Long-lasting transcriptional refractoriness triggered by a single exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine.
Parkinson's disease (PD) is a progressive neurodegenerative disorder whose etiology is thought to have environmental (toxin) and genetic contributions. The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrimidine (MPTP) induces pathological features of PD including loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and striatal dopamine (DA) depletion. We previously described the striatal transcriptional response following acute MPTP administration in MPTP-sensitive C57BL/6J mice. We identified three distinct phases: early (5h), intermediate (24h) and late (72h) and reported that the intermediate and late responses were absent in MPTP-resistant Swiss-Webster (SWR) mice. Here we show that C57BL/6J mice pre-treated with a single 40 mg/kg dose of MPTP and treated 9 days later with 4×20 mg/kg MPTP, display a striatal transcriptional response similar to that of MPTP-resistant SWR mice, i.e. a robust acute response but no intermediate or late response. Transcriptional refractoriness is dependent upon the dose of the priming challenge with as little as 10mg/kg MPTP being effective and can persist for more than 28 days. Priming of SWR mice has no effect on their response to subsequent challenge with MPTP. We also report that paraquat, another free radical producer, also elicits striatal transcriptional alterations but these are largely distinct from those triggered by MPTP. Paraquat-induced changes are also refractory to priming with paraquat. However neither paraquat nor MPTP elicits cross-attenuation. Thus exposure to specific toxins triggers distinct transcriptional responses in striatum that are influenced by prior exposure to the same toxin. The prolonged refractory period described here for MPTP could explain at the molecular level the reported discrepancies between different MPTP administration regimens and may have implications for our understanding of the relationship between environmental toxin exposure and PD.


Nutritional and in vitro antioxidant activity analyses of formulated soymilk dessert.
Soymilk (SM) is nutritionally nearly equal to milk from cows and is free of cholesterol, gluten, and lactose. This study's objective was to formulate a cholesterol-free soymilk dessert (SOD) and compare it's to commercial desserts (CODs). Results indicated that the CODs contain substantial amounts of cholesterol while SOD does not. Soymilk dessert has more protein, and vitamin E than CODs, but less fat and calcium. In addition, the result also highlighted that SOD has higher number of amino acids compared to CODs. The total antioxidant, flavonoids and phenolics content of SOD were significantly higher than CODs. Furthermore, the in vitro antioxidant activity of SOD and CODs by DPPH and ABTS methods revealed that the IC50 of SODs significantly (p < 0.001) lower than CODs, and lower IC50 indicated the higher free radical scavenging power of SODs than CODs. These findings indicated that this non-dairy SOD may provide beneficial protein, as well as minerals, and antioxidants to support the body's various physiological functions.


Cold External Temperatures and Sickle Cell Morbidity in Children: A Retrospective Analysis.
Genetic and environmental factors affect the occurrence of vaso-occlusive crises (VOCs) in patients with sickle cell disease (SCD). Research provides inconsistent evidence on how environmental temperature affects SCD. Edmonton, Alberta, has an increasing SCD population and is the northern-most city in North America with a population of over a million. The objective of this study was to identify whether pediatric patients with SCD experience increased morbidity in cold external temperatures. This study was a retrospective case series. Emergency visits, phone calls, and admission data for VOC in children were recorded from July 2011 to June 2016. Temperatures were recorded and statistically analyzed using descriptive statistics, to determine the relation to VOC. A total of 118 patients with 257 VOC events were reviewed. When analyzing the mean, minimum, and change in temperatures at presentation, the largest percentage of VOC events occurred at mild to moderate temperatures. Temperature data at 24 and 48 hours before the presentation had similar results. When accounting for the relative frequency of extreme weather days, there are increased VOC events with temperature fluctuations >20°C. There was no correlation between mean and minimum temperature change. Fluctuation in temperature of >20°C was associated with increased relative VOC frequency, suggesting that large temperature variability should be avoided in SCD, but a prospective study is required to determine causality.


Desalination feasibility study of an industrial NaCl stream by bipolar membrane electrodialysis.
The industrial implementation of alternative technologies in the processing of saline effluent streams is a topic of growing importance. In this technical feasibility study, the desalination of an industrial saline stream containing about 75 g L(-1) NaCl contaminated with some organic matter using bipolar membrane electrodialysis (EDBM) was investigated on lab-scale. Bipolar membranes of two different manufacturers (PCA - PolymerChemie Altmeier GmbH and FuMA-Tech GmbH) were tested and compared in terms of electrical resistance, current efficiency and purity of the produced acid and base stream. In both cases, almost complete desalination (>99%) was achieved and simultaneously HCl and NaOH were produced with a concentration between 1.5 and 2 M with a relatively good purity. The Fumasep bipolar membranes scored slightly better for electrical resistance and current efficiency. On the other hand, slightly higher current densities were achieved with PCA bipolar membranes. Simultaneously, some information was obtained on the transport behavior of the organic matter present in the saline stream. It was observed that a transport competition occurred between the organic matter and the accompanying chlorides. From this lab-scale study it was concluded that EDBM is a promising and attractive technology in the area of saline effluent reclamation and reuse.


Mediation of metabolic syndrome in the association between long-term co-exposure to road traffic noise, air pollution and incident type 2 diabetes.
Recent studies have linked exposure to road traffic noise or air pollution with incident type 2 diabetes (T2D), but investigation on their co-exposure was limited and underlying mechanisms remain unclear. We hypothesized that long-term co-exposure to road traffic noise and air pollution increases the risk of incident T2D via the development of metabolic syndrome (MetS). This prospective study included 390,834 participants in UK Biobank. Cumulative risk index (CRI), the health-based weighted levels of multiple exposures, was applied to characterize the co-exposure to 24-hour road traffic noise (Lden), particulate matter with aerodynamic diameter ≤ 2.5 µm (PM2.5), and nitrogen dioxide (NO2). Lden was modeled by the Common Noise Assessment Methods in Europe and air pollutant levels were measured by the Land Use Regression model at participants' residential addresses. Incident T2D was ascertained through linkages to inpatient hospital records. MetS was defined by five (central obesity, triglycerides, HDL cholesterol, glucose, and blood pressure) or six factors (C-reactive protein additionally). Cox proportional hazard models were used to assess the association between environmental exposures and incident T2D, and mediation analyses were applied to investigate the role of MetS. After a median of 10.9 years of follow-up, 13,214 (3.4%) incident T2D cases were ascertained. The exposure to Lden, PM2.5, and NO2, as well as their co-exposure, were significantly associated with an elevated risk of incident T2D, with HRs of 1.03 (95%CI: 1.00, 1.05) per 3.5 dB(A) increase in Lden, 1.05 (95%CI: 1.01, 1.10) per 1.3 μg/m3 increase in PM2.5, 1.07 (95%CI: 1.02, 1.11) per 9.8 μg/m3 increase in NO2, and 1.06 (95%CI: 1.02, 1.09) per interquartile range increase in CRI. MetS significantly mediated 43.5%- 54.7% of the CRI-T2D relationship. Long-term co-exposure to road traffic noise and air pollution is associated with an elevated risk of incident T2D, which may partly be mediated by MetS.


The Effect of Religious Intervention Using Prayer for Quality of Life and Psychological Status of Patients with Permanent Pacemaker.
The development of heart disease, followed by the pacemaker implantation, has reduced the quality and psychological problems for patients. Thus, the present study was conducted to determine the effect of prayer on the quality of life and the psychological status of patients with permanent pacemaker. This is a quasi-experimental study in which 75 patients were assigned to experimental and control groups. Religious intervention was conducted for the experimental group, including the Tavasol prayer and four recommended (mustahab) remembrances in 7 sessions. Before and after the intervention, the patients were provided with the quality of life questionnaire and psychological status. Then, the questionnaires were analyzed using descriptive and analytical tests. Before intervention, there was no difference between quality of life status and psychological status of patients, but after intervention, their quality of life increased and their psychological status improved significantly. The implementation of religious intervention based on prayer positively affects the quality of life and psychological status of patients; thus, implementing this intervention is necessary for patients.


Molecular Identification of Two Vector Species, Cacopsylla melanoneura and Cacopsylla picta (Hemiptera: Psyllidae), of Apple Proliferation Disease and Further Common Psyllids of Northern Italy.
The psyllid species Cacopsylla melanoneura (Förster) and Cacopsylla picta (Förster) are vectors of 'Candidatus Phytoplasma mali', the causal agent of apple proliferation, one of the economically most important apple diseases in Europe. Both vectors are present in apple orchards of South Tyrol and Trentino provinces in Northern Italy. As no direct treatment of the disease is possible, monitoring of the psyllids provides information about the vector presence in the orchards and enables targeted control. Thus, fast and reliable identification of the various psyllids occurring in the apple orchards is required. Morphological differentiation is problematic due to extensive resemblance of some psyllid species especially among females and is error-prone for nymphs. Here we present a rapid and cost-effective polymerase chain reaction-restriction fragment length polymorphism method based on the cytochrome c oxidase subunit I region for the molecular identification of the vector species as well as eight further Cacopsylla species present in the orchards. This method was verified through 98.9% consensus with morphologically identified males, through sequencing and subsequent phylogenetic analysis. In case of doubtful morphological identification of females, the method was able to provide a refined species assignment and could also remarkably facilitate the identification of nymphs.


Twelve tips on setting up a new medical school.
Not many set up a new medical school, so those that do usually do it only once. Thus most have no personal previous experience to guide them. To give those setting up a new school some broad issues to think about as they set about their task. The tips were derived from personal experience in the UK and in Africa. The 12 tips identified are engage closely with the parent university from the outset; decide what the medical school is going to concentrate on first; agree on the overall aim of the school; decide who 'owns' the course; agree on the type of pedagogy to be employed; ensure good alignment between the aims, outcomes, learning framework and assessment; plan the assessment along with the rest of the course; make sure the school facilities are sufficient and appropriate to support the aims of the course; appoint the right staff; plan the research programme early; plan the co-ordination between the university and the health services at all levels; communicate, communicate, communicate. It is hoped that these suggestions will be widely applicable to different contexts and assist those in the exciting task of setting up a new school.


The metabolic costs of hostility in healthy adult men and women: cross-sectional and prospective analyses.
Hostility is associated with altered metabolic activity but little research has examined sex and/or age differences using a global index of metabolic dysfunction or examined different aspects of hostility. The moderating effect of sex and age on the associations between three aspects of hostility (cynical attitude, angry affect, quarrelsome behavior in daily living) and metabolic burden (number of metabolic parameters in the higher quartile) were evaluated in 188 healthy men and women (M(age)=41; SD=11.34). Three years later, metabolic burden was measured again in 133 participants. At study onset, quarrelsome behavior was associated with greater metabolic burden in men and women (Beta=.144; p<.05). After 3 yrs, cynical hostility predicted increased metabolic burden among mid-age and older individuals (b=.013 and .046 respectively; p<.001). The aspect of hostility that is most closely associated with metabolic burden depends on the age of the participants and whether measures are concurrent or prospective.


Neurokinin A suppresses a voltage-gated K+ current in smooth muscle cells from rat vas deferens.
The effects of neurokinin A (NKA) on freshly isolated smooth muscle cells from the rat vas deferens were investigated electrophysiologically. NKA (10(-7) M) prolonged the duration of action potentials without affecting resting potentials. Under voltage-clamp conditions, NKA (10(-7) M) suppressed an outward K+ current activated by depolarizing voltage steps. Substance P (SP, 10(-7) M) did not affect the K+ current, suggesting that NKA is more potent in suppressing the K+ current than SP is, as is also true for the contractions of smooth muscles of the rat vas deferens. The suppression of the K+ conductance now reported may contribute to NKA-induced smooth muscle contraction.


Image quality enhancement in variable-refresh-rate AMOLED displays using a variable initial voltage compensation scheme.
In active matrix organic light emitting diode (AMOLED) displays, when a variable refresh rate is applied and the frame rate changes, the image's color and luminance quality in AMOLED displays deteriorates. The frequency-dependent cognitive differences were experimentally demonstrated by using 6.76″ AMOLED displays. This phenomenon is dependent on the emission time and the data programming time on the frame rate. This degradation of the image quality during the frequency switch could be prevented by applying a variable initial voltage (VINI) to the OLED anode. For a frequency change between 60 and 120 Hz, the measured just noticeable color difference (JNCD) decreased from 7.50 to less than 1.00 in luminance, and from 2.34 to 0.02 in color. As our approach can prevent image quality distortion by utilizing an existing compensation pixel structure without additional compensation steps, it will be a promising technique for improving the picture quality in AMOLED displays.


Training of health care professionals on the special needs of children in the management of disasters: experience in Asia, Africa, and Latin America.
Although children are the most vulnerable group in any disaster, limited information exists regarding their unique needs in complex humanitarian emergencies. To review the experiences gained in designing and implementing a training course for international health care professionals in disaster management focused on the needs of children. The format, content, learning objectives, teaching methods, course evaluation, and feedback of a training course on managing complex humanitarian emergencies with a focus on the special needs of children were reviewed. The 5-day course was first conducted at Case Western Reserve University in 1996. Since then, it has been replicated 15 times, annually in the United States, and in 7 overseas venues, including Thailand, Pakistan, Ethiopia, Nicaragua, Panama, Syria, and India. Voluntary US and international faculty used a problem-based learning method to train health care workers from developing countries in providing rapid quality care to child disaster victims. The courses were well received in every venue, as evidenced by active participation of local medical professionals, who organized logistics, recruited participants, and led the process of adapting the course to local needs. A remarkable outcome of this training course has been the development of an international group of highly motivated professionals involved in disseminating information to relief workers at a local level and providing a supportive network among themselves. A comprehensive training program targeted for health care professionals, conducted by mutually respectful local and international faculty, is an effective instrument for disseminating information and enhancing competence to help children in disasters.


Influence of dietary lipids on serum apoproteins AI and B and on intestinal synthesis of apo AI in the early weaning of piglets: comparison of saturated, unsaturated, and medium-chain triglycerides.
Early weaning of piglets induces a rapid decrease in the concentration of all plasma lipoproteins within 2 d. The decline was more progressive when 20% saturated fatty acid (lard) (SF) was added to the diet; saturated fatty acid was more effective than unsaturated fatty acid (sunflower oil) (UF). Medium-chain triglycerides had no protective effect. Intestinal synthesis of apoprotein AI was twofold higher in preweaning piglets than in adults (12.9% of total synthesis vs 5.9%, p less than 0.01) when measured in intestinal mucosa. On day 4 of weaning, synthesis was still at the preweaning level in all groups but on day 7 was maintained only by the SF diet (11.7%). We conclude that long-chain lipids, particularly saturated fatty acids, prevent a decrease in lipoproteins at weaning, mainly by maintaining intestinal apo AI synthesis at a high level.


Efficacy of probucol for the treatment of non-alcoholic steatohepatitis with dyslipidemia: An open-label pilot study.
Oxidative stress plays a pivotal role in the transition from simple steatosis to non-alcoholic steatohepatitis (NASH). Probucol is a lipid-lowering agent with strong antioxidant properties, and is reported to be effective for the treatment of NASH in several studies. The aim of the present study was to evaluate the efficacy of probucol for the treatment of NASH with dyslipidemia. Twenty-six patients with biopsy-proven NASH accompanied by dyslipidemia were treated with 500 mg of probucol daily for 48 weeks. Body mass index, visceral fat area, liver function tests, serum lipids, fibrosis markers, ferritin, adiponectin, leptin, urinary 8-hydroxy-2'-deoxyguanosine (U-8OHdG) and elasticity were measured periodically during the study. Follow-up liver biopsy was performed in 18 patients. Serum levels of aminotransferases, total cholesterol and U-8OHdG significantly decreased (P < 0.01). Levels of hemoglobin A1c (HbA1c), the Homeostasis Model of Assessment - Insulin Resistance index and serum levels of ferritin, type IV collagen 7S and hyaluronic acid significantly decreased (P < 0.05). The serum levels of adiponectin tended to be increased. Liver stiffness significantly decreased from 8.8 ± 6.8 to 6.6 ± 4.0 kPa (P < 0.01). Non-alcoholic fatty liver disease activity scores were significantly improved from 4.2 ± 1.4 to 3.4 ± 1.6 (P < 0.05) and fibrotic stages tended to be improved from 1.6 ± 0.8 to 1.3 ± 1.1, respectively. No adverse effects of this treatment were noted. Probucol improved clinical and histological findings probably through its ability to reduce insulin resistance and oxidative stress. Probucol therapy was safe and effective for Japanese NASH patients with dyslipidemia.


Successful pregnancy after previous conservative treatment of an advanced cervical pregnancy.
Cervical pregnancy was diagnosed at 12 weeks' gestation in a young nulliparous woman presenting with vaginal bleeding. Initial treatment with methotrexate was unsuccessful. The patient was ultimately treated by internal iliac artery ligation, hysterotomy, and intracervical balloon tamponade. Nineteen months after surgery, the patient delivered a healthy infant at 36 weeks' gestation by cesarean section.


Effects of β-Blockers With and Without Vasodilating Properties on Central Blood Pressure: Systematic Review and Meta-Analysis of Randomized Trials in Hypertension.
β-Blockers are less effective than other antihypertensive drug classes in reducing central systolic blood pressure (cSBP) as compared with peripheral SBP (pSBP). Whether this effect is less pronounced with vasodilating β-blockers (VBB) when compared with nonvasodilating β-blockers (NVBB) remains unsettled. We conducted a systematic review and meta-analysis of randomized trials exploring the effects of β-blockers on both pSBP and cSBP in hypertension. We selected 20 studies, for a total of 32 treatment arms (n=21 for NVBB, n=11 for VBB) and 1263 participants (n=962 for NVBB, n=301 for VBB). pSBP decreased from 150 to 133 mm Hg for NVBB and from 145 to 134 mm Hg for VBB. cSBP decreased from 137 to 126 mm Hg for NVBB and from 132 to 123 mm Hg for VBB. SBP amplification (pSBP-cSBP) decreased significantly under VBB (-5.6 mm Hg; 95% confidence interval, -7.8, -3.4 mm Hg), but not under NVBB (-1.1 mm Hg; 95% confidence interval, -3.4, +1.2 mm Hg; P<0.01 versus NVBB). There was high heterogeneity both within and between β-blockers subclasses. In a meta-regression model, the weighted difference in treatment-induced changes in SBP amplification between NVBB and VBB lost its significance after adjustment for mean age and baseline pSBP and heart rate (-2.9±2.3 mm Hg; P=0.22) and was almost abolished after adjustment for treatment-induced heart rate changes (-0.1±0.5 mm Hg; P=0.78). In conclusion, NVBBs, but not VBBs, determine a lower reduction in cSBP than in pSBP. However, the difference in treatment-induced SBP amplification changes between NVBB and VBB is nearly abolished after accounting for differences in heart rate changes.


Role of the Ah locus in suppression of cytotoxic T lymphocyte activity by halogenated aromatic hydrocarbons (PCBs and TCDD): structure-activity relationships and effects in C57Bl/6 mice congenic at the Ah locus.
Previous studies have shown that the generation of cytotoxic T lymphocytes (CTL) following allogeneic tumor challenge is suppressed in Ah-responsive C57Bl/6 mice treated with a single oral dose of the toxic, Ah receptor-binding 3,4,5,3',4',5'-hexachlorobiphenyl (HxCB). The present studies have examined the specific role of the Ah receptor in this immunotoxic response by utilizing HxCB isomers of known, varied affinity for the Ah receptor as well as by comparing effects of high-affinity Ah receptor ligands (3,4,5,3',4',5'-HxCB and 2,3,7,8-tetrachlorodibenzo-p-dioxin [TCDD]) on the CTL response of mice that differ only at the Ah locus, that is, Ah-responsive (Ahbb) and Ah-nonresponsive (Ahdd) congenic C57Bl/6 mice. Correlative changes in thymic weight, serum corticosterone (CS) levels, and spleen cellularity were also measured. The potency of HxCB congeners (3,4,5,3',4',5'-; 2,3,4,5,3',4'-; 2,4,5,2',4',5'-) and 2,3,7,8-TCDD to suppress the CTL response, to reduce spleen cellularity, to cause thymic atrophy, and to elevate serum CS levels was directly correlated with the binding affinity of the congener for the Ah receptor. Furthermore, these parameters of immunotoxicity in Ahdd C57Bl/6 mice were significantly more resistant to alterations induced by either 3,4,5,3',4',5'-HxCB or 2,3,7,8-TCDD as compared to Ahbb C57Bl/6 mice. These results strongly support an Ah receptor-dependent immunotoxic mechanism in suppression of the CTL response following acute exposure to halogenated aromatic hydrocarbons.


Dietary interactions and INR variability: retrospective evaluation of patients couples on oral anticoagulant therapy.
The association between dietary vitamin K intake and International Normalized Ratio (INR) variability in patients on oral anticoagulants treatment (OAT) has been evaluated in several studies. Changes in diet composition are known to lead to INR variability. We evaluated INR over time in married couples on OAT and non-cohabitant couples on OAT, to assess clinical relevance of the diet. Among outpatients receiving OAT we selected 31 married couples. Husbands and wives were then matched by demographic and clinical characteristics to 31 men and 31 women on OAT not married nor living together. We analyzed 6,357 INR measurements recorded from February 1998 to November 2009. We found similar average INR values within married couples and also within non-cohabitant couples. Using mixed models we confirmed INR differences between seasons and the slightly lower INR in non-cohabitant couples compared to married couples; although statistically significant, they were of marginal clinical significance. Within both married and non-cohabitant couples, we did not find statistically or clinically significant differences between men and women over time. The lack of INR differences over time within non-cohabitant couples indicates that diet is not an important determinant of INR over time. Also seasonal INR variations and differences between married and non-cohabitant couples were of little practical importance.


Pathways involved in somatosensory electrical modulation of dorsal cochlear nucleus activity.
Our recent study has shown that somatosensory electrical stimulation may be useful to modulate sound-induced hyperactivity in the dorsal cochlear nucleus (DCN), a neural correlate of certain forms of tinnitus. Somatosensory electrical stimulation induced both suppressive and excitatory effects on neural activity in the DCN of both control and tone-exposed animals. However, it is unclear what neural pathways underlie the somatosensory electrical stimulation-induced effects on DCN activity. To address this issue, we conducted c-fos immunocytochemistry using hamsters and mapped neural activation in both auditory and non-auditory structures following transcutaneous electrical stimulation of the basal part of the pinna. We also conducted tracing experiments to investigate the anatomical relations between the DCN and structures that showed a significant increase in the number of Fos-positive neurons as a result of electrical stimulation. Electrical stimulation of the pinna induced significant increases in the number of Fos-positive neurons in the DCN, spinal trigeminal nucleus (Sp5), dorsal raphe nucleus (DR) and locus coeruleus (LC). Results of tracing experiments indicate that the DCN received inputs from the Sp5, DR and LC. The above results suggest that modulation of DCN activity through somatosensory electrical stimulation may involve both direct pathways via the Sp5 and indirect pathways via the DR and LC. Therefore, relieving tinnitus through somatosensory electrical stimulation may require manipulations of both auditory and non-auditory functions.


Nonselective Laryngeal Reinnervation versus Type 1 Thyroplasty in Patients with Unilateral Vocal Fold Paralysis: A Single Tertiary Centre Experience.
This study compared the voice outcomes of selected patients with unilateral vocal fold palsy (UVFP) who underwent either nonselective laryngeal reinnervation (LR) or Type 1 thyroplasty (thyroplasty) in a Malaysian tertiary centre using multidimensional voice assessments. The study included 16 patients with UVFP who underwent either LR (9 patients) or thyroplasty (7 patients) between 2015 and 2018 who fulfilled the inclusion criteria. The outcomes were measured subjectively and objectively with: (1) voice handicap index-10 (VHI-10- Malay version); (2) auditory perceptual evaluation using the breathiness component of Grade, Roughness, Breathiness, Asthenia, Strain scale; (3) maximum phonation time (MPT); and (4) acoustic analysis (jitter%, shimmer%, and NHR) using OperaVOXTM. The outcomes were measured at baseline, 6 and 12-months postoperative. The comparison of outcomes between pre and postoperative of each group was evaluated using one-way ANOVA test. Mann-Whitney test was used to compare the outcomes between the two groups. Comparison of each group at different time points showed significant improvement of VHI-10 and MPT of LR group between baseline and 12 months (P ≤ 0.05) whereas, the improvement in thyroplasty group was observed at all time points (P ≤ 0.05). When comparing between the two groups at 12 months, the VHI-10 and MPT was significantly better in the LR group than thyroplasty group with P = 0.004 and P = 0.001 respectively. Other outcome measures did not reveal significant difference between the two groups. This observational study showed that LR may be better than thyroplasty in improving VHI-10 and MPT in selected patients with UVFP.


Retraction: A study on the luminescence properties of gamma-ray-irradiated white light emitting Ca2Al2SiO7:Dy3+ phosphors fabricated using a combustion-assisted method.
[This retracts the article DOI: 10.1039/C6RA04913C.].


Enhanced hydrogen storage properties of 1.1MgH2-2LiNH2-0.1LiBH4 system with LaNi5-based alloy hydrides addition.
Significant improvements in the hydrogen sorption properties of the Li-Mg-N-H system have been achieved by adding a small amount of LiBH4. Herein, the hydrogen storage properties of the 1.1MgH2-2LiNH2-0.1LiBH4 system are further enhanced by addition of LaNi5-based (LaNi3.8Al0.75Mn0.45, LaNi4.5Mn0.5, LaNi4Co) alloy hydrides. The refinement of the Li-Mg-B-N-H particles and the metathesis reaction are facilitated by adding LaNi5-based alloy hydrides during the ball milling process. The addition of LaNi5-based alloy hydrides can enhance the hydrogen sorption kinetics, reduce the dehydrogenation temperature and promote a more thorough dehydrogenation of the Li-Mg-B-N-H system. The LaNi5-based alloy hydrides are involved in hydrogen de/hydrogenation reaction. Among the three alloys, LaNi4.5Mn0.5 makes the most obvious improvement on the reaction kinetics, and the dehydrogenation peak temperature is reduced by 12 °C, while the activation energy is reduced by 11% with 10 wt% LaNi4.5Mn0.5 addition. The weakening of the N-H bond and the homogeneous distribution of the LaNi5-based alloy hydrides in the Li-Mg-B-N-H composite have important roles in the reduction of the desorption barrier and the kinetics enhancement.


Do histopathological features of breast cancer in Australian Indigenous women explain the survival disparity? A two decade long study in the Northern Territory.
In the Northern Territory (NT) of Australia, Indigenous women have a lower incidence of breast cancer, but a higher mortality than Non-indigenous women. The aim of this study was to describe and compare breast cancer pathological features related to stage and biological aggression between the two groups. Subjects were identified by extract from the NT Cancer Registry in two separate cohorts, cohort 1 (1991-2000) and cohort 2 (2001-2010). Data from cohort 1 included age, stage, tumor grade and estrogen receptor status (ER) and treatment completion. Additional pathological variables including tumor size, HER2 status, lymphovascular invasion and derived tumor phenotype were available for cohort 2. Bivariate P values for categoric variables were calculated using Fisher's exact tests. The Wilcoxon rank-sum test was used to compare cohort 2. Logistic regression was used to calculate odds ratios. There were 359 (44 indigenous) eligible women in cohort 1 and 526 (100 indigenous) for cohort 2. In cohort 1, in both cohorts, indigenous women were more likely to present at an advanced stage, but there was no difference in ER status or tumor grade. When derived phenotypes were compared, indigenous women were less likely to have better prognosis luminal A tumors, and more likely to have HER2-enriched tumors. This two decade long comparison of the pathological features of breast cancer between indigenous and nonindigenous women of the NT has confirmed that Indigenous women not only present at a later stage than NI women but are also afflicted by poorer prognosis tumors, particularly HER2 enriched.


Systematic review: auditory stimulation and sleep.
Auditory stimulation devices (white and pink noise) are used to mask sounds and facilitate relaxation and sleep; however, the effectiveness of this intervention is not well established. This systematic review examined the scientific literature for the effect of specific types of auditory stimulation on sleep outcomes in adults. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement guided this review. Searches were conducted in 9 databases for intervention studies that could easily be employed in clinical practice. We excluded other types of auditory stimulation (music alone, binaural tones, and synchronization). Two reviewers screened abstracts and full-text articles for eligibility, with conflicts resolved by a third reviewer, and extracted data. Risk of bias was assessed with the Effective Public Health Practice Project Quality Assessment Tool for Quantitative Studies. Thirty-four studies reported results of 1,103 persons participating in 3 categories of interventions: white noise (18), pink noise (11), and 6 multiaudio (some combination of white, pink, music, or silence). Nineteen studies had positive findings in terms of improving sleep outcomes: 6 white noise (33%), 9 pink noise (81.9%), and 4 multiaudio (66.7%). Multiaudio had the lowest (better) risk of bias (mean/standard deviation: 1.67/0.82) compared to white (2.38/0.69) and pink noise (2.36/0.81). Although there was no strong evidence to support use of auditory stimulation, none of the studies reported any adverse effects with short-term application of auditory stimulation during sleep. Future research needs to include confounding factors that can affect outcomes, including one's noise sensitivity, personality, and other conditions or medications that may affect sleep. Capezuti E, Pain K, Alamag E, Chen XQ, Philibert V, Krieger AC. Systematic review: auditory stimulation and sleep. J Clin Sleep Med. 2022;18(6):1697-1709.


Rhizobium induces DNA damage in Caenorhabditis elegans intestinal cells.
In their natural habitat of rotting fruit, the nematode Caenorhabditis elegans feeds on the complex bacterial communities that thrive in this rich growth medium. Hundreds of diverse bacterial strains cultured from such rotting fruit allow C. elegans growth and reproduction when tested individually. In screens for C. elegans responses to single bacterial strains associated with nematodes in fruit, we found that Rhizobium causes a genome instability phenotype; we observed abnormally long or fragmented intestinal nuclei due to aberrant nuclear division, or defective karyokinesis. The karyokinesis defects were restricted to intestinal cells and required close proximity between bacteria and the worm. A genetic screen for C. elegans mutations that cause the same intestinal karyokinesis defect followed by genome sequencing of the isolated mutant strains identified mutations that disrupt DNA damage repair pathways, suggesting that Rhizobium may cause DNA damage in C. elegans intestinal cells. We hypothesized that such DNA damage is caused by reactive oxygen species produced by Rhizobium and found that hydrogen peroxide added to benign Escherichia coli can cause the same intestinal karyokinesis defects in WT C. elegans Supporting this model, free radical scavengers suppressed the Rhizobium-induced C. elegans DNA damage. Thus, Rhizobium may signal to eukaryotic hosts via reactive oxygen species, and the host may respond with DNA damage repair pathways.


Unexpectedly significant stabilizing mechanism of iodous acid on iodic acid nucleation under different atmospheric conditions.
Iodous acid (HIO2) has been shown to play a stabilizing role in the nucleation of iodic acid (HIO3) (He et al., 2021). However, the stabilization effect and specific stabilizing mechanism of HIO2 on HIO3 nucleation under different atmospheric conditions remain unclear. Therefore, we studied these two issues under different temperatures and nucleation precursor concentrations using density functional theory combined with the Atmospheric Cluster Dynamics Code. We found that HIO2 can form clusters with HIO3 via strong hydrogen bonds, halogen bonds, and proton-transfer, substantially enhancing the stability of HIO3 clusters and decreasing the energy barrier of HIO3-based cluster formation at different temperatures and nucleation precursor concentrations. The particle formation rate and cluster concentrations of HIO3-HIO2 nucleation were negatively correlated with temperature and positively correlated with HIO2 concentration. The enhancements by HIO2 on the particle formation rate and cluster concentration of HIO3 nucleation were positively correlated with temperature and HIO2 concentration. Interestingly, even at a low HIO2 concentration (1.0 × 105 molecules cm-3), the enhancement on the particle formation rate and cluster concentration of HIO3 nucleation by HIO2 were both unexpectedly up to 4.1 × 104-fold at 283 K. Therefore, HIO3-HIO2 nucleation can be extremely rapid in cold regions, and the enhancement by HIO2 can be significant, especially in warm regions even at relatively high HIO2 concentrations.


Ion transport by rabbit colon: II. Unidirectional sodium influx and the effects of amphotericin B and amiloride.
The unidirectional influx of Na from the mucosal solution into the epithelium of in vitro descending rabbit colon (JName) determined under short-circuit conditions, is comprised of two components: one represents entry of Na into transporting epithelial cells and is abolished by amiloride which also abolishes Na absorption (JNanet). The other represents diffusional Na entry into paracellular pathways traversing the epithelium. In all instances, exposure of the mucosal surface to amphotericin B increased tissue conductance and JName and elicited K secretion. Tissues showing a spontaneous Isc of approximately 4 microneq/cm2hr did not respond to amphotericin B with increased Isc and JNanet. However, in tissues characterized by a lower Isc under control conditions, amphotericin B increased Isc and JNanet to approximately 4 microneq/cm2 hr. These findings suggest that amphotericin increases JNanet and elicits K secretion by disrupting the normal perm-selectivity of the mucosal membrane. Under these conditions the extrusion of Na from cell-to-serosal solution becomes the rate limiting step in transepithelial Na transport. Finally, a close correlation between JName and JNanet was was observed when the rate of Na absorption varied either spontaneously or experimentally with amiloride, suggesting that the backflux of Na from cell-to-mucosal solution is undetectably small.


Possible involvement of the 90-kDa heat shock protein in the regulation of protein synthesis.
The heme-sensitive eukaryotic initiation factor (eIF)-2 alpha kinase regulates translational activity in reticulocytes by phosphorylation of the smallest subunit of eukaryotic peptide initiation factor 2, eIF-2. Highly purified preparations of the kinase contain an abundant 90-kDa polypeptide which appears to modulate the activity of the enzyme. The physical properties and structural characteristics of the reticulocyte 90-kDa peptide are similar to those of the 90-kDa heat shock protein (hsp 90) from HeLa and other mammalian cells. The reticulocyte and HeLa cell proteins are shown to be immunologically cross-reactive. A direct comparison of the two proteins by one-dimensional peptide mapping of large peptides generated by limited proteolysis and by reversed-phase high performance liquid chromatography analysis of tryptic peptides indicates that they represent the same protein species. Like the 90-kDa reticulocyte protein, HeLa cell hsp 90 causes increased eIF-2 alpha phosphorylation by the heme-sensitive kinase and is a potent inhibitor of protein synthesis in the reticulocyte lysate system. A potential mechanism for the latter inhibition is inferred. These results implicate hsp 90 in the regulation of protein synthesis via its interaction with and perhaps regulation of the heme-sensitive kinase and phosphorylation of eIF-2 alpha.


Human plantar fascial dimensions and shear wave velocity change in vivo as a function of ankle and metatarsophalangeal joint positions.
The plantar fascia (PF), a primary contributor of the foot arch elasticity, may experience slack, taut, and stretched states depending on the ankle and metatarsophalangeal (MTP) joint positions. Since PF has proximodistal site difference in its dimensions and stiffness, the response to applied tension can also be site specific. Furthermore, PF can contribute to supporting the foot arch while being stretched beyond the slack length, but it has never been quantitatively evaluated in vivo. This study investigated the effects of the ankle and MTP joint positions on PF length and localized thickness and shear wave velocity (SWV) at three different sites from its proximal to distal end using magnetic resonance and supersonic shear imaging techniques. During passive ankle dorsiflexion, rise of SWV, an indication of slack length, was observed at the proximal site when the ankle was positioned by 10°-0° ankle plantar flexion with up to 3 mm (+1.5%) increase in PF length. On the other hand, SWV increased at the distal site when MTP joint dorsiflexed 40° with the ankle 30°-20° plantar flexion, and in this position, PF was lengthened up to 4 mm (+2.3%). Beyond the slack length, SWV curvilinearly increased at all measurement sites toward the maximal dorsiflexion angle whereas PF lengthened up to 9 mm (+7.6%) without measurable changes in its thickness. This study provides evidence that the dimensions and SWV of PF change in a site-specific manner depending on the ankle and MTP joint positions, which can diversify foot arch elasticity during human locomotion.NEW & NOTEWORTHY Joint angle dependence and site specificity of the plantar fascial dimensions and SWV were examined by combining sagittal magnetic resonance and supersonic shear imaging techniques. We revealed that the site-specific changes in PF SWV were related to joint angle positions, i.e., PF slackness and elasticity changed in varying combinations of ankle and MTP angle. Our findings suggest that PF can elastically support the foot arch throughout the stance phase of human bipedal locomotion.


An effective preselection criterion for MODY with an increasingly positive genetic testing rate by NGS: results from two cohorts of Chinese children.
The purpose of this study was to determine the frequency of maturity-onset diabetes of the young (MODY) in two selected cohorts of Chinese children with diabetes and clinically suspected MODY, using next-generation sequencing (NGS). Ninety-three children who met the comprehensive criteria of suspected MODY were enrolled in two cohorts. A custom NGS panel or a whole exon group was used for sequencing. We identified 55/93 (59.1%) children with pathogenic and likely pathogenic MODY variants. Forty-two (76.3%) were confirmed to have the GCK (MODY2) mutation. Additionally, five had the HNF1A (MODY3), two the HNF1B (MODY5), one the 17q12 microdeletion (MODY5), two the HNF4A (MODY1), two the ABCC8 (MODY12), and one the PDX1 mutation (MODY4). Of these, 13 novel variants were detected in different genes. By comparing the gene-positive with gene-negative children, we found that discriminatory factors for MODY at diagnosis included lower HbA1c [7.4% vs. 10.2% (53 vs. 86 mmol/mol); P = 0.002], lower body mass index z score (0.2 vs. 1.0; P = 0.01), lower onset age (8.1 vs. 11.2 years; P = 0.001), and lower C-peptide (1.4 vs. 2.5 ng/mL; P = 0.02). In conclusion, the criteria used in this study for screening MODY are effective, and MODY2 is the most common subtype (76%), followed by MODY3 and MODY5. Some rare MODY subtypes have been reported in Chinese children.NEW & NOTEWORTHY We proved the clinical suspicion of maturity-onset diabetes of the young (MODY) according to the comprehensive criterion for next-generation sequencing testing, which helps to identify both common and rare MODYs, leading to accurate diagnosis and personalized treatment.


Value restructures the organization of free recall.
A large body of research illustrates the prioritization of goal-relevant information in memory; however, it is unclear how reward-related memories are organized. Using a rewarded free recall paradigm, we investigated how reward motivation structures the organization of memory around temporal and higher-order contexts. To better understand these processes, we simulated our findings using a reward-modulated variant of the Context Maintenance and Retrieval Model (CMR; Polyn et al., 2009). In the first study, we found that reward did not influence temporal clustering, but instead shifted the organization of memory based on reward category. Further, we showed that a reward-modulated learning rate and source features of CMR most accurately depict reward's enhancement on memory and clustering by value. In a second study, we showed that reward-memory effects can exist in both extended periods of sustained motivation and frequent changes in motivation, by showing equivalent reward effects using mixed- and pure-list motivation manipulations. However, we showed that a reward-modulated learning rate in isolation can support reward's enhancement of memory in pure-list contexts. Overall, we conclude that reward-related memories are adaptively organized by higher-order value information, and contextual binding to value contexts may only be necessary when rewards are intermittent versus sustained.


[Coronary disease extension determines mobilization of endothelial progenitor cells and cytokines after a first myocardial infarction with ST elevation].
Multivessel coronary disease is still a postinfarction prognostic marker despite new forms of reperfusion, such as primary angioplasty. The aim of this study was to determine the time sequence of various sets of endothelial progenitor cells and angiogenic cytokines (vascular endothelial growth factor, hepatocyte growth factor) according to the degree of extension of the postinfarction coronary disease. We studied the release kinetics in 32 patients admitted for a first myocardial infarction with ST elevation, grouped according to whether they had single or multivessel disease, and 26 controls. The patients had a higher number of endothelial progenitor cells and angiogenic cytokines than the controls at all 3 measurements (admission, day 3, and day 7) of the following subsets: CD34, CD34+CD133+, CD34+KDR+, and CD34+CD133+KDR+CD45+(weak); this latter was higher on day 7. The levels of these cell subsets were all higher in the patients with single-vessel disease and at all 3 measurements. The vascular endothelial growth factor levels were raised during the first week and the hepatocyte growth factor showed an early peak on admission for infarction. No significant differences were seen in the cytokines according to coronary disease extension. Although the release kinetics of different subsets of endothelial progenitor cells in patients with a first acute myocardial infarction with ST elevation was similar in those with single vessel disease to those with multivessel disease, the number of circulating endothelial progenitor cells was greater in the patients with single vessel disease. The vascular endothelial growth factor levels were raised during the first postinfarction week and the hepatocyte growth factor were higher on admission.


Caloric content of Daphnia magna as reflect of propanil stress during a short-term exposure and its relationship to long-term responses.
The present study investigates energy stores changes in the aquatic invertebrate Daphnia magna following a 5-d exposure to propanil. Juveniles of D. magna were exposed to sublethal propanil concentrations (0.07, 0.10, 0.21 and 0.55 mgl(-1)) which were used previously to test their effect on reproduction, growth and survival (21 days test) of D. magna. Glycogen, total lipids, proteins, and dry weight were determined in control and exposed daphnids at 24, 48, 72, 96 and 120 h. Data were used to calculate caloric content as biomarker of propanil exposure. Results showed a depletion of energy reserves in D. magna exposed to the herbicide. At 120 h of exposure to the highest propanil concentration (0.5 mgl(-1)), the reduction in daphnid reserves were glycogen (28%), proteins (28%) and lipids (31%), and caloric content was reduced in 27%. On the other hand, we found a positive correlation between caloric content and the chronic parameters intrinsic rate of natural increase and offspring per female when daphnids were exposed for 120 h to the herbicide.


Fast multislice mapping of the myelin water fraction using multicompartment analysis of T2* decay at 3T: a preliminary postmortem study.
Quantitative mapping of the myelin water content can provide significant insight into the pathophysiology of several white matter diseases, such as multiple sclerosis and leukoencephalopathies, and can potentially become a useful clinical tool for early diagnosis of these diseases. In this study, multicompartment analysis of T(2)(*) decay (MCAT(2)(*)) was used for the quantitative mapping of myelin water fraction (MWF). T(2)(*) decay of each voxel at multiple slice locations was acquired in fixed human brains using a multigradient-echo (MGRE) pulse sequence with alternating readout gradient polarities. Compared to prior techniques using Carr-Purcell-Meiboom-Gill (CPMG) acquisition, the MGRE acquisition approach has: 1) a very short first echo time ( approximately 2 ms) and echo-spacing ( approximately 1 ms), which allows for the acquisition of multiple sampling points during the fast decay of the myelin water signal; 2) a low RF duty cycle, which is especially important for achieving acceptable specific absorption rate (SAR) levels at high field strengths. Multicompartment analysis was then applied to the T(2)(*) decay in each pixel using a 3-pool model of white matter to detect the signal arising from the myelin water, myelinated axonal water, and mixed water compartments.


Acid-stable protease inhibiting polypeptides formed from denatured horse plasma by proteolysis.
1. Trypsin digestion of perchloric acid precipitated horse plasma yielded polypeptides with inhibitory properties for trypsin, chymotrypsin and, to a small extent, kallikrein. 2. The Mr of the inhibitory polypeptides were 73,000 and 24,000. 3. The number, enzyme specificity and Mr of the inhibitory polypeptides differed from the values known for the human being. 4. The inhibitory polypeptides were purified by affinity chromatography on Sepharose-trypsin and by gel filtration through Sephadex G-75. 5. Protease inhibitory polypeptides were generated in the same manner by chymotrypsin, elastase, proteinase K, pronase, collagenase, papain and subtilisin. 6. The number and electrophoretic migration of the inhibitory polypeptides obtained with the different enzymes were variable. 7. The enzyme specificity was constant since all polypeptides inhibited only trypsin, chymotrypsin and kallikrein to a small extent. 8. None of the inhibitory polypeptides were immunologically related to native plasma proteins or plasma protease inhibitors.


Linking nitrifying biofilm characteristics and nitrification performance in moving-bed biofilm reactors for polluted raw water pretreatment.
Biofilm physiology was characterized by four biofilm constituents, i.e., polysaccharides, proteins (PN), humic-like substances and phospholipids (PL), for the first time to explore the relationships between biofilm characteristics and nitrification performance in moving-bed biofilm reactors (MBBRs) designed for pretreatment of polluted raw surface water for potable supply. The biofilm compositions depended highly on the balance of microbial decay and nitrification processes. The increased ammonia loading greatly regulated the community structure, promoting the dominance of nitrifiers and their proportions in the nitrifying biofilm. Nitrification rate and activity correlated linearly with the fractions of volatile solids (VS), PN and PL, which were related to nitrification processes in the biofilm. The specific biofilm activity demonstrated an exponential-asymptotic relationship with ratios of PN/VS and PL/VS. Thus, analyzing biofilm characteristics can be valid for estimating nitrification performance in MBBRs, and may offer engineers with basis to optimize MBBR design and operation.


Rapid and inexpensive voltammetric detection of ochratoxin A in wheat matrices.
Produced as toxic metabolites by fungi, mycotoxins, such as ochratoxin A (OTA), contaminate grain and animal feed and cause great economic losses. Herein, we report the fabrication of an electrochemical sensor consisting of an inexpensive and label-free carbon black-graphite paste electrode (CB-G-CPE), which was fully optimized to detect OTA in durum wheat matrices using differential pulse voltammetry (DPV). The effect of carbon paste composition, electrolyte pH and DPV parameters were studied to determine the optimum conditions for the electroanalytical determination of OTA. Full factorial and central composite experimental designs (FFD and CCD) were used to optimize DPV parameters, namely pulse width, pulse height, step height and step time. The developed electrochemical sensor successfully detected OTA with detection and quantification limits equal to 57.2 nM (0.023 µg mL-1) and 190.6 nM (0.077 µg mL-1), respectively. The accuracy and precision of the presented CB-G-CPE was used to successfully quantify OTA in real wheat matrices. This study presents an inexpensive and user-friendly method with potential applications in grain quality control.


Hypokalemic Periodic Paralysis: a case report and review of the literature.
Hypokalemic Periodic Paralysis is one form of Periodic Paralysis, a rare group of disorders that can cause of sudden onset weakness. A case of a 29 year old male is presented here. The patient presented with sudden onset paralysis of his extremities. Laboratory evaluation revealed a markedly low potassium level. The patient's paralysis resolved upon repletion of his low potassium and he was discharged with no neurologic deficits. An association with thyroid disease is well established and further workup revealed Grave's disease in this patient. Although rare, Periodic Paralysis must differentiated from other causes of weakness and paralysis so that the proper treatment can be initiated quickly.


The frequency of factor V Leiden mutation, ACE gene polymorphism, serum ACE activity and response to ACE inhibitor and angiotensin II receptor antagonist drugs in Iranians type II diabetic patients with microalbuminuria.
The aim of present study was to determine if factor V Leiden (FVL) mutation and angiotensin converting enzyme insertion/deletion (ACE I/D) polymorphism are associated with diabetic nephropathy (DN) among Kurdish population from Western Iran. This case-control study comprised 144 unrelated adult type 2 diabetic mellitus patients (T2DM) including 72 patients with microalbuminuria and 72 age and sex matched patients without nephropathy. The ACE I/D polymorphism and FVL mutation were detected by polymerase chain reaction (PCR) and PCR-RFLP, respectively. The frequency of FVL G1691A and ACE D allele in T2DM patients with microalbuminuria were 1.6 and 57%, respectively and in normoalbuminuric T2DM patients were 4.9 and 58.3%, respectively (P > 0.05). ACE genotypes affected on serum ACE activity and a better response to ACE inhibitor therapy (captopril) compared to angiotensin II receptor antagonist (losartan) was obtained with significant reduction of ACE activity in diabetic patients without nephropathy carrying DD genotype. However, the beneficial effect of losartan therapy was observed in microalbuminuric patients with II genotype compared to ID and DD genotypes.


One-step multiplex RT-PCR assay for the detection of peste des petits ruminants virus in clinical samples.
A single-tube one-step multiplex RT-PCR was standardized to amplify both 337 bp and 191 bp fragments of N and M genes of peste des petits ruminants virus (PPRV), respectively, and only a 337 bp fragment of N gene of Rinderpest virus (RPV). The RT-PCR using purified viral RNA was easily adopted for direct detection of PPRV in clinical field samples and its differentiation from RPV. The amplified N and M gene products were confirmed to be PPRV- and RPV-specific by their size in 1.5% agarose gel and restriction analysis. In the assay, the Qiagen one-step RT-PCR kit containing the Ominiscript and Sensiscript reverse transcriptases and Hot star Taq DNA polymerase was utilized. The sensitivity of the assay was found to be 100 fg of PPRV RNA. Compared with a two-step assay, the one-step assay is easier and time-saving as it requires just a single buffer for both reactions, reverse transcription (RT) and PCR. In experimentally infected goats, PPRV was detectable by the one-step RT-PCR in nasal and ocular swabs 7-17 days post infection (p.i.). and in oral swabs 7-15 days p.i. Out of 32 clinical field samples tested, 18 were positive by sandwich ELISA (S-ELISA), while 22 were positive by the one-step RT-PCR.


Listening to and learning from older adult Hurricane Katrina survivors.
The objective of this pilot study was to explore how Hurricane Katrina affected older adult disaster survivors. Participants for this descriptive exploratory pilot study were recruited from churches and senior centers on the Gulf Coast of Mississippi. Of the 224 participants, one hundred provided additional comments at the end of a forced-response questionnaire. Manifest content analysis was used to examine the participants' comments by identifying, coding, and categorizing their responses to the open-ended question. The codes were based on conditions and behaviors that might be exhibited by disaster victims. Themed categories were losses and needs, giving advice, justification for continuing to live in this disaster-prone region, deterrents and facilitators of home evacuation, spirituality and faith, manageability, bereavement, grief, anger, and natural debriefing. The strongest message of these survivors was the need to be heard by public health nurses, other public health officials preparing for disasters, and those in positions to render aid.


The Germin-like protein gene OsGER4 is involved in heat stress response in rice root development.
Rice (Oryza sativa L.) is one of the most important dietary carbohydrate sources for half of the world's population. However, it is not well adapted to environmental stress conditions, necessitating to create new and improved varieties to help ensure sufficient rice production in the face of rising populations and shrinking arable land. Recently, the development of the CRISPR/Cas9 gene editing system has allowed researchers to study functional genomics and engineer new rice varieties with great efficiency compared to conventional methods. In this study, we investigate the involvement of OsGER4, a germin-like protein identified by a genome-wide association study that is associated with rice root development under a stress hormone jasmonic acids treatment. Analysis of the OsGER4 promoter region revealed a series of regulatory elements that connect this gene to ABA signaling and water stress response. Under heat stress, osger4 mutant lines produce a significantly lower crown root than wild-type Kitaake rice. The loss of OsGER4 also led to the reduction of lateral root development. Using the GUS promoter line, OsGER4 expression was detected in the epidermis of the crown root primordial, in the stele of the crown root, and subsequently in the primordial of the lateral root. Taken together, these results illustrated the involvement of OsGER4 in root development under heat stress by regulating auxin transport through plasmodesmata, under control by both ABA and auxin signaling.


No certain predictors for mutation status in a Danish cohort with familial hypercholesterolemia: a descriptive study.
In order to enable clinicians to refer the right persons suspected of familial hypercholesterolemia (FH) for mutation screening, a retrospective study was conducted in a Danish FH cohort. The study comprised 643 probands and 395 relatives, of which 421 individuals had a pathogenic mutation, and 211 had cardiovascular disease (CVD). Logistic regression, Cox regression, and receiver operating characteristics (ROC) curves were used to find optimal predictive variables for mutation status and evaluate risk factors for CVD. Age alone had significant predictive power in both genders. ROC curves and area under the curve plots found no parameters capable of predicting mutation status. The only significant risk factor for CVD in both genders was mutation carrier status. No parameters could decipher mutation status a priori. All individuals fulfilling the FH criteria should therefore be referred in order to facilitate family tracing and genetic counseling.


[Not Available].
Since 2003 bread and fine bakery products must not contain more than 350 μg Deoxynivalenol (DON). As a prerequisite for the label "Geprüfte Qualität"-Thüringen [proved quality Thuringia] and since coming into force of the respective evaluation prescription a total of 25 breads and 41 fine bakery products was investigated by ELISA with regard of this compound. In the 66 samples of the year 2003 no DON concentrations above the limit were detected and in the preparation period 2001/2002 only one sample exceeded the maximum. In several samples, most narrow to the maximum limit, an additional determination by HPLC was performed which resulted in lower DON-concentrations as compared to the values analyzed by ELISA.


Diagnosis and treatment of spontaneous cerebrospinal fluid otorrhea.
Two consecutively operated-on adult cases with spontaneous cerebrospinal fluid otorrhea were reviewed. Three meningoencephaloceles through tegmental defects were found. Each cele was peduculated through a small dural dehiscence partially obstructed by herniated brain. The otic capsule was normal in both cases. Bipolar cautery was used to reduce the size of the meningoencephalocele and to allow this tissue to assist in the closure of the defect. Conchal cartilage was placed through the tegmental defect to act as a self maintaining intracranial repair of the bony dehiscence. These cases and the literature suggest that fistulization of dura is more frequently the cause of spontaneous cerebrospinal fluid otorrhea in adults than is a defect in the otic capsule. Thus, direct surgical inspection of these areas is required.


The effect of obstructed action efficacy on reward-based decision-making in healthy adolescents: a novel functional MRI task to assay frustration.
Frustration is common in adolescence and often interferes with executive functioning, particularly reward-based decision-making, and yet very little is known about how incidental frustrating events (independent of task-based feedback) disrupt the neural circuitry of reward processing in this important age group. While undergoing functional magnetic resonance imaging (fMRI), 45 healthy adolescents played a card game in which they had to guess between two options to earn points, in low- and high-stake conditions. Functioning of button presses through which they made decisions was intermittently blocked, thereby increasing frustration potential. Neural deactivation of the precuneus, a Default Mode Network region, was observed during obstructed action blocks across stake conditions, but less so on high- relative to low-stake trials. Moreover, less deactivation in goal-directed reward processing regions (i.e., caudate), frontoparietal "task control" regions, and interoceptive processing regions (i.e., somatosensory cortex, thalamus) were observed on high-stake relative to low-stake trials. These findings are consistent with less disruption of goal-directed reward seeking during blocked action efficacy in high-stake conditions among healthy adolescents. These results provide a roadmap of neural systems critical to the processing of frustrating events during reward-based decision-making in youths and could help to characterize how frustration regulation is altered in a range of pediatric psychopathologies.


Characteristics of atmospheric aerosol and acidic gases from urban and forest sites in central taiwan.
Measurements of atmospheric fine aerosols, acidic gases and ammonia were made at National Chung Hsing University (Urban) and Huisun forest area (Forest) sites in central Taiwan region during October (highest ozone month). Annular Denuder System (ADS) was used for sampling gaseous (nitrous acid, nitric acid, sulfur dioxide and ammonia) and fine aerosol species (ammonium, nitrate and sulfate). The results showed a significant diurnal variation in nitrous acid and nitric acid concentrations. Nitric acid was produced primarily during daytime in both sites. In the urban site, the average concentration of nitric acid during daytime was 5.8 times higher compared to nighttime while the average nitrous acid concentration during daytime was lower compared to nighttime, due to the photo-dissociation of nitrous acid. Sulfate, nitrate and ammonium were the major constituents of PM(2.5). Higher concentrations of nitrous acid, nitric acid, particulate nitrate and ammonium were recorded at urban site.


Coins in the esophagus. What is the best management?
In order to compare esophagoscopy to the Foley catheter method of removing coins from the esophagus, we reviewed our results with 136 esophagoscopies performed to remove coins during a 15-year period. Fifty-two percent of the patients were under two years of age and 29% were under one year. One hundred and twenty-seven patients had no problems from the anesthesia or the esophagoscopy. Complications related to the endotracheal tube and exacerbations of pre-existing respiratory illnesses occurred in 9 patients. There were no deaths or esophageal perforations. Our results are compared to the published results from the Foley catheter method. In our opinion, esophagoscopy is the procedure of choice for all children with coins in the esophagus.


Engineered diets to improve cancer outcomes.
Cancer cells acquire a diverse range of metabolic adaptations that support their enhanced rates of growth and proliferation. While these adaptations help tune metabolism to support higher anabolic output and bolster antioxidant defenses, they can also decrease metabolic flexibility and increase dependence on nutrient uptake versus de novo synthesis. Diet is the major source of nutrients that ultimately support tumor growth, yet the potential impact of diet is currently underutilized during the treatment of cancer. Here, we review several forms of dietary augmentation therapy including those that alter the content of food, such as energy or macronutrient restriction, and those that alter the timing of food consumption, like intermittent fasting regimens. We discuss how these dietary strategies can be combined with pharmacologic therapies to exaggerate the metabolic liabilities of different cancer types.


UGT2B4 previously implicated in the risk of breast cancer is associated with menarche timing in Ukrainian females.
Age at menarche (AAM) is a multifactorial trait that is regulated by dozens environmental and genetic factors. Recent meta-analysis of GWAS showed significant association of 106 loci with AAM. These polymorphisms need replicating in different ethnic populations in order to confirm their association with menarche timing. This study was aimed to replicate 53 polymorphisms that were previously associated with AAM. DNA samples were collected from 416 Ukrainian young females for further genotyping. After data quality control 47 polymorphisms remained for the association analysis using the linear regression model. SNP rs13111134 located in UGT2B4 showed the most significant association with AAM (0.431years per allele A, padj=0.044 after the Bonferroni correction). Polymorphisms rs7589318 in POMC, rs11724758 in FABP2, rs7753051 in IGF2R, rs2288696 in FGFR1 and rs12444979 in GPRC5B may also contribute to menarche timing. However, none of these associations remained significant after the Bonferroni correction for multiple testing. The obtained results provide evidence that UGT2B4, which was previously associated with predisposition to breast cancer, may play a role in the onset of menarche.


Transepithelial taurine transport in caco-2 cell monolayers.
Here we characterized transepithelial taurine transport in monolayers of cultured human intestinal Caco-2 cells by analyzing kinetic apical and basolateral uptake and efflux parameters. Basolateral uptake was Na(+)- and Cl(-)- dependent and was inhibited by beta-amino acids. Uptake by this membrane showed properties similar to those of the apical TauT system. In both membranes, taurine uptake fitted a model consisting of a non-saturable plus a saturable component, with a higher half-saturation constant and transport capacity at the apical membrane (K(m), 17.1 micromol/L; V(max), 28.4 pmol.cm(-2).5 min(-1)) than in the basolateral domain (K(m), 9.46 micromol/L; V(max), 5.59 pmol.cm(-2).5 min(-1)). The non-saturable influx component, estimated in the absence of Na(+) and Cl(-), showed no significant differences between apical and basolateral membranes (K(D), 89.2 and 114.7 nL.cm(-2) . 5 min(-1), respectively). Taurine efflux from the cells is a diffusive process, as shown in experiments using preloaded cells and in trans-stimulation studies (apical K(D),72.7 and basolateral K(D), 50.1 nL.cm(-2).5 min(-1)). Basolateral efflux rates were significantly lower than passive influx rates. We conclude that basolateral taurine uptake in Caco-2 cells is mediated by a transport mechanism that shares some properties with the apical system TauT. Moreover, calculation of unidirectional and transepithelial taurine fluxes reveals that apical influx of this amino acid is higher than basolateral efflux rates, thereby enabling epithelial cells to accumulate taurine against a concentration gradient.


Magnetic nanocomposite of anti-human IgG/COOH-multiwalled carbon nanotubes/Fe₃O₄ as a platform for electrochemical immunoassay.
An electrochemical immunosensing method was developed based on a magnetic nanocomposite. The multiwalled carbon nanotubes (MWCNTs) were treated with nitric acid to produce carboxyl groups at the open ends. Then, Fe₃O₄ nanoparticles were deposited on COOH-MWCNTs by chemical coprecipitation of Fe²⁺ and Fe³⁺ salts in an alkaline solution. Goat anti-human IgG (anti-hIgG) was covalently attached to magnetic nanocomposite through amide bond formation between the carboxylic groups of MWCNTs and the amine groups of anti-hIgG. The prepared bio-nanocomposite was used for electrochemical sensing of human tetanus IgG (hIgG) as a model antigen. The anti-hIgG magnetic nanocomposite was fixed on the surface of a gold plate electrode using a permanent magnet. The hIgG was detected using horseradish peroxidase (HRP)-conjugated anti-hIgG in a sandwich model. Electrochemical detection of hIgG was carried out in the presence of H₂O₂ and KI as substrates of HRP. Using this method, hIgG was detected in a concentration range from 30 to 1000 ng ml⁻¹ with a correlation coefficient of 0.998 and a detection limit of 25 ng ml⁻¹ (signal/noise=3). The designed immunosensor was stable for 1 month.


Clinical effect of acupuncture on cervical spondylotic radiculopathy: results of a case series.
To observe the effectiveness of acupuncture applied to the cervical region of patients with upper extremity radicular symptoms due to cervical spondylotic radiculopathy (CSR). 15 subjects diagnosed with CSR and with upper extremity pain and/or paraesthesiae for 13.1±18.0 months were selected. The 15 patients had 16 affected limbs and scored a total of 17 symptom scores of pain and/or paraesthesiae. All patients were treated with acupuncture once a week for 4 weeks at up to 10 sites in the cervical paraspinal region centred on the affected area. The severity of the symptoms was recorded using a visual analogue scale (VAS) and functional evaluation was conducted using a Neck Disability Index (NDI). A significant reduction over time was seen for both mean VAS (p<0.0001) and NDI (p<0.0001). Changes were still significant at 4-week follow-up. A 50% reduction in symptoms was scored for 15 of the 17 symptoms scored. Favourable results were seen in nearly 90% of cases. These results show that acupuncture treatment to the cervical region may be effective as a conservative therapy for treating CSR.


Induction of indoleamine 2,3-dioxygenase in livers following hepatectomy prolongs survival of allogeneic hepatocytes after transplantation.
Indoleamine 2,3-dioxygenase (IDO), which catalyzes the breakdown of tryptophan into kyneurenine, has immunologic significance for the induction of maternal tolerance and liver allograft tolerance by inhibiting T-cell activation. In the present study, we compared survival of syngeneic or allogeneic hepatocytes in livers with or without hepatectomy. Subsequently, we investigated gene expression and localization of IDO in the recipient liver. DA and Fisher 344 rats were used in the following experimental groups: group 1, DA hepatocytes transplanted into hepatectomized Fisher 344 rats; group 2, Fisher 344 hepatocytes transplanted into hepatectomized Fisher 344 rats; group 3, DA hepatocytes transplanted into nonhepatectomized Fisher 344 rats; and group 4, Fisher 344 hepatocytes transplanted into nonhepatectomized Fisher 344 rats. After transplantation, the surviving cells were evaluated on day 5. The IDO signal of the recipient liver was detected by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. In the hepatectomized groups subjected to allogeneic or syngeneic hepatocyte transplantation, the number of surviving hepatocytes was greater than in the nonhepatectomized group after transplantation. The IDO signals (RT-PCR) in the hepatectomized groups were stronger than those in the nonhepatectomized groups. Immunohistochemistry demonstrated that the IDO signal is located in liver antigen-presenting cells, such as Kupffer cells or dendritic cells, and not expressed in hepatocytes. Our results demonstrated that IDO is induced in antigen-presenting cells of hepatectomized livers by which subsequently transplanted cells may be protected from rejection by inhibiting indirect or direct recognition of donor antigen and further T-cell activation.


Aerial photography used for spatial pattern analysis of late blight infection in irrigated potato circles.
ABSTRACT Spatial and temporal dynamics of late blight were investigated from color, infrared aerial photographs of five commercial potato fields in the Columbia Basin during epidemics in 1993, 1995, and 1998. Aerial photographs were taken one to four times at 6- to 21-day intervals. Photographs were scanned and pixels, representing approximately 1 m(2) in the field, were used in the analysis. Late blight-infected plants were aggregated as indicated by runs analysis. Significant z-tests were computed for four directions during each sampling date in each of the five fields. Absolute z-values for runs analysis increased, indicating increasing aggregation in the four directions, as disease incidence increased in the early and midphases of the epidemics in each field. Variograms indicated the existence of autocorrelation among infected plants in four directions; the range of influence increased as disease incidence increased except at the highest levels of disease. Late blight was observed to spread in fields as foci. Late blight foci enlarged in size, produced distinct daughter foci, and coalesced. A field where initial inoculum likely originated from infected seed tubers exhibited less initial aggregation than the other fields, perhaps due to a different source of primary inoculum. Aerial photography coupled with spatial analyses of late blight-infected plants was an effective technique to quantitatively assess disease patterns in relatively large fields and was useful in quantifying an intensification of aggregation during the epidemic process on a large scale.


The structural basis for the activation and peptide recognition of bacterial ClpP.
ClpP and its ATPase compartment, ClpX or ClpA, remove misfolded proteins in cells and are of utmost importance in protein quality control. The ring hexamers of ClpA or ClpX recognize, unfold, and translocate target substrates into the degradation chamber of the double-ring tetradecamer of ClpP. The overall reaction scheme catalyzed by ClpXP or ClpAP has been proposed; however, the molecular mechanisms associated with substrate recognition and degradation have not yet been clarified in detail. To investigate these mechanisms, we determined the crystal structures of ClpP from Helicobacter pylori in complex with product peptides bound to the active site as well as in the apo state. In the complex structure, the peptides are zipped with two antiparallel strands of ClpP and point to the adjacent active site, thus providing structural explanations for the broad substrate specificity, the product inhibition and the processive degradation of substrates in the chamber. The structures also suggest that substrate binding causes local conformational changes around the active site that ultimately induce the active conformation of ClpP.


Association Between Culture and Culture-Independent Microtyping in Recalcitrant Chronic Rhinosinusitis.
Many different etiologies have been proposed to be responsible for the pathogenesis of chronic rhinosinusitis, including dysbiosis of the sinus microbiome. Attempts have recently been made to identify a pathogenic organism via advanced culture mechanisms. The purpose of this study is to use culture-dependent and culture-independent means of microtyping to determine whether any association exists between the quantity and quality of bacteria identified in patients with recalcitrant chronic rhinosinusitis. Medical records were retrospectively reviewed for patients with a history of revision sinus surgery and persistent symptoms who underwent endoscopically directed culture and underwent quantitative polymerase chain reaction analysis of the 16S ribosomal RNA of bacteria and fungi from February 1, 2014, to January 1, 2017. A total of 21 patients met the inclusion criteria. Medical records were reviewed to determine the number of bacterial isolates and relative abundance of bacteria and fungi on culture and polymerase chain reaction. Using culture-independent techniques of examining purulent secretions in patients with recalcitrant chronic rhinosinusitis, an average of 3.61 isolates were identified per specimen, compared with culture-dependent methods that revealed 2.10 isolates per specimen ( P < .05). The dominant species identified on each culture was rarely the most abundant species identified using polymerase chain reaction techniques. Traditional culture methodologies may fail to identify potential pathogens or the dominant pathogen in patients with recalcitrant chronic rhinosinusitis with acute exacerbations.


A comparison of timolol and propranolol in essential hypertension.
The antihypertensive efficacy of a new beta-adrenergic receptor inhibiting compound, timolol (MK-950), was evaluated using two treatment protocols: double-blind timolol vs. placebo treatment and double-blind timolol vs. propranolol (10 and 12 patients, respectively). These studies indicate that timolol significantly and safely reduced arterial pressure in mild to moderately severe essential hypertensive patients. The reduction in mean arterial pressure with timolol was equivalent to the pressure reduction with propranolol when the doses of 30 and 120 mg. per day, respectively, were used.


Cellular Uptake and Movement in 2D and 3D Multicellular Breast Cancer Models of Fructose-Based Cylindrical Micelles That Is Dependent on the Rod Length.
While the shape effect of nanoparticles on cellular uptake has been frequently studied, no consistent conclusions are available currently. The controversy mainly focuses on the cellular uptake of elongated (i.e., filaments or rod-like micelles) as compared to spherical (i.e., micelles and vesicles) nanoparticles. So far, there is no clear trend that proposes the superiority of spherical or nonspherical nanoparticles with conflicting reports available in the literature. One of the reasons is that these few reports available deal with nanoparticles of different shapes, surface chemistries, stabilities, and aspects ratios. Here, we investigated the effect of the aspect ratio of cylindrical micelles on the cellular uptake by breast cancer cell lines MCF-7 and MDA-MB-231. Cylindrical micelles, also coined rod-like micelles, of various length were prepared using fructose-based block copolymers poly(1-O-methacryloyl-β-d-fructopyranose)-b-poly(methyl methacrylate). The critical water content, temperature, and stirring rate that trigger the morphological transition from spheres to rods of various aspect ratios were identified, allowing the generation of different kinetically trapping morphologies. High shear force as they are found with high stirring rates was observed to inhibit the formation of long rods. Rod-like micelles with length of 500-2000 nm were subsequently investigated toward their ability to translocate in breast cancer cells and penetrate into MCF-7 multicellular spheroid models. It was found that shorter rods were taken up at a higher rate than longer rods.


Mobile primary renal vein lipoma with an accelerated growth pattern.
Primary intravascular lipoma is a rare proliferation of adipose tissue originating from the wall of blood vessels. We have described an unusual case of a benign, but fast-growing, primary intravascular lipoma of the left renal vein with the mobile edge extending to the cavoatrial junction within just a few months. We have discussed the surgical indications, management, and technical considerations and highlighted the importance of surgical planning for similar cases.


Energy constraint and compensation: Insights from endurance athletes.
The Constrained Model of Total Energy Expenditure predicts that increased physical activity may not influence total energy expenditure, but instead, induces compensatory energetic savings in other processes. Much remains unknown, however, about concepts of energy expenditure, constraint and compensation in different populations, and it is unclear whether this model applies to endurance athletes, who expend very large amounts of energy during training and competition. Furthermore, it is well-established that some endurance athletes consciously or unconsciously fail to meet their energy requirements via adequate food intake, thus exacerbating the extent of energetic stress that they experience. Within this review we A) Describe unique characteristics of endurance athletes that render them a useful model to investigate energy constraints and compensations, B) Consider the factors that may combine to constrain activity and total energy expenditure, and C) Describe compensations that occur when activity energy expenditure is high and unmet by adequate energy intake. Our main conclusions are as follows: A) Higher activity levels, as observed in endurance athletes, may indeed increase total energy expenditure, albeit to a lesser degree than may be predicted by an additive model, given that some compensation is likely to occur; B) That while a range of factors may combine to constrain sustained high activity levels, the ability to ingest, digest, absorb and deliver sufficient calories from food to the working muscle is likely the primary determinant in most situations and C) That energetic compensation that occurs in the face of high activity expenditure may be primarily driven by low energy availability i.e., the amount of energy available for all biological processes after the demands of exercise have been met, and not by activity expenditure per se.


Sensitive chemiluminescence detection of wild-type p53 protein captured by surface-confined consensus DNA duplexes.
A novel chemiluminescence (CL) biosensor for sensitive detection of wild-type p53 protein has been proposed. The wild-type p53 protein in solution was captured by highly specific consensus double-stranded (ds) oligonucleotides (ODNs) preimmobilized onto a gold plate. The cysteine residues on the exterior of the wild-type p53 molecules were then derivatized with N-biotinoyl-N'-(6-maleimidohexanoyl) hydrazide (biotin-Mi) for the attachment of streptavidin-horseradish peroxidase (SA-HRP) complex. The attached HRP molecules could catalyze the CL reaction between luminol and H2O2, producing an enhanced CL signal. The CL intensity was dependent on the surface coverage of the HRP molecules, which was related to the concentration of wild-type p53 protein. Under the optimal experimental conditions, the CL intensity increased linearly with the concentration of wild-type p53 protein from 0.01 to 0.5nM. The detection limit was estimated to be 3.8pM. The proposed method has been successfully utilized for the assay of wild-type p53 protein in normal and cancer cell lysates. The sensing protocol is sensitive, cost-effective, and holds great promise for clinical diagnosis.


DLGAP4 acts as an effective prognostic predictor for hepatocellular carcinoma and is closely related to tumour progression.
Disc large associated protein 4 (DLGAP4) plays an important role in neurological diseases, but the role and mechanism of DLGAP4 in hepatocellular carcinoma (HCC) remain unclear. In this study, the prognostic effect of DLGAP4 on HCC patients was investigated by means of bioinformatics. The correlation of DLGAP4 expression with the prognosis of HCC patients was evaluated by TCGA data analysis, and the correlation between DLGAP4 expression and the clinical characteristics of HCC patients was evaluated by the Wilcoxon signed rank test and logistic regression analysis. Kaplan‒Meier and Cox regression methods were used to assess the effect of DLGAP4 expression level on overall survival, and nomograms were used to illustrate the correlation between DLGAP4 gene expression and HCC risk. The genes related to DLGAP4 in HCC were screened, and GO/KEGG enrichment analysis was performed. Furthermore, in vitro and in vivo experiments were conducted to detect the effect of DLGAP4 expression on the proliferation, migration and metastasis of HCC cells. We also examined the effect of DLGAP4 expression on enriched pathway proteins to explore the possible mechanism. The expression levels of DLGAP4 were significantly higher in HCC cell lines and tissue samples than in normal liver cell lines and tissues. The expression of DLGAP4 was significantly associated with clinical characteristics. Survival analysis showed that high expression of DLGAP4 was associated with a poor prognosis in HCC. Multivariate analysis showed that high expression of DLGAP4 was an independent risk factor affecting the overall survival rate in HCC patients. By means of ROC curve analysis and nomograms, we determined the value of DLGAP4 expression in the diagnosis and prognosis evaluation of HCC. GO/KEGG enrichment analysis showed that the PPAR signalling pathway was differentially enriched in patients with high expression of DLGAP4. According to in vitro and in vivo experiments, DLGAP4 knockdown inhibited the proliferation and metastasis of HCC cells and decreased the expression of PPARβ/δ protein. In contrast, overexpression of DLGAP4 promoted the proliferation and metastasis of HCC cell, and increased the expression of PPARβ/δ protein.In contrast, overexpression of DLGAP4 promoted the proliferation and metastasis of HCC cells and increased the expression of PPARβ/δ protein. The results show a close correlation between DLGAP4 expression and clinicopathological features of HCC, and DLGAP4 can be used as a prediction biomarker of HCC.


The structure of the menaquinones with a tetrahydrogenated isoprenoid side-chain.
Menaquinones with a tetrahydrogenated isoprenoid side-chain of Oerskovia turbata and Brevibacterium lipolyticum were cyclized to the chromenyl acetate derivatives, which were then submitted to ozonolysis, followed by reduction with dimethylsulfide. The mass-spectrometric analyses of the ozonolysis products revealed the ion peaks at m/e 464 (M+), 449, 422, 407, 267 and 225. These results suggest that the two saturated double bonds are located continuously in the second and third units of the chain starting from the quinone ring, and the menaquinones are designated as 2-methyl-3-II,III-tetrahydromultiprenyl-1,4-naphthoquinone.


Immunoelectron-microscopic demonstration of elastase in emphysematous lungs of tight-skin mice.
The tight-skin (Tsk) mouse has recently been proposed as a genetic model of emphysema. A morphometric study has shown that emphysema develops quickly, between 15 days and 1 month after birth. Previous biochemical and ultrastructural investigations of the lungs of 1- and 2-month-old Tsk mice revealed the presence of an ongoing elastolytic process. The goal of the present study was to investigate the role of mouse leukocyte elastase (MLE) in the development of emphysema in 1-month-old Tsk mice. Using electron microscopy and an immunogold labeling technique with rabbit anti-MLE IgG, MLE was localized within the lung neutrophils of control and Tsk mice. MLE was also found associated with elastin in the alveolar septa of Tsk but not of control mice. Little or no labeling was associated with other components (collagen, pneumocytes, and endothelium) of alveolar septa of Tsk mice. Lung elastin of control mice, or of control mice rendered emphysematous with porcine pancreatic elastase, showed negligible gold particle density when incubated with gold-conjugated rabbit IgG. Thus, under the present experimental conditions, an aspecific labeling of elastin is unlikely. This study indicates that MLE may be one of the factors responsible for the rapid development of emphysema in Tsk mice.


Detection of reactive oxygen species in isolated, perfused lungs by electron spin resonance spectroscopy.
The sources and measurement of reactive oxygen species (ROS) in intact organs are largely unresolved. This may be related to methodological problems associated with the techniques currently employed for ROS detection. Electron spin resonance (ESR) with spin trapping is a specific method for ROS detection, and may address some these technical problems. We have established a protocol for the measurement of intravascular ROS release from isolated buffer-perfused and ventilated rabbit and mouse lungs, combining lung perfusion with the spin probe 1-hydroxy-3-carboxy-2,2,5,5-tetramethylpyrrolidine (CPH) and ESR spectroscopy. We then employed this technique to characterize hypoxia-dependent ROS release, with specific attention paid to NADPH oxidase-dependent superoxide formation as a possible vasoconstrictor pathway. While perfusing lungs with CPH over a range of inspired oxygen concentrations (1-21 %), the rate of CP* formation exhibited an oxygen-dependence, with a minimum at 2.5 % O2. Addition of superoxide dismutase (SOD) to the buffer fluid illustrated that a minor proportion of this intravascular ROS leak was attributable to superoxide. Stimulation of the lungs by injection of phorbol-12-myristate-13-acetate (PMA) into the pulmonary artery caused a rapid increase in CP* formation, concomitant with pulmonary vasoconstriction. Both the PMA-induced CPH oxidation and the vasoconstrictor response were largely suppressed by SOD. When the PMA challenge was performed at different oxygen concentrations, maximum superoxide liberation and pulmonary vasoconstriction occurred at 5% O2. Using a NADPH oxidase inhibitor and NADPH-oxidase deficient mice, we illustrated that the PMA-induced superoxide release was attributable to the stimulation of NADPH oxidases. The perfusion of isolated lungs with CPH is suitable for detection of intravascular ROS release by ESR spectroscopy. We employed this technique to demonstrate that 1) PMA-induced vasoconstriction is caused "directly" by superoxide generated from NADPH oxidases and 2) this pathway is pronounced in hypoxia. NADPH oxidases thus may contribute to the hypoxia-dependent regulation of pulmonary vascular tone.


Helmet Fit Assessment and Concussion Risk in Youth Ice Hockey Players: A Nested Case-Control Study.
Injury surveillance has shown that concussions are the most common injury in youth ice hockey. Research examining the criteria for ensuring the correct fit of protective equipment and its potential relationship with concussion risk is very limited. To evaluate the association between helmet fit and the odds of experiencing a concussion among youth ice hockey players. Nested case-control within a cohort study. Calgary, Alberta, Canada. Data were collected for 72 concussed, 41 nonconcussion-injured, and 62 uninjured ice hockey players aged 11 to 18 years. Helmet-fit assessments were conducted across players and encompassed helmet specifications, condition, certification, and criteria measuring helmet fit. Using a validated injury-surveillance system, we identified participants as players with suspected concussions or physician-diagnosed concussions or both. One control group comprised players who sustained nonconcussion injuries, and a second control group comprised uninjured players. Helmet-fit criteria (maximum score = 16) were assessed for the concussed players and compared with each of the 2 control groups. The primary outcome was dichotomous (>1 helmet-fit criteria missing versus 0 or 1 criterion missing). Logistic and conditional logistic regression were used to investigate the effect of helmet fit on the odds of concussion. The primary analysis (54 pairs matched for age, sex, and level of play) suggested that inadequate helmet fit (>1 criterion missing) resulted in greater odds of sustaining a concussion when comparing concussed and uninjured players (odds ratio [OR] = 2.67 [95% CI = 1.04, 6.81], P = .040). However, a secondary unmatched analysis involving all participants indicated no significant association between helmet fit and the odds of sustaining a concussion when we compared concussed players with nonconcussion-injured players (OR = 0.98 [0.43, 2.24], P = .961) or uninjured players (OR = 1.66 [0.90, 3.05], P = .103). Inadequate helmet fit may affect the odds of sustaining a concussion in youth ice hockey players. Future investigators should continue to evaluate this relationship in larger samples to inform helmet-fit recommendations.


Coronavirus disease 2019 crisis in Paris: A differential psychological impact between regular intensive care unit staff members and reinforcement workers.
Intensive care unit (ICU) healthcare workers (HCWs) are at the forefront of the coronavirus disease 2019 pandemic. To overcome the lack of human resources during this crisis, some ICUs had to mobilise staff from a reinforcement pool, with no or outdated ICU experience. This study aimed to investigate and to compare the psychological impact of the pandemic on regular ICU staff members and reinforcement workers. Self-assessment questionnaires were completed by HCWs who worked from March 1 to April 30, 2020, in our 16-bed neurological ICU at La Pitié-Salpêtrière Hospital in Paris, France, which was converted to a COVID ICU. The Hospital Anxiety and Depression Scale, the Post-traumatic Stress Disorder Checklist for DSM-5, McGill Quality of Life Questionnaire-Revised, and 10-item Connor-Davidson Resilience Scale were used to assess anxiety, depression and post-traumatic stress disorder, quality of life, and resilience, respectively. Sixty-nine ICU HCWs completed the survey (37 from the team of regular staff members, i.e., from the public health service, and 32 from a reinforcement pool, either from non-ICU public health service or from private healthcare interim employment agencies). Prevalence of anxiety, depression, and post-traumatic stress disorder symptoms was high, at 19%, 9%, and 16%, respectively, with limited impairment in quality of life or resilience scores. Depression symptoms were observed more in regular staff members than in welcomed reinforcement workers, at 16% and 0%, respectively. These results revealed that during the pandemic, HCWs from the team of regular staff members were at greater risk of developing psychological disorder compared with reinforcement workers, with higher levels of depressive symptoms.


GATA4-Twist1 Signalling in Disturbed Flow-Induced Atherosclerosis.
Endothelial cell (EC) dysfunction (enhanced inflammation, proliferation and permeability) is the initial trigger for atherosclerosis. Atherosclerosis shows preferential development near branches and bends exposed to disturbed blood flow. By contrast, sites that are exposed to non-disturbed blood flow are atheroprotected. Disturbed flow promotes atherosclerosis by promoting EC dysfunction. Blood flow controls EC function through transcriptional and post-transcriptional mechanisms that are incompletely understood. We identified the developmental transcription factors Twist1 and GATA4 as being enriched in EC at disturbed flow, atheroprone regions of the porcine aorta in a microarray study. Further work using the porcine and murine aortae demonstrated that Twist1 and GATA4 expression was enhanced at the atheroprone, disturbed flow sites in vivo. Using controlled in vitro flow systems, the expression of Twist1 and GATA4 was enhanced under disturbed compared to non-disturbed flow in cultured cells. Disturbed flow promoted Twist1 expression through a GATA4-mediated transcriptional mechanism as revealed by a series of in vivo and in vitro studies. GATA4-Twist1 signalling promoted EC proliferation, inflammation, permeability and endothelial-to-mesenchymal transition (EndoMT) under disturbed flow, leading to atherosclerosis development, as shown in a combination of in vitro and in vivo studies using GATA4 and Twist1-specific siRNA and EC-specific GATA4 and Twist1 Knock out (KO) mice. We revealed that GATA4-Twist1-Snail signalling triggers EC dysfunction and atherosclerosis; this work could lead to the development of novel anti-atherosclerosis therapeutics.