Goldthioglucose causes brain norepinephrine and serotonin depletion correlated with increased body weight.
Goldthioglucose (GTG) injected i.p. in mice is known to cause hyperphagia and obesity which is related to ventromedial hypothalamic damage and norepinephrine (NE) depletion in females. In the present experiment 6 doses of GTG were tested in males. After 160 days the monoamine content of whole brain was measured. Norepinephrine (NE) and serotonin (SER) were depleted without changes in dopamine content. Brain NE and SER were both negatively correlated with body weight. These experiments extend earlier studies by suggesting that GTG obesity in mice may be caused by NE depletion in males as well as females and by suggesting that the obesity is also a function of serotonin depletion.


Quality assurance in home laboratory testing.
In review, one is compelled to the notion that a variety of the aforementioned thoughts become pre-eminent in assuring quality. The selection of the tests available for home testing is crucial. They should be divided into categories of single encounter tests and multiple use tests. The single encounter implies a test that has an extremely high degree of reliability and is likely to achieve an answer to the question asked. This should relate to a disease or process for which potential favorable treatment can be achieved or which may have a major favorable impact on public health. In this category one thinks in terms of the worldwide prevalence of hepatitis B and other infectious diseases that are particularly common in third world countries. Yet, these are not "markets" likely to be able to afford this testing. Similarly, these societies are not currently sophisticated in terms of application of preventive measures. On the other hand, major benefits could be projected from the other category of testing, namely, therapeutic monitoring in the hands of individuals who will repetitively test for the same substance in the same manner. This includes not only diabetes but other conditions that are monitored for drug therapy, including seizure disorders and bronchospasm. Inherent in this aspect is the requirement for meaningful and ongoing instruction in proper testing methodology and recording of results. The incorporation of some type of memory device to enforce this aspect of testing appears extremely desirable, if not mandatory. Finally, we must consider the potential for misuse of the single test type of device. One suspects that it would be highly desirable that any test made available for self-testing should also be mandated as accessible through certified laboratories at the request of an individual, which would at least provide reliable performance of the test with a quality result. The development of the concept of quality assurance in home testing is in its infancy and will require continuing evolution.


The diagnostic value and molecular characterisation of an Echinococcus multilocularis antigen gene clone.
A diagnostic Echinococcus multilocularis antigen gene (EM4) has been expressed using the Escherichia coli expression vector pGEX-1 resulting in the high level synthesis of a readily purifiable, soluble, non-denatured peptide fused to the 26-kDa glutathione-S-transferase of Schistosoma japonicum. This recombinant antigen, on testing by enzyme-linked immunosorbent assay (ELISA) with heterologous human antisera, demonstrated 100% E. multilocularis specificity. Specific anti-EM4 antibody immunoprecipitated a single 66-kDa protein from protoscolex total RNA directed in vitro translation products indicating the probable involvement of post-translational modification in the production of the native EM4 antigens. Southern blotting analysis suggests that the EM4 native antigens are coded for by a single-copy gene and that the genomic organisation of the EM4 related genes in other parasites is not conserved. The nucleotide sequence of the cloned EM4 cDNA molecule has been obtained and the derived amino acid sequence shows no significant homology with other existing protein sequences.


Functional status impairment at six-month follow-up is independently associated with child physical abuse mechanism.
Children with abusive injuries have worse mortality, length-of-stay, complications, and healthcare costs compared to those sustaining an accidental injury. Long-term functional impairment is common in children with abusive head trauma but has not been examined in a cohort with heterogeneous body region injuries. To assess for an independent association between child physical abuse and functional impairment at discharge and six-month follow-up. Seriously injured children (<15 years) treated at seven pediatric trauma centers. Functional status was compared between child physical abuse and accidental injury groups at discharge and six-month follow-up. Functional impairment was defined at discharge ("new domain morbidity") as a change from pre-injury ≥2 points in any of the six domains of the Functional Status Scale (FSS), and impairment at six-month follow-up as an abnormal total FSS score. Children with abusive injuries accounted for 10.5% (n = 45) of the cohort. New domain morbidity was present in 17.8% (n = 8) of child physical abuse patients at discharge, with 10% (n = 3) of children having an abnormal FSS at six-months. There were no differences in new domain morbidity at hospital discharge between children injured by abuse and or accidental injury. However, children injured by physical abuse were 4.09 (2.15, 7.78) times more likely to have functional impairment at six months. Child physical abuse is an independent risk factor for functional impairment at six-month follow-up. Functional status measurement for this high-risk group of children should be routinely measured and incorporated into trauma center quality assessments.


Design and psychometric evaluation of the fathers' fear of childbirth scale: a mixed method study.
Fear of childbirth is reported in 13% of fathers, and it may have adverse consequences for the fathers' health as well as their families. To reduce the fear of childbirth in the expectant fathers, an appropriate screening tool is needed. Due to the lack of a valid and reliable questionnaire to measure fathers' fear of childbirth, this study was conducted to develop the Fathers' Fear of Childbirth Scale and evaluate its psychometric properties. This mixed method study was conducted in two phases. In the qualitative phase (or item generation), semi-structured interviews were conducted with 20 expectant fathers, and a literature review was performed to generate the Fathers' Fear of Childbirth Scale items pool. In the quantitative phase (or psychometric evaluation), reliability as well as face, content, and construct validity of this scale were evaluated. To establish construct validity, exploratory and confirmatory factor analyses were performed. Reliability was evaluated through internal consistency and composite reliability measures. The primary version of Fathers' Fear of Childbirth Scale contained 32 items, which were reduced to 17 items while establishing construct validity. Exploratory factor analysis extracted two factors, namely fear of childbirth process (12 items) and fear of hospital (5 items). These factors explained 50.82% of the total variance. Goodness of fit indices within the confirmatory factor analysis was acceptable. Internal consistency and composite reliability indices of all the factors were greater than 0.70. The Fathers' Fear of Childbirth Scale has a suitable validity and reliability for assessing fear of childbirth in fathers. It is a simple report instrument that can be easily implemented by health care professionals.


Dehydrogenation of Ammonia Borane by Platinum-Nickel Dimers: Regulation of Heteroatom Interspace Boosts Bifunctional Synergetic Catalysis.
Regulation of the atom-atom interspaces of dual-atom catalysts is essential to optimize the dual-atom synergy to achieve high activity but remains challenging. Herein, we report an effective strategy to regulate the Pt1 -Ni1 interspace to achieve Pt1 Ni1 dimers and Pt1 +Ni1 heteronuclear dual-single-atom catalysts (HDSACs) by tailoring steric hindrance between metal precursors during synthesis. Spectroscopic characterization reveals obvious electron transfers in Pt1 Ni1 oxo dimers but not in Pt1 +Ni1 HDSAC. In the hydrolysis of ammonia borane (AB), the H2 formation rates show an inverse proportion to the Pt1 -Ni1 interspace. The rate of Pt1 Ni1 dimers is ≈13 and 2 times higher than those of Pt1 and Pt1 +Ni1 HDSAC, manifesting the interspace-dependent synergy. Theoretical calculations reveal that the bridging OH group in Pt1 Ni1 dimers promotes water dissociation, while Pt1 facilitates the cleavage of B-H bonds in AB, which boosts a bifunctional synergy to accelerate H2 production cooperatively.


Understanding the role of Beclin1 in mouse embryonic stem cell differentiation through CRISPR-Cas9-mediated gene editing.
Autophagy is a vacuolar pathway for the regulated degradation and recycling of cellular components. Beclin1, a Bcl2-interacting protein, is a well-studied autophagy regulator. Homozygous loss of Beclin1 in mice leads to early embryonic lethality. However, the role of Beclin1 in regulating the pluripotency of embryonic stem cells and their differentiation remains poorly explored. To study this, we generated Beclin1-Knockout (KO) mouse embryonic stem cells (mESCs) using the CRISPR-Cas9 genome-editing tool. Interestingly, Beclin1-KO mESCs did not show any change in the expression of pluripotency marker genes. Beclin1-KO mESCs also displayed active autophagy, suggesting the presence of Beclin1-independent autophagy in mESCs. However, loss of Beclin1 resulted in compromised differentiation of mESCs in vitro and in vivo due to misregulated expression of transcription factors. Our results suggest that Beclin1 may play an autophagy-independent role in regulating the differentiation of mESCs.


2-Amino-pyrimidinium hydrogen sulfate.
In the crystal structure of the title compound, C(4)H(6)N(3) (+)·HSO(4) (-), hydrogen sulfate anions self-assemble through O-H⋯O hydrogen bonds, forming chains along the b axis, while the cations form centrosymmetric pairs via N-H⋯N hydrogen bonds. The 2-amino-pyrimidinium pairs are linked to the sulfate anions via N-H⋯O hydrogen bonds, forming a two-dimensional network parallel to (10[Formula: see text]). In addition, weak inter-molecular C-H⋯O contacts generate a three-dimensional network.


Nutritional and dietary diversity status of under-5 children and adolescent girls among forcibly displaced Myanmar nationals living in Bhasan Char relocation camp, Bangladesh: a cross-sectional survey.
To generate baseline evidence regarding the nutritional and dietary diversity status of under-5 children and adolescent girls among forcibly displaced Myanmar nationals (FDMN) relocated to Bhasan Char relocation camp of Bangladesh. Cross-sectional survey. Bhasan Char relocation camp, Bangladesh, 7 November 2021-12 November 2021. 299 under-5 children (both male and female) and 248 adolescent girls (11-17 years) were surveyed. Anthropometric indices and nutritional status of the study participants. Nearly 17% of the adolescent girls were suffering from severe thinness/thinness, while 5% were overweight/obese. Severe thinness was more prevalent (2% vs 3.9%) in older adolescents (15-17 years) than their younger counterparts (11-14 years). The prevalence of severe stunting and stunting in adolescents were 14% (95% CI 11.21 to 16.87%) and 29% (95% CI 25.93 to 31.59%), respectively. One-third of the surveyed under-5 children were severely (8.50% (95% CI 5.60 to 11.33%)) or moderately (23.08% (95% CI 20.24 to 25.90%)) stunted, 27% were either severely (4.43% (95% CI 1.60 to 7.27%)) or moderately (22.98% (95% CI 20.15 to 25.81%)) underweight and 12% were severely (1.21% (95% CI 0.00 to 4.04%)) or moderately (10.88% (95% CI 8.05 to 13.72%)) wasted. The prevalence of moderate and severe acute malnutrition in children was low. Surveyed adolescents took a mean of 3.10 (SD 1.03) of nine food groups and 25% (95% CI 22.97 to 28.64%) of under-5 children took minimum diversified diet. The survey respondents mostly consumed carbohydrate-based poorly diversified diets. Nutritional status of the participants did not show any statistically significant association to the dietary diversity status. A significant number of surveyed under-5 children and adolescent girls of relocated FDMN living in Bhasan Char of Bangladesh were suffering from thinness, stunting, underweight and wasting. Dietary diversity was poor among the surveyed population.


Dataset of the intermediate competition in challenge MALIN: Indoor-outdoor inertial navigation system data for pedestrian and vehicle with high accuracy references in a context of firefighter scenario.
This paper provides a multiple sensor dataset collected by the CyborgLOC team during the intermediate competition of the Challenge MALIN (MAîtrise de la localisation INdoor), which is a competition for indoor/outdoor real-time positioning. The sensors, including a GNSS receiver Ublox NEO-M8N, a Realsense D435i stereo camera, three Xsens MTi-300 and one PERSY (PEdestrian Reference SYstem), are mounted on different parts of the subject's body. The PERSY is a foot-mounted positioning device with a tri-axial accelerometer, a tri-axial gyroscope, a tri-axial magnetometer as well as a GNSS receiver Ublox M8T. The two scenarios are designed in a training centre of firefighters CFIS (Fire and Rescue Training Centre) in Blois, France to simulate the situation of firefighters during interventions. With total distances around 2 km for each scenario, the travelled trajectories passed through challenging environments including indoor, outdoor, urban canyon. The indoor part contains different stair levels, from the underground up to the 6th floor. The travel modes are vehicles and pedestrians. Several classical activities of firefighters are realized such as walking, running, stair-climbing, side-walking, crawling, passing above/below obstacles, carrying a stretcher, ladder climbing, etc. High accurate ground truth of stationary points and enclosing volumes are provided by the organizers of the competition, i.e., the Directorate General of Armaments (DGA: Direction Générale de l'Armement). Provided with raw data, they allow the evaluation of the positioning performances. This dataset is available on the data repository https://doi.org/10.5281/zenodo.4290789.


Altered amniotic fluid leptin levels in twin-twin transfusion syndrome with concurrent placental insufficiency.
To measure amniotic fluid leptin levels in fetuses with twin-twin transfusion syndrome (TTTS) with and without placental insufficiency (PI) and determine its usefulness as a biomarker of PI. A retrospective case control study of TTTS stage III patients from 2009 to 2011 was conducted. Cases were pregnancies with PI (TTTS-PI, n = 18) matched by stage, gestational age, and degree of cardiomyopathy to controls without PI (TTTS, n = 26). PI was strictly defined using biometric parameters. Amniotic fluid from recipient twins (RT) was taken during second trimester fetoscopic laser therapy. Leptin concentrations were determined and compared to growth parameters and birth weight. RT-adjusted leptin was 66% higher in TTTS-PI (p = 0.016) compared to TTTS controls. Cases had significantly higher growth discordance (p = 0.004) and lower RT birth weight (p = 0.041) compared to controls. Significantly higher adjusted leptin levels were observed at birth in the TTTS-PI group when comparing those with SGA donor twins to those of normal weight (p = 0.016). These data suggest a role for leptin in pregnancies complicated by TTTS with placental insufficiency. However, further studies are needed to define its mechanism and potential role as a biomarker in amniotic fluid for placental pathophysiology.


The diagnostic value of cerebrospinal fluids procalcitonin and lactate for the differential diagnosis of post-neurosurgical bacterial meningitis and aseptic meningitis.
Distinguishing between post-neurosurgical bacterial meningitis (PNBM) and aseptic meningitis is difficult. This study aims to evaluate the combined diagnostic value of CSF procalcitonin and lactate as novel PNBM markers in hospitalized post-neurosurgery patients. This study was performed using CSF samples, collected by lumbar puncture, from 178 PNBM-suspected patients enrolled in a retrospective clinical study. The levels of CSF procalcitonin and lactate were appropriately assayed and the combined diagnostic value of these markers was assessed using receiver operating characteristic (ROC) curves, a two by two table, and non-parametric tests. Fifty of the 178 patients were diagnosed with PNBM, based on the clinical symptoms and laboratory results. These PNBM patients showed significantly elevated levels of CSF procalcitonin and CSF lactate compared with the non-PNBM group (p<0.001 for both). It was revealed that the cut-off values for the diagnosis of PNBM were: 0.075ng/mL (sensitivity, 68%; specificity, 73%) for procalcitonin and 3.45mmol/L (sensitivity, 90%; specificity, 85%) for lactate. A serial test combining the levels of these two markers showed decreased sensitivity (64%) and increased specificity (91%), compared with either marker alone. In contrast, a parallel test combining the levels of these both markers showed increased sensitivity (96%) and decreased specificity (65%), compared with either marker alone. Our study shows that the combined use of CSF procalcitonin and lactate can reliably distinguish between PNBM and non-PNBM and can be included in the design of diagnostic approaches to circumvent the shortcomings of conventional methods.


Effects of biochar amendment on bacterial and fungal communities in the reclaimed soil from a mining subsidence area.
Biochar amendment of soil is well known to improve soil fertility and microbial function. However, little is known about the effect of biochar addition to reclaimed soil in coal mining subsidence area on microbial community. A plant soil cultivation experiment was conducted with wheat grown and four treatments were included: P and K fertilizer (CK); NPK inorganic fertilizer (NPK); NPK inorganic fertilizer and straw (NPKS); and NPK inorganic fertilizer and biochar (NPKB). The results indicated that biochar amendment significantly increased the concentrations of NH4+-N, total N, and available P and K compared with the NPK. Biochar addition also significantly increased the grain yield and total biomass of wheat. Furthermore, biochar amendment treatment increased the absolute abundance and altered the community structure of soil bacteria and fungi in the reclaimed soil. Illumina MiSeq sequencing showed that the addition of biochar increased α-diversity of bacteria and relative abundances of Proteobacteria, Actinobacteria, and Bacteroidetes, whereas the relative abundance of Firmicutes were decreased by 61%. However, biochar addition did not change the relative abundance of dominant fungal phyla. Redundancy analysis (RDA) suggested that total N, available P, and K contents were the key factors correlated with changes in microbial community structure. Overall, our results suggest that biochar amendment in reclaimed soil in coal mine subsidence area could increase wheat yield and abundance and alter microbial community compositions.


Estimating the prevalence of stress among Indian students during the COVID-19 pandemic: A cross-sectional study from India.
Since December 2019, the COVID-19 pandemic has posed a substantial threat with its associated high mortality, infection, and risk of psychological stress. A large number of students are affected because of a prolonged break from academic activities and staying at home. The focus of this study is to understand the stress levels of Indian students, any psychological imbalances, and their major hurdles during the COVID-19 lockdown. Using a snowball sampling method, an online survey of the Perceived Stress Scale (PSS) was conducted on students across India. Along with their demographic details, the participants also reported their study patterns and challenges during their confinement period. The statistical scores for the responses were calculated and the demographic variables analysed. The levels indicated by the PSS were compared, and variance and regression analyses were performed. We observed that students were generally stressed during lockdown and the pandemic. Females (mean = 3.03) were more stressed than males (mean = 2.61) as they were constantly under pressure because of stressful life events (OR = 0.752, 95% CI = 2.425-310.642) and apprehensive about their studies (RII = 0.67, OR = 2.168, 95% CI = 0.332-6.691). During the pandemic, students' mental health needs to be continually monitored as they are stressed owing to fear as well as about their studies and future careers.


Use of bot and content flags to limit the spread of misinformation among social networks: a behavior and attitude survey.
The COVID-19 infodemic is driven partially by Twitter bots. Flagging bot accounts and the misinformation they share could provide one strategy for preventing the spread of false information online. This article reports on an experiment (N = 299) conducted with participants in the USA to see whether flagging tweets as coming from bot accounts and as containing misinformation can lower participants' self-reported engagement and attitudes about the tweets. This experiment also showed participants tweets that aligned with their previously held beliefs to determine how flags affect their overall opinions. Results showed that flagging tweets lowered participants' attitudes about them, though this effect was less pronounced in participants who frequently used social media or consumed more news, especially from Facebook or Fox News. Some participants also changed their opinions after seeing the flagged tweets. The results suggest that social media companies can flag suspicious or inaccurate content as a way to fight misinformation. Flagging could be built into future automated fact-checking systems and other misinformation abatement strategies of the social network analysis and mining community.


Raoultella terrigena: Current state of knowledge, after two recently identified clinical cases in Eastern Europe.
Raoultella terrigena is a rarely found opportunistic pathogen that can cause healthcare-associated infections with high mortality. It is important to differentiate it from Klebsiella species.


Aminothiazole derivatives with antidegenerative activity on cartilage.
A series of 2-dialkylamino-N-(4-substituted thiazolyl-2)acetamides and 3-dialkylamino-N-(4-substituted thiazolyl-2)propionamides were synthesized and evaluated for their anti-inflammatory activity. Encouraging results led us to investigate the effect of these compounds on NO production and GAGs release. Their effects were evaluated in vitro on the metabolism of pig cartilage, treated with IL-1beta. The amount of glycosaminoglycans (GAGs) and the production of nitric oxide (NO) in the culture medium were determined. The results, obtained, showed that all compounds, in the presence of IL-1beta, blocked the cartilage breakdown, with different behavior. A quantitative structure-activity relationship (QSAR) study was performed.


Kramers nodal line metals.
Recently, it was pointed out that all chiral crystals with spin-orbit coupling (SOC) can be Kramers Weyl semimetals (KWSs) which possess Weyl points pinned at time-reversal invariant momenta. In this work, we show that all achiral non-centrosymmetric materials with SOC can be a new class of topological materials, which we term Kramers nodal line metals (KNLMs). In KNLMs, there are doubly degenerate lines, which we call Kramers nodal lines (KNLs), connecting time-reversal invariant momenta. The KNLs create two types of Fermi surfaces, namely, the spindle torus type and the octdong type. Interestingly, all the electrons on octdong Fermi surfaces are described by two-dimensional massless Dirac Hamiltonians. These materials support quantized optical conductance in thin films. We further show that KNLMs can be regarded as parent states of KWSs. Therefore, we conclude that all non-centrosymmetric metals with SOC are topological, as they can be either KWSs or KNLMs.


Comparison of health-care utilization and expenditures for minimally invasive vs. open colectomy for benign disease.
Adoption of minimally invasive approaches continues to increase, and there is a need to reassess outcomes and cost. We aimed to compare open versus minimally invasive colectomy short- and long-term health-care utilization and payer/patient expenditures for benign disease. This is a retrospective analysis of IBM® MarketScan® Database patients who underwent left or right colectomy for benign disease between 2013 and 2018. Outcomes included total health-care expenditures, resource utilization, and direct workdays lost up to 365 days following colectomy. The open surgical approach (OS) was compared to minimally invasive colectomy (MIS) with subgroup analysis of laparoscopic (LS) and robotic (RS) approaches using inverse probability of treatment weighting. Of 10,439 patients, 2531 (24.3%) had open, 6826 (65.4%) had laparoscopic, and 1082 (10.3%) had robotic colectomy. MIS patients had shorter length of stay (LOS; mean difference, - 1.71, p < 0.001) and lower average total expenditures (mean difference, - $2378, p < 0.001) compared with open patients during the index hospitalization. At 1 year, MIS patients had lower readmission rates, and fewer mean emergency and outpatient department visits than open patients, translating into additional savings of $5759 and 2.22 fewer days missed from work for health-care visits over the 365-day post-discharge period. Within MIS, RS patients had shorter LOS (mean difference, - 0.60, p < 0.001) and lower conversion-to-open rates (odds ratio, 0.31 p < 0.001) during the index hospitalization, and lower hospital outpatient visits (mean difference, - 0.31, p = 0.001) at 365 days than LS. MIS colectomy is associated with lower mean health-care expenditures and less resource utilization compared to the open approach for benign disease at index operation and 365-days post-discharge. Health-care expenditures for LS and RS are similar but shorter mean LOS and lower conversion-to-open surgery rates were observed at index operation for the RS approach.


Soft tissue coverage of the upper extremity: an overview.
Prehension is a complex function of the hand that gives it mechanical precision combined with a standard sensory pattern. The priority in soft tissue reconstruction for the upper extremity is to restore function. Significant injury to the upper extremity may result after trauma because of various etiologies. The timing and choice of soft tissue coverage for upper extremity defects warrant special consideration to avoid prolonged immobilization, which can result in joint stiffness, tendon adhesions, scar contractures, and ultimately, loss of function. This article reviews the various reconstructive options and considerations involved in providing coverage for upper extremity soft tissue defects.


Aminoguanidine inhibits ventricular fibrosis and remodeling process in isoproterenol-induced hypertrophied rat hearts by suppressing ROS and MMPs.
Aminoguanidine (AG), a well known inhibitor of advanced glycation end products, has been reported to attenuate cardiac hypertrophy and fibrosis. However, the underlying mechanism by which AG exerts its anti-fibrotic activity is not well understood. Reactive oxygen species (ROS) and matrix metalloproteinases (MMPs) are implicated as playing a major role in the development of cardiac fibrosis. Hence, the present study was designed to investigate the effect of AG on ROS generation and MMPs during the progress of hypertrophic growth. Isoproterenol (ISO) (7 mg/kg/day, s.c., for 15 days) was used to induce cardiac hypertrophy in experimental adult Wistar rats. ISO-treated rats were co-treated with AG (50 mg/kg/day, i.p., for 15 days). Ventricular collagen deposition, gelatinase activity of MMP-2 and MMP-9, and the level of tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) were investigated. In addition, in silico docking of MMP-2 and MMP-9 proteins, ROS generation, and nuclear translocation of NF-κB-p65 were also studied. AG co-treatment markedly attenuated the ISO-induced hypertrophic growth and fibrosis. Heart-weight-to-body weight ratio and ventricular collagen levels were normalized upon AG co-treatment. A significantly decreased level of ventricular ROS generation (p < 0.001) and NF-κB-p65 nuclear translocation was observed in the rat hearts co-treated with AG. Furthermore, in silico docking analysis revealed that AG interacts at the active site of MMP-2 and MMP-9. Anti-fibrotic and anti-hypertrophic activities of AG were mainly attributed to its ROS quenching efficacy and its direct interaction with MMP-2 and MMP-9.


MMSPE-RP-HPLC method for the simultaneous determination of methimazole and selected metabolites in fish homogenates.
A simple and rapid high-performance liquid chromatography method with ultraviolet detection was developed for the determination of the thyreostatic compound methimazole (1-methyl-2-mercaptoimidazole, MET) and metabolites 2-mercaptoimidazol (SHMET), N-methylthiourea (MTU) and N-methylhydantoin (MEH) from zebrafish (D. rerio) whole body homogenates using mixed mode solid phase extraction technique for sample pre-treatment. The highly polar compounds were separated on a difunctionally bonded silica based reverse phase column using gradient elution. Retention factors ranged between 1.53 and 5.66. The method was linear between 0.1 and 30 microg/ml, the detection limits were 0.4 ng for MET and SHMET, 0.6 ng for MTU and 2.6 ng for MEH. Extraction method was exhibited average recovery rates of 85.2-97.6%.


Arsenic availability, toxicity and direct role of GSH and phytochelatins in As detoxification in the green alga Stichococcus bacillaris.
Accumulation and toxicity of inorganic arsenic forms As(III) and As(V) to the green microalga Stichococcus bacillaris depended on environmental variables. pH of exposure and to a lesser extent elevated concentrations of humic acid, chloride and orthophosphate ions affected arsenic accumulation and its toxicity. As(V) was more toxic than As(III), especially at the near neutral pH 6.8. Intracellular As(V) uptake by algal cells was greater at pH 6.8 than at 8.2. In response to As(III) and As(V) the alga produced phytochelatins (PC(2-3)), but at As(V) exposure, their levels in cells were higher than with As(III), suggesting higher As(V) than As(III) availability and uptake. Arsenic in algal cells occurred in various complexes with non-protein SH groups. Some of these complexes dissociated under acidic conditions, but others were able to dissociate only at an alkaline pH. The former consisted of SH groups of phytochelatins. Those dissociating at an alkaline pH involved SH groups from both glutathione (GSH) and phytochelatins (PC) or their derivatives. In the predominant acid-stable mixed As-SH complex, the ratio of SH (PC(2)) to SH (GSH) was 2:1, which suggests that one molecule of PC(2) (containing two SH groups) together with one molecule of GSH were involved in intracellular complexation of each As atom. This is the first demonstration of GSH involvement in arsenic complexation, in vivo. The intracellular concentration of As was greater than that of non-protein SH groups which suggests that not all the arsenic in algal cells was complexed and detoxified by thiol groups.


Advances in Nitric Oxide Signalling and Metabolism in Plants.
More than 15,000 scientific articles published since the late 1950s related to RNS action or detection in various plant materials are listed in the Web of Science database [...].


Role of adhesion molecules and inflammation in Venezuelan equine encephalitis virus infected mouse brain.
Neuroinvasion of Venezuelan equine encephalitis virus (VEEV) and subsequent initiation of inflammation in the brain plays a crucial role in the outcome of VEEV infection in mice. Adhesion molecules expressed on microvascular endothelial cells in the brain have been implicated in the modulation of the blood brain barrier (BBB) and inflammation in brain but their role in VEEV pathogenesis is not very well understood. In this study, we evaluated the expression of extracellular matrix and adhesion molecules genes in the brain of VEEV infected mice. Several cell to cell adhesion molecules and extracellular matrix protein genes such as ICAM-1, VCAM-1, CD44, Cadherins, integrins, MMPs and Timp1 were differentially regulated post-VEEV infection. ICAM-1 knock-out (IKO) mice infected with VEEV had markedly reduced inflammation in the brain and demonstrated a delay in the onset of clinical symptoms of disease. A differential regulation of inflammatory genes was observed in the IKO mice brain compared to their WT counterparts. These results improve our present understanding of VEEV induced inflammation in mouse brain.


Design, synthesis and cytotoxic activities of novel β-amino alcohol derivatives.
Three series of novel β-amino alcohols possessing an N-anthranyl group have been obtained using tryptophan as the major starting material. These compounds were screened for cytotoxic activity against five human cancer cell lines in vitro by MTT assay, and some of them exhibited potential ability to be anticancer agents. Structure-activity relationship was carefully investigated. Only the compounds possessing small substituents (H or CH(3)) at C-6 position showed the same activity as cisplatin (DDP) did.


DUSP16 promotes cancer chemoresistance through regulation of mitochondria-mediated cell death.
Drug resistance is a major obstacle to the treatment of most human tumors. In this study, we find that dual-specificity phosphatase 16 (DUSP16) regulates resistance to chemotherapy in nasopharyngeal carcinoma, colorectal cancer, gastric and breast cancer. Cancer cells expressing higher DUSP16 are intrinsically more resistant to chemotherapy-induced cell death than cells with lower DUSP16 expression. Overexpression of DUSP16 in cancer cells leads to increased resistance to cell death upon chemotherapy treatment. In contrast, knockdown of DUSP16 in cancer cells increases their sensitivity to treatment. Mechanistically, DUSP16 inhibits JNK and p38 activation, thereby reducing BAX accumulation in mitochondria to reduce apoptosis. Analysis of patient survival in head & neck cancer and breast cancer patient cohorts supports DUSP16 as a marker for sensitivity to chemotherapy and therapeutic outcome. This study therefore identifies DUSP16 as a prognostic marker for the efficacy of chemotherapy, and as a therapeutic target for overcoming chemoresistance in cancer.


Distal pancreatectomy with celiac artery resection acquires satisfactory survival for locally advanced pancreatic neck/body cancer.
s As a curative surgical procedure for pancreatic neck-body cancer with invasion to celiac artery (CA), the security and efficacy of distal pancreatectomy (DP) with en bloc resection of the celiac artery (DP-CAR) remain controversial. The purpose of this study was to identify the postoperative outcomes of DP-CAR. A retrospectively analysis between January 2010 and January2019 was performed in a single center. 21 patients who underwent DP-CAR and 71 patients who underwent traditional DP for pancreatic neck-body cancer were included. Postoperative morbidity, mortality, overall survival (OS) and disease-free survival (DFS) were evaluated. There were no significant differences in major complications and mortality between two groups. The patients in DP-CAR group had more T4 tumor (61.9 vs 7.0%, P < 0.001). DP-CAR group had similar R0 resection compared with DP group (71.4% vs 87.3%, P = 0.090). The patients in DP-CAR group suffered more gastric ulcer, DGE and elevated levels of postoperative hepatic enzymes. OS (27.4 vs 32.6 months) and DFS (14.9 vs 19.5 months) between DP-CAR and DP groups were comparative (P = 0.305; P = 0.065). For the patients who had pancreatic neck-body cancer with invasion to CA, DP-CAR is safety and could achieve satisfactory R0 resection, OS, and DFS.


Beneficial effect of taurine on testicular ischemia-reperfusion injury in rats.
To evaluate the effect of taurine, a potent antioxidant, on testicular ischemia-reperfusion injury due to excess reactive oxygen species produced by neutrophils after testicular torsion-detorsion. A total of 60 adult male Sprague-Dawley rats were randomly divided into three groups, each containing 20 rats. The control group underwent a sham operation of the left testis. In the torsion-detorsion group, the left testis was rotated 720 degrees counterclockwise for 2 hours. The treatment group underwent the same surgical procedure as the torsion-detorsion group, but taurine was administered intravenously at repair of the testicular torsion. One half of the rats in each group underwent orchiectomy 4 hours after detorsion for measurement of myeloperoxidase activity, an indicator of neutrophil accumulation in the testis, and for evaluation of tissue malondialdehyde, an indicator of intratesticular reactive oxygen species content. The remainder were killed at orchiectomy 3 months after detorsion for analysis of testicular spermatogenesis. Unilateral testicular torsion-detorsion caused a significant increase in myeloperoxidase activity and the malondialdehyde level and a significant decrease in testicular spermatogenesis in the ipsilateral testes. The decrease in ipsilateral testicular spermatogenesis involved a reduction in testicular weight, mean seminiferous tubular diameter, number of germ cell layers, and mean testicular biopsy score. The rats treated with taurine had a significant decrease in myeloperoxidase activity and malondialdehyde level and a significant increase in testicular spermatogenesis in the ipsilateral testes compared with the torsion-detorsion group. The results of our study have shown that the administration of taurine exerts a beneficial effect on testicular ischemia-reperfusion injury. This effect might be partly the result of a reduction in reactive oxygen species generation by diminishing neutrophil recruitment to the testis.


Clinical risk models for preterm birth less than 28 weeks and less than 32 weeks of gestation using a large retrospective cohort.
To develop risk prediction models for singleton preterm birth (PTB) < 28 weeks and <32 weeks. Using a retrospective cohort of 267,226 singleton births in Ontario hospitals, we included variables from the first and second trimester in multivariable logistic regression models to predict overall and spontaneous PTB < 28 weeks and <32 weeks. During the first trimester, the area under the curve (AUC) for prediction of PTB < 28 weeks for nulliparous and multiparous women was 68.5% (95% CI: 63.5-73.6%) and 73.4% (68.6-78.2%), respectively, while for PTB < 32 weeks it was 68.9% (65.5-72.3%) and 75.5% (72.3-78.7%), respectively. AUCs for second-trimester models were 72.4% (95% CI: 69.7-75.1%) and 78.2% (95% CI: 75.8-80.5%), respectively, in nulliparous and multiparous women. Predicted probabilities were well-calibrated within a wide range around expected base prevalence for the study outcomes. Our prediction models generated acceptable AUCs for PTB < 28 weeks and <32 weeks with good calibration during the first and second trimester.


Plasminogen activator inhibitor in plasma is related to testosterone in men.
Low plasma testosterone and high levels of the rapid inhibitor of plasminogen activator (PA-I) have been proposed as risk factors for myocardial infarction. In this study, the relationship between testosterone and PA-I activity levels in middle-aged men without thrombotic antecedent was investigated. In 54 normogonadic men (testosterone, 7.3 to 29.1 nmol/L), PA-I was related positively to body mass index (BMI) and triglycerides and negatively to testosterone. When these variables were controlled, the relation between PA-I and testosterone remained significant (P less than .01). In the 41 normogonadic men with BMI less than 25, testosterone was the only variable to influence PA-I. Fibrinolytic activity was evaluated by the euglobulin lysis plate method and the specific measurement of functional tissue plasminogen activator. The basal fibrinolytic activity and the response to venous occlusion were essentially controlled by PA-I but were not significantly related to testosterone. In 17 men with severe hypogonadotrophinic hypogonadism (testosterone less than 3 nmol/L), PA-I was significantly increased (18.5 +/- 1.8 AU/mL, mean +/- SE) compared with 9.5 +/- 0.8 AU/mL in 41 normogonadic men of normal weight (P less than .001). However, 14 hypogonadic men had a hypertriglyceridemia or a BMI greater than 25, which could explain high PA-I levels. This study shows that the level of the inhibitor of plasminogen activator is partly dependent on hormonal status in men and provides a link between independently established epidemiologic data.


Properties of Saccharomyces cerevisiae wee1 and its differential regulation of p34CDC28 in response to G1 and G2 cyclins.
Wee1 is a protein kinase that negatively regulates p34cdc2 kinase activity. We have identified a Saccharomyces cerevisiae wee1 homolog encoded by the SWE1 gene. SWE1 overexpression arrests cells in G2 with short spindles whereas deletion of SWE1 did not alter the cell cycle but did eliminate the G2 delay observed in mih1- mutants. Swe1 immunoprecipitates were capable of tyrosine phosphorylating and inactivating p34CDC28 complexed with Clb2, a G2-type cyclin, but not p34CDC28 complexed with Cln2, a G1-type cyclin, consistent with the inability of Swe1 overexpression to inhibit the G1/S transition. These results suggest that specific cyclin subunits target p34CDC28 for distinct regulatory controls which may be important for ensuring proper p34CDC28 function during the cell cycle.


Traceless splicing enabled by substrate-induced activation of the Nostoc punctiforme Npu DnaE intein after mutation of a catalytic cysteine to serine.
Inteins self-catalytically cleave out of precursor proteins while ligating the surrounding extein fragments with a native peptide bond. Much attention has been lavished on these molecular marvels with the hope of understanding and harnessing their chemistry for novel biochemical transformations including coupling peptides from synthetic or biological origins and controlling protein function. Despite an abundance of powerful applications, the use of inteins is still hampered by limitations in our understanding of their specificity (defined as flanking sequences that permit splicing) and the challenge of inserting inteins into target proteins. We examined the frequently used Nostoc punctiforme Npu DnaE intein after the C-extein cysteine nucleophile (Cys+1) was mutated to serine or threonine. Previous studies demonstrated reduced rates and/or splicing yields with the Npu DnaE intein after mutation of Cys+1 to Ser+1. In this study, genetic selection identified extein sequences with Ser+1 that enabled the Npu DnaE intein to splice with only a 5-fold reduction in rate compared to the wild-type Cys+1 intein and without mutation of the intein itself to activate Ser+1 as a nucleophile. Three different proteins spliced efficiently after insertion of the intein flanked by the selected sequences. We then used this selected specificity to achieve traceless splicing in a targeted enzyme at a location predicted by primary sequence similarity to only the selected C-extein sequence. This study highlights the latent catalytic potential of the Npu DnaE intein to splice with an alternative nucleophile and enables broader intein utility by increasing insertion site choices.


Pollination: Influencing bee behaviour with caffeine.
Plant secondary metabolites found in floral nectar can affect the behaviour of pollinating insects, but how these changes benefit plants directly is little understood. An experimental study with bumblebees shows that recalling a caffeine-enhanced odour memory can increase flower visitation.


The influence of α-Al2O3 addition on microstructure, mechanical and formaldehyde adsorption properties of fly ash-based geopolymer products.
Fly ash-based geopolymer with α-Al(2)O(3) addition were synthesized and used to remove formaldehyde from indoor air. The microstructure, mechanical and formaldehyde adsorption properties of the geopolymer products obtained were investigated. The results showed that α-Al(2)O(3) addition with appropriate amount (such as 5 wt%) increased the geopolymerization extent, resulting in the increase of surface area and compressive strength. In addition, the improvement of structural ordering level for geopolymer sample with 5 wt% α-Al(2)O(3) addition was found through FTIR analysis. By contrast, excessive addition (such as 10 wt%) had the opposite effect. The test of formaldehyde adsorption capacity confirmed that fly ash-based geopolymer product exhibited much better property of adsorbing indoor formaldehyde physically and chemically than fly ash itself. The surface area was an important but not unique factor influencing the adsorption capacity of geopolymers.


From Psychologische Forschung to psychological research: a rough journey through a century.
Psychologische Forschung started as a journal "für Psychologie und ihre Grenzgebiete" and became strongly associated with the Berlin school of Gestalt psychology. Parallel to the fate of that school, the Journal was discontinued after 1938 and re-appeared only 1949. A number of years with variable and broad editorial boards and without a clear profile followed. In 1974 the Journal switched to English as the first German psychology journal and became Psychological Research. Gradually and without any abrupt changes-as indicated e.g. by analyses of citing and cited journals-the current profile as "An International Journal of Perception, Attention, Memory, and Action" was developed. During the last one to two decades the number of papers, the number of contributing countries, and the impact increase.


Amino acid profile and protein quality in tuber and leaf of Coccnia abyssinica (Lam.) (Cogn.) accessions of Ethiopia.
The protein content and amino acid profile of Anchote (Coccinia abyssinica) leaves and tubers were determined from ten different accessions taken from Debre Zeit Agricultural Research Center, Ethiopia. Crude protein content was determined by Kjeldahl method and amino acid profile was analyzed using performic acid oxidation and acid hydrolysis by ninhydrin-derivatized analysis with amino acid analyzer. Crude protein content of Anchote tuber ranged from 10.70% ± 0.26% to 13.72% ± 0.10%, whereas the crude protein content in leaves were ranged between 30.38 ± 0.01% ("240407-1") and 35.42 ± 0.05% ("223109-1"). Total amino acid content ranged from 45.12 to 62.89 and 67.31 to 75.69 g/100 g protein for tuber and leaf samples, respectively. The mean values of essential, conditionally essential and nonessential amino acids were 37.22 & 36.79%; 28.62 & 24.10%; and 34.16 & 39.11% for tubers and leaves, respectively. Arginine in tubers and glutamic acid in leaves ranked the highest of all amino acids; while the least dominant essential amino acid was methionine in both parts. Among the essential amino acids, leucine was dominant in all accessions tested with values ranged from 3.12 to 5.32 g/100 g protein in tubers and from 5.15 to 5.65 g/100 g protein in leaves. In general, the average amino acid content was higher in the leaves (71.08 g/100 g protein) compared to the tubers (51.11 g/100 g protein). The nutritional quality of Coccinia abyssinica leaves and tubers range as follows: total essential amino acids (TEAA)/ total amino acids (TAA) (37.57 & 36.82%), TEAA/total non-essential amino acids (TNEAA) ratio (0.60 & 0.58), The predicted protein efficiency ratio (P-PER) (1.22 & 1.80), Essential amino acid index (EAAI) (35.28 & 53.93%), Predicted biological value (P-BV) (26.76 & 47.09%), Nutritional index (4.11 & 17.71%), and Amino acid score (73 & 108) for tuber and leaf sample, respectively. A significant variability was observed in protein and amino acid profile among accessions and plant parts, and the leaf part were found to be richer in protein content and associated nutritional quality.


Key considerations in the design of real-world studies.
Randomized controlled clinical trials (RCTs) are the gold standard for evaluating the safety and efficacy of pharmaceutical drugs, but in many cases their costs, duration, limited generalizability, and ethical or technical feasibility have caused some to look for real-world studies as alternatives. However, real-world studies may be less convincing due to the lack of randomization and blinding. In this article, we discuss some key considerations in the design of real-world studies, which include experimental studies (e.g., hybrid or pragmatic clinical trials and non-randomized single-arm clinical trials with external controls) and non-experimental studies (e.g., cohort studies, cross-sectional studies, and case-control studies). Causal inference plays a critical role in the derivation of robust real-world evidence (RWE) from the analysis of real-world data (RWD). Therefore, we apply the hypothetical strategy, along with the concept of potential outcome, to lay out these key considerations, and we hope these considerations are helpful for the design, conduct, and analysis of real-world studies.


An Evolutionary Perspective on the Impact of Genomic Copy Number Variation on Human Health.
Copy number variants (CNVs), deletions and duplications of segments of DNA, account for at least five times more variable base pairs in humans than single-nucleotide variants. Several common CNVs were shown to change coding and regulatory sequences and thus dramatically affect adaptive phenotypes involving immunity, perception, metabolism, skin structure, among others. Some of these CNVs were also associated with susceptibility to cancer, infection, and metabolic disorders. These observations raise the possibility that CNVs are a primary contributor to human phenotypic variation and consequently evolve under selective pressures. Indeed, locus-specific haplotype-level analyses revealed signatures of natural selection on several CNVs. However, more traditional tests of selection which are often applied to single-nucleotide variation often have diminished statistical power when applied to CNVs because they often do not show strong linkage disequilibrium with nearby variants. Recombination-based formation mechanisms of CNVs lead to frequent recurrence and gene conversion events, breaking the linkage disequilibrium involving CNVs. Similar methodological challenges also prevent routine genome-wide association studies to adequately investigate the impact of CNVs on heritable human disease. Thus, we argue that the full relevance of CNVs to human health and evolution is yet to be elucidated. We further argue that a holistic investigation of formation mechanisms within an evolutionary framework would provide a powerful framework to understand the functional and biomedical impact of CNVs. In this paper, we review several cases where studies reveal diverse evolutionary histories and unexpected functional consequences of CNVs. We hope that this review will encourage further work on CNVs by both evolutionary and medical geneticists.


School demands and subjective health complaints among Swedish schoolchildren: a multilevel study.
As children spend a great deal of their time in school, the climate in the classroom can constitute a resource, but also a risk factor in the development of the pupils' health. The aim of the present study was to determine the extent to which demands in the classroom are associated with subjective health complaints in Swedish schoolchildren. Data from the 2001/2002 and 2005/2006 Swedish cross-national Health Behaviour in School-aged Children (HBSC) survey were analysed using a multilevel logistic regression technique. The study demonstrated a substantial variation between school classes in pupils' subjective health complaints. In school classes with high demands, the odds of having subjective health complaints was about 50% higher than in school classes with low demands. Further, the results indicated that these effects were mediated by sex so as to girls being more affected by high levels of demands in the school class. The findings are important since they point at the crucial role that teachers play in creating a favourable school climate. Therefore interventions aiming at supporting teachers to set realistic demands and expectations are one way to improve the school climate. Such interventions should also make clear the need to take into consideration the fact that the school class effect was mediated by sex, i.e. girls being more vulnerable to high level of school class demands.


Pharmacokinetic properties and bioavailability of methimazole.
The pharmacokinetics of methimazole following therapeutic doses were studied in healthy subjects, in thyrotoxic and hypothyroid patients before and after treatment to euthyroidism, and in patients with renal or hepatic insufficiency, using a highly sensitive gas chromatographic-mass spectrometric assay. Following intravenous administration of 10mg to healthy subjects, methimazole had an initial distribution half-life (t1/2 alpha) of 0.10 to 0.23 hours and an elimination half-life (t1/2 beta) of 4.9 to 5.7 hours. The absolute bioavailability after oral administration of 10mg methimazole in the fasting state was high, with a mean of 93%. The pharmacokinetic profiles showed small interindividual variations, although one of the hypothyroid patients had a rapid elimination half-life, in both the hypothyroid and euthyroid state (2.6 and 2.4 hours, respectively). The elimination rate was not enhanced in the thyrotoxic patients but was slightly prolonged in the hypothyroid patients. There was no influence of renal insufficiency, but a prolonged elimination half-life was observed in patients with hepatic failure, the prolongation being proportional to the degree of impairment. Thus, the pharmacokinetics of methimazole are relatively simple with small interindividual variations. In general, there are no pharmacokinetic reasons to adjust dosage in the treatment of thyrotoxicosis, except in the rare case of concomitant advanced hepatic insufficiency.


Association between obesity and chronic obstructive pulmonary disease in Moroccan adults: Evidence from the BOLD study.
The Moroccan cross-sectional study aimed to investigate obesity in association to chronic obstructive pulmonary disease in Fez city. A cross-sectional survey was carried out in Moroccan adults. Anthropometric and spirometry measurements were performed using standardized guidelines. Among the 744 participants, 53.9% of were women, with a mean age of 55.27 years (SD = 10.29). Nearly all women declared themselves to be never smokers, while 21% of men were current smokers. Overall, chronic obstructive pulmonary disease prevalence decreased with body mass index (p = 0.01) and waist circumference (p < 0.001). The same trends were also observed in women. The adjusted regression analysis showed a significant independent association between chronic obstructive pulmonary disease and decreasing overweight (ORa: 0.66; CI95% (0.40-0.98)), obesity (ORa: 0.66 CI95%: (0.36-0.89)), and a decreasing waist circumference-abdominal obesity (ORa: 0.58 CI95%: (0.34-0.99)) in the whole population. The same association remains significant in women for overweight (ORa: 0.18 CI95%: (0.06-0.54)) and for waist circumference-abdominal obesity (ORa: 0.40 CI95%: (0.19-0.85)). All these associations disappeared for men. Chronic obstructive pulmonary disease decreases with the increase in body mass index and waist circumference. The effect of waist circumference on the chronic obstructive pulmonary disease was greater among women, regardless of the tobacco factor. A multicenter study would help to confirm the accuracy of these findings in a larger sample of the Moroccan population. Developed lifestyle programs in patients with chronic obstructive pulmonary disease should be considered.


Induction of metallothionein in the Reuber H-35 rat hepatoma cell.
The feasibility of using the Reuber H-35 rat hepatoma cell (RH-35 cells) as model for studying metallothionein induction was examined. The RH-35 cells were treated with Cd, a toxic metal which is known to induce metallothionein. The LC50 after a 3-h treatment was 70 microM. The value was significantly higher (P < 0.05) if the cells were pre-treated with a sublethal dose of CdCl2 (5 microM) for 2 days, indicating that pre-treatment with a low dose of Cd can protect against a subsequent higher dose of the same metal. Both the mRNA and the gene product metallothionein can be identified in the cells 2 days after treatment with 5 microM Cd. In addition to Cd, Zn and Cu were also able to induce the expression of metallothionein to various degrees. The results indicate that the MT gene is present in RH-35 cells and is responsive to treatment with various metals. Thus, this cell line can be used as a model to study metallothionein induction.


Sex-Dependent Effects of Nephron Ift88 Disruption on BP, Renal Function, and Cystogenesis.
Primary cilia regulation of renal function and BP in health and disease is incompletely understood. This study investigated the effect of nephron ciliary loss on renal physiology, BP, and ensuing cystogenesis. Mice underwent doxycycline (DOX)-inducible nephron-specific knockout (KO) of the Ift88 gene at 2 months of age using a Cre-LoxP strategy. BP, kidney function, and renal pathology were studied 2 and 9 months after DOX (Ift88 KO) or vehicle (control). At 2 months post-DOX, male, but not female, Ift88 KO, compared with sex-matched control, mice had reduced BP, enhanced salt-induced natriuresis, increased urinary nitrite and nitrate (NOx) excretion, and increased kidney NOS3 levels, which localized to the outer medulla; the reductions in BP in male mice were prevented by L-NAME. At 9 months post-DOX, male, but not female, Ift88 KO mice had polycystic kidneys, elevated BP, and reduced urinary NOx excretion. No differences were observed in plasma renin concentration, plasma aldosterone, urine vasopressin, or urine PGE2 between Ift88 KO and control mice at 2 or 9 months post-DOX. Nephron cilia disruption in male, but not female, mice (1) reduces BP prior to cyst formation, (2) increases NOx production that may account for the lower BP prior to cyst formation, and (3) induces polycystic kidneys that are associated with hypertension and reduced renal NO production.


Impaired Cellular Immune Responses During the First Week of Severe Acute Influenza Infection.
Cellular immune responses are not well characterized during the initial days of acute symptomatic influenza infection. We developed a prospective cohort of human subjects with confirmed influenza illness of varying severity who presented within a week after symptom onset. We characterized lymphocyte and monocyte populations as well as antigen-specific CD8+ T-cell and B-cell responses from peripheral blood mononuclear cells using flow cytometry and enzyme-linked immunospot assays. We recruited 68 influenza-infected individuals on average 3.5 days after the onset of symptoms. Three patients required mechanical ventilation. Influenza-specific CD8+ T-cell responses expanded before the appearance of plasmablast B cells. However, the influenza-specific CD8+ T-cell response was lower in infected subjects than responses seen in uninfected control subjects. Circulating populations of inflammatory monocytes were increased in most subjects compared with healthy controls. Inflammatory monocytes were significantly reduced in the 3 subjects requiring mechanical ventilation. Inflammatory monocytes were also reduced in a separate validation cohort of mechanically ventilated patients. Antigen-specific CD8+ T cells respond early during acute influenza infection at magnitudes that are lower than responses seen in uninfected individuals. Circulating inflammatory monocytes increase during acute illness and low absolute numbers are associated with very severe disease.


Role of bacterial RNA polymerase gate opening dynamics in DNA loading and antibiotics inhibition elucidated by quasi-Markov State Model.
To initiate transcription, the holoenzyme (RNA polymerase [RNAP] in complex with σ factor) loads the promoter DNA via the flexible loading gate created by the clamp and β-lobe, yet their roles in DNA loading have not been characterized. We used a quasi-Markov State Model (qMSM) built from extensive molecular dynamics simulations to elucidate the dynamics of Thermus aquaticus holoenzyme's gate opening. We showed that during gate opening, β-lobe oscillates four orders of magnitude faster than the clamp, whose opening depends on the Switch 2's structure. Myxopyronin, an antibiotic that binds to Switch 2, was shown to undergo a conformational selection mechanism to inhibit clamp opening. Importantly, we reveal a critical but undiscovered role of β-lobe, whose opening is sufficient for DNA loading even when the clamp is partially closed. These findings open the opportunity for the development of antibiotics targeting β-lobe of RNAP. Finally, we have shown that our qMSMs, which encode non-Markovian dynamics based on the generalized master equation formalism, hold great potential to be widely applied to study biomolecular dynamics.


Three different types of clinical suicide.
A total of 149 inpatients were identified who had committed suicide in two Swiss psychiatric institutions in the years 1960-1981. Using Research Diagnostic Criteria, 49 were diagnosed as schizophrenics, 75 as depressives, and 9 as alcoholics. The first two groups were significantly overrepresented and the third one underrepresented when compared with a control sample. There were considerable differences between the individual diagnostic groups of clinical suicides: schizophrenic suicides were characterized by a disturbed early social adjustment, a high degree of later disability and an unfavorable course of their illness, depressive suicides were much less handicapped, although they presented a much higher long-term suicidal potential, and alcoholic suicides demonstrated no signs of suicidal behavior in the clinic and committed suicide unexpectedly after experiencing negative life events. These findings have therapeutic implications.


Culturally diverse families of young children with ASD in Sweden: Parental explanatory models.
Research suggests that families' knowledge and cultural perceptions of autism spectrum disorder (ASD), and beliefs about its etiology and prognosis, can affect parents' recognition of the first signs of autism in their children and influence help seeking and treatment decisions. This study investigated explanatory models of autism among parents of young children with ASD in the multicultural context of Sweden. Seventeen parents from diverse cultural, ethnic and linguistic backgrounds participated in semi-structured interviews. A deductive approach to qualitative content analysis was used to analyze data. Five domains of the Explanatory Model supplementary module of the Cultural Formulation Interview (CFI) were used as coding categories, operationalized as 'Parents' understanding of autism'; 'Autism prototypes'; 'Causal explanations'; 'Course of autism', and 'Help seeking and treatment expectations'. The results showed that parents' prior knowledge of autism and experience of young children's typical developmental trajectories, as well as the opinions of children's grandparents and preschool teachers, affected symptom recognition and help seeking. There were differences in parents' explanatory models before and after ASD diagnosis. Initial interpretations of the disorder included medical conditions and reaction to environmental influences, while genetic, supernatural/religious factors, and vaccinations were mentioned as definite causes after obtaining a clinical diagnosis. Parents also held multiple explanatory models, influenced by the views of family members and information obtained from media or from health care professionals. Parents' treatment decisions included use of available state-funded support services, and complementary and alternative treatments. The results demonstrate the utility of the CFI's Explanatory Model supplementary module in autism research. Implications for clinical practice are discussed.


A computer-assisted image-processing system for the analysis of autoradiographs of cerebral metabolic activity.
A computerized image-processing system has been developed for quantitative analyses of the autoradiographs obtained with the [14C]deoxyglucose method. By means of this system, these cerebral metabolic images can be digitized and the resultant data can be manipulated for image construction, enhancement, enlargement, and microdensitometric analysis. It is also possible to generate quantitative color-coded metabolic maps that display the distribution of the actual rates of local glucose utilization throughout the entire central nervous system with a resolution conservatively estimated to be equivalent to that of a full-width-half-maximum of approximately 100 micron.


Different expression patterns of Bcl-2, Bcl-xl, and Bax proteins after sublethal forebrain ischemia in C57Black/Crj6 mouse striatum.
Ischemic injury in neurons can be strongly reduced by a preceding sublethal ischemic episode, of which the mechanism is poorly understood. Although changes in the expression of apoptosis-related proteins (Bcl-2, Bcl-xl, and Bax) have been considered to be crucially important in ischemic injury, the roles these proteins play in ischemic preconditioning induced by sublethal forebrain ischemia have not been elucidated. Therefore, we investigated the transcription and expression of Bcl-2, Bcl-xl, and Bax in striatum of mice subjected to sublethal forebrain ischemia and lethal ischemia, with or without ischemic preconditioning. Sublethal forebrain ischemia was induced in C57Black/Crj6 (C57BL/6) mice by 6 minutes of bilateral common carotid artery occlusion. The transcription and expression of Bcl-2 family genes were detected by reverse transcription-polymerase chain reaction, Western blot, and immunofluorescent staining. No detectable neuronal loss was induced in striatum by 6 minutes of bilateral common carotid artery occlusion. Transcription and expression of Bcl-2 and Bcl-xl were increased after sublethal forebrain ischemia, which attenuated the DNA fragmentation induced by lethal ischemia. The transcription and expression of Bax remained unchanged. Upregulation of Bcl-2 and Bcl-xl but not Bax may have a role in protective ischemic preconditioning. This result indicates a potential strategy for further ischemic neuronal injury therapies.


Sensitive voltammetric determination of tyrosine using multi-walled carbon nanotubes/4-aminobenzeresulfonic acid film-coated glassy carbon electrode.
A chemically modified electrode is constructed based on the multi-walled carbon nanotubes (MWNTs)/4-aminobenzeresulfonic acid (4-ABSA) film-coated glassy carbon electrode. The electrocatalytic oxidation of tyrosine (Tyr) is investigated on the surface of the MWNTs/4-ABSA-modified electrode using cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The prepared modified electrode shows voltammetric responses with high sensitivity and selectivity for Tyr in optimal conditions, which makes it very suitable for sub-micromolar detection of Tyr. A sensitive oxidation peak at +0.64 V is employed to determine Tyr. Good linear relationship between the oxidation peak current and the Tyr concentration in the range of 1x10(-7) to 5x10(-5) mol/L is obtained in phosphate buffer solution with pH 7.0. By use of modified electrode, the voltammetric detection limit for Tyr in DPV measurements is 8x10(-8) mol/L (S/N=3). Good sensitivity, selectivity and stability of the low-cost modified electrode make it very suitable for the determination of trace amounts of Tyr in pharmaceutical and clinical preparations.


Computational protein design: Advances in the design and redesign of biomolecular nanostructures.
Computational protein design facilitates the continued development of methods for the design of biomolecular structure, sequence and function. Recent applications include the design of novel protein sequences and structures, proteins incorporating nonbiological components, protein assemblies, soluble variants of membrane proteins, and proteins that modulate membrane function.


[Relationship between perioperative anxiety and postoperative recovery].
One day before surgery and three days postoperatively, 118 cholecystectomy patients were investigated by means of several self-report anxiety-question(naire)s. On the basis of these, the patients were assigned to either the category more anxious postoperatively (A+) or the category less anxious postoperatively (A-). A+ patients rated preoperatively lower and postoperatively higher on the anxiety-question(naire)s than A- patients, and they stayed longer in hospital postoperatively.


Association of Cardiovascular Disease Risk Factors with Late Cardiotoxicity and Survival in HER2-positive Breast Cancer Survivors.
Breast cancer and cardiovascular (CV) diseases often share the same risk factors. It is increasingly important to identify risk factors for CV events in patients with high-risk breast cancer and explore optimal treatment regimens. Early HER2-positive breast cancer patients at our institution between January 1998 and October 2009 were reviewed. Primary outcome was late-severe-CV-event-free survival, and late severe CV events were defined as cardiovascular death, cardiomyopathy, symptomatic heart failure, and myocardial infarction developing 2+ years after breast cancer diagnosis. Kaplan-Meier plots, Cox proportional hazard regressions, and restricted mean survival time were used to evaluate outcomes. We identified 2,448 consecutive eligible patients with a median follow-up time of 111.0 months (interquartile range, 52.0-151.8 months). One hundred and thirty-six patients had late severe CV events and 752 died of any cause [533 (70.9%) died of primary breast cancer; 12 (1.6%) died of cardiovascular disease]. Hypertension [HR, 1.546; 95% confidence interval (95% CI), 1.030-2.320; P = 0.036] and history of coronary artery disease (CAD; HR, 3.333; 95% CI, 1.669-6.656; P < 0.001) were associated with worse late-severe-CV-event-free survival. Anthracycline-containing regimens (HR, 1.536; 95% CI, 0.979-2.411; P = 0.062) was not a significant risk factor for CV events in multivariate analysis. Regimens containing both anthracycline and anti-HER2 therapy were prognostic for better OS (HR, 0.515; 95% CI, 0.412-0.643; P < 0.001). Hypertension and CAD history were independent prognostic factors for late severe CV events. Adding anti-HER2 agents to anthracycline-containing regimens did not substantially increase the risk for late severe cardiotoxicity and conferred better overall survival.


Benchmarking mechanical ventilation services in teaching hospitals.
The purpose of this investigation was to examine the technical efficiency of mechanical ventilation nonsurgery (DRG 475) among University Hospital Consortium (UHC) hospitals that consists of volunteer, teaching hospitals across the nation. The data for this study was retrieved from the 1997 UHC database that includes charge and discharge information for 69 hospitals. Data on 7961 patients classified with mechanical ventilation were aggregated to the hospital level. We retained data from a total of 62 hospitals, the other seven hospitals had missing data. The research questions were (1) Do UHC hospitals differ significantly in their efficiencies in the treatment of mechanically ventilated patients? (2) What inputs and outputs contribute most to the inefficiencies associated with mechanical ventilation? Of the 62 hospitals analyzed using data envelopment analysis technique, 10 were considered efficient and 52 were inefficient as compared to their benchmark peers. Efficient and inefficient hospitals did significantly differ between the transferred output variable and between the respiratory, laboratory, and radiology input variables. All inputs demonstrated excessive resource utilization among inefficient hospitals as compared to efficient hospitals. A total reduction of about $19 million dollars in ancillary services would need to occur for inefficient hospitals to approach the frontier of efficient hospitals. This study demonstrates that mechanical ventilation is costly, yet the specified ancillary services are capable of being reduced yielding technical efficiency as demonstrated by 10 efficient hospitals.


Developmental stability in Brassica cretica: the effect of crossing distance on fluctuating asymmetry in cotyledon morphology.
In the present investigation of Brassica cretica, a wild relative of the cultivated cabbage, B. oleracea, we performed an extensive crossing experiment, involving self-pollinations, random outcrosses within populations and hybridizations between populations or species, to evaluate the relationship between crossing distance and developmental stability, estimated as the absolute difference between the right and left lobe of the cotyledons. The frequency distribution of the right-minus-left scores had a narrower peak than expected for normally-distributed data, but there was no directional asymmetry or antisymmetry. Despite evidence for inbreeding depression in seedling biomass and cotyledon size, the type of cross had negligible influence on cotyledon asymmetry. Separate analyses of between-population hybrids revealed differences among progenies from different pairs of populations and a tendency for the F1 hybrid means to decrease with the geographic distance separating the parent populations, but only for the two size variables. Based on these and other observations, we propose that the degree of cotyledon asymmetry is unrelated to genome-wide characteristics, such as the level of heterozygosity and genomic co-adaptation, and that cotyledon asymmetry is unrelated to the level of genetic stress experienced by each individual. Hence, there is no reason to consider measures of asymmetry as more sensitive indicators of genetic health than conventional fitness variables.


Psychosocial outcomes of e-feedback of radiotherapy for breast cancer patients: a randomized controlled trial.
This study aims to test the effectiveness on psychosocial outcomes of electronic feedback knowledge of radiotherapy intervention (e-Re-Know) for breast cancer patients. Randomized controlled trial in one university hospital in Finland was carried out. Breast cancer patients (n = 126) in the radiotherapy (RT) department were randomly assigned into two groups: intervention (the e-Re-Know and standard education) and control group (standard education). The e-Re-Know intervention consisted of e-feedback after response to the knowledge test delivered by e-mail. Instruments were completed before commencing first RT (M1), after concluding last RT (M2) and 3 months after last RT (M3). The main outcomes were anxiety and QOL. Compared with the control group, the patients in the intervention group reported a marginally significant improvement in anxiety and significant improvement in QOL over time. The e-Re-Know seems to have positive effects on psychosocial outcomes for breast cancer patients. They might gain additional value from the e-Re-Know over a longer time period. Further research needs to focus more on development of e-feedback in patient education.


Estimation from current-status data in continuous time.
The nonparametric maximum likelihood estimator for current-status data has been known for at least 40 years, but only recently have the mathematical-statistical properties been clarified. This note provides a case study in the important and often studied context of estimating age-specific immunization intensities from a seroprevalence survey. Fully parametric and spline-based alternatives (also based on continuous-time models) are given. The basic reproduction number R0 exemplifies estimation of a functional. The limitations implied by the necessarily rather restrictive epidemiological assumptions are briefly discussed.


Feasibility of magnetic nano adsorbent impregnated with activated carbon from animal bone waste: Application for the chromium (VI) removal.
Chromium is the heavy metal which existing in the effluents cause extensive discomfort to the environmental components. Bone waste is widely generated in food processing industries and restaurants. It is now used by switching into activated carbon. By co-precipitation procedure, the activated carbon is coated with a nano adsorbent. The Fe3O4-BAC adsorbent potential was established in this study via several batch tests. The adsorbing adverts had super magnetic behavior, and the magnetization value was 22 emu/g. The SEM imaging of the Fe3O4-BAC shows an improved morphology of 100-446 nm, and the nanoparticles were monodispersed. The present investigation also delves into the study of system parameters on the removal of metal ions. Optimal adsorption has been found at the acidic pH at the contact time of 60min for the adsorbent amount of 5 g/L. Maximum capacity of adsorption by nano adsorbent was 27.86 mg/g. Thermodynamic and isotherm tests have established the process viability. In addition, the kinetic studies establish the inclination of the studied Fe3O4-BAC towards pseudo-first order models. Hence, Fe3O4-BAC could be potential adsorbent to remove chromium from an aqueous solution.


Stroke Risk Related to Coronavirus Disease-2019: What Have We Learned?
Since the intial outbreak of the coronavirus-2019 (COVID-19) in December 2019, a variety of neurologic manifestations have been linked to this virus, including stroke. Comprehensive review of worldwide studies using various methodologies indicated a correlation of increased stroke risk in patients with COVID-19. The literature reivew also revealed increased morbidity and mortality among patients with COVID-19 and stroke as compared to those with only stroke. This pandemic, with its related healthcare staffing shortages, revealed the requisite to utilize innovative technologies such as Tele-Neurology, as well as public health campaigns focusing on stroke recognition and early treatment.


Patchy and laminar terminations of medial geniculate axons in monkey auditory cortex.
The object of this study was to identify the terminal distributions of thalamocortical axons arising in chemically characterized subdivisions of the medial geniculate complex. Large injections of wheat germ agglutinin-conjugated horseradish peroxidase or small injections of Phaseolus vulgaris leucoagglutinin were made in the medial geniculate complex of Macaca fuscata. The terminal distributions of labeled axons in the cortex were correlated with auditory cortical fields demonstrable by different intensities of immunoreactivity for parvalbumin. Fibers from the ventral nucleus terminated mainly in layer IV and deep portion of layer III (IIIB), with additional terminations in layers I-IIIA and in layer VI. In layers IIIB-IV, a major terminal plexus was formed by a small number of dense patches, 300-500 microns in diameter, surrounded by smaller satellite patches. The patches conformed to a similarly lobulated pattern of parvalbumin fiber immunoreactivity. Terminations of some individually labeled thalamocortical fibers were restricted to a single patch, whereas others innervated more than one patch by collateral branches. Fibers from the dorsal nuclei ending in areas of less dense parvalbumin immunoreactivity surrounding the primary auditory cortex formed much larger terminal patches centered largely in layer IIIB. Fibers from the magnocellular nucleus had relatively few terminal branches but innervated extremely wide areas by collaterals of single axons. Two types of axons arose from the magnocellular nucleus, one terminating preferentially in middle cortical layers and the other exclusively in layer I. These may arise respectively from parvalbumin- and calbindin-immunoreactive cell populations in the magnocellular nucleus.


Role of shear wave elastography in predicting the metabolic and androgenic alterations in patients with polycystic ovary syndrome.
To evaluate the variation in tissue stiffness caused by the changes in ovarian volume and stroma in polycystic ovary syndrome (PCOS) using a novel method of ultrasonography, that is shear wave elastography (SWE). The current study also aimed to evaluate the potential applications of this method in predicting the metabolic and androgenic alterations in patients with PCOS. The present study included 33 patients with PCOS. The blood samples for the metabolic and androgenic parameters and SWE values pertaining to the patients were obtained on the same day during the early follicular phase. The predictive ability of SWE to reflect the metabolic and androgenic abnormalities was evaluated using the receiver operating characteristic curve (ROC) analysis. The mean SWE value pertaining to the group with higher total testosterone levels was significantly lower, compared to the group with normal testosterone levels (p = 0.041). The ROC analysis revealed that the predictive potential of SWE was statistically significant in regard to the serum testosterone levels alone (area under the curve [AUC] = 0.755, 95% confidence interval [CI]: 0.573-0.938, p = 0.041). There was no significant relationship between the SWE values and metabolic parameters. Based on the results of the present study, decreased SWE values appear to be associated with increased serum testosterone levels. However, the present study did not observe any significant relationship between the SWE values and metabolic parameters. SWE can be used as a practical and non-invasive method to predict the serum testosterone levels during the follow-up evaluations of the patients with PCOS.


The endocannabinoid system modulates stress, emotionality, and inflammation.
The physiological and behavioral effects of stress are well characterized. Endocannabinoids are produced on demand and function to attenuate many of the physiological effects of the stress response. The endocannabinoid system is made up of cannabinoid receptors, the fatty acid signaling molecules that bind to and activate these receptors, and the enzymes that synthesize and catabolize these endocannabinoid signaling molecules. Cannabinoid research has recently grown substantially, due in no small part to the development of genetic research models as well as highly selective pharmaceutical tools. The purpose of this minireview is to discuss a subset of the many parallels between cannabinoid and behavioral neuroimmunology research, with specific discussion of interactions between the endocannabinoid system and psychological stress, emotionality, and inflammation.


The primary structure of hemoglobin D from the Aldabra giant tortoise, Geochelone gigantea.
The complete primary structures of alpha D-2- and beta-globin of hemoglobin D (Hb D) from the Aldabra giant tortoise, Geochelone gigantea, have been constructed by amino acid sequencing analysis in assistance with nucleotide sequencing analysis of PCR fragments amplified using degenerate oligonucleotide primers. Using computer-assisted sequence comparisons, the alpha D-2-globin shared a 92.0% sequence identity versus alpha D-globin of Geochelone carbonaria, a 75.2% versus alpha D-globin of Aves (Rhea americana) and a 62.4% versus alpha A-globin of Hb A expressed in adult red blood cells of Geochelone gigantea. Additionally, judging from their primary structures, an identical beta-globin was common to the two hemoglobin components, Hb A and Hb D. The alpha D-2- and beta-globin genes contained the three-exon and two-intron configurations and showed the characteristic of all functional vertebrate hemoglobin genes except an abnormal GC dinucleotide instead of the invariant GT at the 5' end of the second intron sequence. The introns of alpha D-2-globin gene were both small (224-bp/first intron, 227-bp/second intron) such that they were quite similar to those of adult alpha-type globins; the beta-globin gene has one small intron (approximately 130-bp) and one large intron (approximately 1590-bp). A phylogenetic tree constructed on primary structures of 7 alpha D-globins from Reptilia (4 species of turtles, 2 species of squamates, and 1 species of sphenodontids) and two embryonic alpha-like globins from Aves (Gullus gullus) and Mammals (Homo sapiens) showed the following results: (1) alpha D-globins except those of squamates were clustered, in which Sphenodon punctatus was a closer species to birds than turtles; (2) separation of the alpha A- and alpha D-globin genes occurred approximately 250 million years ago after the embryonic alpha-type globin-genes (pi' and zeta) first split off from the ancestor of alpha-type globin gene family.


The changing landscape of atherosclerosis.
Emerging evidence has spurred a considerable evolution of concepts relating to atherosclerosis, and has called into question many previous notions. Here I review this evidence, and discuss its implications for understanding of atherosclerosis. The risk of developing atherosclerosis is no longer concentrated in Western countries, and it is instead involved in the majority of deaths worldwide. Atherosclerosis now affects younger people, and more women and individuals from a diverse range of ethnic backgrounds, than was formerly the case. The risk factor profile has shifted as levels of low-density lipoprotein (LDL) cholesterol, blood pressure and smoking have decreased. Recent research has challenged the protective effects of high-density lipoprotein, and now focuses on triglyceride-rich lipoproteins in addition to low-density lipoprotein as causal in atherosclerosis. Non-traditional drivers of atherosclerosis-such as disturbed sleep, physical inactivity, the microbiome, air pollution and environmental stress-have also gained attention. Inflammatory pathways and leukocytes link traditional and emerging risk factors alike to the altered behaviour of arterial wall cells. Probing the pathogenesis of atherosclerosis has highlighted the role of the bone marrow: somatic mutations in stem cells can cause clonal haematopoiesis, which represents a previously unrecognized but common and potent age-related contributor to the risk of developing cardiovascular disease. Characterizations of the mechanisms that underpin thrombotic complications of atherosclerosis have evolved beyond the 'vulnerable plaque' concept. These advances in our understanding of the biology of atherosclerosis have opened avenues to therapeutic interventions that promise to improve the prevention and treatment of now-ubiquitous atherosclerotic diseases.


Freshwater fishes maintain multi-trait phenotypic stability across an environmental gradient in aqueous calcium.
Reductions in a limiting nutrient might be expected to necessitate compromises in the functional traits that depend on that nutrient; yet populations existing in locations with low levels of such nutrients often do not show the expected degradation of functional traits. Indeed, logperch (Percina caprodes), pumpkinseed sunfish (Lepomis gibbosus) and yellow perch (Perca flavescens) residing in low-calcium water in the Upper St. Lawrence River were all previously found to maintain levels of scale calcium comparable to those of conspecific populations in high-calcium water. Yet it remains possible that the maintenance of one functional trait (i.e., scale calcium) under nutrient-limited (i.e., low calcium) conditions could come at the expense of maintaining other functional traits that depend on the same nutrient. The present study therefore examines other calcium-dependent traits, specifically skeletal element sizes and bone densities in the same fish species in the same area. Using radiographs of 101 fish from the three species across four locations (two in high-calcium water and two in low-calcium water), this new work documents multi-trait "homeostasis" along the gradient of water calcium. That is, no effect of calcium regime (low-calcium vs. high-calcium) was detected on any of the measured variables. Further, effect sizes for the skeletal traits were very low - lower even than effect sizes previously documented for scale calcium. These results thus show that native fishes maintain phenotypic stability across a suite of functional traits linked to calcium regulation, perhaps pointing to an "organismal-level homeostasis" scenario rather than a "trait-level homeostasis" scenario.


Differential Effects of Whole Red Raspberry Polyphenols and Their Gut Metabolite Urolithin A on Neuroinflammation in BV-2 Microglia.
Whole red raspberry polyphenols (RRW), including ellagic acid, and their gut-derived metabolite, urolithin A (UroA), attenuate inflammation and confer health benefits. Although results from recent studies indicate that polyphenols and UroA also provide neuroprotective effects, these compounds differ in their bioavailability and may, therefore, have unique effects on limiting neuroinflammation. Accordingly, we aimed to compare the neuroprotective effects of RRW and UroA on BV-2 microglia under both 3 h and 12 and 24 h inflammatory conditions. In inflammation induced by lipopolysaccharide (LPS) and ATP stimulation after 3 h, RRW and UroA suppressed pro-inflammatory cytokine gene expression and regulated the JNK/c-Jun signaling pathway. UroA also reduced inducible nitric oxide synthase gene expression and promoted M2 microglial polarization. During inflammatory conditions induced by either 12 or 24 h stimulation with LPS, UroA-but not RRW-dampened pro-inflammatory cytokine gene expression and suppressed JNK/c-Jun signaling. Taken together, these results demonstrate that RRW and its gut-derived metabolite UroA differentially regulate neuroprotective responses in microglia during 3 h versus 12 and 24 h inflammatory conditions.


Nutritional Components of Wheat Based Food: Composition, Properties, and Uses.
Wheats (bread and durum wheats) and their main end-use products (particularly bread and pasta) have an important role in the Mediterranean diet as they substantially contribute to nutrient intake [...].


Combined evaluation of proliferation and apoptosis to calculate IC50 of VPA-induced PANC-1 cells and assessing its effect on the Wnt signaling pathway.
Pancreatic ductal adenocarcinoma (PDAC) is among the most deadly cancers. Since most patients develop resistance to conventional treatments, new approaches are in urgency. Valproic acid (VPA) was shown to induce apoptosis and reduce proliferation in PANC-1 cells. Wnt signaling pathway is known to be involved in apoptosis and PDAC onset. However, VPA-induced apoptosis and its impact on Wnt signaling in PDACs are not linked, yet. We aimed to calculate IC50 of VPA-induced PANC-1 cells by combined analyses of proliferation and apoptosis, while assessing its effect on Wnt signaling pathway. PANC-1 was induced with increased VPA doses and time points. Three independent proliferation and apoptosis assays were performed utilizing carboxyfluorescein succinimidyl ester and Annexin V/PI staining, respectively. Flow cytometry measurements were analyzed by CellQuest and NovoExpress. Taqman hydrolysis probes and SYBR Green PCR Mastermix were assessed in expression analyses of Wnt components utilizing 2-ΔΔCt method. Cell proliferation was inhibited by 50% at 2.5 mM VPA that evoked a significant apoptotic response. Among the screened Wnt components and target genes, only LEF1 exhibited significant four-fold upregulation at this concentration. In conclusion, cancer studies mostly utilize MTT or BrdU assays in estimating cell proliferation and calculating IC50 of drugs, which provided conflicting VPA dosages utilizing PANC-1 cells. Our novel combined approach enabled specific, accurate and reproducible IC50 calculation at single cell basis with no apparent effect on Wnt signaling components. Future studies are needed to clarify the role of LEF1 in this model.


Activity-dependent plasticity of synaptic efficacy at inhibitory junctions.
Despite a considerable amount of investigation on long-term potentiation, the question of whether this process occurs at inhibitory synapses has remained controversial until studies of these junctions have been achieved in the Mauthner cell of Teleosts. In this preparation, inhibitory long-term potentiation similar to that occurring at hippocampal excitatory synapses has been demonstrated.


Expression domains of neuroD (nrd) in the early postembryonic zebrafish brain.
NeuroD acts as one of the earliest transcription factors promoting differentiation in newborn neurons immediately after determination by neurogenin1 (ngn1). Here, we show the expression of neuroD in the 2 days postfertilization (dpf) zebrafish brain by in situ hybridization on sections. Generally, neuroD expressing cells lie one to several cell rows away from the ventricular surface, i.e., they seem to flank proliferative cells. However, most cells of the gray matter lie even more peripheral and are unstained. Highly specific local patterns of neuroD expressing cells are observed along the entire rostrocaudal zebrafish brain axis at that age with characteristic neuroD expression free zones (e.g., preoptic region and hypothalamus). Interestingly, these regions where neuroD expression is absent display a higher proliferative activity compared to neuroD-positive areas. To date it is an open question, whether this negative correlation of neuroD-expression and proliferation has a causal background.


The changing global patterns of female breast cancer incidence and mortality.
One in ten of all new cancers diagnosed worldwide each year is a cancer of the female breast, and it is the most common cancer in women in both developing and developed areas. It is also the principal cause of death from cancer among women globally. We review the descriptive epidemiology of the disease, focusing on some of the key elements of the geographical and temporal variations in incidence and mortality in each world region. The observations are discussed in the context of the numerous aetiological factors, as well as the impact of screening and advances in treatment and disease management in high-resource settings.


Global Publication Trends and Research Hotspots of Revision Hip and Knee Arthroplasty: A 21-Year Bibliometric Approach.
As the number of primary hip and knee arthroplasties increases, revision cases correspondingly demonstrate high relative growth, gaining increasing attention. The present research aimed to investigate subject characteristics in revision hip and knee arthroplasty (RHKA) research using a bibliometric approach. Publications related to RHKA from 2000 to 2020 were searched in the Web of Science database. WPS Office, CiteSpace, VOSviewer, and Bibliometrix were used to analyze the results. Bibliometric analysis revealed 3290 records. Fifty-nine countries published manuscripts on RHKA. The United States contributed most and also had the highest number of international collaborations. The most relevant institution was the Mayo Clinic. Berry DJ and Parvizi J were the most productive and academic influential authors in RHKA, respectively. The most productive journal was the Journal of Arthroplasty. Co-occurrence analysis demonstrated "infection" to be the trend in RHKA. Thematic analysis displayed 16 keywords in hip arthroplasty and 14 keywords in knee arthroplasty. The present study observed an increasing trend of research papers in RHKA. Institutions and scholars from the United States were found to dominate the field. Periprosthetic joint infection was likely a potential development trend and hotspot of RHKA.


Factors that influence infertile couples' selection of reproductive medicine centers---A cross-sectional questionnaire study.
The number of infertile women undergoing in vitro fertilization (IVF) cycles has increased annually. Due to this competitive environment, we designed a questionnaire and aimed to investigate factors affecting the choice of reproductive medicine center among infertile couples. This was a retrospective cross-sectional study that analyzed questionnaires provided by the reproductive medicine center of the Kaohsiung Veterans General Hospital from January 2018 to June 2018. In the questionnaire, there are six categories (environment and equipment, service quality, patient safety, medical quality, information acquisition channel and other) and 36 items. The identified factors were scored and then weighted using principal component analysis. Most of the 100 identified infertile women were aged 31-35 years, were married 1-3 years, and had a university education level. In the weight analysis, "Clean outpatient clinic and medical equipment" had the greatest weight in the dimension of environment and equipment. The item with the greatest weight in the dimension of service quality was "Waiting time for registration, charging, and receiving medicine". In the dimension of patient safety, "Privacy is highly respected by medical personnel" had the highest weight. The item with the greatest weight in the dimension of medical quality was "Success rate of reproductive medicine center". The three items with the highest weights in the dimension of information acquisition channel were "Newspapers and magazines", "TV media", and "Facebook page and website of our hospital". In the other dimensions, the two with the greatest weights were "Reputation of the hospital" and "Reputation of physicians". In the infertile couples' view, optimal reproductive medicine centers should have a high success rate and great reputation on the internet and in mass media. Additionally, a short waiting time and high levels of privacy and confidentiality are also imperative.