In-depth profiling, characterization, and comparison of the ginsenosides among three different parts (the root, stem leaf, and flower bud) of Panax quinquefolius L. by ultra-high performance liquid chromatography/quadrupole-Orbitrap mass spectrometry.
Despite Panax quinquefolius L. serving as a crucial source for food additives, healthcare products, and herbal medicines, unawareness of the metabolome differences among three parts (root, PQR; stem leaf, PQL; flower bud, PQF) seriously restricts its quality control. Ultra-high performance liquid chromatography/quadrupole-Orbitrap mass spectrometry (UHPLC/Q-Orbitrap-MS) was fully utilized to comprehensively identify and compare the ginsenoside compositions among PQR, PQL, and PQF. Metabolite profiling and characterization were performed by coupling reversed-phase UHPLC (a CSH C18 column) and improved untargeted data-dependent MS2 acquisition in the negative mode. A novel vehicle, "Ginsenoside Sieve," was proposed by developing fixed tolerance (± 10 mDa), discrete mass defect filtering (MDF) based on the m/z features of 499 known ginsenosides, which assisted in the screening of 71 (from 3453 ions), 89 (from 6842), and 84 (from 7369) target precursor masses for PQR, PQL, and PQF, respectively. The newly established data-dependent acquisition (DDA) approach exhibited 14% improvement in characterization of targeted components (using a PQL sample), and comparable performance in identifying the unknown, compared with conventional DDA. We could characterize 347 saponins (147 from PQR, 173 from PQL, and 195 from PQF), and 157 thereof not ever-isolated from the Panax genus. These potentially new saponins have 63 unknown masses. Subsequent untargeted metabolomics analysis unveiled 20 marker saponins, among which m-Rb1, Rb1, Ro, m-Rb2, and m-Rb1 isomer are the most important diagnostic for differentiating the three parts. Conclusively, the established improved DDA represents a potent ginsenoside characterization strategy, and the results obtained in this work would benefit better quality control of P. quinquefolius. Graphical abstract.


Negative pressure wound therapy for children with an open abdomen.
The utility of negative pressure wound therapy (NPWT) in the management of adults with an open abdomen has been well documented. We reviewed our experience with NPWT in the management of infants and children with this condition. The records of all children who were treated with NPWT for an open abdomen between March 2005 and September 2009 at a single children's hospital were reviewed. Twenty-five subjects were identified. They included children who developed abdominal compartment syndrome after a laparotomy (n = 12) or in whom the abdomen could not be safely closed at the time of laparotomy (n = 13). NWPT was accomplished with the vacuum-assisted closure (VAC®) system in all patients. The median duration for NPWT was 4.5 days. In 16 subjects, the abdomen was closed successfully after NPWT. In 14 children, the abdominal wall fascia was successfully approximated, and two children underwent a patch abdominal closure. But nine subjects died before an abdominal closure could be attempted. Only two (12.5%) children developed enterocutaneous fistulae. NPWT is a reliable tool for infants and children with an open abdomen. Wound management was facilitated and abdominal wall closure was ultimately achieved in all survivors. Enterocutaneous fistulae developed in two children, however, these were likely due to underlying bowel injury and would have occurred despite variations in management of the open abdomen.


Benchmarks and determinants of adherence to stroke performance measures.
Develop achievable benchmarks for 9 stroke performance measures (PM) and to identify organizational factors associated with adherence. Adherence rates and achievable benchmarks were determined for 9 PM within a study of patients (n=2294) admitted with acute ischemic stroke at 17 hospitals. Baseline information regarding hospital characteristics and stroke-specific processes of care were collected, and multi-level models were used to test the association of these factors with adherence. Benchmarks were >or=90% for 8 of the 9 PM. After controlling for clustering, only use of standing orders was associated with adherence to PM, including: dysphagia screening, venous thrombosis prophylaxis, consideration of tPA, and provision of educational material. High levels of adherence are achievable for several acute stroke PM. Use of standing orders is associated with adherence to PM requiring immediate action on admission.


Super-Resolved q-Space deep learning with uncertainty quantification.
Diffusion magnetic resonance imaging (dMRI) provides a noninvasive method for measuring brain tissue microstructure. q-Space deep learning(q-DL) methods have been developed to accurately estimate tissue microstructure from dMRI scans acquired with a reduced number of diffusion gradients. In these methods, deep networks are trained to learn the mapping directly from diffusion signals to tissue microstructure. However, the quality of tissue microstructure estimation can be limited not only by the reduced number of diffusion gradients but also by the low spatial resolution of typical dMRI acquisitions. Therefore, in this work we extend q-DL to super-resolved tissue microstructure estimation and propose super-resolvedq-DL (SR-q-DL), where deep networks are designed to map low-resolution diffusion signals undersampled in the q-space to high-resolution tissue microstructure. Specifically, we use a patch-based strategy, where a deep network takes low-resolution patches of diffusion signals as input and outputs high-resolution tissue microstructure patches. The high-resolution patches are then combined to obtain the final high-resolution tissue microstructure map. Motivated by existing q-DL methods, we integrate the sparsity of diffusion signals in the network design, which comprises two functional components. The first component computes sparse representation of diffusion signals for the low-resolution input patch, and the second component maps the low-resolution sparse representation to high-resolution tissue microstructure. The weights in the two components are learned jointly and the trained network performs end-to-end tissue microstructure estimation. In addition to SR-q-DL, we further propose probabilistic SR-q-DL, which can quantify the uncertainty of the network output as well as achieve improved estimation accuracy. In probabilistic SR-q-DL, a deep ensemble strategy is used. Specifically, the deep network for SR-q-DL is revised to produce not only tissue microstructure estimates but also the uncertainty of the estimates. Then, multiple deep networks are trained and their results are fused for the final prediction of high-resolution tissue microstructure and uncertainty quantification. The proposed method was evaluated on two independent datasets of brain dMRI scans. Results indicate that our approach outperforms competing methods in terms of estimation accuracy. In addition, uncertainty measures provided by our method correlate with estimation errors, which indicates potential application of the proposed uncertainty quantification method in brain studies.


Induction of atypical cell death in thyroid carcinoma cells by the indirubin derivative 7-bromoindirubin-3'-oxime (7BIO).
The indirubin derivative 7-bromoindirubin-3'-oxime (7BIO) has already shown anticancer properties by causing cell death in some tumour cell lines and may be a new therapeutic option for treatment-resistant tumour cells. Since dedifferentiated and anaplastic thyroid carcinomas do not take up radioiodine and are insensitive to chemotherapeutic treatment and external radiation, direct cell death induction in these tumour cells may be a promising approach. We thus investigated the effect of 7BIO on thyroid carcinoma cell lines of different histological origins and characterized the type of cell death induction by 7BIO. Cell viability was measured with MTT assay. Cell death was analysed by caspase 3/7 activity, lactate dehydrogenase liberation, caspase cleavage products, DNA fragmentation, cell cycle phase distribution and LC3B analysis. After 7BIO treatment, cell viability was reduced in all 14 thyroid carcinoma cell lines investigated. Treated cells showed DNA fragmentation, cell cycle arrest and lactate dehydrogenase liberation but no LC3B cleavage. Caspase activation following 7BIO treatment was found in five of six cell lines investigated. Interestingly, inhibition of caspases had no effect on viability of the cells after 7BIO incubation. Our results indicate that 7BIO efficiently killed dedifferentiated thyroid carcinoma cells. It induced a non-classical kind of cell death that was caspase-independent and includes DNA fragmentation. 7BIO and related indirubin components thus may have value as a new therapeutic option for dedifferentiated thyroid cancer irrespective of the exact target molecules and the kind of cell death they induce.


Contemporary management of extracranial vascular malformations.
Vascular malformations are congenital vascular anomalies that originate because of disorganized angiogenesis, most commonly from spontaneous somatic genetic mutations. The modern management of vascular malformations requires a multidisciplinary team that offers patients the gamut of medical, surgical, and percutaneous treatment options with supportive care. This manuscript discusses the standard and contemporary management strategies surrounding extracranial vascular malformations and overgrowth syndromes.


Mobile telephone use among Melbourne drivers: a preventable exposure to injury risk.
To determine the rate of handheld mobile telephone use among motor vehicle drivers. Observational study of motor vehicle drivers at three times (10: 00-11: 00; 14: 00-15: 00; 17: 00-18: 00) on three consecutive Fridays in October 2002 at 12 highway sites in metropolitan Melbourne. Rates of mobile phone use overall and by sex and age group, highway site (major metropolitan road, central business district, freeway exit ramp) and time of day (morning, afternoon, evening). 315 of 17 023 drivers were observed using mobile phones (18.5 users/1000 drivers; 95% CI, 16.5-20.6). Men had a slightly higher rate of use (19.0; 95% CI, 16.5-21.6) than women (17.5; 95% CI, 14.1-20.9), but the difference was not significant. Older drivers (50 years or more) had a significantly lower rate (4.8; 95% CI, 2.5-7.0) than middle-aged (21.9; 95% CI, 18.8-25.1) or young drivers (23.2; 95% CI, 18.9-27.5). Central business district drivers had a slightly, but not significantly, higher rate (20.5; 95% CI, 16.8-24.3) compared with those on major metropolitan roads (16.7; 95% CI, 13.3-20.2) or freeway exit ramps (18.2; 95% CI, 14.8-21.6). The rate of mobile phone use was significantly higher in the evening (23.5; 95% CI, 19.8-27.3) compared with the morning (16.0; 95% CI, 12.6-19.4) and afternoon (15.2; 95% CI, 11.9-18.4). Mobile phone use is common among Melbourne metropolitan drivers despite restrictive legislation. This issue needs to be further addressed by Victoria Police and public health and education agencies. Similar research is indicated to determine the extent of mobile phone use in other states.


Inconsistent, uncoordinated, and reactive: The current state of sibling psychosocial care.
Although providing sibling psychosocial services is a standard of care in pediatric oncology, initial survey research suggests that this standard is rarely achieved and siblings' support needs remain unmet. Which sibling psychosocial services are available and how centers provide such services is unknown. To identify targetable services gaps, this qualitative study characterizes current sibling psychosocial care practices at select pediatric cancer centers across the United States. Semi-structured interviews were conducted with a purposive sample of psychosocial care providers (N = 27) working across the United States in pediatric oncology centers of varied sizes. Interviews queried providers regarding sibling-focused parent psychoeducation, psychosocial screening, comprehensive assessment, and psychosocial support offerings. Interview data were analyzed using Applied Thematic Analysis. Across cancer centers, sibling care practices did not align with consensus-based recommendations. The nature and availability of sibling-focused psychoeducation, screening, assessment, and support were variable between and within centers. Siblings themselves were largely absent from sibling psychosocial care, and care was rarely sibling-specific. The flow of information about siblings was discontinuous and uncoordinated across the care continuum, resulting in psychosocial care provided reactively, typically in response to parental concerns. Sibling psychosocial care provision falls short of established care recommendations, leaving sibling psychosocial needs unmet. Findings highlight the need for tools and strategies to facilitate the implementation of sibling psychosocial care across the care continuum, to support siblings' psychosocial functioning across the life course.


Analysis of presenting symptoms in prostatism.
A prospective evaluation was done of 84 patients who were selected for transurethral prostatectomy based on the presenting symptoms and findings at cystoscopy. In addition, urodynamic studies were performed but the results were not made available to the urologist who selected the patients for surgery. Postoperative symptom analysis and repeat urodynamic examinations were done at 3 months in 68 patients and at 12 months in 50. There was no significant association between irritative symptoms and uninhibited detrusor contractions. Furthermore, no associations were identified between obstructive symptoms and infravesical obstruction as defined by urodynamic criteria. The study failed to identify a need for routine invasive urodynamic investigation of patients with benign prostatic hypertrophy.


A First Estimate of the Annual Prevalence of Basivertebral Nerve Ablation Candidates in a Spine Clinic.
Emerging literature supports the use of basivertebral nerve ablation (BVNA) for a specific cohort of patients with chronic low back pain and Type 1 or Type 2 Modic changes from vertebral levels L3-S1. The early literature warrants further evaluation. Studies establishing the efficacy of BVNA use highly selective patient criteria. Provide a first estimate of the prevalence of BVNA candidates in a spine clinic over a year using the foundational studies patient selection criteria? A retrospective review of four fellowhsip trained spine physiatrists patient encounters at a large academic medical center using relevant ICD-10 codes to isolate chronic low back pain without radiating symptoms from January 1, 2019 to January 1, 2020. Charts were then reviewed by a team of physicians for exclusionary criteria from the foundational studies which have demonstrated benefit from BVNA. MRI's from qualifying charts which did not meet exclusionary criteria were then independently reviewed by four physician for localization and characterization of Modic changes. The relevant diagnostic codes query yielded 338 unique patient records. Based on exclusionary criteria or lack of imaging availability, 318 charts were eliminated. The remaining 20 charts qualified for imaging review. There were 11 charts in which there was 100% agreement between all reviewers regarding the presence and either Type 1 or Type 2 Modic changes between vertebral levels L3 to S1. Accordingly, the prevalence of eligibility for BVNA was 3% (11/338, 95% CI 1-5%). The population which may benefit from BVNA is small. Our study demonstrated that over a year, the prevalence for BVNA candidacy using the foundational studies criteria was 3% (95% CI 1% - 5%). While physicians may be tempted to use less stringent selection criteria in practice, upon doing so they cannot cite the foundational studies as evidence for the outcomes they expect to achieve. Those outcomes will require more studies which formally assess the benefits of BVNA when selection criteria are relaxed.


Chain collapse of an amyloidogenic intrinsically disordered protein.
Natively unfolded or intrinsically disordered proteins (IDPs) are under intense scrutiny due to their involvement in both normal biological functions and abnormal protein misfolding disorders. Polypeptide chain collapse of amyloidogenic IDPs is believed to play a key role in protein misfolding, oligomerization, and aggregation leading to amyloid fibril formation, which is implicated in a number of human diseases. In this work, we used bovine κ-casein, which serves as an archetypal model protein for amyloidogenic IDPs. Using a variety of biophysical tools involving both prediction and spectroscopic techniques, we first established that monomeric κ-casein adopts a collapsed premolten-globule-like conformational ensemble under physiological conditions. Our time-resolved fluorescence and light-scattering data indicate a change in the mean hydrodynamic radius from ∼4.6 nm to ∼1.9 nm upon chain collapse. We then took the advantage of two cysteines separated by 77 amino-acid residues and covalently labeled them using thiol-reactive pyrene maleimide. This dual-labeled protein demonstrated a strong excimer formation upon renaturation from urea- and acid-denatured states under both equilibrium and kinetic conditions, providing compelling evidence of polypeptide chain collapse under physiological conditions. The implication of the IDP chain collapse in protein aggregation and amyloid formation is also discussed.


The dramatic 3D IVUS imaging demonstrating a dislodged coronary stent.
A 78-year-old female underwent cardiac evaluation because she had presented with typical effort-induced chest pain. Coronary angiography revealed severe stenoses in the proximal left anterior descending coronary artery (LAD) and ostium of the diagonal branch. Then, a stent was deployed in the LAD covering the takeoff of the branch. Next, we tried to deploy an additional stent in the branch, but the new stent was stripped off the balloon platform. We demonstrate here the dramatic 3D intravascular ultrasound (IVUS) images of a dislodged stent, indicating that 3D IVUS imaging should allow the precise location and statement of lost stent.


A pre-visit website with question prompt sheet for counselees facilitates communication in the first consultation for breast cancer genetic counseling: findings from a randomized controlled trial.
The initial breast cancer genetic counseling visit is mainly educational, with large amounts of relatively standard information and little counselee participation. Counselors might provide more counselee-specific information if counselees would participate more. A pre-visit website providing computer-tailored information and a question prompt sheet (QPS) might help counselees to pursue a more active role. Counselees were randomized to receive usual care (UC) or UC plus the pre-visit website. The QPS questions were sent to the counselor before the visit. All counselees completed a baseline questionnaire, and visits were videotaped. Intervention-group counselees (n = 102) did not ask more questions than UC-group counselees (n = 90). However, counselees in the intervention group more often shared their agenda (B = 10.37; confidence interval (CI) 2.68-18.06; P = 0.01), directed the communication (B = 0.41; CI 0.28-0.53; P = 0.01), and paraphrased the counselors' words (B = 5.18; CI 0.43-9.92; P = 0.03). Counselors introduced and answered the QPS questions. As a result, they provided more information about the topics of these questions, and the information provided was more specific to whether there was an indication for DNA testing. A pre-visit website with QPS helped counselees to communicate more assertively. As a result, the information provided was more counselee specific, without affecting the visit duration.


Mathematical models for accurate prediction of atmospheric visibility with particular reference to the seasonal and environmental patterns in Hong Kong.
Atmospheric visibility impairment has gained increasing concern as it is associated with the existence of a number of aerosols as well as common air pollutants and produces unfavorable conditions for observation, dispersion, and transportation. This study analyzed the atmospheric visibility data measured in urban and suburban Hong Kong (two selected stations) with respect to time-matched mass concentrations of common air pollutants including nitrogen dioxide (NO(2)), nitrogen monoxide (NO), respirable suspended particulates (PM(10)), sulfur dioxide (SO(2)), carbon monoxide (CO), and meteorological parameters including air temperature, relative humidity, and wind speed. No significant difference in atmospheric visibility was reported between the two measurement locations (p > or = 0.6, t test); and good atmospheric visibility was observed more frequently in summer and autumn than in winter and spring (p < 0.01, t test). It was also found that atmospheric visibility increased with temperature but decreased with the concentrations of SO(2), CO, PM(10), NO, and NO(2). The results showed that atmospheric visibility was season dependent and would have significant correlations with temperature, the mass concentrations of PM(10) and NO(2), and the air pollution index API (correlation coefficients mid R: R mid R: > or = 0.7, p < or = 0.0001, t test). Mathematical expressions catering to the seasonal variations of atmospheric visibility were thus proposed. By comparison, the proposed visibility prediction models were more accurate than some existing regional models. In addition to improving visibility prediction accuracy, this study would be useful for understanding the context of low atmospheric visibility, exploring possible remedial measures, and evaluating the impact of air pollution and atmospheric visibility impairment in this region.


Nicotine patch therapy prior to quitting smoking: a meta-analysis.
To evaluate the incremental efficacy of starting nicotine patch treatment prior to quitting compared to the current regimen of starting patch treatment on the target quit day. Meta-analysis of four eligible studies using pre-cessation patch treatment, located by database search and contacts with cessation researchers. The studies all compared starting treatment with nicotine patch prior to the target quit date to starting active treatment at the quit date, some in the context of concurrent mecamylamine treatment. The primary end-point for the analysis was continuous abstinence for at least 28 days assessed at 6 weeks following quit day; 6-month outcomes were also examined. Compared to starting active patch treatment on quit day, pre-cessation treatment with nicotine patches was found to double the odds of quitting. This was true both at 6 weeks [pooled odds ratio (OR) = 1.96, 95% confidence interval (CI): 1.31-2.93] and 6 months (pooled OR = 2.17, 95% CI: 1.46-3.22) treatment outcomes. Mecamylamine co-treatment did not modify these effects. Across the four studies analyzed, pre-cessation patch treatment was found to produce a robust increase in quit rates compared to current regimens starting patch at quit day. Pre-cessation patch use represents a promising innovation in smoking cessation therapy with potential beneficial implications for improved public health by further increasing quitting success.


MiR-291a-3p regulates the BMSCs differentiation via targeting DKK1 in dexamethasone-induced osteoporosis.
Osteoporosis is a skeleton disease affecting 55% of people over age 60, and the number is still increasing due to an ageing population. One method to prevent osteoporosis is to increase the formation of new bone while preventing the resorption of older bone. Thus, osteogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs) is of great importance in improving the treatment of osteoporosis. On the other hand, glucocorticoids (GCs) are widely used to treat the chronic inflammatory disorders, but long-term exposure to GCs can induce osteoporosis. In present study, we treated BMSCs with dexamethasone (DEX) to simulate GC-induced osteoporosis. MTT assay, ALP activity, and Alizarin Red were used to evaluate the role miRNA-291a-3p in the DEX-induced osteogenic differentiation suppression. Further, we used qPCR and western blot to investigate the mechanisms of miRNA-291a-3p affecting BMSCs differentiation. The results showed that miRNA-291a-3p could improve the cell viability, osteogenic differentiation, and ALP activity, which are suppressed by DEX in BMSCs. Furthermore, we found that the osteogenesis genes Runx2, DMP1, and ALP were upregulated whereas the lipogenic genes C/EBPα and PPARγ were downregulated when miRNA-291a-3p mimics were transfected. Additionally, we demonstrated that miRNA-291a-3p promoted BMSCs' osteogenic differentiation by directly suppressing DKK1 mRNA and protein expression and subsequently activating Wnt/β-catenin signaling pathway. Our study suggests that miR-291a-3p plays an important role in preventing osteoporosis and may serve as a potential miRNA osteoporosis biomarker.


Enzyme replacement therapy on hypophosphatasia mouse model.
Hypophosphatasia (HPP) is an inborn error of metabolism caused by deficiency of the tissue-nonspecific alkaline phosphatase (TNSALP), resulting in a defect of bone mineralization. Natural substrates for this ectoenzyme accumulate extracellulary including inorganic pyrophosphate (PPi), an inhibitor of mineralization, and pyridoxal 5-phosphate (PLP), a co-factor form of vitamin B6. Enzyme replacement therapy (ERT) for HPP by functional TNSALP is one of the therapeutic options. The C-terminal-anchorless human recombinant TNSALP derived from Chinese hamster ovary cell lines was purified. TNSALP-null mice (Akp2 (-/-) ), an infantile model of HPP, were treated from birth using TNSALP and vitamin B6 diet. Long-term efficacy studies of ERT consisted of every 3 days subcutaneous or intravenous injections till 28 days old (dose 20 U/g) and subsequently every 3 days intravenous injections for 6 months (dose 10 U/g). We assessed therapeutic effect by growth and survival rates, fertility, skeletal manifestations, and radiographic and pathological finding. Treated Akp2 (-/-) mice grew normally till 4 weeks and appeared well with a minimum skeletal abnormality as well as absence of epilepsy, compared with untreated mice which died by 3 weeks old. The prognosis of TNSALP-treated Akp2 (-/-) mice was improved substantially: 1) prolonged life span over 6 months, 2) improvement of the growth, and 3) normal fertility. After 6 months of treatment, we found moderate hypomineralization with abnormal proliferative chondrocytes in growth plate and articular cartilage. In conclusion, ERT with human native TNSALP improves substantial clinical manifestations in Akp2 (-/-) mice, suggesting that ERT with anchorless TNSALP is also a potential therapy for HPP.


Serum anti-Müllerian hormone levels in women are unstable in the postpartum period but return to normal within 5 months: a longitudinal study.
Anti-Müllerian hormone (AMH) levels fall during pregnancy but the amount of time required for AMH levels to return to normal has not been accurately determined. We have previously shown that AMH levels have yet to return to normal in some women at 3-months postpartum. In this study, AMH levels were examined at 1- and 5-months postpartum to examine whether AMH levels had returned to normal within this interval. Longitudinal study involving 38 pregnant women, with serum samples taken in the first trimester, third trimester, 1-month postpartum, 5-months postpartum and 4-6 years postpartum. Participants were recruited from a tertiary maternity clinic (single centre). All women in the study were intending to breastfeed exclusively for at least 5 months, with all 38 participants achieving this at 1-month postpartum and 36/38 after 5 months. Serum AMH concentrations had not returned to expected non-pregnant levels by 1-month postpartum. At 5-months postpartum, mean AMH concentrations were similar to expected non-pregnant levels but the rank order of AMH concentrations was still dissimilar to the non-pregnant state. The regulation of AMH secretion appears to be distinctly different in non-pregnant, pregnant and postpartum populations. This may affect the conclusions that can be drawn from AMH measurements in women during pregnancy and the postpartum period.


Prevalence and risk factors of nocturnal enuresis among children ages 5-12 years in Xi'an, China: a cross-sectional study.
Nocturnal enuresis (NE) has a negative impact on children's health and imposes a long-term burden on families. With economic development and cultural improvements, parents and medical professionals pay more attention to NE. The aim of this study was to investigate the prevalence and risk factors of NE among children ages 5-12 years in Xi'an, China. A stratified cluster sampling method was used to conduct a cross-sectional study of NE in 10 kindergartens and 20 primary schools in Xi'an. We used univariate analysis to compare the prevalences of characteristics such as gender, duration of disposable diaper (DD) use, toilet training onset time, daily living habits, academic performance, and family history of NE. Logistic regression analysis was used to calculate odds ratio and to determine risk factors of NE. The study included 6568 children ages 5-12 years, of which 262 (3.99%) had NE. The prevalence rates of NE decreased with age, with the highest prevalence at age 5 (9.09% for boys; 6.03% for girls). However, the prevalence increased with duration of DD use. Children experienced more NE if they never accepted toilet training (7.83%) or if they drank sugary beverages during the day (5.36%). Sleep disorders, sweets intake, drinking low amounts of plain water during the day, and family history of NE, were statistically associated with NE. NE was closely associated with a family history of NE, being male, long-term use of DD, delayed toilet training, drinking sugary beverages and/or consuming little plain water, and sleep disorders. A supportive parental attitude towards NE and timely medical treatment can improve the quality of life of enuretic children.


2-Alkyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indoles as novel 5-HT6 receptor agonists.
A series of 2-alkyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indoles were synthesized and evaluated for their 5-HT6 activity. The most potent agonist in this series was 5-chloro-2-methyl-3-(1,2,3,6-tetrahydropyridin-4-yl)-1H-indole with an IC50=7.4 nM in 3H-LSD binding and an EC50=1.0 nM in a functional assay measuring production of cyclic AMP.


An ultrastructural study of the projections from the midbrain periaqueductal gray to spinally projecting, serotonin-immunoreactive neurons of the medullary nucleus raphe magnus in the rat.
In this triple-label, electron microscopic study in the rat, a lesion of the midbrain periaqueductal gray (PAG) was made so that the distribution and targets of degenerating PAG terminals could be identified in the medullary nucleus raphe magnus (NRM). Spinally projecting NRM neurons were identified by the retrograde transport of wheat germ agglutinin-horseradish peroxidase from the cervical cord. We also used immunocytochemistry to define the subpopulation of NRM neurons which were serotonin-immunoreactive. We report that both serotonergic and non-serotonergic neurons of the medulla, which project to the spinal cord, receive monosynaptic inputs from the PAG.


[Hyperemesis gravidarum: A review].
Vomiting of pregnancy is a physiological symptom of the first trimester and is a frequent reason for consultation as well as hospitalization in the severe forms (hyperemesis gravidarum), which complicate 0.3 to 4% of the pregnancies and represent the first cause of hospitalization in the first trimester. Hyperemesis gravidarum may be responsible for a loss of weight with dehydration and/or hypokalemia. The use of scores such as PUQE-modified or NVPQOL may allow an objective and accurate assessment of symptoms and impairment of quality of life. Organic disease should be always eliminated and hospitalization may be necessary to effectively treat vomiting and correct any electrolyte disorders.


(E)-2-(3,5-Di-meth-oxy-benzyl-idene)indan-1-one.
The title chalcone, C18H16O3, was prepared by a solventless base-promoted Claisen-Schmidt condensation and, upon recrystallization from ethanol, obtained in 56% yield. The dihedral angle between the indanone ring system and the benzene ring is 2.54 (4) ° and the C atoms of the methoxy groups deviate from the benzene ring by 0.087 (1) and 0.114 (1) Å. In the crystal, π-stacking is the predominant inter-molecular force, with the mol-ecules stacking into columns running parallel to the b axis of the unit cell.


In vivo binding of N-nitrosopyrrolidine and N-nitrosohexamethyleneimine to non-purine sites on rat liver DNA.
Liver DNA and RNA were isolated from rats treated with the liver carcinogens N-nitrosopyrrolidine (NPYR) and N-nitrosohexamethyleneimine (NHX). After hydrolysis in 70% perchloric acid (100 degrees C, 1.0 h), 70% of the radioactivity in both the DNA and RNA hydrolysates chromatographed as a single peak. The material from both hydrolysates had comparable Rf values on cation exchange and Sephadex G-10 chromatography. Subsequent experiments indicated this material was volatile. After depurination (0.1 M HCl) of the DNA from NPYR- and NHX-treated rats, Sephadex G-10 chromatography separated only a single radioactive peak which co-eluted with the apurinic acid at the void volume. The material which comprised this peak was not volatile. After dialysis of the same 0.1 M HCl hydrolysate from NHX-treated rats, 98% of the radioactivity remained attached to the apurinic acid. These 2 cyclic nitrosamines appear to produce alkylating species that: (1) are capable of extensive, if not exclusive, phosphotriester formation; or (2) have 2 active sites that cross-link to keep purines attached to apurinic acid after 0.1 M HCl hydrolysis.


Future perspectives on aptamer for application in food authentication.
Food fraudulence and food contamination are major concerns, particularly among consumers with specific dietary, cultural, lifestyle, and religious requirements. Current food authentication methods have several drawbacks and limitations, necessitating the development of a simpler, more sensitive, and rapid detection approach for food screening analysis, such as an aptamer-based biosensor system. Although the use of aptamer is growing in various fields, aptamer applications for food authentication are still lacking. In this review, we discuss the limitations of existing food authentication technologies and describe the applications of aptamer in food analyses. We also project several potential targets or marker molecules to be targeted in the SELEX process. Finally, this review highlights the drawbacks of current aptamer technologies and outlines the potential route of aptamer selection and applications for successful food authentication. This review provides an overview of the use of aptamer in food research and its potential application as a molecular reporter for rapid detection in food authentication process. Developing databases to store all biochemical profiles of food and applying machine learning algorithms against the biochemical profiles are urged to accelerate the identification of more reliable biomarker molecules as aptamer targets for food authentication.


Metabolic engineering of a Lactobacillus plantarum double ldh knockout strain for enhanced ethanol production.
Lactobacillus plantarum ferments glucose through the Embden-Meyerhof-Parnas pathway: the central metabolite pyruvate is converted into lactate via lactate dehydrogenase (LDH). By substituting LDH with pyruvate decarboxylase (PDC) activity, pyruvate may be redirected toward ethanol production instead of lactic acid fermentation. A PDC gene from the Gram-positive bacterium Sarcina ventriculi (Spdc) was introduced into an LDH-deficient strain, L. plantarum TF103, in which both the ldhL and ldhD genes were inactivated. Four different fusion genes between Spdc and either the S. ventriculi promoter or three Lactococcus lactis promoters in pTRKH2 were introduced into TF103. PDC activity was detected in all four recombinant strains. The engineered strains were examined for production of ethanol and other metabolites in flask fermentations. The recombinant strains grew slightly faster than the parent TF103 and produced 90-130 mM ethanol. Although slightly more ethanol was observed, carbon flow was not significantly improved toward ethanol, suggesting that a further understanding of this organism's metabolism is necessary.


Value of Ambulatory Modified Radical Mastectomy.
Modified radical mastectomy (MRM) still is largely performed in inpatient settings. This study sought to determine the value (expenditures and complications) of ambulatory MRM. Health Care Utilization Project (HCUP) state databases from 2016 were queried for patients who underwent MRM. The study examined rates of 30-day readmission for surgical-site infection (SSI) or hematoma, charges by index care setting, and predictors of 30-day readmission. Overall, 8090 patients underwent MRM: 5113 (63 %) inpatient and 2977 (37 %) ambulatory patients. Compared with the patients who underwent inpatient MRM, those who underwent ambulatory MRM were older (61 vs. 59 years), more often white (66 % vs. 57 %), in the lowest income quartile (28 % vs. 21 %), insured by Medicare (43 % vs. 33 %) and residents in a small metro area (6 % vs. 4 %) (all p < 0.01). Of the 5113 patients treated as inpatients, 126 (2.5 %) were readmitted, whereas 50 (1.7 %) of the ambulatory patients were readmitted (p = 0.02). The adjusted charge for inpatient MRM without readmission was $113,878 (range, $107,355-120,402) compared with $94,463 (range, $86,021-102,907) for ambulatory MRM, and the charge for inpatient MRM requiring readmission was $159,355 (range, $147,142-171,568) compared with $139,940 (range, $125,808-154,073) for ambulatory MRM (all p < 0.01). This difference remained significant after adjustment for hospital length of stay. Adjusted logistic regression showed that the ambulatory setting was protective for readmission (odds ratio, 0.49; 95 % confidence interval, 0.35-0.70; p < 0.01). The analyses suggest that ambulatory MRM is both safe and less expensive. The findings advocate that MRM, a last holdout of inpatient care within breast surgical oncology, can be transitioned to the ambulatory setting for appropriate patients.


A novel and high-throughput approach to assess photosynthetic thermal tolerance of kelp using chlorophyll α fluorometry.
Foundation seaweed species are experiencing widespread declines and localized extinctions due to increased instability of sea surface temperature. Characterizing temperature thresholds are useful for predicting patterns of change and identifying species most vulnerable to extremes. Existing methods for characterizing seaweed thermal tolerance produce diverse metrics and are often time-consuming, making comparisons between species and techniques difficult, hindering insight into global patterns of change. Using three kelp species, we adapted a high-throughput method - previously used in terrestrial plant thermal biology - for use on kelps. This method employs temperature-dependent fluorescence (T-F0 ) curves under heating or cooling regimes to determine the critical temperature (Tcrit ) of photosystem II (PSII), i.e., the breakpoint between slow and fast rise fluorescence response to changing temperature, enabling rapid assays of photosynthetic thermal tolerance using a standardized metric. This method enables characterization of Tcrit for up to 48 samples per two-hour assay, demonstrating the capacity of T-F0 curves for high-throughput assays of thermal tolerance. Temperature-dependent fluorescence curves and their derived metric, Tcrit , may offer a timely and powerful new method for the field of phycology, enabling characterization and comparison of photosynthetic thermal tolerance of seaweeds across many populations, species, and biomes.


Assessment Tools for Evaluation of Oral Feeding in Infants Younger Than 6 Months.
Feeding difficulty is common in infants younger than 6 months. Identification of infants in need of specialized treatment is critical to ensure appropriate nutrition and feeding skill development. Valid and reliable assessment tools help clinicians objectively evaluate feeding. To identify and evaluate assessment tools available for clinical assessment of bottle- and breastfeeding in infants younger than 6 months. CINAHL, HaPI, PubMed, and Web of Science were searched for "infant feeding" and "assessment tool." The literature (n = 237) was reviewed for relevant assessment tools. A secondary search was conducted in CINAHL and PubMed for additional literature on identified tools. Eighteen assessment tools met inclusion criteria. Of these, 7 were excluded because of limited available literature or because they were intended for use with a specific diagnosis or in research only. There are 11 assessment tools available for clinical practice. Only 2 of these were intended for bottle-feeding. All 11 indicated that they were appropriate for use with breastfeeding. None of the available tools have adequate psychometric development and testing. All of the tools should be used with caution. The Early Feeding Skills Assessment and Bristol Breastfeeding Assessment Tool had the most supportive psychometric development and testing. Feeding assessment tools need to be developed and tested to guide optimal clinical care of infants from birth through 6 months. A tool that assesses both bottle- and breastfeeding would allow for consistent assessment across feeding methods.


Virtual treatment of basilar aneurysms using shape memory polymer foam.
Numerical simulations are performed on patient-specific basilar aneurysms that are treated with shape memory polymer (SMP) foam. In order to assess the post-treatment hemodynamics, two modeling approaches are employed. In the first, the foam geometry is obtained from a micro-CT scan and the pulsatile blood flow within the foam is simulated for both Newtonian and non-Newtonian viscosity models. In the second, the foam is represented as a porous media continuum, which has permeability properties that are determined by computing the pressure gradient through the foam geometry over a range of flow speeds comparable to those of in vivo conditions. Virtual angiography and additional post-processing demonstrate that the SMP foam significantly reduces the blood flow speed within the treated aneurysms, while eliminating the high-frequency velocity fluctuations that are present within the pre-treatment aneurysms. An estimation of the initial locations of thrombus formation throughout the SMP foam is obtained by means of a low fidelity thrombosis model that is based upon the residence time and shear rate of blood. The Newtonian viscosity model and the porous media model capture similar qualitative trends, though both yield a smaller volume of thrombus within the SMP foam.


Methane oxidation in heavy metal contaminated Mollic Gleysol under oxic and hypoxic conditions.
Soils are the largest terrestrial sink for methane (CH4). However, heavy metals may exert toxicity to soil microorganisms, including methanotrophic bacteria. We tested the effect of lead (Pb), zinc (Zn) and nickel (Ni) on CH4 oxidation (1% v/v) and dehydrogenase activity, an index of the activity of the total soil microbial community in Mollic Gleysol soil in oxic and hypoxic conditions (oxia and hypoxia, 20% and 10% v/v O2, respectively). Metals were added in doses corresponding to the amounts permitted of Pb, Zn, Ni in agricultural soils (60, 120, 35 mg kg(-1), respectively), and half and double of these doses. Relatively low metal contents and O2 status reflect the conditions of most agricultural soils of temperate regions. Methane consumption showed high tolerance to heavy metals. The effect of O2 status was stronger than that of metals. CH4 consumption was enhanced under hypoxia, where both the start and the completion of the control and contaminated treatment were faster than under oxic conditions. Dehydrogenase activity, showed higher sensitivity to the contamination (except for low Ni dose), with a stronger effect of heavy metals, than that of the O2 status.


Macular pigment and reduced foveal short-wavelength sensitivity in retinitis pigmentosa.
Some patients with retinitis pigmentosa (RP) show a reduced foveal short-wavelength sensitivity that cannot be attributed to a reduction in the sensitivity of the short-wavelength cone system. To determine whether an increased amount of macular pigment (xanthophyll) might account for this finding, we derived estimates of the two-way optical density of the macular pigment of five such RP patients as well as of five normals. The spectral reflectance of the foveal region of each subject was obtained from digitized images of the bleached fundus provided by a television-based reflectometer. The density spectra of the macular pigment, melanin, and oxygenated hemoglobin were fit by a least-squares procedure to the log of the ratio of parafoveal to foveal spectral reflectance in order to obtain a quantitative estimate of the contribution of each of these ocular pigments to foveal short-wavelength reflectance. By this analysis, the two-way densities of the macular pigment, melanin, and oxyhemoglobin of the RP patients were not significantly different from those of the normals. Therefore, the reduced foveal short-wavelength sensitivity of these patients was not due to an increased amount of macular pigment, but may result instead from morphological abnormalities in the foveal cones such that a normal amount of macular pigment screens the cones more effectively.


Disposable biosensor based on cathodic electrochemiluminescence of tris(2,2-bipyridine)ruthenium(II) for uric acid determination.
A new method for uric acid (UA) determination based on the quenching of the cathodic ECL of the tris(2,2-bipyridine)ruthenium(II)-uricase system is described. The biosensor is based on a double-layer design containing first tris(2,2-bipyridine)ruthenium(II) (Ru(bpy)3(2+)) electrochemically immobilized on graphite screen-printed cells and uricase in chitosan as a second layer. The uric acid biosensing is based on the ECL quenching produced by uric acid over the cathodic ECL caused by immobilized Ru(bpy)3(2+) in the presence of uricase. The use of a -1.1 V pulse for 1s with a dwelling time of 10s makes it possible to estimate the initial enzymatic rate, which is used as the analytical signal. The Stern-Volmer type calibration function shows a dynamic range from 1.0×10(-5) to 1.0×10(-3)M with a limit of detection of 3.1×10(-6)M and an accuracy of 13.6% (1.0×10(-4)M, n=5) as relative standard deviation. Satisfactory results were obtained for urine samples, creating an affordable alternative for uric acid determination.


Primary lymph-node staging with 68Ga-PSMA PET in high-risk prostate cancer: pathologic correlation with extended pelvic lymphadenectomy specimens.
This study aims to assess the diagnostic efficacy of Gallium-68-prostate-specific membrane antigen positron emission tomography (PET)/computed tomography (CT) (68Ga PSMA PET-CT) in primary nodal staging of high-risk prostate cancer (PCa) when compared to pathologic findings of extended pelvic lymph-node dissection (eLND). The records of high-risk PCa patients who were preoperatively staged through 68Ga PSMA PET-CT and who underwent robot-assisted radical prostatectomy with eLND either alone or as part of multimodal definitive therapy between August 2016 and November 2019 were retrospectively reviewed. Surgeons were not blinded to the results of the 68Ga PSMA PET-CT scan. Pathologic uptake was defined as any anomalous uptake which was not better explained by another cause and was suggestive of PCa. The reference standard for this study was the pathologic confirmation using a node-based analysis. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for 68Ga PSMA PET-CT were calculated in a per-patient analysis using IBM SPSS Statistics version 25. Seventeen patients met the selection criteria. Mean age was 63 years (range 44-77) and mean and median preoperative serum prostate specific antigen was 19.25 and 9 ng/ml (range 6-131), respectively. The most common pathologic Gleason score was 8 (52.9% of cases). Seven patients (41%) had positive surgical margins and were submitted to adjuvant radiotherapy. Mean number of per patient removed lymph-nodes was 13 (±2.19). 68Ga PSMA PET-CT showed findings compatible with lymph node metastases in 4/17 patients and with locally-confined disease in 13/17 patients. Following pathologic confirmation, the per-patient sensibility of the 68Ga PSMA PET-CT was calculated at 75% (1 false negative) and the specificity at 92.3% (1 false positive) for detection of lymph node metastasis on primary staging of high-risk PCa patients. Positive and negative predictive value were 75% and 92.3%, respectively; accuracy of the test was calculated at 88.2%. All patients were submitted to 68Ga PSMA PET-CT re-evaluation 6 months after surgery and tested negative for local, nodal, or distant recurrence of disease. 68Ga PSMA PET-CT appears to have a high negative predictive value for local lymph node metastases in high-risk primary PCa when compared to pathologic findings of eLND. Its role in the primary nodal staging of high-risk PCa patients worths further evaluation.


Contrast-enhanced ultrasound features of histologically proven focal nodular hyperplasia: diagnostic performance compared with contrast-enhanced CT.
To investigate and compare contrast-enhanced ultrasound (CEUS) in the characterisation of histologically proven focal nodular hyperplasia (FNH) with contrast-enhanced computed tomography (CECT). CEUS was performed in 85 patients with 85 histologically proven FNHs. Enhancement, centrifugal filling, spoke-wheel arteries, feeding artery and central scarring were reviewed and correlated with lesion size or liver background. Independent factors for predicting FNH from other focal liver lesions (FLLs) were evaluated. Forty-seven FLLs with CECT were randomly selected for comparison of diagnostic performance with CEUS. Centrifugal filling was more common (P = 0.002) and the significant predictor (P = 0.003) in FNHs ≤3 cm. Lesion size or liver background has no significant influence on the detection rate of the spoke-wheel arteries and feeding artery (P > 0.05). Central scarring was found in 42.6 % of FNHs ≥3 cm (P = 0.000). The area under the ROC curve, sensitivity and specificity showed no significant differences between CEUS and CECT (P > 0.05), except that the sensitivity of CEUS was better for reader 1 (P = 0.041). CEUS is valuable in characterising centrifugal filling signs or spoke wheels in small FNHs and should be employed as the first-line imaging technique for diagnosis of FNH. • The confident diagnosis of focal nodular hyperplasia is important in liver imaging. • The centrifugal filling sign is useful for diagnosis of FNHs ≤3 cm. • Contrast-enhanced ultrasound and contrast-enhanced CT have similar diagnostic performance for FNH. • CEUS should be the first-line imaging technique for the diagnosis of FNH.


Treatment of seborrhoeic dermatitis of the scalp with a topical solution of urea, lactic acid, and propylene glycol (K301): results of two double-blind, randomised, placebo-controlled studies.
Alternative treatments for seborrhoeic dermatitis are needed because of the increasing risk of anti-fungal resistance to existing therapies. To investigate the efficacy, safety and tolerability of topical scalp treatment with K301 solution. Two multi-centre, randomised, double-blind studies were conducted. Study I: 4 weeks of once-daily treatment with either one form of K301 (a or b) or placebo, followed by 4 weeks of maintenance treatment three times-per-week. Study II: 4 weeks of K301 (a) or placebo once-daily. Study I: 98 patients enrolled (K301a + b, n = 51; placebo, n = 47) and 83 completed; 201 entered Study II (K301a, n = 136; placebo, n = 65) and 195 completed. Erythema and desquamation sum score at 4 weeks, mean (SD) values were 2.4 (2.0) for K301a + b and 3.2 (2.2) for placebo in Study I (P = 0.025) and 2.5 (1.9) for K301a and 3.2 (1.8) for placebo in Study II (not significant). In both studies, 4-week desquamation scores were significantly improved for K301 vs. placebo (P < 0.05). Both studies showed significant improvements in symptomatic investigator and patient assessments for K301 over placebo after 4 weeks (P < 0.05). Treatment-related adverse events were generally mild and included some smarting or burning upon application. The K301 was well tolerated and associated with clinically meaningful improvements in seborrhoeic dermatitis endpoints.


Food and Trauma: Anthropologies of Memory and Postmemory.
Much has been written about the multifaceted significance of food and eating from an anthropological perspective; the same can be said about the role of food in collective identity construction and nation building. In contrast, the nexus of food, memory, psychological trauma, and disordered eating has been less explored. The aim of this interdisciplinary article is to synthesize available knowledge on this topic by engaging with research literature in fields such as food history, anthropology, sociology, and psychiatry as well as autobiographical works, cookbooks, etc. One main section of the article focuses on the role of food and cooking in exile and refuge. Another section deals with the role of food in the aftermath of historical trauma, whereas a final section discusses various works on disordered eating in the wake of traumatic experiences. In sum, the dual nature of food and cooking-at once concrete and abstract, material and symbolic-offers an arena in which ambivalent memories of trauma can take on tangible form. The concept of postmemory may be useful in understanding how food and cooking can function both as a vehicle and as a remedy for intergenerational trauma.


Involvement of quinolinic acid in the neuropathogenesis of amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is the most common adult-onset motor neuron disease characterized by a progressive degeneration of central and peripheral motor neurons, leading to the atrophy of voluntary muscles. It has been previously demonstrated that the kynurenine pathway (KP), the major biochemical pathway for tryptophan metabolism, is dysregulated in ALS. In particular, the neuroactive intermediate, quinolinic acid (QUIN) has been shown to accumulate with a concomitant decrease in other neuroprotective and immunomodulatory KP metabolites. Furthermore, multiple biochemical phenomena associated with QUIN cytotoxicity are present in ALS, suggesting that QUIN may play a substantial role in the pathogenesis of ALS. This review highlights the potential roles of QUIN in ALS, and explores KP modulation as a therapeutic candidate in ALS. This article is part of the Special Issue entitled 'The Kynurenine Pathway in Health and Disease'.


COST-EFFECTIVENESS OF TREATMENTS FOR MILD-TO-MODERATE OBSTRUCTIVE SLEEP APNEA IN FRANCE.
Untreated obstructive sleep apnea-hypopnea syndrome (OSAHS) is associated with excessive daytime sleepiness, increased risk of cardiovascular (CV) disease, and road traffic accidents (RTAs), which impact survival and health-related quality of life. This study, funded by the French National Authority for Health (HAS), aimed to assess the cost-effectiveness of different treatments (i.e., continuous positive airway pressure [CPAP], dental devices, lifestyle advice, and no treatment) in patients with mild-to-moderate OSAHS in France. A Markov model was developed to simulate the progression of two cohorts, stratified by CV risk, over a lifetime horizon. Daytime sleepiness and RTAs were taken into account for all patients while CV events were only considered for patients with high CV risk. For patients with low CV risk, incremental cost-effectiveness ratio (ICER) of dental devices versus no treatment varied between 32,976 EUR (moderate OSAHS) and 45,579 EUR (mild OSAHS) per quality-adjusted life-year (QALY), and CPAP versus dental devices, above 256,000 EUR/QALY. For patients with high CV risk, CPAP was associated with a gain of 0.62 QALY compared with no treatment, resulting in an ICER of 10,128 EUR/QALY. The analysis suggests that it is efficient to treat all OSAHS patients with high CV risk with CPAP and that dental devices are more efficient than CPAP for mild-to-moderate OSAHS with low CV risk. However, out-of-pocket costs are currently much higher for dental devices than for CPAP (i.e., 3,326 EUR versus 2,430 EUR) as orthodontic treatment is mainly non-refundable in France.


Effects of the chemokine CCL2 on blood-brain barrier permeability during ischemia-reperfusion injury.
The chemokine CCL2 is considered as one of the main effectors driving postischemic infiltration of monocytes into the brain parenchyma. New experimental data, however, suggest that CCL2 could also participate in blood-brain barrier (BBB) 'opening' during the transmigration of monocytes. The current study examines the role of CCL2 in regulating BBB permeability after ischemia in vitro. To address this issue, an in vitro BBB model (coculture of astrocytes and brain endothelial cells) was subjected to 5 h of oxygen glucose deprivation, followed by reoxgenation (in vitro ischemia/reperfusion (I/R)) for 0 to 48 h. During reperfusion, there was a biphasic enhancement of barrier permeability, with a 200-fold increase in barrier permeability to FITC-albumin at 6 h and a further period of disruption around 24 h. The latter coincided with increased secretion of CCL2 by both astrocytes and brain endothelial cells and increased levels of the CCL2 receptor, CCR2. Applying antisense oligonucleotide or neutralizing antibody to block CCL2 significantly decreased I/R-induced enhancement of BBB permeability (approximately twofold) and redistribution of tight-junction (TJ) proteins (occludin, zonula occluden-1, 2, claudin-5). Similarly, absence of CCR2 from endothelial cells caused stabilization of TJ complexes and decreased the permeability of brain endothelial barrier during in vitro I/R. These data suggest CCL2/CCR2 has an important role in regulating brain endothelial permeability and might be a potential novel therapeutic target for stroke.


Update on lacrimal gland neoplasms: Molecular pathology of interest.
Lacrimal gland neoplasms are rare and much of our knowledge of the behavior and molecular pathogenesis of these tumors comes from study of the similar, but more numerous salivary gland neoplasms. After briefly discussing the classification of lacrimal gland neoplasms, I review three areas of emerging knowledge in the pathogenesis of these neoplasms: (1) the concept of adenoid cystic carcinoma with high-grade transformation and the associated cytogenetic changes; (2) recent analysis of the MYB-NFIB gene fusion in adenoid cystic carcinoma, and; (3) overexpression of HER2 in malignant salivary and lacrimal neoplasms.


Effects of solvent and substituent on the electronic absorption spectra of some substituted Schiff bases: a chemometrics study.
A series of Schiff bases were studied for their delicate changes in absorption electronic spectra by changing substituents and solvents. UV/vis absorbance spectra of Schiff base derivatives of different substituents ranging from electron withdrawing to electron donating (Br, CF(3), Cl, CN, CO(2)H, F, Me, NO(2), OH, OMe, H) were studied in different solvents (acetonitrile, chloroform, cyclohexane, dioxane, dimethylsulfoxide and methanol). Linear relationships were established to investigate the effect of solute structure and solvatochromic parameters of solvents on the absorbance spectra. Meaningful chemical factors and then regression models were provided utilizing factor analysis (FA) and multiple linear regression (MLR). It was found that the frequency of maximum absorbance was mainly controlled by the solvent's dipolarity/polarizability. The λ(max) of the ortho-nitro derivative represented the largest dependency on solvents' polarity/polarizability so that it can be used as a solvatochromic probe.


How parents search, interpret, and evaluate genetic information obtained from the internet.
This study describes how parents of a child referred for genetic services searched the Internet for information, summarizes how they interpreted and evaluated the information they obtained, and identifies barriers that they encountered. Audio-taped interviews were conducted with 100 ethnically diverse families referred to a pediatric genetics clinic. After transcription, coded text was entered into a software program (QSR N6) for searching and data retrieval. Matrices were created to systematically categorize and compare families' Internet use. Eighty-three percent of families obtained Internet information about the diagnosis, the clinic visit, and/or treatment and services. Those not conducting searches lacked access, Internet experience, or a diagnostic term and had lower incomes and less education, regardless of ethnicity. Families sought information in preparation for the clinic visit but barriers to obtaining and interpreting relevant information were common. Parents' Internet searching experiences illustrate common barriers to obtaining and understanding genetic information. Identifying them can help genetic counselors facilitate parents' searches for relevant information.


Molecular characterization of subcutaneous panniculitis-like T-cell lymphoma reveals upregulation of immunosuppression- and autoimmunity-associated genes.
Subcutaneous panniculitis-like T cell lymphomas represent a rare and difficult to diagnose entity of cutaneous T cell lymphomas. SPTL affects predominantly young adults and presents with multifocal subcutaneous nodules and frequently associated autoimmune features. The pathogenesis of SPTL is not completely understood. The aim of this study was to unravel molecular pathways critical to the SPTL pathogenesis. Therefore, we analyzed 23 skin samples from 20 newly diagnosed SPTL patients and relevant control samples of adipose and non-malignant panniculitis tissue by using gene expression microarray, quantitative PCR, and two-colour immunohistochemistry. Interestingly, indoleamine 2,3-dioxygenase (IDO-1), an immunotolerance-inducing enzyme, was among the most highly overexpressed genes in all comparisons. The expression of Th1-specific cytokines, known to be associated with autoimmune inflammation (i.e. IFNG, CXCR3, CXCL9, CXCL10, CXCL11, and CCL5), were also significantly increased. Confirmed using immunohistochemistry, the morphologically malignant lymphocytes expressed CXCR3 and CXCL9. IDO-1 expression was found both in some morphologically malignant lymphocytes rimming the adipocytes and in surrounding CD11c(-) CD68(-) cells but not in CD11c(+) dendritic cells in the microenvironment. The proportion of FoxP3+ cells in SPTL exceeded that in the benign panniculitis samples. Our results indicate that the up regulation of the tolerogenic IDO-1 together with the up regulation of IFNG, CXCR3 ligands, and CCL5 are features of SPTL lesions. We anticipate that the IFNG-inducible IDO-1 expression contributes to the formation of an immunosuppressive microenvironment, favorable for the malignant T cells. This study provides a relevant molecular basis for further studies exploring novel therapeutic means for subcutaneous T cell lymphoma.


Halovibrio salipaludis sp. nov., Isolated from Saline-Alkaline Soil.
A Gram-staining-negative, halophilic, aerobic, oval-shaped or vibrio-shaped, motile by a polar flagellum strain, designated YL5-2T, was isolated from natural saline-alkaline wetland soil of Binhai new district, Tianjin, China. Strain YL5-2T grew optimally at 35 °C, pH 7.5-8.0, and in the presence of 10-25% (w/v) NaCl on MA medium. Phylogenetic analyses based on 16S rRNA gene sequences showed that the isolate belonged to the genus Halovibrio and exhibited high sequence similarity of 97.7% to Halovibrio variabilis DSM 3050T. The sole respiratory ubiquinone of strain YL5-2T is Q-9, and the dominant fatty acids were C18:1ω9c, C16:0, C19:0 cycloω8c, and Summed Feature 8. The major polar lipids were diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), phosphatidylglycerol (PG), phosphatidylcholine (PC), and lipid (L). The DNA G+C content of the strain was 62.1 mol%. The average nucleotide identity (ANI) based on whole genome sequences of strain YL5-2T and Halovibrio variabilis DSM 3050T was 93.85%, and the dDDH value between these two strains was determined to be 52.0%. Phenotypic, chemotaxonomic, phylogenetic, and genomic analyses suggested that strain YL5-2T represent a novel species of the genus Halovibrio, for which the name Halovibrio salipaludis sp. nov. is proposed. The type strain is YL5-2T (=KCTC 52852T=ACCC 19971T).


The nuclear DNA longevity in cryopreserved boar spermatozoa assessed using the Sperm-Sus-Halomax.
The aim of this experimental study was to evaluate the dynamics of nuclear DNA fragmentation in frozen-thawed (FT) boar spermatozoa incubated over time. Using the Sperm Chromatin Dispersion test (Sperm-Sus-Halomax), this study focused special attention on resolving the hypothesis that the original halo shapes around the sperm head could show dynamic changes over the postthawing incubation time. Twenty FT sperm samples from five boars (four per boar) were incubated at 37 °C during 168 hours and sperm motility (assessed using computer-assisted sperm analysis), viability (evaluated using the LIVE/DEAD Sperm Viability Kit), and nuclear DNA fragmentation were analyzed at 0, 0.5, 2, 4, 6, 24, 48, 72, and 168 hours. The percentages of motile and viable spermatozoa progressively decreased during incubation, with no motile and viable spermatozoa less than 10% in all boars at 24 hours of incubation. Four different halo shapes around the sperm head were considered in the Sperm Chromatin Dispersion test: normal, small, large scattered (typical fragmented nuclear DNA), and absent halo, all of them coexisting at the same time in the boar FT semen samples. Sperm with a large scattered halo did not change during postthaw, consistently showing percentages less than 5% over time in all boars. In contrast, the other three sperm populations showed a dynamic evolution over incubation time, characterized by a gradual reduction of sperm with normal halo, proportional to the increment in the sperm showing a small halo, followed by a switch between the sperm with a small halo and sperm with no halo. These results suggest that three of these four sperm populations, those showing small, large scattered, and absent halo, represent spermatozoa with different degrees of nuclear DNA damage, which should be taken into consideration to indicate the percentage of sperm with fragmented nuclear DNA in boar FT semen samples.


Lymphatic Embolization for the Management of Post-operative Chyle Leaks Following Solid Tumor Resection in Pediatric Patients.
Chyle leaks are a common post-operative complication following solid-tumor resection in pediatric patients. Current treatments for persistent chyle leaks are limited, leading many patients to experience prolonged hospitalization, nutritional deficits and/or delays in cancer therapies. Lymphatic embolization is an emerging treatment option for chyle leaks, however, limited reports exist of its use in pediatric populations. We conducted a retrospective review of pediatric patients (<18) who underwent lymphangiogram with intent for lymphatic embolization for the management of chyle leaks following solid-tumor resection between 2017 and 2022. Seven patients underwent a total of 11 attempted lymphatic embolization procedures after current standard of care treatments failed to resolve the leak. Lymphangiograms identified a chyle leak in 6 of 7 patients and embolization had a technical success rate of 73%. The complication rate was 9% and complications were limited to one episode of inadvertent gastric wall perforation that did not result in a gastric leak. Lymphatic embolization was ultimately associated with chyle leak resolution in 100% of patients within a median of 24 days, however, repeat embolization was required in 5 of 7 patients (83%). Lymphatic embolization appears to be a safe and effective treatment for persistent chyle leaks in pediatric patients, leads to a direction reduction in chyle output, and has high rates of technical and clinical success. Complete resolution of the chyle leak may require multiple embolization procedures. Further work is needed to determine whether earlier intervention may offer benefit for the management of pediatric chyle leaks. IV.


Analysis of the breath hydrogen test for carbohydrate malabsorption: validation of a pocket-sized breath test analyser.
To assess the validity and clinical application of a hand-held breath hydrogen (H2) analyzer (BreatH2, Europa Scientific, Crewe, UK). Breath samples of patients referred to the Gastroenterology Unit, Women's and Children's Hospital, North Adelaide, South Australia, for confirmation of the diagnosis of carbohydrate malabsorption were analysed with the Quintron microlyzer (Quintron Instrument Co., Milwaukee, USA) and the BreatH2 analyser, using the Quintron microlyzer as the gold standard. Twenty-nine breath H2 tests (BHT) were performed in 29 patients aged 2 months to 61 years. The sensitivity and specificity of the BreatH2 analyser in detecting a positive BHT using the Quintron microlyser as the gold standard were 0.90 and 0.95 with positive and negative predictive values of 0.90 and 0.95, respectively. There was one false positive and one false negative reading. Bland-Altman plots showed a high degree of agreement between the values obtained with two different methods. The diagnosis of carbohydrate malabsorption, using a portable breath H2 analyser (BreatH2), achieved an acceptable degree of sensitivity and specificity, enabling it to be used where no alternative is available.


Wavelet analysis of the atmospheric flows over real urban morphology.
Winds are the basic forces for atmospheric transport such as pollutant removal and pedestrian thermal comfort. The transport capability is commonly measured in terms of length and velocity scales. In this connection, the flows in the atmospheric surface layer (ASL) over the Kowloon Peninsula, Hong Kong (HK) are scrutinized by the large-eddy simulation (LES) to characterize the motion scales over real urban morphology. Apart from statistical analysis, the streamwise fluctuating velocity u' is examined by both wavelet and energy spectrum in which a primary peak is consistently shown at streamwise wavelength 70 m ≤ λx ≤ 300 m. A secondary peak at a longer wavelength 800 m ≤ λx ≤ 3000 m, however, is unveiled by wavelet only. It denotes the existence of intermittent turbulence structures whose sizes are much larger than those of buildings. Further wavelet analysis reveals that majority energy-carrying eddies are enlarging (tens to hundreds of meters) from the roughness sublayer (RSL) to the inertial sublayer (ISL). Analogous to its smooth-wall and schematic rough-wall counterparts, the turbulence kinetic energy (TKE) over urban areas is peaked in the ISL which is carried by eddies of size 50 m ≤ λx ≤ 1000 m. The (horizontal) spatial distribution of energy-carrying eddies is further visualized to compare the crucial motion scales in the RSL and ISL. Finally, conditional sampling is used to demystify the contribution to vertical momentum flux u'w' in terms of streamwise wavelength and quadrants. The results advance our fundamental understanding of ASL transport processes, fostering sustainable environmental policy.


Cost effectiveness of chest computed tomography after lung cancer resection: a decision analysis model.
Postoperative surveillance with chest computed tomography (CT) is often performed in patients who have undergone resection of non-small cell lung cancer (NSCLC), despite lack of supporting data. This study involves the creation of a decision analysis model to predict the cost effectiveness of postoperative surveillance CT. A decision analysis model was created in which a hypothetical cohort of patients underwent annual chest CT after resection of a stage IA NSCLC. The incidence of second primary lung cancer (SPLC), sensitivity and specificity of CT, as well as survival after resection of initial primary and SPLC were derived from published literature. The cost of CT and other procedures prompted by a positive finding on CT was calculated from Medicare reimbursement schedules. Cost effectiveness was defined as a cost of less than 60,000 dollars per quality-adjusted life-year gained in the cohort under surveillance compared with controls under no surveillance. In the initial (base case) analysis, the cost of surveillance CT was 47,676 dollars per quality-adjusted life-year gained, implying cost effectiveness. However, factors that rendered surveillance CT cost ineffective were (1) age at entry into the surveillance program greater than 65 years, (2) cost of CT greater than 700 dollars, (3) incidence of SPLC of less than 1.6% per patient per year of follow-up, and (4) a false positive rate of surveillance CT greater than 14%. Surveillance with postoperative CT may be a cost-effective intervention to detect SPLC in selected patients with previously resected stage IA NSCLC.


[Isobutyramide activates transcription of human fetal gamma-globin gene selectively].
To examine the effect of isobutyramide synthesized in our laboratory on expression of globin genes in MEL cells transfected with the recombinant construct mu LCRA gamma psi beta delta beta MEL. The transformant cells were cultured in the medium containing different concentrations of isobutyramide for four days. The human gamma-, beta- and mouse alpha-globin mRNA were determined by RNase protection analysis. The inducible and dose-dependent expression of the human gamma-, beta- and mouse alpha- globin gene were observed. The induction of the human gamma-globin gene was significant stronger than that of the beta-globin gene. Under 2.5 mmol/L-5 mmol/L of isobutyramide, the induction of the human gamma-globin gene was even more effective than that of mouse alpha-globin gene. Isobutyramide can effectively and selectively activate transcription of the human gamma-globin gene at a certain degree. This function, together with the advantages of nontoxic and long halflife makes isobutyramide a promising application in the treatment of beta-thalassemia and sickle cell anemia.


Survival of methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus spp. for an extended period of transport.
This study determined the survivability of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) for extended periods of time and temperatures using a standard swab for assessment. Our study showed that transportation in Liquid Amies medium could be performed at room temperature or 4°C for up to 14 days without a decrease in recovery of MRSA or VRE.


Duodenojejunostomy leaks after pancreaticoduodenectomy.
A duodenojejunostomy (DJ) or gastrojejunostomy (GJ) leak is a potentially fatal complication after pancreaticoduodenectomy (PD). However, due to its rarity, this complication has not been fully characterized. We reviewed 3,029 PDs performed at our institution over a 26-year period and identified patients who suffered a leak at the DJ or GJ anastomosis. Perioperative data from patients with such a leak were examined in detail and were compared to patients who did not experience such a leak after PD. A total of 13 patients experienced a DJ or GJ leak after PD, amounting to a 0.4% leak rate. Common clinical signs of a leak included an acute abdomen, enterocutaneous fistula, and a fever. Twelve of thirteen patients also had a leukocytosis, with five patients having a peak white blood cell count exceeding 30,000 cells/mm(3). The median time interval between surgery and diagnosis of the DJ or GJ leak was 10 days; three patients were diagnosed after being discharged from the hospital and one patient was diagnosed on the day of their planned discharge. In a multivariate model, perioperative risk factors for a DJ or GJ leak included a preoperative BUN-to-creatinine ratio > 20 (odds ratio = 6, p = 0.01), intraoperative blood loss > or =1 l (odds ratio = 6, p = 0.03), and a total pancreatectomy (odds ratio = 7, p = 0.005). In the DJ or GJ leak group, 12 of 13 patients were managed operatively. The median postoperative length of stay was 35 days after PD, and four patients died within 4 months of surgery as a result of their complicated postoperative course. DJ or GJ leaks occur infrequently after PD, but are associated with substantial morbidity. The clinical presentation is usually delayed, and surgical management is the preferred approach. Early diagnosis, attention to preoperative volume status, and continued efforts to control blood loss may minimize the impact of DJ or GJ leaks in some instances.


Stabilization mechanism of arsenic-sulfide slag by density functional theory calculation of arsenic-sulfide clusters.
Stabilization of arsenic sulfur slag (As‒S slag) is of high importance to prevent the release of deadly As pollutants into environment. However, the molecular understanding on the stability of As‒S slag is missing, which in turn restricts the development of robust approach to solve the challenge. In this work, we investigated the structure-stability relationship of As‒S slag with adopting various As‒S clusters as prototypes by density functional theory (DFT). Results showed that the configuration of S multimers-covering-(As2S3)n is the most stable structure amongst the candidates by the analysis of energies and bonding characteristics. The high stability is explained by orbital composition that the 4p-orbital (As) binding with 3p-orbital (S) decreases energy level of highest occupied molecular orbital (HOMO). Inspired from the calculations, an excess-S-based hydrothermal method was successfully proposed and achieved to promote the stabilization of As‒S slag. Typically, the As concentration from the leaching test of stabilized As‒S slag is only 0.8 mg/L, which is much lower than the value from other stabilized slag.


The role of phospholipase A2 in lipid peroxidation-induced fall of membrane potential of rat liver mitochondria.
Cumene hydroperoxide (230 microM)-induced fall of the membrane potential takes place only in Ca2(+)-loaded mitochondria. Inhibitor of phospholipase A2 p-bromphenacyl bromide prevents uncoupling of mitochondria, having no effect on the accumulation of lipid peroxidation products.


Analysis of influence of deformation modes of retaining structures on deformation of a side shield tunnel.
In the process of foundation pit excavation, different retaining structures and support stiffness may lead to different deformation modes of retaining structures. The soil displacement cause by the deformation of the retaining structure is calculated by the virtual image technique. Meanwhile, the collaborative deformation model for rotation and dislocation is introduced to analyze the tunnel longitudinal deformation caused by different deformation modes as well as the tunnel maximum displacement equivalent field, and two case verifications are carried out. The study shows that there is a large difference in the size and distribution law of the soil displacement field caused by different enclosure structure deformation modes. The horizontal displacement of soil caused by the cantilever type always shows a "cantilever type" curve with increasing horizontal distance from the enclosure structure, while the composite type, inner convex type and kicker type develop from the "bow" to the "cantilever type" curve. The vertical displacement field of the soil is in the shape of a "spoon" and the soil exhibits a certain bulge deformation below the critical depth. The critical depths of the composite type and inner convex type are similar, while the kick type is the largest and the cantilever type is the smallest. The influence area of the maximum horizontal displacement of the tunnel outside the pit of the inner convex type and the composite type is basically the same. The influence area of the cantilever mode is the smallest, while the influence depth of the kick-in mode is higher than that of the other three deformation modes.


The protective role of alpha-lipoic acid on the appearance of fibronectin and laminin in renal tubules following diazinon exposure: An experimental immunohistochemical study.
Extracellular matrix (ECM) exerts a major role in maintaining the structure and developmental processes of tissues. To form the tubular basement membrane in the kidney, sulfate proteoglycans, collagen, laminin, fibronectin, and other glycoproteins congregate in the ECM. As an insecticide, diazinon (DZN) may alter the proportion of ECM by cholinesterase activity inhibition and oxidative stress. The naturally, alpha-lipoic acid (ALA) plays an effective and therapeutic role in the treatment of toxicities and diseases in the body. In the current study, an attempt was made to evaluate the impacts of alpha-lipoic acid on the distribution of fibronectin and laminin in the renal tubules of male Wistar rats following exposure to diazinon. In this study, the animal groups comprised 30 adult male Wistar rats (almost three months old) randomly distributed into the following groups; control, DZN (40 mg/kg), DZN + ALA (40 mg/kg+100 mg/kg), ALA (100 mg/kg), and sham. The rats were anesthetized after six weeks. Blood sampling was performed, and kidneys were removed for immunohistochemistry study. Diazinon reduced the distribution of fibronectin and laminin and significantly inhibited cholinesterase activity in the renal tubules. Furthermore, urea and creatinine levels were higher in diazinon than in other groups. ALA in the co-treatment group enhanced cholinesterase activity and distribution of both glycoproteins in the renal tubules. Urea and creatinine levels were meaningfully diminished in the DZN + ALA group. The nephrotoxic effect of diazinon in vivo was the reduced distribution of laminin and fibronectin, probably induced by cholinesterase activity inhibition. As an antioxidant with specific properties, ALA reduces the nephrotoxic effects of diazinon by multifarious mechanisms.


HPV self-sampling in cervical cancer screening: the effect of different invitation strategies in various socioeconomic groups - a randomized controlled trial.
Participation in cervical cancer screening varies by socioeconomic status. The aims were to assess if offering human papilloma virus (HPV) self-sampling kits has an effect on screening participation among various socioeconomic groups and to determine if two invitation strategies for offering self-sampling influence the participation rate equally. The study was based on registry data that were applied to data from a randomized controlled trial (n=9,791) measuring how offering HPV self-sampling affected screening participation. The women received either 1) a self-sampling kit mailed directly to their homes (directly mailed group); 2) an invitation to order the kit (opt-in group); or 3) a standard second reminder to attend regular cytology screening (control group). The participation data were linked to registries containing socioeconomic information. Women in the directly mailed group participated significantly more than women in the control group, regardless of their socioeconomic status, but the largest effects were observed in Western immigrants (participation difference [PD]=18.1%, 95% CI=10.2%-26.0%) and social welfare recipients (PD=15.2%, 95% CI=9.7%-20.6%). Compared with the control group, opt-in self-sampling only had an insignificant effect on participation among women who were immigrants, retired, or less educated. Western immigrants had a significantly higher increase in participation than native Danish women when kits were mailed directly compared with the opt-in strategy (PD=18.1%, 95% CI=10.2%-26.2% and PD=5.5%, 95% CI=2.9%-8.1%, respectively, P=0.01). All socioeconomic groups benefited from the directly mailed strategy in terms of higher screening participation, but Western immigrants and lower socioeconomic groups seemed to benefit the most. Immigrants and some lower socioeconomic groups only had insignificant benefits of opt-in self-sampling. The directly mailed strategy might be preferable to opt-in self-sampling because it ensures that ethnic minority groups obtain benefits of introducing HPV self-sampling in an organized cervical cancer screening program. Current Controlled Trials NCT02680262. Registered February 10, 2016.


Detection of enterotoxigenic Escherichia coli in piggeries in Victoria by DNA hybridisation using K88, K99, LT, ST1 and ST2 probes.
Rectal swabs collected from piglets with diarrhoea from commercial pig farms were examined for the presence of enterotoxigenic Escherichia coli (ETEC) using DNA hybridisation methods. The probes specifically detected genes for the K88 and K99 fimbrial antigens and the heat-labile and heat-stable enterotoxins. DNA hybridisation methods detected more ETEC than could be detected by either enzyme-linked immunosorbent assay (ELISA) or slide agglutination methods, and also offered the opportunity to test for fimbrial antigens and toxins concurrently. The DNA hybridization method was shown to be applicable to ETEC detection in mixed growths cultured directly from rectal swabs to filters. The method eliminates the need for toxin tests using animals and enables very large numbers of samples to be investigated. The use of toxin probes has revealed large numbers of ETEC with uncharacterized fimbrial antigens.


Low dose aminoglutethimide without hydrocortisone for the treatment of advanced postmenopausal breast cancer.
One hundred and one postmenopausal patients with advanced breast cancer were enrolled in a randomized phase II clinical trial to investigate the clinical and hormonal response to aminoglutethimide administered at daily doses of 2 x 125 mg, 3 x 125 mg or 2 x 250 mg, with no addition of hydrocortisone. Among 71 evaluable patients 25% showed objective tumor response (three complete, 15 partial), at all three dose levels and irrespective of the major tumor site. Previous treatment with Tamoxifen had been successful in 75%. Out of the 18 responding patients 10 had estrogen receptor positive, four had estrogen receptor negative tumors; the receptor status was unknown in four other patients. Progression-free interval was more than 700 days in 50% of the responders. Drowsiness caused early drug withdrawal in one patient. Side-effects were very mild, comparing favorably with standard therapy of 250 mg aminoglutethimide q.i.d. plus hydrocortisone. Plasma estrogen levels were reduced by all doses to the same 50% or less as in patients on standard treatment. In nine out of 27 patients a further decrease of estrone levels could be monitored with clinically improved results in five. Plasma cortisol and mineralocorticoids remained normal throughout more than 6 months. The original role of hydrocortisone administration to suppress a reflex rise of ATH in 'medical adrenalectomy' with standard dose aminoglutethimide is no longer tenable. Further phase III comparative clinical results pending, low dose aminoglutethimide as an aromatase inhibitor may at present be considered as an appropriate second-line endocrine treatment with low toxicity and expense.


Measuring the Hubble constant with a sample of kilonovae.
Kilonovae produced by the coalescence of compact binaries with at least one neutron star are promising standard sirens for an independent measurement of the Hubble constant (H0). Through their detection via follow-up of gravitational-wave (GW), short gamma-ray bursts (sGRBs) or optical surveys, a large sample of kilonovae (even without GW data) can be used for H0 contraints. Here, we show measurement of H0 using light curves associated with four sGRBs, assuming these are attributable to kilonovae, combined with GW170817. Including a systematic uncertainty on the models that is as large as the statistical ones, we find [Formula: see text] and [Formula: see text] for two different kilonova models that are consistent with the local and inverse-distance ladder measurements. For a given model, this measurement is about a factor of 2-3 more precise than the standard-siren measurement for GW170817 using only GWs.


Clinical management. Where medicine meets managements. Heroes and heroin.
A Middlesbrough general practice caters exclusively for drug addicts. There is opposition to this model, with some preferring to see all practices able to care for drug misusers. Practice nurses are seen as key to good service provision in primary care.


Extraction of nobiletin from Citrus Unshiu peels by supercritical fluid and its CRE-mediated transcriptional activity.
Polymethoxyflavone (PMF) is one of bioactive compounds in Citrus Unshiu and included mainly in the peels rather than the fruits, seeds and leaves. Supercritical CO2 extraction is one candidate for selective extraction of polymethoxyflavone and in this study, supercritical CO2 extraction with/without ethanol entrainer from Citrus Unshiu peels was examined at a temperature of 333K and a pressure of 30MPa. CRE (cyclic AMP response element)-mediated transcriptional assay was examined by using the extracts from supercritical fluid extraction. The results showed that extracts including nobiletin increased with increasing ethanol concentration in supercritical CO2 and the elapsed extraction time. Extracts at ethanol concentration of 5 mol% showed high CRE-mediated transcription activity. This can be caused by activity of the extract including nobiletin in addition to the other methoxylated flavonoid species such as tangeretin. Extracts at ethanol concentration of 50% showed the highest CRE-mediated transcription activity, which can be attributed to flavonoid glycoside such as hesperidin. From our investigations, flavonoid glycoside can be one of promoters of CRE-mediated transcription activity.


An electron microscope study of the cortico-pretecto-olivary projection in the cat by a combined degeneration and horseradish peroxidase tracing technique.
The anterior pretectal nucleus (PTA) of the cat was observed electron microscopically after motor cortical ablation and horseradish peroxidase (HRP) injection into the inferior olive of the same animal. Direct synaptic connections were found between degenerated cortico-pretectal axon terminals and dendrites of pretecto-olivary projection neurons retrogradely labeled with HRP in the ventrolateral part of the PTA. Therefore, this combined method revealed that the PTA is a relay station of the cortico-olivary projection.


Lack of 17β-estradiol reduces sensitivity to insulin in the liver and muscle of male mice.
The importance of estrogens for glucose homeostasis has been demonstrated by clinical, pharmacological, and experimental studies. Male mice lacking the aromatase gene (ArKO mice), which encodes an enzyme involved in estrogen synthesis, develop glucose- and insulin-intolerance. However, it remains unclear whether insulin signaling is actually impaired in the liver and muscle of ArKO mice. We examined the effects of estrogen-deficiency on insulin signaling by quantifying phosphorylation levels of protein kinase B (Akt) in the liver and muscle and by examining the expression levels of insulin-target genes in the liver. Insulin administration enhanced phosphorylation levels of Akt in the liver and muscle of wild-type (WT) mice, ArKO mice, and ArKO mice supplemented with 17β-estradiol (E2), but insulin was less effective in ArKO mice. Gene expression analysis revealed that alterations induced by insulin in WT liver were also observed in ArKO liver, but the degree of altered expression in a subset of genes was smaller in ArKO mice than in WT mice. E2 supplementation improved the insulin responses of some genes in ArKO mice. Thus, these findings suggest that insulin signaling in the liver and muscle of ArKO mice is less efficient than in WT mice, which contributes to whole-body glucose intolerance in ArKO mice.


Can environmental DNA (eDNA) be used for detection and monitoring of introduced crab species in the Baltic Sea?
The need to detect and monitor introduced marine species has increased with the increasing number of marine invasions. To complement standard detection and monitoring techniques, new approaches using environmental DNA (eDNA) have recently been developed. However, most of the eDNA work has focused on vertebrate species in spatially limited freshwater habitats while benthic invertebrates in coastal environments have received much less attention. Here, we evaluated the suitability of the eDNA approach for detecting benthic, hard-shelled, crustacean mud crab species in a brackish water environment. We demonstrated for the first time that eDNA from an introduced mud crab Rhithropanopeus harrisii can be successfully amplified in aquarium water samples and detected in the brackish water environment. However, the detection rate was rather low. This suggests that in contrast to freshwater vertebrates, it may be more challenging to develop a highly sensitive eDNA method for detecting crustacean species in a marine environment.


Local delivery of poxvirus vaccines for melanoma.
The development of vaccines for melanoma has been accelerated by the identification of melanoma-associated antigens, a better understanding of basic immunologic principles, and the ability to construct complex vectors for immunization. The location and context in which T-cell priming occurs significantly influences the type and magnitude of immune response. Furthermore, there is a delicate balance between the generation of tumor-specific immunity and the emergence of tumor escape variants. We have focused on the direct intra-tumoral delivery of poxvirus vaccines expressing costimulatory molecules as a strategy for overcoming local immunosuppression in the treatment of established melanoma. Poxviruses provide potent danger signals and, in the presence of costimulation, local administration provides a mechanism to prime tumor-specific T-cell responses. The clinical application of this approach will likely depend on the ability to induce systemic anti-tumor immunity following local injection and we are evaluating this in current clinical trials. These studies may have important implications for the design of vaccine strategies for melanoma and other tumors.


Publisher Correction: Five decades of eukaryotic transcription.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Suprasellar yolk-sac tumor in two sisters.
The familial occurrence of intracranial tumors is rare except in patients with phacomatoses. The occurrence of suprasellar yolk-sac tumors in two sisters without phacomatoses is reported. The pertinent literature is reviewed, and the possible role of heredity in the pathogenesis of these tumors is discussed briefly.


Synergistic effects and mechanisms of plasma coupled with peracetic acid in enhancing short-chain fatty acid production from sludge: Motivation of reactive species and metabolic tuning of microbial communities.
Suitable waste activated sludge (WAS) pretreatments that boost short-chain fatty acid (SCFA) production from anaerobic fermentation are essential for carbon emission reduction and sludge resource utilization. This study established an efficient WAS pretreatment process combining atmospheric pressure plasma jet (APPJ) with peracetic acid (PAA). The maximum SCFA production (6.5-fold that of the control) largely increased under the optimal conditions (PAA dosage = 25 mg/g VSS (volatile suspended solids), energy consumption = 20.9 kWh/m3). APPJ/PAA pretreatment enhanced the production of multiple reactive species (including OH, CH3C(O)O, 1O2, ONOO-, O2-, and eaq-) and strengthened the effects of H2O2, heat, and light. This synergistically solubilized WAS and released organic substrates for SCFA-producing microbes. In addition, the enrichment of SCFA-producing bacteria and the decrease in SCFA-consuming bacteria favored SCFA accumulation. The key genes encoding for the main substrate metabolism and SCFA production in the metabolic pathway of fermentation were also enhanced.


Metformin as treatment for overweight and obese adults: a systematic review.
We wanted to determine whether metformin is an effective medication for treatment of overweight or obese adults who do not have diabetes mellitus or polycystic ovary syndrome (PCOS). We searched MEDLINE (1966-2003), EMBASE (1986-2003), Allied and Complementary Medicine Database (1985-2003), International Pharmaceutical Abstracts (1970-2003), the Cochrane Library, American College of Physicians Journal Club, Database of Abstracts of Reviews of Effects, Cochrane Controlled Trials Register, MEDLINE In-Process & Other Non-Indexed Citations, reference lists of retrieved articles, and articles by selected authors and pharmaceutical manufacturers. Inclusion criteria were being obese or overweight determined by a BMI of 25 kg/m2 or greater or waist-to-hip ratio (WHR) of more than 0.8, metformin use, and aged 18 years or older. Exclusion criteria were a diagnosis of diabetes mellitus, polycystic ovarian syndrome or descriptors of polycystic ovarian syndrome, human immunodeficiency virus infection, and concomitant antipsychotic medications. Trials were graded on an 11-point Jadad scale. Only randomized controlled and blinded trials were accepted. Two reviewers independently extracted data from each trial. Primary outcomes measured were changes in BMI, WHR, and weight. Fifty-seven potentially relevant studies were initially identified; 48 were excluded because of lack of randomization, lack of blinding, failure to meet inclusion or exclusion criteria, inaccessible outcomes, or improper study design. Nine clinical trials met criteria for validity assessment. Four studies used the parameter of waist-to-hip ratio, 3 studies included BMI, and 8 used weight. Two of the 9 studies showed a small reduction in WHR. Insufficient evidence exists for the use of metformin as treatment of overweight or obese adults who do not have diabetes mellitus or polycystic ovary syndrome. Further studies are needed to answer this clinical question.