. The SPIM-FRET technique enabled us to follow nuclear and cytosolic Ca(2+) dynamics in Arabidopsis root tip cells, deep inside the organ, in response to different stimuli. A relevant physiological phenomenon, namely Ca(2+) signal percolation, predicted in previous studies, has been directly visualized.


Exploring Electrostatic Effects on the Hydrogen Bond Network of Liquid Water through Many-Body Molecular Dynamics.
To probe the dynamic nature of the hydrogen bond network in water, linear and nonlinear infrared spectra of dilute HOD in H2O are computed from many-body molecular dynamics simulations with the MB-pol potential, which have been shown to accurately predict the properties of water from the gas to the condensed phase. The effects of various approximations to the many-body expansion of the dipole moment surface on the OD-stretch absorption line shapes are analyzed at different levels of theory. The interplay between effects associated with the variation of the HOD dipole moment and instantaneous nuclear configurations causes qualitative differences in the absorption profiles, which are traced back to how induction contributions are treated within the many-body formalism. Further analysis of the multidimensional infrared spectra demonstrates that the spectral diffusion of the OD stretching frequencies depends explicitly on the level of truncation in the many-body expansion of the dipole moment in the short-time regime that is associated with intact hydrogen-bond dynamics. In contrast, the long-time evolution of spectral diffusion, describing collective rearrangements of the hydrogen-bond network, is effectively independent of the details with which many-body contributions to the dipole moment are represented.


Caroli's disease - a report of two siblings.
A 26-year-old man had suffered from several episodes of right upper-quadrant pain for 6 months. Abdominal ultrasonography showed multiple saccular dilatations of the intrahepatic biliary tract, with hepatolithiasis at the bilateral hepatic lobe. Abdominal computed tomography also revealed saccularly dilated intrahepatic ducts with hepatolithiasis. Communication between saccular dilatations of the intrahepatic biliary tract and normal bile ducts was demonstrated by endoscopic retrograde cholangiopancreatography. Choledochal cyst type V (Caroli's disease) was diagnosed. The patient's 29-year-old sister was also diagnosed with Caroli's disease based on abdominal sonography. An ultrasonography survey was carried out on the family. Reports of Caroli's disease occurring in two siblings are rare in the literature.


Stomatal Conductance and Sulfur Uptake of Five Clones of Populus tremuloides Exposed to Sulfur Dioxide.
Plants of five clones of Populus tremuloides Michx. were exposed to 0, 0.2 or 0.5 microliter per liter SO(2) for 8 hours in controlled environment chambers. In the absence of the pollutant, two pollution-resistant clones maintained consistently lower daytime diffusive conductance (LDC) than did a highly susceptible clone or two moderately resistant clones. Differences in LDC among the latter three clones were not significant. At 0.2 microliter per liter SO(2), LDC decreased in the susceptible clone after 8 hours fumigation while the LDC of the other clones was not affected. Fumigation with 0.5 microliter per liter SO(2) decreased LDC of all five clones during the fumigation. Rates of recovery following fumigation varied with the clone, but the LDC of all clones had returned to control values by the beginning of the night following fumigation. Night LDC was higher in the susceptible clone than in the other clones. Fumigation for 16 hours (14 hours day + 2 hours night) with 0.4 microliter per liter SO(2) decreased night LDC by half. Sulfur uptake studies generally confirmed the results of the conductance measurements. The results show that stomatal conductance is important in determining relative susceptibility of the clones to pollution stress.


Ambulatory EEG telemetry: how good is it?
When someone asks the question, how good is ambulatory EEG telemetry, there is no correct answer. There are many manufacturers of ambulatory EEG technology. Each device has its own strengths and weaknesses. What one is really interested in when one asks such a question needs to be defined in terms of expectations and technical capabilities for the piece of equipment under discussion. Systems exist or can be easily modified to be as sophisticated as the best of the inpatient units. However, is that level of sophistication needed for the ambulatory based recordings? Again, the answer to that is dependent on the ordering physician's expectations. Below is a discussion of the different clinical expectations that are frequently encountered and the needed requirements for an ambulatory system to properly address them.


Advance care planning conversations with palliative patients: looking through the GP's eyes.
Although it is often recommended that general practitioners (GPs) initiate advance care planning (ACP), little is known about their experiences with ACP. This study aimed to identify GP experiences when conducting ACP conversations with palliative patients, and what factors influence these experiences. Dutch GPs (N = 17) who had participated in a training on timely ACP were interviewed. Data from these interviews were analysed using direct content analysis. Four themes were identified: ACP and society, the GP's perceived role in ACP, initiating ACP and tailor-made ACP. ACP was regarded as a 'hot topic'. At the same time, a tendency towards a society in which death is not a natural part of life was recognized, making it difficult to start ACP discussions. Interviewees perceived having ACP discussions as a typical GP task. They found initiating and timing ACP easier with proactive patients, e.g. who are anxious of losing capacity, and much more challenging when it concerned patients with COPD or heart failure. Patients still being treated in hospital posed another difficulty, because they often times are not open to discussion. Furthermore, interviewees emphasized that taking into account changing wishes and the fact that not everything can be anticipated, is of the utmost importance. Moreover, when patients are not open to ACP, at a certain point it should be granted that choosing not to know, for example about where things are going or what possible ways of care planning might be, is also a form of autonomy. ACP currently is a hot topic, which has favourable as well as unfavourable effects. As GPs experience difficulties in initiating ACP if patients are being treated in the hospital, future research could focus on a multidisciplinary ACP approach and the role of medical specialists in ACP. Furthermore, when starting ACP with palliative patients, we recommend starting with current issues. In doing so, a start can be made with future issues kept in view. Although the tension between ACP's focus on the patient's direction and the right not to know can be difficult, ACP has to be tailored to each individual patient.


Headache in autoimmune diseases.
Autoimmune diseases are a group of heterogeneous inflammatory disorders characterized by systemic or localized inflammation, leading to ischemia and tissue destruction. These include disorders like systemic lupus erythematosus and related diseases, systemic vasculitides, and central nervous system (CNS) vasculitis (primary or secondary). Headache is a very common manifestation of CNS involvement of these diseases. Although headache characteristics can be unspecific and often non-diagnostic, it is important to recognize because headache can be the first manifestation of CNS involvement. Prompt recognition and treatment is necessary not only to treat the headache, but also to help prevent serious neurological sequelae that frequently accompany autoimmune diseases. In this review, we discuss headache associated with autoimmune diseases along with important mimics.


Immune cells: plastic players along colorectal cancer progression.
Inflammatory cells are involved in tumour initiation and progression. In parallel, the adaptive immune response plays a key role in fighting tumour growth and dissemination. The double-edged role of the immune system in solid tumours is well represented in colorectal cancer (CRC). The development and progression of CRC are affected by the interactions between the tumour and the host's response, occurring in a milieu named tumour microenvironment. The role of immune cells in human CRC is being unravelled and there is a strong interest in understanding their dynamics as to tumour promotion, immunosurveillance and immunoevasion. A better definition of immune infiltration would be important not only with respect to the 'natural history' of CRC, but in a clinically relevant perspective in the 21st century, with respect to its post-surgical management, including chemotherapy responsiveness. While it is becoming established that the amount of tumour-infiltrating lymphocytes influences the post-surgical progression of early-stage CRC, the relevance of this immune parameter as to chemotherapy responsiveness remains to be clarified. Despite recent experimental work supporting the notion that infiltrating immune cells may influence chemotherapy-mediated tumour cell death, tumour-infiltrating cells are not employed to identify patients who are more likely to benefit from adjuvant treatment. This review focuses on studies addressing the role of innate and adaptive immune cells along the occurrence and the progression of potentially curable CRC.


Measurements of electron-induced neutrons as a tool for determination of electron temperature of fast electrons in the task of optimization laser-produced plasma ions acceleration.
High intensity laser-plasma interaction has attracted considerable interest for a number of years. The laser-plasma interaction is accompanied by generation of various charged particle beams, such as high-energy proton and ions with high charge to mass ratio (Q/M; same as multi-charged ions). Results of simultaneous novel measurements of electron-induced photonuclear neutrons (photoneutron), which are a diagnostic of the laser-plasma interaction, are proposed to use for optimization of the laser-plasma ion generation. The proposed method is demonstrated by the laser irradiation with the intensity of 1 × 10(21) W/cm(2) on the metal foil target. The photoneutrons are measured by using NE213 liquid scintillation detectors. Heavy-ion signal is registered with the CR-39 track detector simultaneously. The measured signals of the electron-induced photoneutrons are well reproduced by using the Particle and Heavy Ion Transport code System. The results obtained provide useful approach for analyzing the various laser based ion beams.


FvZFP1 confers transgenic Nicotiana benthamiana resistance against plant pathogens and improves tolerance to abiotic stresses.
Zinc finger proteins can induce plant resistance and activate the expression of molecules involved in the resistance pathway in response to harsh environmental conditions. Previously, we found that a novel Fragaria vesca zinc finger protein interacts with the P6 protein encoded by a strawberry vein banding virus. However, the molecular mechanism of the zinc finger protein in plant stress resistance is still unknown. In this study, we reported the identification and functional characterization of the RING finger and CHY zinc finger domain-containing protein 1 (FvZFP1). The overexpression of FvZFP1 in Nicotiana benthamiana enhanced resistance to tobacco mosaic virus (TMV) and Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) infection by increasing ROS content. Additionally, FvZFP1 overexpression upregulated salicylic acid (SA) response-related gene expression as well as SA accumulation following TMV and Pst DC3000 infection. Furthermore, FvZFP1 overexpression resulted in increased salinity and drought stress tolerance by increasing SOD activity and decreasing MDA content. Overexpression of FvZFP1 also activated the ABA pathway under salinity or drought conditions. To our knowledge, this is the first study on the involvement of F. vesca zinc finger protein in crosstalk between biotic and abiotic stress signaling pathways, suggesting that FvZFP1 is a candidate gene for the improvement of resistance in response to multiple stresses.


Using MeSH (medical subject headings) to enhance PubMed search strategies for evidence-based practice in physical therapy.
Evidence-based practice (EBP) is an important paradigm in health care. Physical therapists report lack of knowledge and time constraints as barriers to EBP. The purpose of this technical report is to illustrate how Medical Subject Headings (MeSH), a controlled vocabulary thesaurus of indexing terms, is used to efficiently search MEDLINE, the largest component of PubMed. Using clinical questions, this report illustrates how search terms common to physical therapist practice do or do not map to appropriate MeSH terms. A PubMed search strategy that takes advantage of text words and MeSH terms is provided. A search of 139 terms and 13 acronyms was conducted to determine whether they appropriately mapped to a MeSH term. The search results were categorized into 1 of 5 outcomes. Nearly half (66/139) of the search terms mapped to an appropriate MeSH term (outcome 1). When a search term did not appropriately map to a MeSH term, it was entered into the MeSH database to search for an appropriate MeSH term. Twenty-one appropriate MeSH terms were found (outcomes 2 and 4), and there were 52 search terms for which an appropriate MeSH term was not found (outcomes 3 and 5). Nearly half of the acronyms did not map to an appropriate MeSH term, and an appropriate MeSH term was not found in the database. The results are based on a limited number of search terms and acronyms. Understanding how search terms map to MeSH terms and using the PubMed search strategy can enable physical therapists to take full advantage of available MeSH terms and should result in more-efficient and better-informed searches.


Comparing the conformational behavior of a series of diastereomeric cyclic urea HIV-1 inhibitors using the low mode:monte carlo conformational search method.
The conformational flexibility of a series of diastereomeric cyclic urea HIV-1 protease inhibitors has been examined using the Low Mode:Monte Carlo conformational search method. Force fields were validated by a comparison of the energetic ordering of the minimum energy structures on the AMBER/GBSA(water), OPLSAA/GBSA(water) and HF/6-311G/SCRF(water) surfaces. The energetic ordering of the minima on the OPLSAA /GBSA(water) surface was in better agreement with the quantum calculations than the ordering on the AMBER/GBSA(water) surface. An ensemble of low energy structures was generated using OPLSAA/GBSA(water) and used to compare the molecular shape and flexibility of each diastereomer to the experimentally determined binding affinities and crystal structures of closely related systems. The results indicate that diastereomeric solution-phase energetic stability, conformational rigidity and ability to adopt a chair conformation correlate strongly with experimental binding affinities. Rigid body docking suggests that all of the diastereomers adopt solution-phase conformations suitable for alignment with the HIV-1 protease; however, these results indicate that the binding affinities are dependent upon subtle differences in the P1/P1' and P2/P2' substituent orientations.


Olfactory ensheathing cell membrane properties are shaped by connectivity.
Olfactory ensheathing cells (OECs) have been repeatedly implicated in mediating plasticity, particularly in situ in the olfactory nerve in which they support the extension of olfactory sensory neuron (OSN) axons from the olfactory epithelium to the olfactory bulb (OB). OECs are specialized glia whose processes surround OSN axon fascicles within the olfactory nerve and across the OB surface. Despite their purported importance in promoting axon extension, and following transplants, little is known about either morphology or biophysical properties of OECs in situ. In particular, cell-cell interactions that may influence OEC function are largely unexplored. Here, we studied OEC connectivity and morphology in slice preparations, preserving tissue structure and cell-cell interactions. Our analyses showed that OECs form a matrix of cellular projections surrounding axons, unique among glia, and express high levels of connexin-43. Lucifer Yellow injections revealed selective dye coupling among small subgroups of OECs. Two types of OECs were biophysically distinguished with whole-cell voltage-clamp recordings: (1) with low-input resistance (R(i)), linear current profiles, and frequently dye coupled; and (2) with high R(i), nonlinear current profiles, and infrequent dye coupling. Pharmacological blockade of gap junctions changed OEC membrane properties such that linear OECs became nonlinear. Double recordings indicated that the appearance of the nonlinear current profile was associated with the loss of electrical coupling between OECs. We conclude that the diversity of OEC current profiles can be explained by differences in gap-junction connectivity and discuss implications of this diversity for OEC influences on axon growth and excitability.


A fluorescence-based, high-throughput sphingomyelin assay for the analysis of Niemann-Pick disease and other disorders of sphingomyelin metabolism.
Sphingomyelin is an important lipid component of cell membranes and lipoproteins that can be hydrolyzed by sphingomyelinases into ceramide and phosphorylcholine. The Type A and B forms of Niemann-Pick disease (NPD) are lipid storage disorders due to the deficient activity of the enzyme acid sphingomyelinase and the resultant accumulation of sphingomyelin in cells, tissues, and fluids. In this paper we report a new, enzymatic method to quantify the levels of sphingomyelin in plasma, urine, or tissues from NPD patients and mice. In this assay, bacterial sphingomyelinase is first used to hydrolyze sphingomyelin to phosphorylcholine and ceramide. Alkaline phosphatase then generates choline from the phosphorylcholine, and the newly formed choline is then used to generate hydrogen peroxide in a reaction catalyzed by choline oxidase. Finally, with peroxidase as a catalyst, hydrogen peroxide reacts with the Amplex Red reagent to generate a highly fluorescent product, resorufin. These enzymatic reactions are carried out simultaneously in a single 100-microl reaction mixture for 20 min. Use of a 96-well microtiter plate permits automated and sensitive quantification using a plate reader and fluorescence detector. This procedure allowed quantification of sphingomyelin over a broad range from 0.02 to 10 nmol, similar in sensitivity to a recently described radioactive method using diacylglycerol kinase and 50 times more sensitive than a colorimetric, aminoantipyrine/phenol-based assay. To validate this new assay method, we quantified sphingomyelin in plasma, urine, and tissues from normal individuals and from NPD mice and patients. The sphingomyelin content in adult homozygous or heterozygous NPD mouse plasma and urine was significantly elevated compared to that of normal mice. Moreover, the accumulated sphingomyelin in the tissues of NPD mice was 4 to 15 times higher than that in normal mice depending on the tissue analyzed. The sphingomyelin levels in plasma from several Type B NPD patients also was significantly elevated compared to normal individuals of the same age. Based on these results, we propose that this new, fluorescence-based procedure can provide simple, fast, sensitive, and reproducible sphingomyelin quantification in tissues and fluids from normal individuals and NPD patients. It could also be a useful tool for the study of other sphingomyelin-related diseases and in a variety of research settings where sphingomyelin quantification is required.


Understanding protein-ligand interactions: the price of protein flexibility.
In order to design selective, high-affinity ligands to a target protein, it is advantageous to understand the structural determinants for protein-ligand complex formation at the atomic level. In a model system, we have successively mapped the factor Xa binding site onto trypsin, showing that certain mutations influence both protein structure and inhibitor specificity. Our previous studies have shown that introduction of the 172SSFI175 sequence of factor Xa into rat or bovine trypsin results in the destabilisation of the intermediate helix with burial of Phe174 (the down conformation). Surface exposure of the latter residue (the up conformation) is critical for the correct formation of the aromatic box found in factor Xa-ligand complexes. In the present study, we investigate the influence of aromatic residues in position 174. Replacement with the bulky tryptophan (SSWI) shows reduced affinity for benzamidine-based inhibitors (1) and (4), whereas removal of the side-chain (alanine, SSAI) or exchange with a hydrophilic residue (arginine, SSRI) leads to a significant loss in affinity for all inhibitors studied. The variants could be crystallised in the presence of different inhibitors in multiple crystal forms. Structural characterisation of the variants revealed three different conformations of the intermediate helix and 175 loop in SSAI (down, up and super-up), as well as a complete disorder of this region in one crystal form of SSRI, suggesting that the compromised affinity of these variants is related to conformational flexibility. The influence of Glu217, peripheral to the ligand-binding site in factor Xa, was investigated. Introduction of Glu217 into trypsin variants containing the SSFI sequence exhibited enhanced affinity for the factor Xa ligands (2) and (3). The crystal structures of these variants also exhibited the down and super-up conformations, the latter of which could be converted to up upon soaking and binding of inhibitor (2). The improved affinity of the Glu217-containing variants appears to be due to a shift towards the up conformation. Thus, the reduction in affinity caused by conformational variability of the protein target can be partially or wholly offset by compensatory binding to the up conformation. The insights provided by these studies will be helpful in improving our understanding of ligand binding for the drug design process.


Determination of cocaine and benzoylecgonine by derivatization with iodomethane-D3 or PFPA/HFIP in human blood and urine using GC/MS (EI or PCI mode).
A method for the simultaneous detection and quantification of cocaine and benzoylecgonine from human blood and urine has been developed. Cocaine and benzoylecgonine were extracted from blood and urine with solid-phase columns containing C18 packing material. Clean, emulsion-free extracts were obtained. The analytes were derivatized with PFPA/HFIP or iodomethane-D3. The underivatized cocaine and derivatized benzoylecgonine were determined by GC/MS with positive chemical ionization (PCI) and the selected ion monitoring mode. Benzoylecgonine was derivatized with iodomethane-D3 to cocaine-D3. Both derivatives were chromatographed on a CP-SIL 5 capillary column. The recovery of extraction was greater than 70%. The detection limit for the PFPA/HFIP derivatives (20 ng/mL) was better than that for iodomethane-D3 derivatives (40 ng/mL). The procedure is simple, rapid, and reproducible. Standard curves were linear and the procedure was suitable for routine analysis. Using fluorescence polarization immunoassay (TDx, Abbott) (cutoff 100 ng/mL), along with one of the GC/MS methods described, we found no false positive or false negative results.


Rejuvant®, a potential life-extending compound formulation with alpha-ketoglutarate and vitamins, conferred an average 8 year reduction in biological aging, after an average of 7 months of use, in the TruAge DNA methylation test.
The search continues for possible interventions that delay and/or reverse biological aging, resulting in extended healthspan and lifespan. Interventions delaying aging in animal models are well established; however, most lack validation in humans. The length of human lifespan makes it impractical to perform survival analysis. Instead, aging biomarkers, such as DNA methylation (DNAm) clocks, have been developed to monitor biological age. Herein we report a retrospective analysis of DNA methylation age in 42 individuals taking Rejuvant®, an alpha-ketoglutarate based formulation, for an average period of 7 months. DNAm testing was performed at baseline and by the end of treatment with Rejuvant® supplementation. Remarkably, individuals showed an average decrease in biological aging of 8 years (p-value=6.538x10-12). Furthermore, the supplementation with Rejuvant® is robust to individual differences, as indicated by the fact that a large majority of participants decreased their biological age. Moreover, we found that Rejuvant® is of additional benefit to chronologically and biologically older individuals. While continued testing, particularly in a placebo-controlled design, is required, the nearly 8-year reversal in the biological age of individuals taking Rejuvant® for 4 to 10 months is noteworthy, making the natural product cocktail an intriguing candidate to affect human aging.


Pharmacology of endothelium-derived nitric oxide and nitrovasodilators.
Nitric oxide is the active chemical species responsible for the vasodilator action of nitroglycerin, nitroprusside, and related nitrovasodilators. The most potent vasodilator and inhibitor of platelet aggregation known, nitric oxide was recently discovered to occur endogenously as the endothelium-derived relaxing factor. The pharmacology of endothelium-derived nitric oxide is virtually identical to that of the clinically used nitrovasodilators. Although endothelium-derived relaxing factor or endothelium-derived nitric oxide seems to be important in animals, its significance in humans still needs to be shown. We review the recent discoveries in the identification, biosynthesis, metabolism, and biologic actions of endothelium-derived nitric oxide, its significance in humans, and its relation to the clinically used nitrovasodilators.


Photocycloaddition of arenes and allenes.
In this work, we report on a new intramolecular para cycloaddition of arenes with allenes, yielding attractive rigid scaffolds bearing several reactive functionalities to build in further diversity. Bicyclo[2.2.2]octadiene-type products and benzoxepine acetals are formed in this reaction, in ratios and yields depending on the substitution pattern on the aromatic ring, the nature of the chromophore, and the tether. This unprecedented reaction has remarkable features that distinguish it from many other photochemical transformations: it is particularly robust with respect to substituents, it can be scaled up without a notable loss of efficiency, and it can lead to structures with a high degree of complexity in low to good yields. All photochemical precursors could be synthesized readily in three steps. We confirmed the compatibility of the nitrogen atom in the photocycloaddition step, which gives access to a bicyclo[2.2.2]octadiene scaffold with two points that allow further diversification. This reaction was scaled up to multigram quantities without erosion of the typically high yields in photocycloadducts. Sequential deprotection of the N- or C-terminus of bicyclic amino acids gave access to two conformationally constrained unnatural amino acids with different dispositions of the two anchor points.


[Introduction of biologically active fragments of interferon-alpha2 and insulin into the artificial protein albebetin affects immunogenicity of the final construct].
The immunogenicity of the artificial protein albebetin and its derivatives with active peptide fragments was investigated. We also studied the influence of the peptides on the immunogenicity of the whole construct and contribution of each component to the immunogenicity. Two of three studied proteins contained active peptides from human IFN-alpha and insulin. Three continuous antigenic sites with different immunogenic potential were recognized in the chimerical proteins. The interferon fragment was the immunodominant site in the albeferon and albeferon-insulin molecules, while the insulin fragment displayed low immunogenic activity. All continuous B-epitopes are located at the boundaries of the secondary structure elements and at the predicted surface-located sites of albebetin molecule. Thus, peptide fragments attached to the artificial protein carrier can influence immunogenicity of the resulting construct.


Mango Peel Pectin: Recovery, Functionality and Sustainable Uses.
Concerns regarding the overconsumption of natural resources has provoked the recovery of biopolymers from food processing biomass. Furthermore, the current market opportunity for pectin in other areas has increased, necessitating the search for alternative pectin resources. This is also a step towards the sustainable and circular green economy. Mango peel is the byproduct of agro-processing and has been used for high value-added components such as polysaccharide biopolymers. Pectin derived from the peel is yet to be exploited to its greatest extent, particularly in terms of its separation and physiochemical properties, which limit its applicability to dietary fiber in culinary applications. The functionality of the mango peel pectin (MPP) strongly depends on the molecular size and degree of esterification which highlight the importance of isolation and characterisation of pectin from this novel resource. This article therefore provides a useful overview of mango peel as a potential biomaterial for the recovery of MPP. Different extraction techniques and the integrated recovery were also discussed. The utilisation of MPP in different industrial schemes are also detailed out from different perspectives such as the pharmaceutical and biotechnology industries. This review convincingly expresses the significance of MPP, providing a sustainable opportunity for food and pharmaceutical development.


Metamorphic records of multiple seismic cycles during subduction.
Large earthquakes occur in rocks undergoing high-pressure/low-temperature metamorphism during subduction. Rhythmic major-element zoning in garnet is a common product of such metamorphism, and one that must record a fundamental subduction process. We argue that rhythmic major-element zoning in subduction zone garnets from the Franciscan Complex, California, developed in response to growth-dissolution cycles driven by pressure pulses. Using electron probe microanalysis and novel techniques in Raman and synchrotron Fourier transform infrared microspectroscopy, we demonstrate that at least four such pressure pulses, of magnitude 100-350 MPa, occurred over less than 300,000 years. These pressure magnitude and time scale constraints are most consistent with the garnet zoning having resulted from periodic overpressure development-dissipation cycles, related to pore-fluid pressure fluctuations linked to earthquake cycles. This study demonstrates that some metamorphic reactions can track individual earthquake cycles and thereby opens new avenues to the study of seismicity.


Conformations of cycloundecane.
Cycloundecane (1) was shown to exist at -183.1 degrees C as a mixture of the [12323] (approximately 59%) and [335] (approximately 41%) conformations. Populations were determined from the (13)C NMR spectrum, and assignments were based on the (13)C spectra, calculated free energies and chemical shifts, and information from the literature, including X-ray studies of solid derivatives and calculated barriers.


Risk factors of asthma exacerbation based on asthma severity: a nationwide population-based observational study in South Korea.
Asthma exacerbation, associated with many risks factors, can reflect management failure. However, little is known about how risk factors are associated with exacerbation, according to asthma severity. We aimed to investigate differences in risk factors in patients with different asthma severity and evaluate whether risk factors differed between frequent exacerbators and patients with single exacerbation. Nationwide population-based observational study. Korean National Sample Cohort database. We included 22 130 adults with asthma diagnoses more than twice (ICD-10 (International Classification of Diseases, Tenth revision) codes J45 and J46) and one prescription for asthma medication from 2010 to 2011. Asthma exacerbation was defined as having a corticosteroid (CS) burst characterised by a prescription of high-dose oral CS for ≥3 days or one systemic CS injection, hospitalisation or emergency department visit. Among severities, history of CS bursts was significantly associated with exacerbation. In mild and moderate asthma, exacerbation was significantly associated with age ≥45 years, being female, gastro-oesophageal reflux disease and chronic rhinitis. High medication possession ratio (MPR≥50%), compared with low MPR (<20%) showed adjusted ORs of 0.828 (95% CI 0.707 to 0.971) and 0.362 (0.185 to 0.708) in moderate and severe asthma, respectively. In severe asthma, compared with mild asthma, only allergic rhinitis and history of hospitalisation were strongly associated with exacerbation. When comparing frequent exacerbators to patients with single exacerbation, age ≥45 years, atopic dermatitis, anxiety and history of CS burst were significant risk factors in mild and moderate asthma, whereas no risk factors were significant in severe asthma. Different associations between risk factors and asthma exacerbations based on asthma severity suggest that patients with mild asthma require greater attention to their age and comorbidities, whereas those with severe asthma require greater attention to hospitalisation history and drug adherence.


Cloning and Expression of Targeting CuZn-SOD to Central Nervous System.
Oxygen-derived free radicals are thought to be involved in the pathogenesis of a wide range of neurological disorders. Targeted delivery of CuZn-SOD to neurons in central nervous system may have therapeutic value in such diseases. The gene encoding human CuZn-SOD was fused to tetanus toxin fragment C geneto construct a fusion gene, then it was cloned into prokaryotic expression vector pET-22b( ) and baculovirus vector pFastBacHTb, and was expressed in E.coli and Tn-5B1-4 cells, respectively. The recombinant fusion protein has a subunit molecular mass of 68 kD and is recognized by both anti-CuZn-SOD and anti-tetanustoxin antibody. By pyrogallol autooxidation assay, it is shown that the CuZn-SOD moiety retains substantial enzymatic activity, where the TTC moiety might deliver the fusion protein to neurons in central nervous system. So, CuZn-SOD/TTC may be a useful agent for the targeted delivery of CuZn-SOD to neurons.


Management of the unexpected result: compensated hypothyroidism.
The combination of elevated serum thyrotropin and normal serum thyroxine is called compensated or subclinical hypothyroidism. This most commonly represents clinically silent autoimmune thyroiditis. Whether this condition warrants treatment or simply observation is still debated. The risk of developing overt hypothyroidism is high in females with elevated thyrotropin above 10 mU/l and/or positive thyroid microsomal antibodies. Males are also at high risk of progression towards overt hypothyroidism, regardless of antibody status or degree of thyrotropin elevation. We advise routine treatment of only those at high risk of developing overt hypothyroidism.


Synthesis of a series of methyl beta-glycosides of (1----6)-beta-D-galacto-oligosaccharides having one residue deoxygenated at position 3.
Methyl beta-glycosides of beta-(1----6)-linked D-galactobioses (13 and 16) and -galactotrioses (21, 24, and 26) containing a 3-deoxy-beta-D-xylo-hexopyranosyl moiety either as one of the end units or the internal unit have been synthesized. The extension of the oligosaccharide chain was achieved, inter alia, by the use of two newly synthesized glycosyl donors derived from 3-deoxy-D-xylo-hexopyranose, namely, 2,4,6-tri-O-benzoyl-3-deoxy-a-D-xylo-hexopyranosyl chloride (8) and 2,4-di-O-benzoyl-6-O-bromoacetyl-3-deoxy-a-D-xylo-hexopyranosyl chloride (10). Glycosylation reactions were mediated by silver triflate under base-deficient conditions.


Evidence for a contribution of the APOE (but not the ACE) gene to the sleep profile of non-demented elderly adults.
This study aims to investigate alleles of the human apolipoprotein E (APOE) and of the angiotensin-converting enzyme (ACE) genes as risk factors for poor quality of sleep in elderly individuals with no major cognitive decline. This cross-sectional, analytical study was conducted with 163 participants aged 75 years in average and 85% female. Sociodemographic, anthropometric and clinical data were gathered, and sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth scale, with patient followed for years prior to these evaluations to rule out onset of major mental disorders. Genotyping of classic polymorphic sites for the ApoE (rs429358 and rs7412) and the ACE (rs4646994) genes used peripheral DNA. A total of 63% of the subjects reported poor quality of sleep assessed by the PSQI whereas 54 (33%) reported daytime sleepiness through the Epworth scale. A significant correlation was observed between APOE and PSQI, with a greater frequency of the poor nighttime sleep quality phenotype among ε2 carriers, whereas no correlation was found among any of the sleep scores and the ACE genotypes. Thus, we suggest a correlation between APOE alleles and scale-assessed sleep quality scores in older adults, with no implications for ACE alleles, in a context devoid of cognitive impairment.


A cascade oxidation/[4 + 1] annulation of sulfonium salts for synthesis of polyfunctional furans: DMSO as one carbon source.
A novel DMSO-involved cascade reaction of stabilized sulfonium salts has been established for direct construction of polyfunctional furans. This one-pot sequential reaction involving in situ generated α-methylene sulfonium salts was followed by [4 + 1] annulation with sulfur ylides. Notably, DMSO plays a very important role in this transformation, not only as a solvent but also as one carbon source.


Electrokinetic chromatographic estimation of the enantioselective binding of nomifensine to human serum albumin and total plasma proteins.
This report is the first evidence of enantioselective binding of nomifensine to human serum albumin (HSA) and plasma proteins. The overall process with HSA included: (i) consistent experimental design along two independent sessions; (ii) incubation of nomifensine-HSA designed mixtures; (iii) ultrafiltration for separating the unbound enantiomers fraction; (iv) electrokinetic chromatography (EKC) using heptakis-2,3,6-tri-O-methyl-β-cyclodextrin as chiral selector to provide experimental data for enantiomers (first, E1, and second, E2, eluted ones); and (v) a recent direct equation allowing univariate tests and robust statistics to provide consistent parameters and uncertainty. A significant enantioselectivity to HSA (2.7 ± 0.1) was encountered, related to a 1:1 stoichiometry and log affinity constants of 3.24 ± 0.10 and 3.67 ± 0.08 for E1 and E2, respectively. The protein binding (PB) estimated at physiological concentration levels was 40 ± 5 and 63 ± 4% for E1 and E2, respectively. The use of synthetic human sera allowed in vitro estimation of the total plasma PB for the racemate (61 ± 5%; coincident with in vivo values), and its enantiomers (58 ± 7 and 64 ± 4% for E1 and E2, respectively). Comparison allowed the relative importance of HSA respect to other plasma proteins for binding nomifensine to be established.


Early Executive Function at Age Two Predicts Emergent Mathematics and Literacy at Age Five.
Previous work has shown that individual differences in executive function (EF) are predictive of academic skills in preschoolers, kindergartners, and older children. Across studies, EF is a stronger predictor of emergent mathematics than literacy. However, research on EF in children below age three is scarce, and it is currently unknown whether EF, as assessed in toddlerhood, predicts emergent academic skills a few years later. This longitudinal study investigates whether early EF, assessed at two years, predicts (emergent) academic skills, at five years. It examines, furthermore, whether early EF is a significantly stronger predictor of emergent mathematics than of emergent literacy, as has been found in previous work on older children. A sample of 552 children was assessed on various EF and EF-precursor tasks at two years. At age five, these children performed several emergent mathematics and literacy tasks. Structural Equation Modeling was used to investigate the relationships between early EF and academic skills, modeled as latent factors. Results showed that early EF at age two was a significant and relatively strong predictor of both emergent mathematics and literacy at age five, after controlling for receptive vocabulary, parental education, and home language. Predictive relations were significantly stronger for mathematics than literacy, but only when a verbal short-term memory measure was left out as an indicator to the latent early EF construct. These findings show that individual differences in emergent academic skills just prior to entry into the formal education system can be traced back to individual differences in early EF in toddlerhood. In addition, these results highlight the importance of task selection when assessing early EF as a predictor of later outcomes, and call for further studies to elucidate the mechanisms through which individual differences in early EF and precursors to EF come about.