Overexpression of SmMYC2 enhances salt resistance in Arabidopsis thaliana and Salvia miltiorrhiza hairy roots.
Soil salinity significantly affects both Salvia miltiorrhiza growth and development as well as seed germination throughout field cultivation and production. The basic helix-loop-helix (bHLH) transcription factor (TF) MYC2 contributes significantly to plant stress resistance as a key regulator of the jasmonic acid signaling pathway. In transgenic S. miltiorrhiza hairy roots, SmMYC2 has been shown to promote the accumulation of tanshinone and salvianolic acid, but its role in S. miltiorrhiza of resistance to abiotic stress is unclear. Herein, we found methyl jasmonate (MeJA), NaCl, and PEG treatment all significantly increased SmMYC2 expression. In response to salt stress, SmMYC2 overexpression in yeast increased its rate of growth. Additionally, overexpression of SmMYC2 transgenic Arabidopsis thaliana and S. miltiorrhiza hairy root showed that it might improve salt resistance in transgenic plant. In particular, compared to WT, overexpression of SmMYC2 transgenic Arabidopsis had higher levels of three antioxidant enzymes (superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT)), proline (Pro) content, and ABA-dependent and ABA-independent genes expression. They also had lower levels of malondialdehyde (MDA) and reactive oxygen species (ROS) accumulation. What's more, overexpression of SmMYC2 increases the expression of flavonoid synthesis genes and the accumulation of related components in Arabidopsis. These findings imply that SmMYC2 functions as a positive regulator that regulates plant tolerance to salt through ABA-dependent and independent signaling pathways.


Functional aspects of evolution in a cluster of salivary protein genes from mosquitoes.
The D7 proteins are highly expressed in the saliva of hematophagous Nematocera and bind biogenic amines and eicosanoid compounds produced by the host during blood feeding. These proteins are encoded by gene clusters expressing forms having one or two odorant-binding protein-like domains. Here we examine functional diversity within the D7 group in the genus Anopheles and make structural comparisons with D7 proteins from culicine mosquitoes in order to understand aspects of D7 functional evolution. Two domain long form (D7L) and one domain short form (D7S) proteins from anopheline and culicine mosquitoes were characterized to determine their ligand selectivity and binding pocket structures. We previously showed that a D7L protein from Anopheles stephensi, of the subgenus Cellia, could bind eicosanoids at a site in its N-terminal domain but could not bind biogenic amines in its C-terminal domain as does a D7L1 ortholog from the culicine species Aedes aegypti, raising the question of whether anopheline D7L proteins had lost their ability to bind biogenic amines. Here we find that D7L from anopheline species belonging to two other subgenera, Nyssorhynchus and Anopheles, can bind biogenic amines and have a structure much like the Ae. aegypti ortholog. The unusual D7L, D7L3, can also bind serotonin in the Cellia species An. gambiae. We also show through structural comparisons with culicine forms that the biogenic amine binding function of single domain D7S proteins in the genus Anopheles may have evolved through gene conversion of structurally similar proteins, which did not have biogenic amine binding capability. Collectively, the data indicate that D7L proteins had a biogenic amine and eicosanoid binding function in the common ancestor of anopheline and culicine mosquitoes, and that the D7S proteins may have acquired a biogenic amine binding function in anophelines through a gene conversion process.


Acute splenic irradiation reduces brain injury in the rat focal ischemic stroke model.
Removing the spleen prior to ischemic stroke abrogates immunologic response to brain injury and reduces cerebral infarction. However, the effectiveness of splenectomy for neuroprotection after stroke has not been established. Moreover, the risks of the surgical splenectomy in stroke patients create a major obstacle to removing the spleen's inflammatory response. We hypothesized that acute splenic irradiation will ablate splenic cells and thereby will diminish stroke progression. Male adult Sprague Dawley rats were subjected to 2-hour middle cerebral artery occlusion (MCAO), then CT scanned for spleen localization and irradiated to the lateral splenic region with 8Gy of Cobalt 60 at 3, 4, 6 or 8 hrs after start of cerebral ischemia. Untreated controls underwent the same procedures except that sham irradiation was applied. At 2 or 7 days after ischemia the rats were euthanized, and brains recovered for the assessment of brain injury and the extent of neuroinflammation. Irradiation at 3 hrs reduced spleen weight and lymphocyte blood levels after stroke. Splenic irradiation at 3 and 4 hrs after start of ischemia significantly reduced cerebral infarction volumes measured at 48 hrs and 7 days, respectively. The histological analysis on day 7 revealed reduced counts of microglia, infiltrating T cells, and apoptotic neurons in the rats irradiated at 4 hrs. The noninvasive single-dose procedure of splenic irradiation performed within a time interval of up to 4 hours offers neuroprotection against ischemic stroke possibly by abrogating deployment of splenic cells to the brain.


Spiritual coping, psychosocial adjustment, and physical health in youth with chronic illness: a meta-analytic review.
The current systematic review and meta-analysis aimed to assess the strength of the relationships between religious/spiritual coping strategies and psychosocial adjustment and physical health in youth with chronic illness. Faced with medical stressors and uncertainty about their illness, spiritual beliefs and behaviours are important for youth with chronic illness. Research suggests that some spiritual coping strategies are helpful (positive), while others are not (negative), and these dimensions of spiritual coping are important predictors of functioning among youth with chronic illness. Fourteen studies, published between 1990 and 2015, met inclusion criteria for the meta-analysis and were analysed using both a fixed effects model and random effects model (REM). Findings revealed significant, small to moderate associations between negative spiritual coping and more concurrent internalising problems (REM r = .34), lower quality of life (REM r = -.34), and poorer health (REM r = -.08). Under the fixed, but not REM, the combined effects showed small to moderate significant relationships between positive spiritual coping and fewer internalising problems (r = -.19) and better physical health (r = .19). The results reveal that spiritual coping is an important coping strategy for paediatric patients. Consistent with findings among adults with chronic illness, negative spiritual coping puts paediatric patients at risk for psychosocial maladjustment and poorer health. Intervention research is needed to determine if targeting spiritual coping improves health and psychosocial well-being.


Development of a semi-open chamber system for the gas exchange measurement of whole-canopy under steady and unsteady states in cucumber seedlings.
Large-scale data on the photosynthetic characteristics of whole crop canopy is crucial for improving yield. However, current data collection methods remain challenging, and the time constraints associated with photosynthetic data collection further complicate matters. Developing a practical yet easy-to-use tool for collecting whole-canopy data is essential to address these challenges. Furthermore, it is necessary to obtain instantaneous measurements of photosynthetic rate over a wide range of CO2 concentrations under an unsteady state to enable faster data collection and obtain reliable biochemical limits of carbon assimilation. This study developed a semi-open chamber system with steady and unsteady state measurement techniques to collect biochemical photosynthetic data from an entire cucumber canopy, emphasizing the correction procedures for CO2 concentration of unsteady state measurements applicable regardless of chamber scale. After constructing a semi-open chamber system, we described how to correct measurement errors according to chamber volume. In order to assess the accuracy of the newly developed system, an analysis was conducted to determine the overall measurement error resulting from variations in the reference, sample CO2 concentration, and leakage flow rate. The total measurement error was accurate to no more than 10%. Furthermore, the difference between the photosynthetic rate of the single leaf and that of the whole-canopy was not significant in Rubisco activity-limited carboxylation range. In addition, the Farquhar-von Caemmerer-Berry (FvCB) model parameters and the photosynthetic rate estimation values were compared to evaluate the steady- and unsteady state measurement methods between the cucumber seedlings' single-leaf and whole-canopy. The average root mean square error of the FvCB model in the steady (standard A-Ci response) and unsteady states (800 to 400 ramp) of the chambers was 1.4 and 2.3, respectively. Results show that the developed system is suitable for measuring the gas exchange rate of the cucumber canopy. We demonstrate the correction method for measurement errors to enable the gas exchange rate of the whole-canopy even in an unsteady state. The correction method of the measurement system of the gas exchange rate for the whole- canopy can be applied regardless of the volume of the chamber, and it can be applied simply to other chamber systems. In addition, an unsteady state measurement method for fast data collection was also applicable. However, it was deemed necessary to identify a more optimal measurement range by conducting measurements across a broader range of values.


WITHDRAWN: Vaccine hesitancy in the University of Malta Faculties of Health Sciences, Dentistry and Medicine vis-à-vis influenza and novel COVID-19 vaccination.
This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.


Pharmacokinetics and Pharmacodynamics of Edoxaban, a Non-Vitamin K Antagonist Oral Anticoagulant that Inhibits Clotting Factor Xa.
Edoxaban, a once daily non-vitamin K antagonist oral anticoagulant, is a direct, selective, reversible inhibitor of factor Xa (FXa). In healthy subjects, single oral doses of edoxaban result in peak plasma concentrations within 1.0-2.0 h of administration, followed by a biphasic decline. Exposure is approximately dose proportional for once daily doses of 15-150 mg. Edoxaban is predominantly absorbed from the upper gastrointestinal tract, and oral bioavailability is approximately 62 %. Food does not affect total exposure to edoxaban. The terminal elimination half-life in healthy subjects ranges from 10 to 14 h, with minimal accumulation upon repeat once daily dosing up to doses of 120 mg. The steady-state volume of distribution is approximately 107 L, and total clearance is approximately 22 L/h; renal clearance accounts for approximately 50 % of total clearance, while metabolism and biliary secretion account for the remaining 50 %. Intrinsic factors, such as age, sex and race, do not affect edoxaban pharmacokinetics after renal function is taken into account. Oral administration of edoxaban results in rapid changes in anticoagulatory biomarkers, with peak effects on anticoagulation markers (such as anti-FXa), the prothrombin time and the activated partial thromboplastin time occurring within 1-2 h of dosing.


Test of a hypothesis of territory regulation in an insectivorous bird by experimentally increasing prey abundance.
Food availability is frequently hypothesized to be important in the regulation of territorial size. Recent theory suggests animals should respond to increased food availability by decreasing their territory. Most demonstrations of this relationship between food and territory are correlative, and few experimental tests of this hypothesis have been conducted.A field-experimental mainpulation was conducted to test three predictions of the hypothesis that food is a proximate stimulus for regulation of territory. The Rufous-sided Towhee, an insectivorous bird that is a permanent resident of chaparral in Arizona, was used to test the predictions that weekly area, total area, and fluctuations in area would be smaller within experimentally manipulated territories. Food resources were increased within five experimental territories and the response was compared with five control territories.The results did not support any of the three predictions. The hypothesis that food is a proximate stimulus for regulating territorial size was rejected. Two alternative hypotheses, that habitat quality or competition are proximate stimuli for regulating territories, could not be rejected.


High prevalence of shoplifting in patients with eating disorders.
Shoplifting, prevalent in patients diagnosed with bulimia nervosa (BN), is a serious behavioral problem in eating disorder (ED) patients. However, little is known about its overall presence, etiology, and consequences. This study aimed to determine whether shoplifting occurs before or after the onset of ED and to investigate the prevalence and correlates of shoplifting in ED patients. This was a cross-sectional study of 284 treatment-seeking female patients aged 13-45 with EDs [171 anorexia nervosa (AN); 113 BN]. Shoplifting, impulsive behaviors (self-injury, suicide attempt, sexual promiscuity, alcohol, and illicit drug use), depression, self-esteem, and clinical features of EDs were assessed with an interview. Lifetime shoplifting prevalence was 28.5% (81/284) with 70.4% (57/81) occurring before ED onset. Multivariate logistic regression analysis revealed that depression [odds ratio (OR), 2.63; 95% confidence interval (CI), 1.24-5.60], alcohol abuse (OR, 3.91; 95% CI 1.34-11.38), illicit substance use (OR, 14.42; 95% CI, 1.65-125.86), and self-esteem (OR, 0.90; 95% CI; 0.82-0.99) were associated with lifetime shoplifting, while illness duration, BN, and ED symptom severity were not. Shoplifting is common in ED patients and precedes ED onset in most patients with a shoplifting history, although the causal relationship between shoplifting and EDs remains inconclusive. Shoplifting may be associated with impulsive behaviors (e.g., alcohol and illicit drug use), depression, and low self-esteem, but not with ED severity. Future research should focus on the unrecognized role of shoplifting as a marker to identify patients at risk of impulsive behaviors and consider treatment options. Level V, observational cross-sectional descriptive study.


Synthesis and luminescence of nano-insulators doped with lanthanide ions.
This paper reviews the syntheses, particle-size measurements and various aspects of the optical spectra of lanthanide ion doped insulating nanomaterials, with the focus upon the sesquioxides, and it contrasts their behaviour with bulk materials.


Plasminogen activator inhibitor type-1 and interleukin-6 in haemolytic uraemic syndrome.
Because haemolytic uraemic syndrome (HUS) is an important cause of renal dysfunction in children, the availability of prognostic markers of disease severity could assist in identifying those at risk of developing long-term sequelae. The aim of this study was to test the hypothesis that plasma levels of plasminogen activator inhibitor type-1 (PAI-1) and interleukin-6 (IL-6) in children at the time of diagnosis of HUS would predict renal function outcome in terms of glomerular filtration rate (GFR). Fourteen children suffering from diarrhoeal HUS were studied. Plasma samples were assayed for PAI-1 and IL-6, and GFR was measured at intervals after discharge from hospital. Twelve months following their recovery from HUS, the children were allocated to one of two outcome groups depending on whether GFR was above (Good Outcome, n = 9), or below (Poor Outcome, n = 5) 80 mL/min per 1.73 m2. Elevated concentrations of PAI-1 were found in 4 of 5 Poor Outcome and 4 of 9 Good Outcome children. At the same time, increased concentrations of IL-6 were observed in 3 of 5 Poor Outcome and 3 of 9 Good Outcome children. Renal function continued to be compromised in four Poor Outcome children 36 months after diagnosis. Our data show that PAI-1 and IL-6 are elevated in the plasma of some children at the time of diagnosis of HUS, but that neither is a definitive prognostic marker of poor outcome 3 years later.


Comparative analysis of pinning techniques for supracondylar humerus fractures in paediatrics: A systematic review and meta-analysis of randomized controlled trials.
Supracondylar humeral fractures (SCHFs) rank among the frequently observed fractures in children. Nonetheless, there exists a dearth of consensus regarding the optimal surgical approach. This meta-analysis aims to thoroughly evaluate and compare two distinct pinning techniques (cross pinning versus lateral pinning) for SCHFs, using data from Randomized controlled trials (RCTs). Literature review was done using PubMed, CINAHL, Scopus, and The Cochrane Library for RCTs comparing the two pinning methods and providing information on at least one of the following: Loss of Baumann's angle, loss of carrying angle, elbow function assessed based on Flynn criteria, pin tract infection, and iatrogenic ulnar nerve injury. Random effect model was used to calculate standardized mean difference or Odds Ratio (OR) for the outcomes. Review Manager 5.4.1. was used to perform quality assessment and statistical analysis. A total of 22 RCTs were included. 20 studies reported data for iatrogenic ulnar nerve injury, the OR was calculated to be 3.76 (95% CI 1.75-8.06), showing a significantly lower risk of surgical ulnar nerve injury with the lateral technique. However, no significant difference was found between the pinning techniques in regard to the other outcomes. In comparison to lateral pinning, the utilization of cross pinning technique exposes the patient to a heightened susceptibility of iatrogenic nerve injury. Therefore, it is recommended that surgeons prioritize the implementation of the lateral pinning technique whenever feasible, as it offers greater protection against iatrogenic ulnar nerve injury. For the other intraoperative and postoperative outcomes, both surgical techniques yield comparable results.


Stabilities of N-acetyl-beta-D-glucosaminidase (NAG) isoenzymes in urine: advantage of NAG isoenzyme B measurement in clinical applications.
N-Acetyl-beta-D-glucosaminidase (NAG) is a widely used urinary enzyme for the assessment of renal diseases. We studied the stabilities of NAG isoenzymes in urine at 37 degrees C by enzyme assay and ELISA using a model simulating in vivo conditions. The stabilities were found to be affected by the pH. Under mild acidic condition (about pH 6), there was no significant loss of enzymatic activity of NAG isoenzyme A, enzymatic activity of NAG isoenzyme B and immunological activity of NAG isoenzyme B even after 8 h incubation. In contrast, under alkaline condition (about pH 8), the enzymatic activity of NAG isoenzyme A was rapidly lost, whereas both enzymatic and immunological activities of NAG isoenzyme B were maintained at more than 80% of their initial values. Also, we found that the ratios of endogenous NAG isoenzyme B to total NAG were elevated in alkaline urine samples. These results indicate that NAG isoenzyme A, which is a major isoenzyme in normal urine (pH 5-7), seems to be inactivated in alkaline urine. Our results suggest that for alkaline urine, NAG isoenzyme B should be measured to avoid misinterpretation of total NAG enzymatic activities.


Are hormonal contraceptives teratogenic?
The widespread use of hormonal contraceptives for a prolonged time in women during the child-bearing period necessitates that appropriate precautions be taken to ensure safety for the patient as well as for her progeny. Hormonal administration during or prior to pregnancy may be potentially teratogenic. Although there have been many reports during the last decade, it has been very difficult to document conclusively such a relationship. Over-all, it seems that hormonal use prior to pregnancy does not lead to an increase in the frequency of chromosomal aberrations or of congenital malformations. The use of certain hormones during pregnancy, on the other hand, may lead to an increase in the incidence of congenital malformations, probably in the genetically predisposed fetus. In view of this concept hormonal contraceptives should not be used to treat threatened abortion, and their use as a pregnancy test should be abandoned. Since the question of the safety of the inadvertent administration of pills during early pregnancy has not been resolved, the mother should be informed of the potential risks.


Evolutionary history of inquiline social parasitism in Plagiolepis ants.
Social parasitism, i.e. the parasitic dependence of a social species on another free-living social species, is one of the most intriguing phenomena in social insects. It has evolved to various levels, the most extreme form being inquiline social parasites which have lost the worker caste, and produce only male and female sexual offspring that are reared by the host worker force. The inquiline syndrome has been reported in 4 species within the ant genus Plagiolepis, in Europe. Whether inquiline social parasitism evolved once or multiple times within the genus remains however unknown. To address this question, we generated data for 5 inquiline social parasites - 3 species previously described and 2 unidentified species - and their free-living hosts from Europe, and we inferred their phylogenetic relationships. We tested Emery's rule, which predicts that inquiline social parasites and their hosts are close relatives. Our results show that inquiline parasitism evolved independently at least 5 times in the genus. Furthermore, we found that all inquilines were associated with one of the descendants of their most related free-living species, suggesting sympatric speciation is the main process leading to the emergence of the parasitic species, consistent with the stricter version of Emery's rule.


Analysis of DR and DQ gene products of the DR4 haplotype in patients with IDDM: possible involvement of more than one locus.
Fifteen DR4-bearing haplotypes from twelve patients with insulin-dependent diabetes mellitus (IDDM) were analyzed serologically, cellularly, and biochemically. The HLA-Dw composition of these DR4-positive haplotypes was Dw4 (46%), Dw14 (22%), and Dw10 (33%). The biochemical analysis by two-dimensional electrophoresis (2D-PAGE) of the DR beta chains showed that each Dw specificity is characterized by a specific DR4 beta chain that appears to be identical in normal and diabetic individuals. Analysis of DQ beta chains in the DR4-bearing haplotypes revealed that certain Dw specificities such as Dw4 are characterized by the presence of either the DQw7 (formerly DQw3.1) or DQw8 (formerly DQw3.2) alleles, which generate the Dw4.1 or Dw4.2 subtypes, respectively. Others such as Dw14 and Dw10 are characterized by the presence of the DQw8 allele. In our sample of 12 patients the Dw4.2 (Dw4, DR4 beta I-4 DQw8) and Dw10 (Dw10, DR4 beta I-1, DQw8) subtypes were predominant. It is concluded that individual DR beta and DQ beta gene products from the DR4-bearing haplotype of IDDM patients are identical to those of normal control subjects and that Dw14 as well as Dw10 are involved in disease susceptibility. We suggest that disease susceptibility may be influenced by more than one locus within the HLA-D region.


Multivariate analysis of risk factors for metastasis in retinoblastoma treated by enucleation.
Retinoblastoma, when it kills by metastasis, almost always does so within 5 years of enucleation. The median time to death was 6.4 months in unilateral cases and 14.2 months in bilateral cases. Multivariate statistical analysis of 361 cases of retinoblastoma indicated that histologic detection of invasion of the tumor into the optic nerve or orbit were the risk factors most highly predictive of death from retinoblastoma. Choroidal invasion was not significantly associated with a fatal outcome. Histologic evidence of a cataract, failure to diagnose retinoblastoma clinically, and bilaterality were also significant risk factors. The authors believe that in at least two of the cases of bilateral retinoblastoma death did not result from metastasis to the brain as was originally diagnosed, but resulted from the development of an independent primary intracranial neuroblastic tumor, a syndrome designated "trilateral retinoblastoma."


Epidemiology of mutant Plasmodium falciparum parasites lacking histidine-rich protein 2/3 genes in Eritrea 2 years after switching from HRP2-based RDTs.
Eritrea was the first African country to complete a nationwide switch in 2016 away from HRP2-based RDTs due to high rates of false-negative RDT results caused by Plasmodium falciparum parasites lacking hrp2/hrp3 genes. A cross-sectional survey was conducted during 2019 enrolling symptomatic malaria patients from nine health facilities across three zones consecutively to investigate the epidemiology of P. falciparum lacking hrp2/3 after the RDT switch. Molecular analyses of 715 samples revealed the overall prevalence of hrp2-, hrp3-, and dual hrp2/3-deleted parasites as 9.4% (95%CI 7.4-11.7%), 41.7% (95% CI 38.1-45.3%) and 7.6% (95% CI 5.8-9.7%), respectively. The prevalence of hrp2- and hrp3-deletion is heterogeneous within and between zones: highest in Anseba (27.1% and 57.9%), followed by Gash Barka (6.4% and 37.9%) and Debub zone (5.2% and 43.8%). hrp2/3-deleted parasites have multiple diverse haplotypes, with many shared or connected among parasites of different hrp2/3 status, indicating mutant parasites have likely evolved from multiple and local parasite genetic backgrounds. The findings show although prevalence of hrp2/3-deleted parasites is lower 2 years after RDT switching, HRP2-based RDTs remain unsuitable for malaria diagnosis in Eritrea. Continued surveillance of hrp2/3-deleted parasites in Eritrea and neighbouring countries is required to monitor the trend.


Mitochondrial respiratory parameters in cardiac tissue: a novel method of assessment by using saponin-skinned fibers.
Respiratory parameters of cardiac mitochondria were determined in the bundles of cardiac fibers skinned by using saponin that specifically removed sarcolemma, but left intracellular structures intact. In the assay medium which simulated the ion composition of cardiac cytoplasm maximal value of state 3 oxygen consumption per mol cytochromes aa3 was close to that value for isolated mitochondria. Ischemia and isopreterenol treatment were found to affect respiratory parameters of mitochondria in saponin-skinned fibers, among them creatine-stimulated respiration decreased most significantly, (3-4)-times under these conditions. The method described can be easily applied for determination of the mitochondrial respiratory parameters in small (5-10 mg) biopsy samples from human heart.


Effect of different amino acid patterns on semen quality of boars fed with low-protein diets.
The objective of the present study was to determine the effect of different amino acid patterns on the semen quality of boars fed with low-protein diets. Twenty-four boars were randomly divided into 4 groups (HP, LP1, LP2, and LP3). HP boars received 17% crude protein diet with a lysine:threonine:tryptophan:arginine (Lys:Thr:Trp:Arg) ratio of 100:50:20:104. Other boars received 13% CP and similar Lys levels (0.84%) with Lys:Thr:Trp:Arg ratios of 100:50:20:71, 100:76:38:71, and 100:76:38:120 for LP1, LP2, and LP3, respectively. These results showed sperm motility in the LP3 group was higher than in HP group during the 13-22 week period. The total sperm number, acrosome integrity ratio, and the effective total sperm number in LP3 and LP2 was higher than in other groups, and the abnormality ratio was lower than in other groups during the 13-18 week period. During 19-22 week period, in LP1 and LP3 groups, total sperm number and effective total sperm number were higher than in other groups, abnormality ratio was lower, and acrosome integrity ratio was higher than in the HP group. Nitric oxide synthase activity of seminal plasma and nitric oxide concentration of spermatozoa were significantly higher in the LP3 group than in other groups. Furthermore, mRNA expression of androgen receptor in testes was up-regulated in LP3. In conclusion, we suggest that the optimum ratio of Lys:Thr:Trp:Arg in a 13% CP diet for boars is 100:76:38:120, which results in similar or better reproductive performances than a 17% CP diet.


Outcome of patients with HER2-positive breast cancer treated with or without adjuvant trastuzumab in the Finland Capecitabine Trial (FinXX).
Little information is available about survival outcomes of patients with HER2-positive early breast cancer treated with adjuvant capecitabine-containing chemotherapy with or without trastuzumab. One thousand and five hundred patients with early breast cancer were entered to the Finland Capecitabine trial (FinXX) between January 2004 and May 2007, and were randomly assigned to receive either three cycles of adjuvant TX (docetaxel, capecitabine) followed by three cycles of CEX (cyclophosphamide, epirubicin, capecitabine; TX-CEX) or three cycles of docetaxel followed by three cycles of CEF (cyclophosphamide, epirubicin, fluorouracil; T-CEF). The primary endpoint was recurrence-free survival (RFS). The study protocol was amended in May 2005 while study accrual was ongoing to allow adjuvant trastuzumab for patients with HER2-positive cancer. Of the 284 patients with HER2-positive cancer accrued to FinXX, 176 (62.0%) received trastuzumab after amending the study protocol, 131 for 12 months and 45 for nine weeks. The median follow-up time was 6.7 years. Patients with HER2-positive cancer who received trastuzumab had better RFS than those who did not (five-year RFS 89.2% vs. 75.9%; HR 0.41, 95% CI 0.23-0.72; p = 0.001). Patients treated with trastuzumab for 12 months or nine weeks had similar RFS. There was no significant interaction between trastuzumab administration and the type of chemotherapy. Four (2.3%) patients treated with trastuzumab had heart failure or left ventricular dysfunction, three of these received capecitabine. Adjuvant trastuzumab improves RFS of patients treated with TX-CEX or T-CEF. Few patients had cardiac failure.


Ribosomal proteins of sea urchin eggs. I. Characterization of cytoplasmic ribosomal proteins.
Ribosomal proteins from the eggs of sea urchin, Pseudocentrotus depressus, were analyzed by two-dimensional polyacrylamide gel electrophoresis (PAGE) and sodium dodecyl sulfate (SDS)-PAGE. Thirty different proteins including three acidic proteins were detected in the small subunit. The large subunit was found to contain at least 43 different proteins, 42 basic and one acidic. The ribosomal proteins from the small subunit have molecular weights ranging from 11,900 to 51,700 (average molecular weight: 25,600). The molecular weights of the large subunit proteins range from 12,700 to 76,300 (average molecular weight: 28,700).


Common medical ethical issues faced by healthcare professionals in KSA.
There are growing concerns about ethical issues in the healthcare system. This study was conducted to determine the nature of common ethical issues faced by healthcare providers in a tertiary-care hospital in KSA. This cross-sectional study comprised a self-administered questionnaire given to the physicians working at King Abdulaziz Medical City Hospital-Riyadh, Ministry of National Guard Health Affairs (KAMC-RD, MNGHA). We used a convenience sampling technique during symposia and conferences. We distributed 240 questionnaires amongst the physicians and recorded a response rate of 80%; 68% (136) of the respondents were men, while 82.5% were Saudis. The mean age of the group was 34.08 ± 10.43 years. Only 69% (138) of the physicians had ever received any formal teaching in bioethics. Most physicians (77.5%) demanded clear guidelines to help them to take appropriate ethical decisions on therapeutic futility, whereas 54% felt that they sometimes overtreat their patients. This study reported a lack of knowledge in certain healthcare-related ethical issues in a significant proportion of the physicians. There is a need for a standard educational agenda for medical ethics for healthcare providers, not only during medical school but also after graduation and during clinical rounds.


Clinical examination, critical care ultrasonography and outcomes in the critically ill: cohort profile of the Simple Intensive Care Studies-I.
In the Simple Intensive Care Studies-I (SICS-I), we aim to unravel the value of clinical and haemodynamic variables obtained by physical examination and critical care ultrasound (CCUS) that currently guide daily practice in critically ill patients. We intend to (1) measure all available clinical and haemodynamic variables, (2) train novices in obtaining values for advanced variables based on CCUS in the intensive care unit (ICU) and (3) create an infrastructure for a registry with the flexibility of temporarily incorporating specific (haemodynamic) research questions and variables. The overall purpose is to investigate the diagnostic and prognostic value of clinical and haemodynamic variables. The SICS-I includes all patients acutely admitted to the ICU of a tertiary teaching hospital in the Netherlands with an ICU stay expected to last beyond 24 hours. Inclusion started on 27 March 2015. On 31 December 2016, 791 eligible patients fulfilled our inclusion criteria of whom 704 were included. So far 11 substudies with additional variables have been designed, of which six were feasible to implement in the basic study, and two are planned and awaiting initiation. All researchers received focused training for obtaining specific CCUS images. An independent Core laboratory judged that 632 patients had CCUS images of sufficient quality. We intend to optimise the set of variables for assessment of the haemodynamic status of the critically ill patient used for guiding diagnostics, prognosis and interventions. Repeated evaluations of these sets of variables are needed for continuous improvement of the diagnostic and prognostic models. Future plans include: (1) more advanced imaging; (2) repeated clinical and haemodynamic measurements; (3) expansion of the registry to other departments or centres; and (4) exploring possibilities of integration of a randomised clinical trial superimposed on the registry. NCT02912624; Pre-results.


Proteasome subunit RPT2a promotes PTGS through repressing RNA quality control in Arabidopsis.
RNA quality control (RQC) and post-transcriptional gene silencing (PTGS) target and degrade aberrant endogenous RNAs and foreign RNAs, contributing to homeostasis of cellular RNAs. In plants, RQC and PTGS compete for foreign and selected endogenous RNAs; however, little is known about the mechanism interconnecting the two pathways. Using a reporter system designed for monitoring PTGS, we revealed that the 26S proteasome subunit RPT2a enhances transgene PTGS by promoting the accumulation of transgene-derived short interfering RNAs without affecting their biogenesis. RPT2a physically associated with a subset of RQC components and downregulated the protein level. Overexpression of the RQC components interfered with transgene silencing, and impairment of the RQC machinery reinforced transgene PTGS attenuated by rpt2a. Overall, we demonstrate that the 26S proteasome subunit RPT2a promotes PTGS by repressing the RQC machinery to control foreign RNAs.


Prevalence, clinical manifestations, laboratory findings, treatment, and outcome of intermediate syndrome in anticholinesterase pesticide intoxication of dogs: A retrospective study.
Organophosphates and carbamates are important anticholinesterase intoxicants of humans and dogs. Intermediate syndrome (IMS) typically occurs 7-96 h following a toxicity-associated acute cholinergic crisis (ACC), and manifests clinically as weakness of the proximal limb, respiratory, and neck flexor muscles. The aim of this study was to describe the prevalence, clinical findings, and outcome of IMS in dogs. The medical records of a veterinary teaching hospital were searched for dogs diagnosed with ACC, IMS, or both, between 2017 and 2021. Case files were retrospectively reviewed. Six historical IMS cases were additionally reviewed. Thirty-two dogs were diagnosed with anticholinesterase intoxication during the search period, of which 23 (72 %) were only diagnosed with ACC, seven (22 %) progressed from ACC to IMS, and two (6 %) were only diagnosed with IMS. Duration of hospitalisation was longer in the IMS group compared to the ACC only group (P = 0.005). When all dogs with IMS (n = 15, including the six historical cases) were considered, survival was 100 %, including four (27 %) that required positive pressure mechanical ventilation following respiratory failure. Serum butyrylcholine esterase activity, a marker of cholinesterase activity, was below reference interval when first measured in 14 (93 %) of dogs; however, was not a useful as a recovery marker. IMS should be suspected in dogs demonstrating respiratory, neck, and proximal limb muscle paresis or paralysis, especially following clinical signs consistent with ACC. Absence of clinical signs consistent with ACC or butyrylcholine esterase activity within the reference interval does not exclude IMS as a differential.


Within-subject consistency and between-subject variability in Bayesian reasoning strategies.
It is well known that people tend to perform poorly when asked to determine a posterior probability on the basis of a base rate, true positive rate, and false positive rate. The present experiments assessed the extent to which individual participants nevertheless adopt consistent strategies in these Bayesian reasoning problems, and investigated the nature of these strategies. In two experiments, one laboratory-based and one internet-based, each participant completed 36 problems with factorially manipulated probabilities. Many participants applied consistent strategies involving use of only one of the three probabilities provided in the problem, or additive combination of two of the probabilities. There was, however, substantial variability across participants in which probabilities were taken into account. In the laboratory experiment, participants' eye movements were tracked as they read the problems. There was evidence of a relationship between information use and attention to a source of information. Participants' self-assessments of their performance, however, revealed little confidence that the strategies they applied were actually correct. These results suggest that the hypothesis of base rate neglect actually underestimates people's difficulty with Bayesian reasoning, but also suggest that participants are aware of their ignorance.


Occipital nerve stimulation for medically refractory hypnic headache.
Hypnic headache is a rare, primary headache disorder that exclusively occurs regularly during sleep. We present a case of hypnic headache successfully managed with occipital nerve stimulation. A 64-year-old female presented with a four-year history of a right occipital headache that regularly awakened her from sleep. The headache, which was dull and throbbing, would awaken her regularly at 4:00 am, five hours after bedtime at 11:00 pm. No photophobia, nausea or vomiting, lacrimation, or other autonomic symptoms were present. The headache was refractory to various medical treatments, including indomethacin, flunarizine, propranolol. She underwent a trial of occipital nerve stimulation with a lead electrode using a medial approach. During the ten-day trial stimulation, she reported almost complete relief from hypnic headache. Chronic occipital nerve stimulation replicated the trial results. The attacks of hypnic headache recurred in one year with loss of stimulation-induced paresthesia; a subsequent x-ray showed electrode migration. After revision of the electrode to the original location, the effectiveness of the occipital nerve stimulation against hypnic headache was achieved again, and this effect has been consistent through 36 months of follow-up. Occipital nerve stimulation was effective in a patient with chronic, refractory hypnic headache.


Antitumor activity and cross-resistance of carmethizole hydrochloride in preclinical models in mice.
Carmethizole hydrochloride [1-methyl-2-methylthio-4,5-bis(hydroxymethyl)imidazole-4', 5'-bis(N-methylcarbamate)hydrochloride, NSC 602,668; hereafter called carmethizole] is a new antitumor drug that has shown relatively broad activity in initial evaluations against several murine tumors and human tumor xenografts in vivo. The present studies were designed to address questions about carmethizole's activity against established disease, its activity on different treatment schedules, and the extent of its cross-resistance with established drugs. Human MX-1 mammary carcinoma, human NCI-H82 small-cell lung carcinoma, and human LOX amelanotic melanoma xenografts in athymic mice were used to determine the drug's activity against established disease; the NCI-H82 lung-tumor xenograft in athymic mice was used to explore its schedule dependence; and a series of drug-resistant murine leukemias provided an in vivo cross-resistance profile. When injected i.p., carmethizole exhibited antitumor activity against advanced-stage s.c. MX-1 mammary, s.c. NCI-H82 lung, and i.p. LOX melanoma xenografts and was as effective against established disease (MX-1 and LOX) as it was against early-stage disease (no data are available for early-stage NCI-H82). The therapeutic effect of carmethizole was not route-dependent, as was evidenced by the similar delays observed in tumor growth following i.p. and i.v. administration. The use of a split-dose schedule on a single day instead of one bolus injection yielded an increase in the total dose delivered, resulting in an increased delay in tumor growth. Murine leukemias resistant to vincristine (VCR), amsacrine (AMSA), or methotrexate (MTX) were not cross-resistant to carmethizole. However, murine leukemias resistant to doxorubicin (ADR), melphalan (L-PAM), cisplatin (DDPt), 1-beta-D-ara-binofuranosylcytosine (ara-C), and 5-fluorouracil (5-FU) were cross-resistant to carmethizole, suggesting that patients who have previously been treated with any of these agents might be less likely to respond to carmethizole than those who have had no opportunity to develop resistance to any of these compounds. We anticipate that the information derived from these studies may be useful in the design of clinical trials of carmethizole and may stimulate additional basic research on the mechanism of action of this new agent.


Exploring the Mechanism of Baicalin Intervention in Breast Cancer Based on MicroRNA Microarrays and Bioinformatics Strategies.
To explore the mechanism of baicalin intervention in breast cancer based on microRNA microarrays. The inhibitory rate of baicalin intervention in MCF-7 breast cancer cells was determined by MTT. Then, the miRNA microarrays were used to validate the key microRNAs. After that, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to validate microRNA, hsa-miR-15a, hsa-miR-100, hsa-miR-16, and hsa-miR-7t. Finally, the potential targets of these key microRNAs are predicted by miRWalk, and DAVID was utilized for gene ontology (GO) enrichment analysis and pathway enrichment analysis. Baicalin may inhibit the proliferation of MCF-7 cells in a dose-dependent and time-dependent manner. The concentration of baicalin 150 μmol/L was determined for the subsequent miRNA chip research. A total of 92 upregulated microRNAs and 35 downregulated microRNAs were obtained. The upregulated miRNAs include hsa-miR-6799-5p, hsa-miR-6126, hsa-miR-4792, hsa-miR-6848-5p, hsa-miR-3197, hsa-miR-6779-5p, and hsa-miR -654-5p. The downregulated miRNAs include hsa-miR-3911, hsa-miR-504-5p, hsa-miR-30a-3p, hsa-miR-193b-3p, and hsa-miR-181b-5p. Then, differentially expressed miRNA was verified by qRT-PCR. The results showed that the expression of hsa-miR-15a, hsa-miR-100, hsa-miR-16, and hsa-let-7c was upregulated (P < 0.05), which was consistent with the results of the miRNA microarray. The enrichment analysis showed that baicalin might regulate the DNA-templated proliferation, DNA-templated transcription, p53 signaling pathway, etc., of MCF-7 breast cancer cells through miRNA. Baicalin inhibits the proliferation of breast cancer cells. It may achieve antitumor effects through regulating microRNAs so as to affect the DNA replication (such as cellular response to DNA damage stimulus and DNA binding), RNA transcription (such as regulation of transcription, DNA-templated, transcription from RNA polymerase II promoter, and transcription factor binding), protein synthesis (such as mRNA binding, Golgi apparatus, and protein complex), endocytosis, pathways in cancer, p53 signaling pathway, and so on.


Melatonin Sensitizes OVCAR-3 Cells to Cisplatin through Suppression of PI3K/Akt Pathway.
This study examined the effect of melatonin on oxidative stress, expression of pro-apoptotic protein, anti-apoptotic proteins, and the activity of the PI3K/Akt signaling pathway in the human ovarian cancer cell line (OVCAR3). OVCAR3 cells were treated with cisplatin, melatonin, cisplatin + melatonin, and siRNA Akt. Reactive oxygen species levels were assessed. The expression of the proteins was determined by Western blot. Melatonin administration significantly increased intracellular ROS generation, the cleavage of caspase 3 and decreased phosphorylation of Akt. Combination therapy of cisplatin and melatonin increases apoptosis in the OVCAR-3 cells by inhibiting of PI3K/Akt signaling pathway and exacerbating oxidative stress.


Porous organic materials for iodine adsorption.
The nuclear industry will continue to develop rapidly and produce energy in the foreseeable future; however, it presents unique challenges regarding the disposal of released waste radionuclides because of their volatility and long half-life. The release of radioactive isotopes of iodine from uranium fission reactions is a challenge. Although various adsorbents have been explored for the uptake of iodine, there is still interest in novel adsorbents. The novel adsorbents should be synthesized using reliable and economically feasible synthetic procedures. Herein, we discussed the state-of-the-art performance of various categories of porous organic materials including covalent organic frameworks, covalent triazine frameworks, porous aromatic frameworks, porous organic cages, among other porous organic polymers for the uptake of iodine. This review discussed the synthesis of porous organic materials and their iodine adsorption capacity and reusability. Finally, the challenges and prospects for iodine capture using porous organic materials are highlighted.


Lipid and metabolic syndrome traits in coronary artery disease: a Mendelian randomization study.
Mendelian randomization (MR) of lipid traits in CAD has provided evidence for causal associations of LDL-C and TGs in CAD, but many lipid trait genetic variants have pleiotropic effects on other cardiovascular risk factors that may bias MR associations. The goal of this study was to evaluate pleiotropic effects of lipid trait genetic variants and to account for these effects in MR of lipid traits in CAD. We performed multivariable MR using inverse variance-weighted and MR-Egger methods in large (n ≥ 300,000) GWAS datasets. We found that 30% of lipid trait genetic variants have effects on metabolic syndrome traits, including BMI, T2D, and systolic blood pressure (SBP). Nonetheless, in multivariable MR analysis, LDL-C, HDL-C, TGs, BMI, T2D, and SBP are independently associated with CAD, and each of these associations is robust to adjustment for directional pleiotropy. MR at loci linked to direct effects on HDL-C and TGs suggests locus- and mechanism-specific causal effects of these factors on CAD.


Six sesquiterpenoids from the stems and leaves of Chrysanthemum morifolium Ramat and their anti-asthma activities.
Six previously undescribed sesquiterpenoids, chrysanthterpenoids H-M (1-6), were isolated from the stem and leaves of Chrysanthemum morifolium Ramat. Structure elucidation of isolated compounds was unambiguously determined based on extensive 1D and 2D NMR spectroscopic analyses. Furthermore, computational prediction of ECD was used to propose the absolute configurations of the compounds. All compounds were evaluated for their anti-asthma effects on RBL-2H3 cells in vitro. The results showed that Compounds 2 and 3 significantly inhibited the release of β-aminohexosidase and improved RBL-2H3 degranulation by chromogenic substrate and high-content imaging. These results suggest that Compounds 2 and 3 may exhibit anti-asthma activities.


Periodic Remodeling in a Neural Circuit Governs Timing of Female Sexual Behavior.
Behaviors are inextricably linked to internal state. We have identified a neural mechanism that links female sexual behavior with the estrus, the ovulatory phase of the estrous cycle. We find that progesterone-receptor (PR)-expressing neurons in the ventromedial hypothalamus (VMH) are active and required during this behavior. Activating these neurons, however, does not elicit sexual behavior in non-estrus females. We show that projections of PR+ VMH neurons to the anteroventral periventricular (AVPV) nucleus change across the 5-day mouse estrous cycle, with ∼3-fold more termini and functional connections during estrus. This cyclic increase in connectivity is found in adult females, but not males, and regulated by estrogen signaling in PR+ VMH neurons. We further show that these connections are essential for sexual behavior in receptive females. Thus, estrogen-regulated structural plasticity of behaviorally salient connections in the adult female brain links sexual behavior to the estrus phase of the estrous cycle.


Low-cost device for avoiding bulk susceptibility artifacts in chemical-selective fat saturation MR of the head and neck.
An inexpensive, commercially available travel pillow filled with a suspension of attapulgite provided good suppression of inhomogeneous chemical-selective fat saturation in imaging of the head and neck. This device is assembled from readily available materials at a low cost and compares favorably with a commercially available perfluorochemical-filled device.


Modulation of Na+/alanine cotransport in liver sinusoidal membrane vesicles by internal divalent cations.
Rat liver basolateral plasma membrane (blLPM) vesicles resuspended in 5 mM Mg2(+)-, Ca2(+)-, Mn2(+)- or Co2(+)-containing media exhibited a markedly lower rate of Na(+)-stimulated L-alanine transport. Divalent cation inhibition of L-alanine uptake was dose dependent, and was observed only when the vesicles were pre-loaded with the divalent cations. The presence or absence of the metal ions in the extravesicular incubation media had no effect on L-alanine transport. Conversely, pretreatment of the vesicles with 0.2 mM of either EGTA or EDTA resulted in higher initial rates of L-alanine transport. This stimulation was overcome by addition of excess divalent cation to the vesicle suspension solution. Since these blLPM vesicles are primarily oriented right-side-out, the divalent cation inhibition of L-alanine transport appears to be a result of their interaction with cytosolic components of the cell membrane. Total Na+ flux as measured with 22Na+ was not affected by intravesicular 5 mM Mg2+ or Ca2+, indicating that the inhibition was not due to dissipation of the Na+ gradient. These observations suggest that intracellular divalent cations may serve to modulate L-alanine transport across the liver cell plasma membrane.


Prognostic factors in women treated for ovarian yolk sac tumour: a retrospective analysis of 84 cases.
Ovarian yolk sac tumour (OYST) is a very rare malignancy arising in young women. Our study aimed to evaluate long-term outcomes and to identify prognostic parameters likely to help make appropriate risk-based decisions about therapy in this disease. This retrospective study is based on prospectively recorded OYST cases at the Institut Gustave-Roussy. A univariate analysis using the logrank test evaluated possible associations between survival and patient or disease covariates. The multivariate analysis was performed using the Cox proportional hazard regression method. Between 1976 and 2006, 84 patients were registered. Since 1991, most of the patients have undergone fertility-sparing surgery. With a median follow-up of 71 months, the overall 5-year and event-free survival rates are 84% and 79%, respectively. In the multivariate model only the absence of ascites and a favourable serum AFP decline rate were significantly associated with better overall survival. Patients with a poor prognosis factor such as an unfavourable serum AFP decline may be considered for aggressive treatment whereas those with good prognostic factors could be given less courses of chemotherapy.


Multiple-endpoint in vitro carcinogenicity test in human cell line TK6 distinguishes carcinogens from non-carcinogens and highlights mechanisms of action.
Current in vitro genotoxicity tests can produce misleading positive results, indicating an inability to effectively predict a compound's subsequent carcinogenic potential in vivo. Such oversensitivity can incur unnecessary in vivo tests to further investigate positive in vitro results, supporting the need to improve in vitro tests to better inform risk assessment. It is increasingly acknowledged that more informative in vitro tests using multiple endpoints may support the correct identification of carcinogenic potential. The present study, therefore, employed a holistic, multiple-endpoint approach using low doses of selected carcinogens and non-carcinogens (0.001-770 µM) to assess whether these chemicals caused perturbations in molecular and cellular endpoints relating to the Hallmarks of Cancer. Endpoints included micronucleus induction, alterations in gene expression, cell cycle dynamics, cell morphology and bioenergetics in the human lymphoblastoid cell line TK6. Carcinogens ochratoxin A and oestradiol produced greater Integrated Signature of Carcinogenicity scores for the combined endpoints than the "misleading" in vitro positive compounds, quercetin, 2,4-dichlorophenol and quinacrine dihydrochloride and toxic non-carcinogens, caffeine, cycloheximide and phenformin HCl. This study provides compelling evidence that carcinogens can successfully be distinguished from non-carcinogens using a holistic in vitro test system. Avoidance of misleading in vitro outcomes could lead to the reduction and replacement of animals in carcinogenicity testing.


Prevalence, clinical manifestations, and biochemical data of type 2 diabetes mellitus versus nondiabetic symptomatic patients with COVID-19: A comparative study.
There is a scarcity of data regarding the effect of Type 2 diabetes mellitus (T2DM) and associated comorbidities on the clinical presentation and outcome of symptomatic patients with -COVID-19 infection in comparison with non-diabetic patients. We described and compared the clinical presentation and radiological and hematological data of a cohort of symptomatic COVID19 positive T2DM diabetic patients (n = 59) versus another cohort of non-diabetic symptomatic COVID19 positive patients (n =244) diagnosed at the same time from January 2020 to May 2020. Associated comorbidities were -assessed, and the Charlson Comorbidity Index was calculated. The outcomes including duration of hospitalization, duration of Intensive Care Unit (ICU) stay, duration of mechanical ventilation, and duration of O2 -supplementation were assessed. Prevalence of T2DM in symptomatic COVID19 positive patients was 59/303 (=19.5%). Diabetic patients had higher prevalence of hypertension, chronic kidney disease (CKD) and cardiac dysfunction [coronary heart disease (CHD)], and congestive heart failure (CHF). Charlson Comorbidity score was significantly higher in the T2DM patients (2.4± 1.6) versus the non-diabetic -patients (0.28 ± 0.8; p: < 0.001). Clinically and radiologically, T2DM patients had significantly higher percentage of pneumonia, severe pneumonia and ARDS versus the non-diabetic patients. Hematologically, diabetic patients had significantly higher C-reactive protein (CRP), higher absolute neutrophilic count (ANC) and lower counts of lymphocytes and eosinophils compared to non-diabetic patients. They had significantly higher systolic and diastolic blood pressures, longer duration of hospitalization, ICU stay, mechanical ventilation and oxygen therapy. CRP was correlated significantly with the duration of stay in the ICU and the duration for oxygen supplementation (r = 0.37 and 0.42 respectively; p: <0.01). T2DM patients showed higher inflammatory response to COVID 19 with higher absolute neutrophilic count (ANC) and CRP with lower lymphocytic and eosinophilic counts. Diabetic patients had more comorbidities and more aggressive course of the disease with higher rate of ICU admission and longer need for hospitalization and oxygen use.


Simultaneous Detection of Morphine and Codeine in the Presence of Ascorbic Acid and Uric Acid and in Human Plasma at Nafion Single-Walled Carbon Nanotube Thin-Film Electrode.
In clinical settings, the dosing and differential diagnosis of the poisoning of morphine (MO) and codeine (CO) is challenging due to interindividual variations in metabolism. However, direct electrochemical detection of these analytes from biological matrices is inherently challenging due to interference from large concentrations of anions, such as ascorbic acid (AA) and uric acid (UA), as well as fouling of the electrode by proteins. In this work, a disposable Nafion-coated single-walled carbon nanotube network (SWCNT) electrode was developed. We show facile electron transfer and efficient charge separation between the interfering anions and positively charged MO and CO, as well as significantly reduced matrix effect in human plasma. The Nafion coating alters the voltammetric response of MO and CO, enabling simultaneous detection. With this SWCNT/Nafion electrode, two linear ranges of 0.05-1 and 1-10 μM were found for MO and one linear range of 0.1-50 μM for CO. Moreover, the selective and simultaneous detection of MO and CO was achieved in large excess of AA and UA, as well as, for the first time, in unprocessed human plasma. The favorable properties of this electrode enabled measurements in plasma with only mild dilution and without the precipitation of proteins.


Androgen receptor phosphorylated at Ser815: The expression and function in the prostate and tumor-derived cells.
Androgen is beneficial for the prostate with normal functions but creates a risk for prostate cancer progression. How androgen receptor (AR) mediates these various androgen actions remains elusive. AR conserves a phosphorylation motif within its ligand-binding domain throughout species. Here, we have found AR phosphorylated at Ser815 (P-AR) is expressed in normal tissues of both human and mouse prostates. P-AR begins expression in association with prostatic development and castration decreases its expression levels in the mouse prostate. Functional analysis of AR in prostate cancer PC-3 cells showed ligand-induced AR nuclear translocation and transactivation were disturbed by its phosphorylation at Ser815. Moreover, P-AR suppressed oncogenic AKT signaling suggesting a suppressive function for prostate cancer development. In fact, AR phosphorylation levels progressively decrease in human prostates as cancer worsens. These findings showed androgen might utilize P-AR to self-antagonize oncogenic signals and cancer progression believed to be regulated by non-phosphorylated AR (NonP-AR). By differing its target genes and signal regulations from those of NonP-AR, P-AR co-expression with NonP-AR may be the molecular basis for androgen to balance its actions and to control disease developments.


RNA methylations in human cancers.
RNA methylations, as the prevalent post-transcriptional modifications, are critical in regulating various biological processes, such as RNA transcription, splicing, structure, stability, and translation. Its dysregulation is closely related to the occurrence of human malignancies. The advance of high-throughput sequencing technology facilitates the investigations about how methylation of coding and non-coding RNAs regulates cancer progression through reshaping the transcriptomics. Here, we review the current progress about the regulatory role of several representative RNA modifications in cancers, including N6-methyladenosine (m6A), 5-methylcytosine (m5C), N1-methyladenosine (m1A) and 2'-O-methylation (Nm). Meanwhile, we also discuss the potential clinical value of RNA methylation in diagnostic and therapeutic implications of human cancers.


Trophic eggs and parental foraging for young by the catfish Bagrus meridionalis of Lake Malawi, Africa.
Parental bagrid catfish in Lake Malawi, Africa, appear to feed their young in a manner analogous to birds and social insects. The female produces eggs which are released and consumed by the catfish young. Indirect evidence suggests that the male leaves the nest to forage and returns with benthic invertebrates in its mouth that are fed to the brood. Such behavior is hypothesized to enhance the growth rate of the young and to reduce their susceptibility to predation.


Racial and ethnic disparity in characteristics and outcomes of women with placenta accreta spectrum: a comparative study.
Placenta accreta spectrum (PAS) refers to the spectrum of diagnoses involving abnormally and morbidly adherent trophoblastic tissue to the gravid uterus. These disorders are associated with significant maternal morbidity and mortality. While race/ethnicity is known to impact pregnancy outcomes, racial disparities have not been previously examined in women with PAS. The objective of current study was to compare patient characteristics and perioperative outcomes of women with PAS who underwent cesarean delivery across race/ethnicity. This is a comparative study that retrospectively queried the National Inpatient Sample, a hospital-based inpatient database in the USA. The study cohort was women diagnosed with PAS who underwent cesarean delivery from 10/2015 to 12/2018. The exposure group was race/ethnicity. Main outcomes were (i) patient/pregnancy characteristics and (ii) surgical morbidity for cesarean delivery, assessed in multivariable analysis. A total of 10,535 women comprised the study cohort (White n = 5,230 [49.6%], Black n = 2,045 [19.4%], Hispanic n = 2,540 [24.1%], and Asian n = 720 [6.8%]). Patient demographics, pregnancy characteristics, and hospital factors for the non-White groups significantly differed compared to the White group. Older age, obesity, diabetes, placenta previa, percreta, non-elective surgery, lower median household income, and Medicaid particularly represented the non-White groups. When perioperative outcomes were compared, non-White women were more likely to have any measured complications, hemorrhage/transfusion, and shock/coagulopathy compared to White women. Various sensitivity analyses redemonstrated the main cohort results. In conclusion, this study suggests that there were significant disparities in patient characteristics and outcomes of women with PAS across race/ethnicity.


Ex vivo experimental strategies for assessing unconstrained shoulder biomechanics: A scoping review.
Biomechanical studies of the shoulder often choose an ex vivo approach, especially when investigating the active and passive contribution of individual muscles. Although various simulators of the glenohumeral joint and its muscles have been developed, to date a testing standard has not been established. The objective of this scoping review was to present an overview of methodological and experimental studies describing ex vivo simulators that assess unconstrained, muscular driven shoulder biomechanics. All studies with ex vivo or mechanical simulation experiments using an unconstrained glenohumeral joint simulator and active components mimicking the muscles were included in this scoping review. Static experiments and humeral motion imposed through an external guide, e.g., a robotic device, were excluded. Nine different glenohumeral simulators were identified in 51 studies after the screening process. We identified four control strategies characterized by: (a) using a primary loader to determine the secondary loaders with constant force ratios; (b) using variable muscle force ratios according to electromyography; (c) calibrating the muscle path profile and control each motor according to this profile; or (d) using muscle optimization. The simulators with the control strategy (b) (n = 1) or (d) (n = 2) appear most promising due to its capability to mimic physiological muscle loads.


A clinical evaluation of a headless, titanium, variable-pitched, tapered, compression screw for repair of nondisplaced lateral condylar fractures in thoroughbred racehorses.
To report clinical evaluation of headless compression screws for repair of metacarpal/metatarsal (MC/MT3) condylar fractures in horses. Retrospective case study. Racing Thoroughbreds (n=16) with nondisplaced lateral condylar fractures of MC/MT 3. Medical records (1999-2004) of horses with nondisplaced longitudinal fractures of the lateral condyle of MC/MT3 were reviewed. Pre-operative variables retrieved were: patient age, gender, limb involvement, injury occurrence, fracture length, and width, evidence of palmar comminution and degenerative joint disease, number of pre-injury starts, and pre-injury earnings. Post-operative variables retrieved were: surgical complications, surgical time, number of race starts, and post-operative earnings. MC3 (n=11) and MT3 (5) nondisplaced longitudinal fractures of the lateral condyle were repaired with Acutrak Equine (AE) screws. Left front limb fractures were most common (8) followed by left hind (5) and right front (3). Nine fractures occurred during training and 7 during racing; 4 fractures had palmar comminution. No surgical complications occurred. Of 15 horses that returned to training, 11 (73%) raced 306+/-67 days after injury and had greater mean (+/-SD) post-injury earnings/start ($5290.00+/-$8124.00) than pre-injury ($4971.00+/-$2842.00). Screw removal was not required in any horse. The AE screw is a viable option for repair of nondisplaced lateral condylar MC/MT3 fractures in Thoroughbred racehorses. Adequate stability of nondisplaced lateral condylar fractures can be achieved with a headless tapered compression screw while avoiding impingement on the collateral ligaments and joint capsule of the fetlock joint.


K201 (JTV-519) alters the spatiotemporal properties of diastolic Ca(2+) release and the associated diastolic contraction during β-adrenergic stimulation in rat ventricular cardiomyocytes.
K201 has previously been shown to reduce diastolic contractions in vivo during β-adrenergic stimulation and elevated extracellular calcium concentration ([Ca(2+)](o)). The present study characterised the effect of K201 on electrically stimulated and spontaneous diastolic sarcoplasmic reticulum (SR)-mediated Ca(2+) release and contractile events in isolated rat cardiomyocytes during β-adrenergic stimulation and elevated [Ca(2+)](o). Parallel experiments using confocal microscopy examined spontaneous diastolic Ca(2+) release events at an enhanced spatiotemporal resolution. 1.0 μmol/L K201 in the presence of 150 nmol/L isoproterenol (ISO) and 4.75 mmol/L [Ca(2+)](o) significantly decreased the amplitude of diastolic contractions to ~16% of control levels. The stimulated free Ca(2+) transient amplitude was significantly reduced, but stimulated cell shortening was not significantly altered. When intracellular buffering was taken into account, K201 led to an increase in action potential-induced SR Ca(2+) release. Myofilament sensitivity to Ca(2+) was not changed by K201. Confocal microscopy revealed diastolic events composed of multiple Ca(2+) waves (2-3) originating at various points along the cardiomyocyte length during each diastolic period. 1.0 μmol/L K201 significantly reduced the (a) frequency of diastolic events and (b) initiation points/diastolic interval in the remaining diastolic events to 61% and 71% of control levels respectively. 1.0 μmol/L K201 can reduce the probability of spontaneous diastolic Ca(2+) release and their associated contractions which may limit the propensity for the contractile dysfunction observed in vivo.


Detection of Diverse N-Acyl Homoserine Lactone Signalling Molecules Among Bacteria Associated with Rice Rhizosphere.
Bacterial communities communicate, regulate and coordinate their cooperative activities and physiological process by releasing, sensing and responding to small diffusible signal molecules such as acyl homoserine lactones (AHLs), auto-inducing oligo-peptides (AIPs) and autoinducer-2, a process referred to as Quorum sensing (QS). The QS mediated communication in rhizosphere associated bacterial communities significantly influence traits governing plant-microbe interactions. This study aimed to identify AHL-mediated QS signals in bacterial communities associated with rice rhizosphere using two AHL biosensors reporter strains Chromobacterium violaceum CV026 and Agrobacterium tumefaciens NTL4 (pZLR4). Approximately 375 bacterial isolates isolated from rice rhizosphere and screened using both the biosensors, detected 49 (13%) AHL positive isolates. The BOX-Polymerase Chain reaction (BOX-PCR) fingerprinting profiles of the 49 AHL positive isolates represented 11 distinct cluster groups. Subsequent 16S rRNA gene sequence analysis identified 11 different species affiliated to two different phyla; predominantly γ-proteobacteria, representing 5 genera and 1 genus in α-proteobacteria. Thin-layer chromatography (TLC) analysis detected diverse AHL profiles among the 11 AHL positive isolates with both substituted and unsubstituted acyl side chains of C4, C6 and C8 carbon. Further, AHL production in Acinetobacter lactucae, Aeromonas popoffii, Serratia oryzae, and Rhizobium wuzhouense is being reported for the first time. Detection of diverse AHLs from different groups of rhizobacteria associated with rice indicates that these signalling molecules may be involved in the regulation of rhizobacterial behaviour and symbiotic plant-microbe interactions. Future research on the role of AHLs in trans-kingdom communication particularly plant-microbe interaction using synthetic microbial community will enable in evaluating and developing potential plant specific bioproducts.


Location of additional early gene sequences in the adenoviral chromosome.
Genetic and biochemical analysis has revealed additional early gene sequences in the group C human adenovirus genome. Physical mapping by an improved marker rescue method showed that a group of "early function" mutations previously found by us to map within the left quarter of the genome do not map within the known early sequence (0-11.2) in that region, but instead lie within the coordinates 18.5-22.0. A search for early expression in this region of the genome using saturation hybridization techniques showed the presence of two discrete sets of viral cytoplasmic RNA sequences, present early in infection at low copy number and complementary to sequences on the I strand of the adenovirus genome lying between 11.2-14.5 and 19.8-23.5 untis.


Traumatic superior mesenteric arteriovenous fistula: report of a case and review of the literature.
Penetrating arterial injuries can result in the formation of a traumatic false aneurysm or an arteriovenous fistula. Traumatic arteriovenous fistulas of the mesenteric circulation are extremely rare, with only 15 operated cases reported in the English language literature that involved the superior mesenteric artery and vein. Although surgical intervention has been considered the most successful method to treat traumatic mesenteric arteriovenous fistulas, percutaneous transcatheter embolization has been occasionally advocated in the management of small iatrogenic fistulas. We report a case of a gunshot wound patient who had an 8 cm abdominal aortic false aneurysm, as well as a high-flow arteriovenous communication between the superior mesenteric artery and vein, which were successfully treated by a combination of aorto-superior mesenteric bypass and postoperative percutaneous transcatheter embolization. A review of the literature is also included.


Inclusion of a latissimus dorsi segment in an extended lower trapezius musculocutaneous flap facilitates complex defect reconstruction.
The pedicled lower trapezius musculocutaneous flap (LTMF) can extend far beyond the lateral border of the trapezius muscle, with a reliable blood supply. However, the distal part of the extended LTMF lacks a muscular component, limiting its usage in complex defect reconstruction, which often requires obliteration of dead space and coverage of vital structures. To overcome this limitation, we modified the LTMF by adding a segment of latissimus dorsi muscle (LDM). Between 2014 and 2021, the modified extended LTMF was used to reconstruct complex defects in the head, neck, shoulder, and contralateral chest wall and back in 19 patients. By preserving the interconnections between the branches of the posterior intercostal arteries, we were able to include various amounts of LDM within the extended LTMF. The LDM component was used to obliterate dead space and repair wounds involving cerebrospinal fluid leakage, infection, radioactive osteomyelitis, exposed carotid artery, lung, and implant materials. The average flap size was 30.7 cm × 10.9 cm (range: 25 × 8 cm-40 × 14 cm). The average size of the LDM was 113.9 cm2 (range: 27.7-216.6 cm2). Partial flap necrosis occurred in two patients and the secondary defects were reconstructed using a local flap. The remaining 17 flaps survived completely. The LTMF carrying a segment of the LDM could be considered for patients undergoing reconstruction of complex defects in the head, neck, shoulder, and contralateral chest wall and back and for patients who are ineligible for free flap reconstruction.


Amperometric detection of cholesterol using an indirect electrochemical oxidation method.
The indirect electrochemical oxidation method using bromine species in an organic media for measuring cholesterol was developed. The electrochemical behaviors of cholesterol were examined by cyclic voltammetry in a potential range of -0.5 to 2.0V (vs. Ag/AgCl/saturated KCl). The polarization curve of the steady-state current in the applied potential range of 0-2.0V is reported. The obtained kinetic parameters for the catalytic oxidation of cholesterol support the assumption that positive bromine species can be generated from bromine by undergoing two consecutive electrochemical oxidation steps. The positive bromine acts both as electron mediators and as electrocatalysts. Amperometric detection with an anodic current was investigated, and the calibration curve exhibited a linear relationship between the steady-state current and the concentration of cholesterol in the range of 30-200 μM, from which the sensitivity was calculated to be about 0.2 μA/cm2/μM. Moreover, the amperometric current followed Michaelis-Menten's enzymatic model for cholesterol concentrations in the range of 30 μM to 5mM, which can be applied for cholesterol rapid detection in processed foods.


How do medical and non-medical use of z-drugs relate to psychological distress and the use of other depressant drugs?
Z-drugs are hypnotic drugs used for insomnia with considerable potential of abuse. We investigated the relationship of past-year medical and non-medical use of z-drugs with past-year: i) psychological distress; ii) medical use, non-medical use, and DSM-IV use disorder of Benzodiazepine (BZD) tranquilizers; iii) use and DSM-IV alcohol and marijuana use disorders, recreational drugs with a depressant effect on the central nervous system. Data came from the 2015-2017 NSDUH (n = 128,740). Participants aged 18+ were asked if they had used any Z-Drug medically or non-medically in the past year. We investigated the associations between the three-level z-drugs variable with psychological distress and BZD, alcohol, and marijuana variables in multinomial logistic regression models. Past-year prevalences of z-drug use were 3.3% for medical and 0.5% for non-medical use. Medical and non-medical users of z-drugs had higher risk of psychological distress, compared to non-users. Medical and non-medical users of z-drugs had higher risk of medical use, non-medical use, and BZD use disorders. Compared to non-users of z-drugs, medical users had higher risk of marijuana and alcohol use and alcohol use disorders, while non-medical users had higher risk of marijuana use and marijuana use disorders and alcohol. Z-drug users have elevated risk of use and dependence of BZDs and recreational drugs, possibly due to concurrent prescribing and self-medication.


Prostaglandin and thromboxane in liposomes: suppression of the primary immune response to liposomal antigens.
Liposomes containing lipid A as adjuvant and also containing prostaglandin E2 or thromboxane B2 were examined for the ability to influence induction of humoral immunity against liposomal protein or lipid antigens in rabbits. The protein antigen consisted of cholera toxin that was bound to ganglioside GM1 on the surface of the liposomes. High titers of anti-cholera toxin antibodies were produced and IgM and IgG responses were detected. When the immunizing liposomes contained either prostaglandin E2 or thromboxane B2 as part of the lipid bilayer, the primary immune response, involving both IgM and IgG antibodies, was greatly reduced. The secondary immune response observed after a boosting immunization was not suppressed by liposomal eicosanoids. A similar inhibitory effect on the primary response was observed when liposomal lipid antigens were examined instead of cholera toxin. An inhibitory effect of liposomal prostaglandin E2 on the phagocytic uptake of opsonized liposomes by cultured macrophages was also observed, suggesting that liposomal eicosanoids can have direct local effects on macrophages that might influence the immune response to liposomal antigens.


Automatic quantification of speech intelligibility of adults with oral squamous cell carcinoma.
It has been the aim of the present study to introduce a novel automatic technique for the objective and quantitative assessment of speech intelligibility to the evaluation of postoperative outcome. Forty-six patients with oral carcinomas, mean age 59.8 +/- 10.1 years, and an age-matched control group of 40 subjects without oral diseases. Recordings of a standard text read by the patients and the control group were analyzed by an automatic speech recognition system. For the patients, automatic speech recognition yielded word recognition rates between 8 and 82% (mean 49 +/- 19%), for the control group between 60 and 91% (76 +/- 7%). Automatic evaluation closely correlated with the experts' perceptual evaluation of intelligibility (r = -0.93; p < 0.01). The multi-rater kappa of the experts alone (0.55) differed only slightly from the multi-rater kappa of the experts and the speech recognition system (0.58). For adults with speech disorders, automatic speech recognition may serve as a valuable tool to assess global speech outcome after treatment of oral squamous cell carcinoma objectively and quantitatively for clinical and research purposes.


Diffusion on Membrane Domes, Tubes, and Pearling Structures.
Diffusion is a fundamental mechanism for protein distribution in cell membranes. These membranes often exhibit complex shapes, which range from shallow domes to elongated tubular or pearl-like structures. Shape complexity of the membrane influences the diffusive spreading of proteins and molecules. Despite the importance membrane geometry plays in these diffusive processes, it is challenging to establish the dependence between diffusion and membrane morphology. We solve the diffusion equation numerically on various static curved shapes representative for experimentally observed membrane shapes. Our results show that membrane necks become diffusion barriers. We determine the diffusive half-time, i.e., the time that is required to reduce the amount of protein in the budded region by one half, and find a quadratic relation between the diffusive half-time and the averaged mean curvature of the membrane shape, which we rationalize by a scaling law. Our findings thus help estimate the characteristic diffusive timescale based on the simple measure of membrane mean curvature.


Stroke and mortality risk after atrial fibrillation ablation: lesson from the CABANA trial.
The CABANA trial is a randomized controlled study comparing catheter ablation vs. conventional medical therapy in atrial fibrillation (AF) patients. The results of the study showed that catheter ablation did not have a significant reduction of strokes, deaths, serious bleeding, or cardiac arrest compared to medical therapy. However, a significant improvement in AF recurrences, quality of life, and symptom relief has been shown after catheter ablation compared to drug therapy. The mixed results of the study emphasized an active controversy in the cardiology community on the interpretation of the data and their use in current clinical practice. In this review, we summarized the principal controversy points of the trial describing the strengths and weaknesses of the study design and analysis.


Sensation evoked by bipolar intrapulpal stimulation in man.
Bipolar intrapulpal stimulation was applied to human teeth using the same procedure as in animal experiments. The effects of variation of stimulus parameters on the quality of sensation were studied. A prepain sensation exists which cannot be explained by diffusion of the stimulus to periodontal tissues. When the intensity of stimulation is increased, the prepain sensation is gradually replaced by a pinprick sensation. With long, high intensity stimulation, an acute long lasting very painful sensation appears. To evoke a pinprick sensation the best stimulation seems to be a 50 msec train (0.5 msec, 300 Hz, 0.5 mA). Longer train duration and a higher intensity of current are necessary to evoke a long lasting, acute very painful sensation. Since the exclusively Adelta and C nerve fiber content of the dental pulp is well documented and since it is possible to avoid current diffusion outside the dental pulp cavity, the tooth pulp implantation seems to be a good technic for studying pain, as long as the investigator uses adequate stimulation.


Effects of Heating on Proportions of Azaspiracids 1-10 in Mussels (Mytilus edulis) and Identification of Carboxylated Precursors for Azaspiracids 5, 10, 13, and 15.
Azaspiracids (AZAs) are marine biotoxins that induce human illness following the consumption of contaminated shellfish. European Union regulation stipulates that only raw shellfish are tested, yet shellfish are often cooked prior to consumption. Analysis of raw and heat-treated mussels (Mytilus edulis) naturally contaminated with AZAs revealed significant differences (up to 4.6-fold) in AZA1-3 (1-3) and 6 (6) values due to heat-induced chemical conversions. Consistent with previous studies, high levels of 3 and 6 were detected in some samples that were otherwise below the limit of quantitation before heating. Relative to 1, in heat-treated mussels the average (n = 40) levels of 3 (range, 11-502%) and 6 (range, 3-170%) were 62 and 31%, respectively. AZA4 (4) (range, <1-27%), AZA5 (5) (range, 1-21%), and AZA8 (8) (range, 1-27%) were each ∼5%, whereas AZA7 (7), AZA9 (9), and AZA10 (10) (range, <1-8%) were each under 1.5%. Levels of 5, 10, AZA13 (13), and AZA15 (15) increased after heating, leading to the identification of novel carboxylated AZA precursors in raw shellfish extracts, which were shown by deuterium labeling to be precursors for 5, 10, 13, and 15.


A new platelet function test.
A method for screening EDTA(K3) blood samples for platelet function is described. The general availability of whole blood platelet counters in the clinical laboratory suggested their use to measure platelet aggregation. To simplify the collection and storage of blood samples, a method utilizing EDTA collected blood is described. Addition of calcium and citrate restores platelet function to blood samples even when stored at room temperature for several hours. Thus, the blood sample used to assay RBC, WBC and platelet parameters may also be employed in platelet aggregation. A comparison of this method with aggregometry on 120 subjects indicated a similar response to arachidonate, collagen, ristocetin and ADP.


Allergen-induced increase in non-allergic bronchial reactivity.
Non-allergic bronchial hyper-reactivity is a feature of most patients with asthma. We have measured non-allergic bronchial reactivity to inhaled histamine and methacholine in thirteen asthmatic subjects before and after allergen inhalation in the laboratory. The allergen inhalation produced mild early asthmatic responses (19-40% FEV1 fall) in all thirteen, additional definite late asthmatic responses (17-29% FEV1 fall) in four, and equivocal late asthmatic responses (5-11% FEV1 fall) in five. Following allergen inhalation, non-allergic bronchial reactivity increased in seven for up to 7 days. The seven included all four with definite late asthmatic responses and three of the five with equivocal late asthmatic responses. We conclude that allergens make asthma worse, partly through non-allergic mechanisms, and that avoidance of allergens is important in reducing non-allergic bronchial hyper-reactivity.


Rapid detection of Abeta deposits in APP transgenic mice by Hoechst 33342.
The accumulation of beta-amyloid (Abeta) is the earliest event seen in the neocortex and hippocampus of Alzheimer's disease (AD) patients. Transgenic mouse models of Abeta deposition are excellent tools for validating pharmacological therapies for reducing Abeta burden. Sensitive and rapid probes should be needed for detecting Abeta plaques ex vivo and in vivo in the transgenic mouse models. However, a thioflavin derivative, Pittsburgh Compound-B (PIB), which is a successful PET tracer for detecting Abeta plaques in AD brains, does not visualize Abeta plaques in APP and PS1/APP transgenic mice. Here, we report that Hoechst 33342, a cell-permeable fluorescent probe for staining DNA and nuclei, also detects Abeta plaques in APP Tg mouse. These findings could allow us to rapidly detect Abeta plaques in AD mouse models, and to develop improved compounds for detecting Abeta plaques in vivo in mouse models.


Distribution, speciation, and bioaccumulation of potentially toxic elements in the grey mangroves at Indian Sundarbans, in relation to vessel movements.
Sundarban is the world's largest mangrove wetland and home of 4.6 million people (Indian part), whose principal mode of communication is motorized boats (ferries). This study shed light on the role played by ferry movement in the speciation (following the BCR three-step sequential extraction method), ecological impact and bioaccumulation of potentially toxic elements (PTEs) in plant tissues (root and lamina) of grey mangrove (Avicennia marina) found near the five ferry ghats (ports). One-way ANOVA showed variation in major soil parameters (silt, clay, organic carbon, pH, Electrical conductivity) and PTEs (As, Cd, Cr, Cu, Hg, and Pb) between sites. Sequential extraction revealed that Cd was present in the 'exchangeable' form across the sites, Pb was in the 'reducible' form, and the rest of the PTEs were majorly found in 'residual' phase. Pollution indices revealed moderate to heavy contamination and considerable potential ecological risk due to Cd. Pearson correlation statistics and concentration variations indicate a relation between Pb and ferry movement frequency in the sites. Higher bioconcentration of Pb in the roots of A. marina, indicates phytostabilization action. Translocation factor for Cd in the leaves, indicates phytoextraction by A. marina. Principal component analysis (PCA) and hierarchical cluster analysis (HCA) showed a close association between vehicle movement and Hg, Pb, Silt fraction, electrical conductivity, Cr, and As. This study recommends regular pollution monitoring across Sundarbans, as the PTEs in sediment-plant matrix can impact the higher trophic levels, human health through possible biomagnification in the detritus food chain, and can adversely impact the existing conservation initiatives.


Modulation of thermometric performance of single-band-ratiometric luminescent thermometers based on luminescence of Nd3+ activated tetrafluorides by size modification.
Due to a number of its advantages, luminescence thermometry has been a strongly developed strand of temperature metrology over a period of time. Although there are several different types of luminescent thermometers, recently attention has been focused on a new single-band ratiometric approach, which is based on the excited state absorption phenomenon. Nevertheless, since this process is nontrivial and has not been studied extensively in the context of thermometry to date, a number of studies are necessary to enable the intentional development of highly sensitive thermometers based on this method. One of the important aspects is to investigate the influence of material size and the associated occurrence of surface effects, which is considered in this work. In addition, the research in this paper has been extended to explore the aspect of host material composition. Accordingly, nanocrystals and microcrystals of β-NaYF4:2%Nd3+, β-NaGdF4:2%Nd3+, and LiGdF4:2%Nd3+ were investigated in this work. The influence of surface effects on thermometric parameters was proved, with special emphasis on the useful temperature range. Thus, by increasing the particle size, it was possible to intentionally extend the useful range by even more than 100 K.


Liver hypertrophy in winter flounder following exposure to experimentally oiled sediments.
1. Male winter flounder were exposed to sediments contaminated with Venezuelan crude oil in 3 laboratory experiments of 4-5 months duration. 2. Oil exposure resulted in significant increases in liver weight. This was particularly evident in fish weighing less than 400 g. 3. The enlarged livers of the oil-exposed flounder had reduced concentrations of DNA, protein, Na+ and Zn2+, and increased concentrations of lipid and phospholipid. 4. The reduced DNA and Na+ concentrations suggested liver hypertrophy rather than hyperplasia. 5. The increased phospholipid concentrations suggested growth of membrane structures such as endoplasmic reticulum.


Influence of waxy proteins on wheat resistant starch formation, molecular structure and physicochemical properties.
This study investigated the influence of wheat waxy proteins on type III resistant starch (RS3) formation, molecular structure and physicochemical properties. Waxy deletions led to a significant increase in B- and C-type starch granules, particle size of RS3, and slowly digesting starch content, and a decrease in content of amylose and RS3. X-ray powder diffraction and Fourier-transform infrared spectroscopy analyses revealed high relative crystallinity and long-range (1047/1022 cm-1, IR1) and low short-range (1022/995, IR2) crystalline structures of RS3 in waxy wheat, which suggests that waxy deletions could produce a more ordered crystalline structure and fewer amorphous regions in RS3 crystals. Further laser confocal microscopy Raman spectroscopy analysis found that waxy deletions significantly increased the full width at half maximum and intensity of the bands at 480 cm-1, as well as leading to more ordered RS3 crystals. These changes in molecular structure resulted in improved physicochemical properties of RS3.


Genetic variants of MnSOD and GPX1 and susceptibility to bladder cancer in a Turkish population.
This study was conducted to investigate the association of genetic polymorphisms in the MnSOD and GPX1 genes with the risk and invasiveness of bladder cancer in a Turkish population. This prospectively designed study enrolled 157 patients with bladder cancer (mean age 63.2 ± 10.86 years) and 224 healthy controls (mean age 61.7 ± 8.39 years). Genotyping of the MnSOD Ala-9Val and GPX1 Pro198Leu polymorphisms was carried out by PCR-RFLP. No significant difference was found in MnSOD genotype distributions between the controls and the bladder cancer patients. However, the Leu/Leu genotype of GPX1 was associated with a significantly higher risk of bladder cancer than the Pro/Pro genotype. When stratified according to tumor stage, the Leu/Leu genotype of GPX1 was more frequently observed in bladder cancer patients with high-stage tumors than those with low-stage tumors. Additionally, patients carrying both Ala/Ala of MnSOD and Leu/Leu of GPX1 had the highest risk of developing bladder cancer. In conclusion, the present study indicates that the GPX1 Pro198Leu polymorphism may be associated with the risk and development of invasive bladder cancer. In addition, the combination of the MnSOD Ala/Ala and GPX1 Leu/Leu genotypes may have a synergistic effect on disease risk.


Listeriosis in pregnancy: An umbrella review of maternal exposure, treatment and neonatal complications.
Listeria monocytogenes is a commonly found organism in processed and prepared food and the disease of listeriosis is associated with a high morbidity and mortality. Compared with the general population, the risk of being diagnosed with listeriosis increases during pregnancy. Listeriosis can lead to miscarriage, spontaneous preterm labour and preterm birth, stillbirth and congenital neonatal infections. We conducted a universal review of listeriosis in pregnancy and in the newborn. The EMBASE, PubMed, Cinahl and Web of Science databases were searched for systematic reviews indexed before 1 December 2020. Any systematic reviews evaluating the prevalence, treatment, diagnosis and effects of listeriosis during pregnancy and up to 4 weeks postnatally were included. Eligibility assessment, data extraction and quality assessment by the Methodological Quality Assessment of Systematic Reviews (AMSTAR-2) were performed in duplicate. We identified 397 citations of which nine systematic reviews comprising 330 studies and 487 patients' reviews were included. Most systematic reviews (seven of nine) were of moderate to high quality. Prevention in pregnant women was based on adherence to strict dietary recommendations, such as reheating leftovers until steamed and avoiding unpasteurised dairy products. Listeriosis infections were likely to occur in the third trimester (66%) rather than in the first trimester (3%) of pregnancy. Symptoms are mostly fever and other flu-like symptoms, such as fatigue. Diagnosis was primarily made by culture of the pathogen. Intravenous amoxicillin or ampicillin were first-line treatment. Listeriosis, a rare but serious infectious disease in pregnancy, can cause devastating consequences for the fetus and newborn. Appropriate preventative treatment should be initiated during early pregnancy to avoid complications. Listeria is commonly found in processed and prepared food. Prevention is the best way to avoid listeriosis during pregnancy.


Generation of Human Monoclonal Autoantibody-Producing Cell Lines by Epstein-Barr Virus Transformation of Autoreactive B Lymphocytes and by Somatic Cell Hybridization Techniques: Application to the Analysis of the Autoimmune B Cell Repertoire.
Epstein-Barr virus (EBV) was used to immortalize human peripheral B lymphocytes committed to the production of autoantibodies in healthy subjects and in patients with various autoimmune diseases. EBV-transformed B lymphocytes producing human monoclonal autoantibodies were fused with the human-mouse heterohybridoma F3B6 cells to stabilize the production of monoclonal antibodies (mAb). The present method of generating human B cell clones producing mAbs now makes it possible to analyze in detail the nature of human autoantibodies with respect to antigen-binding specificity, affinity, corresponding autoepitopes, and the variable (V) region structure.


Effects of some mono- and bisquaternary ammonium compounds on the reactivatability of soman-inhibited human acetylcholinesterase in vitro.
Acetylcholinesterase (AChE) inhibited by the organophosphate soman (1,2,2-trimethyl-propylmethylphosphonofluoridate) rapidly becomes resistant to reactivation by oximes due to dealkylation of the soman-enzyme complex. This reaction is called aging. The effect of the four mono- and bisquaternary ammonium compounds tetramethylammonium (TMA), hexamethonium, decamethonium and suxamethonium on the reactivatability of soman-inhibited, solubilized AChE from human erythrocytes was investigated in vitro. All compounds were reversible inhibitors of AChE; the respective dissociation constants and the type of inhibition exhibited considerable differences. The affinities to both the active and the allosteric site were considerably higher for suxamethonium (Kii 81.3 microM; Ki 15.9 microM) and decamethonium (Kii 15.4 microM; Ki 4.4 microM) than for TMA (Kii 1 mM; Ki 289.6 microM) and hexamethonium (Kii 4.5 mM; Ki 331.8 microM). The reactivation experiments were performed in a four-step procedure (soman-inhibition at 0 degree and pH 10, aging at 37 degrees and pH 7.3, reactivation by the oxime HI 6 at 37 degrees and pH 7.3 followed by AChE assay). After these four steps (total duration 55 min), AChE was inhibited by soman to 95-100%. HI 6 could reactivate about 20% of the inhibited enzyme. All effectors increased the AChE reactivatability by HI 6 when added before aging was started. The maximal increase in reactivatability was higher in the presence of 1.6 mM suxamethonium (+35.8%) and 150 microM decamethonium (+40%) than of 22 mM TMA (+22.5%) and 8.3 mM hexamethonium (+19.2%). If the effectors were added after 5 min of aging they increased the activity of soman-inhibited AChE, but to a considerably smaller extent than HI 6. A good correlation of the respective Kii values and the effective concentrations of these drugs was observed, indicating that an allosteric binding site of AChE might be involved in the protective effect of these drugs.