Exercise thallium-201 scintigraphy and prognosis in typical angina pectoris and negative exercise electrocardiography.
Patients with a history of typical angina but negative exercise electrocardiography represent a subgroup with an intermediate likelihood of having coronary artery disease and future cardiac events. A retrospective study of the prognostic utility of stress-redistribution thallium-201 scintigraphy was performed in 190 such patients. A second group of 203 patients with typical angina and a positive exercise electrocardiogram were analyzed for comparative scintigraphic purposes. The cardiac event rate for the 144 negative exercise electrocardiogram patients with normal thallium results was 5 vs 15% in the 46 patients with abnormal thallium results (p = 0.01). These patients were further stratified into high (14 to 18%), intermediate (9%) and low (less than 2%) risk groups for future cardiac events based on combining the thallium results with the percentage of maximal predicted heart rate achieved. A multivariate analysis revealed that an abnormal thallium result was the only significant correlate of future cardiac events. Mechanisms responsible for the discordant finding of a negative exercise electrocardiogram in patients with typical angina include (1) false-positive angina symptomatology in low prevalence coronary artery disease groups in whom the thallium test is negative, and (2) "electrocardiographically silent" ischemia in patients in whom the thallium test is positive. These findings reveal that thallium stress-redistribution scintigraphy can be used to stratify 1-year prognosis in this subgroup of patients with typical angina and negative exercise electrocardiograms.


Carrier-mediated uptake and presentation of a major histocompatibility complex class I-restricted peptide.
Antigenic peptides derived from endogenous or viral proteins can associate with class I or class II major histocompatibility complex (MHC) molecules, while exogenous antigens are endocytosed, processed intracellularly and presented on MHC class II molecules. Here we describe a method that allows the presentation of an MHC class I-restricted antigenic peptide on MHC class I molecules, although it was taken up from the outside. The HLA-A2-restricted influenza virus matrix protein-derived peptide (flu, 57-68) was used either in soluble form or coupled via an S-S bridge to transferrin (Tf-flu). Target cells were incubated with flu or Tf-flu and the effective antigen presentation was detected in a cytotoxicity assay using flu peptide-specific, HLA-A2-restricted CD8+ cytotoxic T lymphocytes. Sensitization of target cells with Tf-flu required 5 to 10 times higher molar concentrations of peptide compared to sensitization with soluble free peptide. The Tf-flu construct was taken up by the cells via the Tf receptor (CD71) as the binding of Tf-flu was blocked by an excess of Tf. In contrast to the flu peptide, cytotoxicity elicited by Tf-flu was blocked by brefeldin A but not by chloroquine nor inhibitors of intracellular reducing steps, like 1-buthionine-(s,r)-sulfoximine or n-ethylmaleimide. Presentation of the flu peptide derived from Tf-flu construct is not hindered in the mutant T2 cell line, which lacks genes coding for transporter proteins for antigenic peptides (TAP1/TAP2) and proteasomes subunits, suggesting that the processing pathway described in this report may involve TAP-independent steps.


Adaptation of the BOXURB model in a southeastern European environment: the case of Athens.
The present work describes the adaptation and application of an operational air quality forecast model in a net grid of (1 x 1) km(2) emission source resolution, covering the Greater Area of Athens, Greece. The model is used to estimate the hourly concentrations of nitrogen oxides at a receptor grid of 17 monitoring stations for the 10-year period 1995-2004. The analysis reveals that the best model performance occurs under heavy-traffic conditions, whereas in rural and industrial areas, the model performance is worse.


Global epidemiological burden of fungal infections in cirrhosis patients: A systematic review with meta-analysis.
Fungal infections (FIs) have serious implications, yet understated in cirrhosis. Therefore, we reviewed the epidemiology and trends of FIs among cirrhotics. Four electronic databases were searched for full-text articles describing prevalence of FIs in cirrhosis. Studies from post-transplant, malignancy and classical-immuno-deficiency patients were excluded. A random-effects meta-analysis was done to pool estimates of FIs (overall, and by type and infection-site), and their variation(I2 ) was explored on moderator-analysis and meta-regression. Risk of bias and asymmetry in estimates was assessed by a checklist and Egger's regression, respectively.(CRD42019142782). Thirty-four low-risk and four moderate-risk studies (31 984 cirrhotics) were included. Pooled estimates of overall FIs (17 studies), invasive fungal infections (IFIs; 17 studies), invasive candidiasis (23 studies) and invasive aspergillosis (16 studies) in cirrhosis were 10.2%(6.0-16.9), 9.5%(5.4-16.2), 4.0%(2.0-8.0) and 2.8%(1.5-5.3), respectively (I2 > 90%;each). Site of FIs in decreasing order of pooled prevalence was pulmonary, urinary tract, bloodstream, peritoneal, oesophageal and cerebral. Geographic differences in these estimates were remarkable, with highest burden of overall FIs from Belgium, the United States and India. Non-albicans-Candida and Aspergillus infections have increased over the last decade in cirrhosis. Intensive-care-unit (ICU)-admitted and acute-on-chronic liver failure (ACLF) patients had the highest prevalence of IFIs. MELD score(cases), bias score and sample size across studies were the predictors of variance in overall FI estimates. Diabetes, steroid and broad-spectrum antibiotic-exposure, and multiple organ failures were the common predispositions reported in patients with FIs. FIs impose a substantial burden in cirrhosis. ACLF and ICU admission should be considered as a host factor for defining IFIs. Epidemiology of FIs can guide interpretation of biomarkers and antifungal treatment in cirrhosis.


ATXN3 promotes prostate cancer progression by stabilizing YAP.
Prostate cancer (PC) is the most common neoplasm and is the second leading cause of cancer-related deaths in men worldwide. The Hippo tumor suppressor pathway is highly conserved in mammals and plays an important role in carcinogenesis. YAP is one of major key effectors of the Hippo pathway. However, the mechanism supporting abnormal YAP expression in PC remains to be characterized. Western blot was used to measure the protein expression of ATXN3 and YAP, while the YAP target genes were measured by real-time PCR. CCK8 assay was used to detect cell viability; transwell invasion assay was used to measure the invasion ability of PC. The xeno-graft tumor model was used for in vivo study. Protein stability assay was used to detect YAP protein degradation. Immuno-precipitation assay was used to detect the interaction domain between YAP and ATXN3. The ubiquitin-based Immuno-precipitation assays were used to detect the specific ubiquitination manner happened on YAP. In the present study, we identified ATXN3, a DUB enzyme in the ubiquitin-specific proteases family, as a bona fide deubiquitylase of YAP in PC. ATXN3 was shown to interact with, deubiquitylate, and stabilize YAP in a deubiquitylation activity-dependent manner. Depletion of ATXN3 decreased the YAP protein level and the expression of YAP/TEAD target genes in PC, including CTGF, ANKRD1 and CYR61. Further mechanistic study revealed that the Josephin domain of ATXN3 interacted with the WW domain of YAP. ATXN3 stabilized YAP protein via inhibiting K48-specific poly-ubiquitination process on YAP protein. In addition, ATXN3 depletion significantly decreased PC cell proliferation, invasion and stem-like properties. The effects induced by ATXN3 depletion could be rescued by further YAP overexpression. In general, our findings establish a previously undocumented catalytic role for ATXN3 as a deubiquitinating enzyme of YAP and provides a possible target for the therapy of PC. Video Abstract.


Effect of topiramate on cognitive function and single units from hippocampal place cells following status epilepticus.
Topiramate, an antiepileptic drug with multiple mechanisms of action, was assessed as a neuroprotective agent following status epilepticus. We administered topiramate or normal saline chronically beginning 1 hour after cessation of lithium pilocarpine-induced status epilepticus. Control animals not subjected to status epilepticus were also treated with topiramate or normal saline. Following completion of the topiramate treatment, animals were tested in the water maze to assess spatial learning and underwent in vivo single-cell place cell recordings. Spontaneous seizure frequency following status epilepticus in the topiramate-treated rats was similar to that in the rats treated with saline. Following status epilepticus, rats had profound deficits in water maze performance and place cell function. Rats subjected to status epilepticus and treated with topiramate were also severely impaired in the water maze, but performed slightly better than rats treated with saline. Following status epilepticus, topiramate-treated rats did not differ from rats treated with normal saline in the platform switch, a test of prefrontal function. Although place cell firing patterns were similar in both the topiramate- and saline-treated rats, rats treated with topiramate had higher information content scores than rats treated with saline. Topiramate-treated animals had less supragranular sprouting following status epilepticus than nontreated rats. Control animals treated with topiramate did not differ from saline-treated controls on any measures. Taken together, this study shows that topiramate administered following status epilepticus has modest neuroprotective effects.


Comprehensive evaluation of NAODESHENG by combining UPLC quantitative fingerprint and antioxidant activity.
The screening of marker compound is of great significance to the quality control of traditional Chinese medicine (TCM). One approach which combines fingerprint and biological evaluation has developed rapidly. Multi-wavelength fusion fingerprints and antioxidant activity screening are integrated in this study to evaluate the quality of NAODESHENG. Characteristic multiwavelength fusion fingerprints of 14 batches of samples were generated at five different wavelengths and evaluated by quantitative fingerprinting with ultra-performance liquid chromatography (UPLC). In the quantitative fingerprinting method, 21 components in NAODESHENG were qualitatively and quantitatively analyzed by external standard method. The antioxidant activities of these 21 components was determined by pre-column antioxidant activity test. Multivariate statistical methods such as hierarchical clustering analysis and principal component analysis(PCA) was used to reduce the dimensions and variables from a large number of original data to screening marker compound with bioactivity. Based on the above results, it is suggested that 3'-Methoxy Puerarin and 11 other components should be used as the quality marker of NAODESHENG. This study demonstrates the feasibility of multi-wavelength fusion fingerprinting combined with antioxidant activity analysis, which associates quality control with bioactivity, providing a reliable and efficient method for quantitative assessment of TCM quality consistency.


Laparoscopic versus open distal gastrectomy for locally advanced gastric cancer after neoadjuvant chemotherapy: safety and short-term oncologic results.
To compare the safety and efficacy of laparoscopic distal gastrectomy (LDG) versus open distal gastrectomy (ODG) in treating locally advanced distal gastric cancer after neoadjuvant chemotherapy (NACT). Forty-four patients with locally advanced distal gastric cancer were enrolled. The patients received neoadjuvant chemotherapy before undergoing surgery. Twenty patients were allocated into LDG after NACT group and 24 patients into ODG after NACT group. Radicalness of oncological resection, surgical safety and recovery were measured and compared. All operations were successfully performed without severe postoperative complications. There were no significant differences in blood loss, mean operation time, complications, distal and proximal resection margin, and number of retrieved lymph nodes between LDG and ODG groups, but LDG group had shorter length of incision and the first aerofluxus time. Laparoscopic distal gastrectomy after NACT has comparable results with open distal gastrectomy in safety and efficacy in the short term.


Preparation and purification of 5'-amino-5'-deoxyguanosine-5'-N-phosphoramidate and its initiation properties with T7 RNA polymerase.
5'-Amino-5'-deoxyguanosine-5'-N-phosphoramidate (GNHP) was synthesised in four steps from guanosine. Its identity was confirmed using spectroscopic and kinetic studies. A chromatographic method for the purification of this unstable compound was developed. GNHP was found to initiate T7 RNAP promoted transcriptions to afford 5'-O3P-NH-RNA, which hydrolyses readily to yield 5'-H2N-RNA that can be conjugated to activated esters.


Comparative analysis of yak milk and bovine milk glycoprotein N/O-glycome by online HILIC-UV-ESI-MS/MS.
Yak milk (YM) has higher protein content than other bovine milk (BM) varieties. The bioactivity of milk glycoproteins is related to N/O-glycans. We qualitatively and quantitatively compared the N/O-glycome of YM and BM glycoproteins using stable isotope labeling combined with hydrophilic interaction chromatography and electrospray ionization mass spectrometry. We identified 79 and 78 N-glycans in YM and BM, respectively. Two N-glycans (H4N5F1A1; H5N4F1) were exclusive to YM. The content ratios of different types of N-glycans differed significantly between YM and BM, with sialylated N-glycans 2.33 times more abundant in YM. Five and seven O-glycans were detected in YM and BM, respectively. Two O-glycans (H1N2; H1N2A1) were exclusive to BM. The bi-sialylated O-glycan, H1N1A2, accounted for 56.1% of O-glycans in YM; it was 5.97 times more abundant in YM than in BM (equal volume basis). This study provides a theoretical basis for the future utilization of YM as a functional food.


An image-guided planning system for endosseous oral implants.
A preoperative planning system for oral implant surgery was developed which takes as input computed tomographies (CT's) of the jaws. Two-dimensional (2-D) reslices of these axial CT slices orthogonal to a curve following the jaw arch are computed and shown together with three-dimensional (3-D) surface rendered models of the bone and computer-aided design (CAD)-like implant models. A technique is developed for scanning and visualizing an eventual existing removable prosthesis together with the bone structures. Evaluation of the planning done with the system shows a difference between 2-D and 3-D planning methods. Validation studies measure the benefits of the 3-D approach by comparing plans made in 2-D mode only with those further adjusted using the full 3-D visualization capabilities of the system. The benefits of a 3-D approach are then evident where a prosthesis is involved in the planning. For the majority of the patients, clinically important adjustments and optimizations to the 2-D plans are made once the 3-D visualization is enabled, effectively resulting in a better plan. The alterations are related to bone quality and quantity (p < 0.05), biomechanics (p < 0.005), and esthetics (p < 0.005), and are so obvious that the 3-D plan stands out clearly (p < 0.005). The improvements often avoid complications such as mandibular nerve damage, sinus perforations, fenestrations, or dehiscences.


Well-differentiated liposarcoma/atypical lipomatous tumor of the oral cavity: report of three cases and review of the literature.
Atypical Lipomatous Tumor/Well Differentiated Liposarcoma (ALT/WDLS) is a soft tissue sarcoma of intermediate malignant behavior, most frequently affecting the retroperitoneum and lower extremities. Oral liposarcomas are very rare neoplasms, the most common histological subtype being ALT/WDLS. In this study, three additional cases of ALT/WDLS located on the tongue (2 cases) and the lower lip (1 case), respectively, are described. Analysis of the salient clinicopathologic features of 63 oral ALT/WDLS cases previously reported in the English language literature, as well as of the 3 cases presented in this study, indicates that the indolent biologic behavior of this tumor justifies its designation as a locally spreading malignant neoplasm, affording a rather conservative surgical approach.


Synthesis of heteroarylpiperazines and heteroarylbipiperidines with a restricted side chain and their affinities for 5-HT1A receptor.
Heteroarylpiperazine and heteroarylbipiperidine derivatives, bearing a 4-piperidine ring instead of an alkylamino side chain to give the semi-rigidity, were prepared and evaluated for their abilities to displace [(3)H]8-OH-DPAT binding to the rat hippocampal synaptic membranes. These compounds showed low to moderate affinities for 5-HT(1A) receptor, with Ki values ranging from 6912 nM to 232 nM. Of these compounds, 8b and 15e exhibited the best affinities for 5-HT(1A) receptor with Ki values of 232 nM and 338 nM, respectively.


Affinity labeling of phosphoglycerate kinase by 5'-[p-(fluorosulfonyl)benzoyl]-1,N6-ethenoadenosine.
Yeast phosphoglycerate kinase is irreversibly inactivated upon incubation with 5'-[p-(fluorosulfonyl)-benzoyl]-1-N6-ethenoadenosine (5'-FSB epsilon A), an analogue to the nucleotide substrate. Marked protection against inactivation occurs with MgATP, ATP, MgADP, ADP, and 3-phosphoglycerate, suggesting that a part of the catalytic center is modified. The time dependence of the inactivation is characterized by a nonlinear kinetic profile. Curve fitting of various models for ligand binding to the enzyme suggested a two-site model. Modification of one of the sites appears to protect the catalytically essential site from modification. Stoichiometric studies show that the relationship between moles of 5'-FSB epsilon A incorporated per mole of enzyme and the residual enzymatic activity also shows nonlinear behavior. An extrapolated value of 1.5 mol of bound label/mol of enzyme corresponds to complete inactivation. The apparent overall pseudo first-order rate constant for the reaction between phosphoglycerate kinase and 5'-FSB epsilon A, as well as the separate rate constants for the modification, exhibit saturation behavior with respect to the concentration of 5'-FSB epsilon A, indicative of a rapid reversible binding of the reagent to the enzyme prior to modification.


Gut-derived metabolites mediating cognitive development in 5-year-old children: Early-life transplant in mice has lasting effects throughout adulthood.
The gut microbiota has been causally linked to cognitive development. We aimed to identify metabolites mediating its effect on cognitive development, and foods or nutrients related to most promising metabolites. Faeces from 5-year-old children (DORIAN-PISAC cohort, including 90 general population families with infants, 42/48 females/males, born in 2011-2014) were transplanted (FMT) into C57BL/6 germ-free mice. Children and recipient mice were stratified by cognitive phenotype, or based on protective metabolites. Food frequency questionnaires were obtained in children. Cognitive measurements in mice included five Y-maze tests until 23 weeks post-FMT, and (at 23 weeks) PET-CT for brain metabolism and radiodensity, and ultrasound-based carotid vascular indices. Children (faeces, urine) and mice (faeces, plasma) metabolome was measured by 1H NMR spectroscopy, and the faecal microbiota was profiled in mice by 16S rRNA amplicon sequencing. Cognitive scores of children and recipient mice were correlated. FMT-dependent modifications of brain metabolism were observed. Mice receiving FMT from high-cognitive or protective metabolite-enriched children developed superior cognitive-behavioural performance. A panel of metabolites, namely xanthine, hypoxanthine, formate, mannose, tyrosine, phenylalanine, glutamine, was found to mediate the gut-cognitive axis in donor children and recipient mice. Vascular indices partially explained the metabolite-to-phenotype relationships. Children's consumption of legumes, whole-milk yogurt and eggs, and intake of iron, zinc and vitamin D appeared to support protective gut metabolites. Overall, metabolites involved in inflammation, purine metabolism and neurotransmitter synthesis mediate the gut-cognitive axis, and holds promise for screening. The related dietary and nutritional findings offer leads to microbiota-targeted interventions for cognitive protection, with long-lasting effects.


Folic acid supplementation influences the distribution of neural tube defect subtypes: A registry-based study.
Periconceptional folic acid (FA) reduces neural tube defect (NTD) risk, but seems to have a varying effect per NTD subtype. We aimed to study the effect of FA supplementation on NTD subtype distribution using data from EUROCAT Northern Netherlands. We included all birth types with non-syndromal NTDs born in 1997-2012. By Fisher's exact test we analyzed possible differences in NTD subtype distribution between a correct FA supplementation group and incorrect FA supplementation group. We found proportionally fewer cervical/thoracic spina bifida cases and more lumbar/sacral spina bifida cases in the correct FA supplementation group, irrespective of the presence of the main NTD risk factors. The effect on NTD subtype distribution was only seen when FA supplementation was started before conception. We conclude that FA not only prevents the occurrence of a significant proportion of NTDs, but might also decrease the severity of NTDs, as long as supplementation is started before conception.


Decadal Changes in Trace Metal Concentrations in Upland Headwater Lakes.
The objective of this study was to assess the current chemistry of trace elements in upland headwater lakes in Ireland and determine their trends during the last decade in response to decreasing emissions. Twenty-nine upland lakes were sampled in 2017-2018; 19 were previously sampled in 2007-2008. The 2017-2018 samples were analyzed for conductivity, pH, DOC, and 18 trace elements. The lakes had low element concentrations; only 7 of 18 trace elements were > 1 µg/L (Fe, Al, Zn, Mn, B, Sr and Ba). Nine elements were assessed for significant decadal changes; four elements decreased (B, Co, Mn, and Sr) and one increased (Pb). Their correlation with conductivity, pH, and DOC and the associated changes in those variables partially explained the observed trends. In general, elements that were correlated with DOC did not decrease, while those that were not correlated decreased between the two periods. Despite decreased anthropogenic emissions, ecosystem recovery and climate perturbations can confound or mask the benefits of emissions reductions.


Development and Implementation of a Surgical Quality Improvement Pathway for Pediatric Intussusception Patients.
Children with intussusception can be admitted or discharged from the emergency department (ED) following enema reduction, but little is known about best practices for surgical follow-up and the need for a return to care. We developed a standardized clinical assessment and management plan (SCAMP) for ileocolic intussusception to enable the discharge from the ED of successfully reduced patients meeting certain criteria with 2 planned follow-up phone calls by surgical personnel after discharge. Outcomes included incidence of complications in discharged patients, bacteremia, the success of follow-up phone calls, rates of recurrent intussusception, and return to care. Of the 118 patient encounters treated through the SCAMP in 2 pilot studies from February 2013 to December 2017, 76% met discharge criteria, of whom 88% underwent outpatient management. There were no instances of bowel perforation, necrosis, or death in the discharged group. No patients developed bacteremia despite withholding antibiotics for the indication of intussusception. Sixty-two percent and 59% of patients received 24-hour follow-up phone calls, and 28% and 55% of patients received second follow-up phone calls in pilots 1 and 2, respectively. Of those successfully discharged, 74% did not return to care, 19% returned for recurrent intussusception, and 7% returned for unrelated symptoms. Nearly all patients who returned to care did so through the ED and not the clinic. Implementation of the SCAMP demonstrated that patients meeting certain criteria could be safely discharged from the ED, avoid antibiotics, and safely undergo phone-based follow-up for concerns of recurrent intussusception.


Delayed profound thrombocytopenia after abciximab administration for coronary stenting in acute coronary syndrome. Case reports and review of the literature.
Profound thrombocytopenia occurring 1 week after drug administration is a seldom described, self-limiting and mostly uneventful immune reaction to abciximab. Quick differential diagnosis is essential, since other forms of thrombocytopenia associated with concomitant antithrombotic therapies may be much more severe and require prompt treatment. Awareness of this reaction may avoid unnecessary and risky discontinuation of other antiplatelet therapies in the critical phase after coronary stenting.


N-(2-(4-hydroxyphenyl)ethyl)-4-chlorocinnamide: a novel antagonist at the 1A/2B NMDA receptor subtype.
A series of N-(2-phenethyl)cinnamides was synthesized and assayed for antagonism at three N-methyl-D-asparate (NMDA) receptor subtypes (NR1A/2A-C). N-(2-(4-hydroxyphenyl)ethyl)-4-chlorocinnamide (6) was identified as a highly potent and selective antagonist of the NR1A/2B subtype.


How does family economic education foster students' economic behavior? The mediating role of economic and entrepreneurial literacy.
Understanding economic behavior will be beneficial for students to manage their economy and finances while they are living apart from their parents. This study aims to investigate the impact of family economic education on the economic behavior of students and examine the role of economic and entrepreneurial literacy. The research data were collected through an online survey from 546 university students in Indonesia, and structural equation modeling with IBM-SPSS-AMOS 28 was utilized to confirm the proposed hypothesis. The findings indicated a robust link between family economic education and the economic behavior of students. Similarly, family economic education can promote the economic and entrepreneurial literacy of students. This study also confirms the direct influence between economic literacy, entrepreneurial literacy, and the economic behavior of students. Lastly, this study notes the essential roles of economic and entrepreneurial literacy in mediating the relationship between family economic education and university students' economic behavior in Indonesia. The results offer valuable insight for policy researchers and educational institutions regarding how to involve economic and entrepreneurial literacy to foster economic behavior among university students.


Effect of homogenization-pressure-assisted enzymatic hydrolysis on the structural and physicochemical properties of lotus-seed starch nanoparticles.
In previous studies, we successfully prepared lotus-seed starch nanoparticles (LS-SNPs) using enzymatic methods. To further improve their performance, we studied the structural, physical and chemical properties of LS-SNPs prepared by high-pressure homogenization (HPH)-assisted enzymatic hydrolysis (EH). HPH treatments at different pressures and frequencies have a significant effect on the particle size and molecular weight of LS-SNPs. Structural analyses showed that LS-SNP and H-LS-SNP both comprised B-type starch crystals. As the homogenization pressure and frequency were increased, the relative crystallinity of H-LS-SNP first increased and then decreased, indicating that HPH treatment affected the double-helix structure of LS-SNPs. The results also show that moderate HPH treatment was beneficial for enzymatic hydrolysis, but when the HPH treatment was further increased, it destroyed the ordered structure of LS-SNPs. Our research showed that H-LS-SNPs with the smallest particle size and the highest crystallinity were obtained under pressure of 150 MPa, a homogenization frequency of five times the original, and a material-to-liquid ratio of 3%. The results indicate that HHP-assisted EH is a suitable method for preparing SNPs. These findings provide new ideas for the preparation of SNPS to meet the needs of food industry.


Spectral sensitivity and colour vision in the ground-dwelling sciurids: results from golden mantled ground squirrels and comparisons for five species.
Behavioural measurements of several indices of visual sensitivity and colour vision for the golden-mantled ground squirrel (Spermophilus lateralis) are reported. The spectral sensitivity functions for this animal show a change from having a single peak at about 520 nm to having a strongly bipartite appearance with peaks at about 540 and 460 nm as the level of light adaptation is increased from low to higher levels. Discrimination tests reveal that these squirrels have dichromatic colour vision with spectral neutral points centered at 507.5 nm. Comparisons are made of the visual capacities of five species of ground-dwelling sciurids, all of which have been tested in the same situations. These comparisons indicate that: (1) the retinas of all of these species contain a small number of functional rods in addition to a much more obvious cone population; (2) the spectral sensitivity functions of these species do not show systematic variations; (3) the cone pigments found in the retinas of these animals have sensitivity peaks at about 440 and 525 nm; (4) all of these species have dichromatic colour vision; (5) there is no evidence for systematic differences in visual sensitivity or colour vision among these five species.


Environmental concentrations, characteristics and risk assessment of microplastics in water and sediment along the Western Cape coastline, South Africa.
Plastic debris is accumulating in all environments globally and South Africa's poor waste management plan has led to an increase in plastic contamination throughout the country. Information about microplastics (MPs) in urban and rural coastal environments in South Africa is poor. The aim of this study was to determine coastal MP concentrations in water (particles/L) and sediment (particles/kg). Sampling took place in summer of 2020 during low tide at 14 sites, along the coast of the Western Cape, South Africa. MPs were extracted and analysed based on shape, color, size and polymer type (using an ATR-FTIR). An ecological risk assessment was done to assess the potential risks posed by MPs in all sample types. Sediment MP concentrations (185.07 ± 15.25 standard error particles/kg) were higher than water (1.33 ± 0.15 particles/L). Gordon's Bay (site 12) had the highest MP concentrations in sediment samples (360 ± 36.74 particles/kg), identifying harbors as the main source for MP contamination. Kalk Bay (site 9) displayed the highest concentration in water samples (4.97 ± 0.18 particles/L), suggesting that the source of MPs are from stormwater outfall pipes and human activities. Filaments were the most dominant MP shape (89%) for all samples, with black/grey (water) and transparent (sediment) being the most dominant colors (31% and 31% respectively). Dominant sizes were 1000-2000 μm in water and 2000-5000 μm in sediment. Polyethylene terephthalate (PET) (29%) was the most dominant polymer type recorded in water samples and natural fibres (mainly cotton) (32%) recorded in sediment. Based on the risk assessment, MPs recorded at Mouille Point (site 6) poses the greatest ecological risk associated with polymers. MP concentrations reported in this study provide a baseline for future studies along the Western Cape coastline of South Africa.


Scapholunate Advanced Collapse: Motion-Sparing Reconstructive Options.
Scapholunate advanced collapse (SLAC) is a predictable pattern of degenerative wrist arthritis that develops as a result of scapholunate dissociation. The purpose of this article is to review outcomes for the various motion-sparing surgical treatments for SLAC wrist.


The establishment of the suspension Epstein-Barr virus producing cell lines from patients with tumoral diseases.
Isolation of the Epstein-Barr virus (EBV) in suspension lymphoblastoid cell lines from human patients with tumor diseases, mainly malignant lymphoma, has been described. It has been shown that the EBV was isolated from human patients with myeloid type of leukemia in 75% of cases. A similar virus was also isolated from patients with Hodgkin's disease and leukemoid reaction of the myeloid type for lung cancer. Morphological, cytochemical, immunological, and cytogenetic characteristics of the cell lines in which the EBV is replicated have been investigated.


Meteorological dependence, source identification, and carcinogenic risk assessment of PM2.5-bound Polycyclic Aromatic Hydrocarbons (PAHs) in high-traffic roadside, urban background, and remote suburban area.
The Polycyclic Aromatic Hydrocarbons (PAHs) bound to ambient fine Particular Matter (PM2.5) are currently drawing a lot of attention due to their adverse health effects increasing lung cancer risk in humans. In this study, The PM2.5 samples were collected by high volume air samplers simultaneously from three different sites (high-traffic roadside, urban background, and remote suburban) in Tehran, Iran during warm and cold seasons (from July 2018 to March 2019), and 16 PAHs were analyzed using Gas Chromatography-Mass Spectrometry (GC-MS). Unlike previous studies, a remote suburban area was chosen so as to observe the spatial differentiation in PM2.5-bound PAH characteristics. In high-traffic roadside site, the average concentration of total PM2.5-bound PAHs (ƩPAHs) was 3.7 times the concentration value in remote suburban area. Average (ƩPAHs) ranged from 5.54 ng/m3 for remote suburban area to 20.67 ng/m3 for high-traffic roadside site. In all sites, seasonal trends of PAH concentrations elucidated high concentrations in the cold season and low concentrations in the warm season. Correlation analysis between ƩPAHs and atmospheric factors (meteorology parameters and criteria air pollutants) indicated the heterogeneous processes play an important role in the level of PAHs. The results of diagnostic ratio (DR) analysis disclosed that the dominant source of PM2.5-bound PAHs was the combustion of liquid fossil fuels. Despite the fact that incremental lifetime cancer risk (ILCR) via inhaling PM2.5-bound PAHs varied significantly in high-traffic roadside site and remote suburban site, its value was beyond the acceptable risk level in both sites. Our results suggested that effective regulations are needed to monitor PAHs concentrations and reduce PAHs emissions from liquid fossil fuel combustion so as to mitigate the potential carcinogenic risk of PAHs in ambient air. The online version contains supplementary material available at 10.1007/s40201-022-00821-2.


Linguistic differences and language design.
A small number of discrete choices ('parameters') embedded within a system of otherwise universal principles create the extensive superficial differences between unrelated languages like English, Japanese, and Mohawk. Most current thinking about the evolution of language ignores or denies the existence of these parameters because it can see no rationale for them. That the human language faculty is organized in this way makes more sense if language is compared to a cipher or code. As such, it would have a purpose of concealing information from some at the same time as it communicates information to others.


Surface-Engineered Extracellular Vesicles in Cancer Immunotherapy.
Extracellular vesicles (EVs) are lipid bilayer-enclosed bodies secreted by all cell types. EVs carry bioactive materials, such as proteins, lipids, metabolites, and nucleic acids, to communicate and elicit functional alterations and phenotypic changes in the counterpart stromal cells. In cancer, cells secrete EVs to shape a tumor-promoting niche. Tumor-secreted EVs mediate communications with immune cells that determine the fate of anti-tumor therapeutic effectiveness. Surface engineering of EVs has emerged as a promising tool for the modulation of tumor microenvironments for cancer immunotherapy. Modification of EVs' surface with various molecules, such as antibodies, peptides, and proteins, can enhance their targeting specificity, immunogenicity, biodistribution, and pharmacokinetics. The diverse approaches sought for engineering EV surfaces can be categorized as physical, chemical, and genetic engineering strategies. The choice of method depends on the specific application and desired outcome. Each has its advantages and disadvantages. This review lends a bird's-eye view of the recent progress in these approaches with respect to their rational implications in the immunomodulation of tumor microenvironments (TME) from pro-tumorigenic to anti-tumorigenic ones. The strategies for modulating TME using targeted EVs, their advantages, current limitations, and future directions are discussed.


[Communication theory and health education].
Health Education can be understood as a communication process, in which a communicator gives a message to receivers through a certain channel with a specific destination. The application of the results of communication research to problems of Health Education is difficult since, on the one hand, communication research does not sufficiently relate to the problems of Health Education and, on the other, the Health Educators often ignore the results of empirical research. Moreover, it is inherent in communication theory to overstimate knowledge as a vehicle of behavior change. The norms, laws and institutions of society often limit the possibilities of Health Education. Another limitation consists in the lack of information concerning many of the factors which cause health damaging behavior. The consequences of these considerations are that efficient Health Education has to be carried out not only on the personal but also on the societal level and that knowledge about the causes of health-injuring behavior must be improved. A model of integrated Health Education is presented.


Distributions of the activities of aspartate aminotransferase isoenzymes in rat retinal layers.
Distributions of the activities of the cytosolic (cAAT) and mitochondrial (mAAT) isoenzymes of aspartate aminotransferase were determined in rat retinal layers. cAAT was highest in the photoreceptor inner segments, inner nuclear layer and inner plexiform layer; mAAT was highest in the inner segments. The high activity in the inner segments indicates that both isoenzymes are involved in energy metabolism in addition to a possible role in neurotransmission.


Alpha-fetoprotein secretion by injured and regenerating hepatocytes in the dog.
Both hepatic injury and partial resection are followed by elevation of serum alpha-fetoprotein (AFP). However, whether injured or regenerating hepatocytes are the site of AFP secretion remains controversial. The effects of 3.5 hr of selective hepatic ischemia to the left (L) lobes (70% hepatic mass) of the canine liver on AFP production and liver regeneration by both L and right (R) hepatic lobes are reported. Twenty-one experimental and 13 control animals were studied. AFP was measured by radioimmunoassay in liver tissue homogenates and serum from both systemic and hepatic venous blood obtained preoperatively and on postoperative Days 2, 4, 6, 7, and 8. Tissue AFP was also assessed by immunofluorescent staining. Hepatic regeneration was quantified by autoradiography and DNA specific activity following the intravenous administration of [3H]thymidine. AFP levels were increased above baseline by postoperative Day 4 in biopsies taken from both L and R liver lobes with peak values occurring on Day 7. Immunofluorescent staining confirmed the presence of intracellular AFP in hepatocytes of both R and L lobes on postoperative Days 2 through 6. Serum AFP became significantly elevated above preoperative values by Day 4 and maximal on Day 6. No difference was observed in AFP levels in systemic, L, or R hepatic venous blood. Hepatocellular DNA synthesis was increased on postoperative Days 2 through 8 in both R and L liver lobes. In conclusion, selective hepatic ischemia results in AFP secretion by both injured and uninjured liver lobes. These results suggest that both regenerating and injured hepatocytes synthesize AFP in the dog.


Endophthalmitis Secondary to Occult Intraocular Eyelashes Following Perforating Gunshot Injury: A Case Report.
This is a retrospective case report in which we describe our findings in two cases of endophthalmitis associated with perforating gunshot injury, in which we documented intraocular intrusion of multiple eyelashes as a plausible source of infection. Two male patients, 22 and 29 years old, respectively, presented with endophthalmitis following primary repair of rupture globe secondary to gunshot injury. Both patients had vitrectomy and silicone oil injection. Preoperative imaging and intraoperative findings confirmed the perforating nature of the projectile. In both patients, we detected eyelashes that were concealed either in the pars plana region or within vitreous exudates. Silicone oil was not removed in both patients to prevent phthisis bulbi and because there was no potential for visual improvement. The postoperative course in both cases was uneventful. Gunshot injuries can inoculate eyelashes impregnated with infectious microorganisms into the eye. In cases presenting with endophthalmitis associated with a gunshot injury, we recommend meticulous examination of the posterior segment and the pars plana region during vitrectomy to exclude the presence of occult lashes.


Structural mechanism of dsDNA recognition by the hMNDA HIN domain: New insights into the DNA-binding model of a PYHIN protein.
The hematopoietic interferon-inducible nuclear (HIN) domain of the PYHIN family of proteins recognizes double-stranded DNA (dsDNA) through different dsDNA-binding modes. These modes apparently confer different roles upon these proteins in the regulation of innate immune responses, gene transcription, and apoptosis. Myeloid cell nuclear differentiation antigen (MNDA), a member of the human PYHIN family, binds DNA and regulates gene transcription in monocytes. However, the mechanism of DNA recognition and DNA-binding modes of human MNDA (hMNDA) remain unclear. Here, we determined the crystal structure of the hMNDA-HIN domain in complex with dsDNA at 2.4 Å resolution, and reveal that hMNDA-HIN binds to dsDNA in a sequence-independent manner. Structure and mutation studies indicated that hMNDA-HIN binds to dsDNA through a unique mode, involving two dsDNA-binding interfaces. Interface I exhibits an AIM2-like dsDNA-binding mode, and interface II has a previously unreported mode of dsDNA-binding. These results provide new insights into the DNA-binding modes of this PYHIN protein.


Renal failure and treatment of a methadone maintenance patient.
A 30-year-old veteran heroin addict being treated with methadone maintenance suffered renal failure. He underwent haemodialysis, peritoneal dialysis and cadaveric renal transplantation while being maintained on methodone. This report illustrates long-term treatment of heroin addicts with renal failure.


Prevalence of human papilloma virus in esophageal carcinomas: a polymerase chain reaction-based study.
Human papilloma virus (HPV) has been repeatedly found in esophageal carcinoma tissues. However, detection rates of HPV DNA in these tumors have varied markedly. Differences in detection methods, sample types and geographic regions of the sample origin have been suggested as potential causes of this discrepancy. This study was undertaken to analyze the prevalence of HPV in esophageal carcinoma. HPV L1 DNA was evaluated in a total of 49 esophageal carcinoma samples, including 44 cases of squamous cell carcinoma (SCC) and 5 cases of adenocarcinoma. Seventeen control samples of esophageal brushings were also analyzed. The HPV L1 fragment was detected using MY09/MY11 primers. In test samples, 17/49 (34.7%) were positive for HPV L1 and, in comparison, none of the control samples were positive. HPV DNA was identified in 17/37 (46%) cases of non-keratinizing SCC and was not identified in any case of esophageal keratinizing SCC and adenocarcinoma. This study defines a significant association of HPV with esophageal non-keratinizing SCC. Our findings raise the possibility that HPV is involved in esophageal carcinogenesis, especially the non-keratinizing type of SCC. Further investigation with a larger sample size over broader geographic areas may be warranted.


2-({1-[2-(Methyl-sulfan-yl)phen-yl]-1H-tetra-zol-5-yl}sulfan-yl)acetic acid.
In the title compound, C10H10N4O2S2, the tetra-zole and benzene rings are almost normal to one another, with a dihedral angle between their planes of 84.33 (9)°. In the crystal, mol-ecules are linked via pairs of bifurcated O-H⋯(N,N) hydrogen bonds, forming inversion dimers with graph-set motif R 4 (4)(12). The dimers are linked by significant π-π inter-actions involving inversion-related tetra-zole rings and inversion-related benzene rings, with centroid-centroid distances of 3.7376 (14) and 3.8444 (15) Å, respectively.


Reduction and recovery of plasma 1,5-anhydro-D-glucitol level in diabetes mellitus.
The plasma concentration of 1,5-anhydro-D-glucitol (AG) was measured in 135 newly diagnosed patients who were referred for oral glucose tolerance tests. AG concentrations in the nondiabetic patients indicated that the mean value of normal AG concentration was 21.8 micrograms/ml (SD = 5.9 micrograms/ml, range 9.6-38.8 micrograms/ml). This distribution of AG concentration was significantly different from that in patients with impaired glucose tolerance (IGT) (13.3 +/- 5.4 micrograms/ml) and definitely different from that in diabetic patients (2.1 +/- 1.8 micrograms/ml). In a standard glucagon test, it was suggested that the decrease of plasma AG was affected not only by glycemic control of the patients but also by pancreatic cell secretory activity. The reduction of AG concentration was more marked in IDDM patients than in NIDDM patients. In longitudinal studies, AG concentration was shown to be sensitive to glycemic control. However, its recovery showed a tendency toward much delay after the improvement of fasting blood glucose or HbA1 concentrations. On the other hand, AG concentration showed negligible diurnal change and no immediate change as a result of diet, oral glucose load, or acute shift of the insulin level in both normal and diabetic subjects.


Incremental diagnostic value of quantitative analysis of double phase Tc-99m MIBI scintimammography for the detection of primary breast cancer additive to visual analysis.
Tc-99m MIBI scintimammography (SMM) is known to be a useful diagnostic tool for primary breast cancer. We conducted this study to establish optimal visual grades for the detection of primary breast cancer and to investigate whether the quantitative indices of double phase SMM could provide incremental diagnostic value additive to visual analysis. Five hundred and twenty highly suspected breast cancer patients (malignant: 370; benign: 150) were included in this study. Double phase Tc-99m MIBI SMM (early: 10 min; delayed: 3 h) was performed after injection of 750 MBq of Tc-99m MIBI. For visual analysis, five scoring method was used. The early and delayed lesion to non-lesion ratios (L/N) and retention index (RI) were calculated. Receiver operating characteristic curve (ROC) analyses was performed to determine the optimal visual grade, to calculate cut-off value of quantitative indices for differentiation malignant and benign diseases and to investigate whether the quantitative indices could provide incremental diagnostic value additive to visual analysis. To investigate the incremental diagnostic value of quantitative index in variable tumor size groups, the patients were subdivided into four groups (group A: size <or= 1 cm, group B: 1 cm < size <or= 3 cm, group C: 3 cm < size <or= 5 cm, group D: size > 5 cm). When over visual grade 3 was used as the cut-off grade for the diagnosis of breast cancer, the sensitivity and specificity were 75.5, 86.4%, respectively. Early L/N of malignant breast disease was significantly higher than that of benign (2.00 +/- 1.88 vs. 0.60 +/- 0.7; p < 0.01). However, delayed L/N and RI had no significant difference between malignant and benign breast diseases. When early L/N of 1.27 was used as the cut-off value, the sensitivity and specificity of SMM were 77.6, 83.3%, respectively. When the early L/N was added to visual grade, the area under curve (AUC) of visual + quantitative analysis (V + Q) was higher than that of visual analysis (V) alone (AUC 0.893 vs. 0.803; p < 0.01). In group A, the AUC of V + Q was higher than that of V alone (0.843 vs. 0.808; p = 0.029). In group B, the AUC of V + Q was also higher (0.913 vs. 0.781; p < 0.01). However, in groups C and D, the AUCs of V + Q and V were not different (0.926 vs. 0.915; p = 0.144: 0.663 vs. 0.570; p = 0.093). For axillary lymph node involvement, the sensitivity, specificity, and of SMM were 66.9, 70.1, and 68%, respectively. From this study, the optimal visual interpretation grades for diagnosis of breast cancer were grades 4 and 5 and cut-off value of early L/N was 1.27. Also, we found that delayed image was not required for breast cancer detection and quantitative index of early L/N provide incremental diagnostic value additive to visual analysis. Especially, when the tumor is small (size <or= 3 cm), the early L/N should be obtained for the diagnosis of breast cancer.


A Highly Luminescent Chiral Tetrahedral Eu4L4(L')4 Cage: Chirality Induction, Chirality Memory, and Circularly Polarized Luminescence.
Chiral lanthanide cages with circularly polarized luminescence (CPL) properties have found potential application in enantioselective guest recognition and sensing. However, it still remains a big challenge to develop a simple and robust method for the diastereoselective assembly of homochiral lanthanide cages in view of the large lability of the Ln(III) ions. Herein, we report the first example of the formation of a enantiopure lanthanide tetrahedral cage via a chiral ancillary ligand induction strategy. One such cage, (Eu4L4)(R/S-BINAPO)4, is assembled by four achiral C3-symmeric tris(β-diketones) (4,4',4″-tris(4,4,4-trifluoro-1,3-dioxobutyl)triphenylamine, L) as faces, four Eu(III) ions as vertices and four chiral R-/S-bis(diphenylphosphoryl)-1,1'-binaphthyl (R/S-BINAPO) as ancillary ligands. X-ray crystallography and NMR and CD spectra confirm the formation of a pair of enantiopure chiral topological tetrahedral cages, (Eu4L4)(R-BINAPO)4 and (Eu4L4)(S-BINAPO)4 (ΔΔΔΔ-1 and ΛΛΛΛ-1). As expected, the tetrahedral cages present strong CPL with |glum| values up to 0.20, while they unexpectedly give ultrahigh luminescent quantum yields (QYs) of up to 81%, the highest value reported in chiral Ln(III) complexes. More impressively, the chiral memory effect for a lanthanide-based assembly is observed for the first time. The chirality of the original cage 1 framework is retained after R/S-BINAPO is replaced by the achiral bis[2-(diphenylphosphino)phenyl] ether oxide (DPEPO), and thus another pair of enantiopure Eu(III) tetrahedral cages, ΔΔΔΔ- and ΛΛΛΛ-[(Eu4L4)(DPEPO)4] (ΔΔΔΔ-2 and ΛΛΛΛ-2), have been isolated. Encouragingly, cage 2 also presents an impressive luminescence quantum yield (QY = 68%) and intense CPL (|glum| = 0.11). This study offers a simple and low-cost synthesis strategy for the preparation of lanthanide cages with CPL properties.


Experiences of living with motor neurone disease: a review of qualitative research.
This review sought to answer the question "what is known about people's experiences of living with MND?". The review followed the guidelines of the Centre of Reviews and Dissemination. Twenty articles met the inclusion criteria and their results were analysed thematically. Data were managed and coded using the software package NVIVO and the analysis was performed in two stages, with the first stage aiming to develop descriptive themes offering an overview of the included data. During the second stage, analytical themes were developed with the explicit aim to answer the review question. The themes that emerged point to the following: (a) people with motor neurone disease (MND) develop experiential knowledge that helps them to live with the disease and (b) while people with MND believe they do not have any control over the disease, they try to have control over their lives through active choices, e.g. how and when to use adaptive equipment. This review highlights the decision-making and knowledge generating processes used by people with MND. Further research is required to explore these processes and their implications for the care of people with MND. Decision-making process by MND patients regarding their care is complex and takes into account the social elements of the disease as well as the medical. Exploring the practical knowledge that patients develop can offer insights on appropriate care for MND patients.


Inhibitors of the hyaluronidases.
The inhibitors of hyaluronidase present in mammalian sera, first described half a century ago, have remained uncharacterized. Because of increased interest in hyaluronidases and their hyaluronan substrate, a study of these inhibitors was undertaken recently. The predominant serum inhibitor is magnesium-dependent and is eliminated by protease or chondroitinase digestion, and by heat. Kinetics of inhibition are similar against hyaluronidases from testis, snake and bee venom. The inhibitor has no effect on Streptomyces hyaluronidase; indicating inhibition is not through protection of the hyaluronan substrate. Circulating inhibition levels are increased in mice following carbon tetrachloride or interleukin-1 injection, inducers of the acute-phase response. Reverse hyaluronan gel zymography reveals a predominant band of 120 kDa relative molecular size. Additional studies indicate that the inhibitor resembles a member of the Kunitz type inter-alpha-inhibitor family. Inhibition of hyaluronidase activity is observed using purified inter-alpha-inhibitor and is reversed by antibodies specific for inter-alpha-inhibitor. This molecule, found in the hyaluronan-rich cumulus mass surrounding mammalian ova and the pericellular coat of fibroblasts and mesothelial cells, may function to stabilize such matrices by protecting against hyaluronidase degradation. Turnover of circulating hyaluronan is extraordinarily rapid, with a half-life of two to five min. Prompt increases in levels of serum hyaluronan occur in patients with shock, septicemia or massive burns, increases that may be partly attributed to suppression by these acute phase reactants of the constant and rapid rates of hyaluronan degradation by hyaluronidase. A literature survey of other hyaluronidase inhibitors is also presented.


Glucocorticoid receptors modulate auditory sensitivity to acoustic trauma.
Glucocorticoids are widely used to treat different hearing disorders yet the exact mechanisms of glucocorticoid action on the inner ear are not known. The inner ear of both humans and experimental animals demonstrate an abundance of glucocorticoid receptors (GRs) in both neuronal and non-neuronal tissues. In this review, we discuss how activation of the hypothalamic-pituitary-adrenal axis can directly modulate hearing sensitivity. Recent findings indicate that several factors define the responsiveness of the peripheral auditory system to glucocorticoids including the concentration of agonist, availability of the GR, and the activation of GR and NF-kappaB. These findings will further our understanding of individual glucocorticoid responsiveness to steroid treatment, and will help improve the development of pharmaceuticals to selectively target GR in the inner ear for individuals with increased sensitivity to acoustic trauma.


High resolution, week-long, locomotion time series from Japanese quail in a home-box environment.
Temporal and spatial patterns of locomotion reflect both resting periods and the movement from one place to another to satisfy physiological and behavioural needs. Locomotion is studied in diverse areas of biology such as chronobiology and physiology, as well as in biomathematics. Herein, the locomotion of 24 visually-isolated Japanese quails in their home-box environment was recorded continuously over a 6.5 days at a 0.5 s sampling rate. Three time series are presented for each bird: (1) locomotor activity, (2) distance ambulated, and (3) zone of the box where the bird is located. These high resolution, week-long, time series consisting of 1.07×10(6) data points represent, to our knowledge, a unique data set in animal behavior, and are publically available on FigShare. The data obtained can be used for analyzing dynamic changes of daily or several day locomotion patterns, or for comparison with existing or future data sets or mathematical models across different taxa.


Flow cytometric reporter assays provide robust functional analysis of signaling complexes.
Conventional assays to probe signaling protein interactions and function involve measurement of luciferase reporter expression within the bulk cell population, with lack of control over target-protein expression level. To address this issue, we have developed a rapid and robust flow cytometric assay for analysis of signaling protein function. A fluorescent reporter and fluorescent tagging of the target protein enables simultaneous assessment of protein expression and signaling within individual cells. We have applied our technique to the analysis of variants of the lipopolysaccharide receptor Toll-like receptor 4 (TLR4) and its adapter protein MyD88, using a NF-кB-responsive promoter driving mScarlet-I expression. The assay enables exclusion of nontransfected cells and overexpressing cells that signal spontaneously. Additionally, our assay allows the identification of protein variants that fail to express. We found that the assays were highly sensitive, with cells expressing an appropriate level of GFP-MyD88 showing approximately 200-fold induction of mScarlet-I by lipopolysaccharide, and we can detect subtle protein concentration-dependent effects of mutations. Importantly, the assay is adaptable to various signaling pathways.


A rapid and reliable PCR-based assay for gene transmission and sex determination in newborn transgenic mice.
This article describes a reliable and rapid method for simultaneous detection of a transgene and sex determination in the newborn mouse pups by PCR using three sets of primers in a single reaction. One set of sense/antisense primers is used to amplify the experimental transgene (androgen receptor gene in this case), the second set for the mouse Y-chromosome-specific SRY gene, and the third set for the beta subunit of the thyroid stimulating hormone (TSH beta), an internal control. This procedure allowed us to promptly analyze pups born from transgenic founders carrying the androgen receptor transgene and, at the same time, establish the sex of the animals. The method is simple, rapid and highly reproducible.


What remains from living cells in bacterial lysate-based cell-free systems.
Because they mimic cells while offering an accessible and controllable environment, lysate-based cell-free systems (CFS) have emerged as valuable biotechnology tools for synthetic biology. Historically used to uncover fundamental mechanisms of life, CFS are nowadays used for a multitude of purposes, including protein production and prototyping of synthetic circuits. Despite the conservation of fundamental functions in CFS like transcription and translation, RNAs and certain membrane-embedded or membrane-bound proteins of the host cell are lost when preparing the lysate. As a result, CFS largely lack some essential properties of living cells, such as the ability to adapt to changing conditions, to maintain homeostasis and spatial organization. Regardless of the application, shedding light on the black-box of the bacterial lysate is necessary to fully exploit the potential of CFS. Most measurements of the activity of synthetic circuits in CFS and in vivo show significant correlations because these only require processes that are preserved in CFS, like transcription and translation. However, prototyping circuits of higher complexity that require functions that are lost in CFS (cell adaptation, homeostasis, spatial organization) will not show such a good correlation with in vivo conditions. Both for prototyping circuits of higher complexity and for building artificial cells, the cell-free community has developed devices to reconstruct cellular functions. This mini-review compares bacterial CFS to living cells, focusing on functional and cellular process differences and the latest developments in restoring lost functions through complementation of the lysate or device engineering.


Endothelin activation and postoperative renal failure after human liver transplantation.
Renal failure is an established risk factor for impaired patient outcome after orthotopic liver transplantation (OLT). As the endothelin pathway is known to be involved in the development of acute renal failure (ARF), we designed a study to clarify its role in ARF following OLT. Twenty consecutive patients with intact kidney function scheduled for their first OLT were prospectively studied. Plasma big endothelin-1 (ET-1) levels were measured before surgery, after graft reperfusion, and on the first and second postoperative day. According to postoperative glomerular filtration rate (GFR), patients were assigned to the acute renal dysfunction group (ARDF) and the non-ARDF group. Each patient's GFR was estimated according to the 4-variable formula used in the modification of diet in renal disease before surgery, daily within the first postoperative week, and at 1, 3, 12, and 24 months after surgery. Postoperative mean big ET-1 levels correlated significantly with the maximum percent decrease of GFR within 3 days after OLT (P < 0.01). The proportion of patients who developed ARDF was significantly correlated to mean postoperative big ET-1 quartiles (P < 0.01). In the ARDF group, the percent decrease of GFR within 24 months was significantly higher (P < 0.05) as compared to the non-ARDF group. In conclusion, patients who develop ARDF immediately after OLT do not fully recover to baseline regarding long-term kidney function. Short-term GFR was significantly correlated with postoperative big ET-1 plasma levels, suggesting renal dysfunction is mediated by the activated endothelin system.


Electrocardiographic and Echocardiographic Imaging of the Heart of Athletes and Patients with Hypertension.
"Athlete's heart syndrome" is a condition characterized by structural, electrophysiologic and functional adaptation of the myocardium to physical activity (training), depending on the activity intensity, duration and type. In athletes left ventricular hypertrophy often resembles comorbid conditions (hypertension or hypertrophic cardiomyopathy) so the differential diagnosis of the disease is very important and crucial, especially in people who are in active training. In fact, if an athlete has finding which indicate thickening of the left ventricle walls, should be distinguished hypertrophy which occurred as a result of many years of training from accidental existence of hypertension or hypertrophic cardiomyopathy in the same person. Therefore, it is important to make a diagnostic difference between healthy and sick heart. The study involved male persons aged 20-45 which have increased muscle mass of the left ventricle due to different etiology. Definite sample included 80 respondents divided into two groups. All respondent underwent interview, clinical examination, ECG and echocardiography. Average systolic blood pressure (SBP) for the athletes were 115.8±7.2 mmHg, and in patients, with hypertension 154.4±3.5 mmHg, average values of diastolic blood pressure (DBP) for the athletes were 74.2±8.1 mmHg in patients, hypertensive 96.2 ± 3.9 mmHg. Values of SBP and DBP were significantly lower in the group of athletes compared to patients with hypertension (p=0.001). The value of the SFO/min was significantly lower in the group of athletes compared to patients with hypertension (p <0.001). There was a statistically significant difference in the sum of SV2 RV5 and between groups of athletes and groups of patients with hypertension (p<0.05). There was no significant difference in the echocardiography parameters between two groups. There was a statistically significant difference in the sum of SV2 and RV5 between groups of athletes and groups of patients with hypertension (p<0.05). ECG parameters, PQ, QRS, QT did not prove to be useful in the differentiation between the groups because no statistically significant differences in their values were found. Echocardiography is a reliable diagnostic tool in differentiating physiologic hypertrophy of athletes compared to hypertrophy in patients with hypertension.


NLK positively regulates Wnt/β-catenin signalling by phosphorylating LEF1 in neural progenitor cells.
Nemo-like kinase (NLK/Nlk) is an evolutionarily conserved protein kinase involved in Wnt/β-catenin signalling. However, the roles of NLK in Wnt/β-catenin signalling in vertebrates remain unclear. Here, we show that inhibition of Nlk2 function in zebrafish results in decreased Lymphoid enhancer factor-1 (Lef1)-mediated gene expression and cell proliferation in the presumptive midbrain, resulting in a reduction of midbrain tectum size. These defects are related to phosphorylation of Lef1 by Nlk2. Thus, Nlk2 is essential for the phosphorylation and activation of Lef1 transcriptional activity in neural progenitor cells (NPCs). In NPC-like mammalian cells, NLK is also required for the phosphorylation and activation of LEF1 transcriptional activity. Phosphorylation of LEF1 induces its dissociation from histone deacetylase, thereby allowing transcription activation. Furthermore, we demonstrate that NLK functions downstream of Dishevelled (Dvl) in the Wnt/β-catenin signalling pathway. Our findings reveal a novel role of NLK in the activation of the Wnt/β-catenin signalling pathway.


Discovery of a first-in-class ANXA3 degrader for the treatment of triple-negative breast cancer.
Triple-negative breast cancer (TNBC) is a nasty disease with extremely high malignancy and poor prognosis. Annexin A3 (ANXA3) is a potential prognosis biomarker, displaying an excellent correlation of ANXA3 overexpression with patients' poor prognosis. Silencing the expression of ANXA3 effectively inhibits the proliferation and metastasis of TNBC, suggesting that ANXA3 can be a promising therapeutic target to treat TNBC. Herein, we report a first-in-class ANXA3-targeted small molecule (R)-SL18, which demonstrated excellent anti-proliferative and anti-invasive activities to TNBC cells. (R)-SL18 directly bound to ANXA3 and increased its ubiquitination, thereby inducing ANXA3 degradation with moderate family selectivity. Importantly, (R)-SL18 showed a safe and effective therapeutic potency in a high ANXA3-expressing TNBC patient-derived xenograft model. Furthermore, (R)-SL18 could reduce the β-catenin level, and accordingly inhibit the Wnt/β-catenin signaling pathway in TNBC cells. Collectively, our data suggested that targeting degradation of ANXA3 by (R)-SL18 possesses the potential to treat TNBC.


Wind dynamics and leaf motion: Approaching the design of high-tech devices for energy harvesting for operation on plant leaves.
High-tech sensors, energy harvesters, and robots are increasingly being developed for operation on plant leaves. This introduces an extra load which the leaf must withstand, often under further dynamic forces like wind. Here, we took the example of mechanical energy harvesters that consist of flat artificial "leaves" fixed on the petioles of N. oleander, converting wind energy into electricity. We developed a combined experimental and computational approach to describe the static and dynamic mechanics of the natural and artificial leaves individually and join them together in the typical energy harvesting configuration. The model, in which the leaves are torsional springs with flexible petioles and rigid lamina deforming under the effect of gravity and wind, enables us to design the artificial device in terms of weight, flexibility, and dimensions based on the mechanical properties of the plant leaf. Moreover, it predicts the dynamic motions of the leaf-artificial leaf combination, causing the mechanical-to-electrical energy conversion at a given wind speed. The computational results were validated in dynamic experiments measuring the electrical output of the plant-hybrid energy harvester. Our approach enables us to design the artificial structure for damage-safe operation on leaves (avoiding overloading caused by the interaction between leaves and/or by the wind) and suggests how to improve the combined leaf oscillations affecting the energy harvesting performance. We furthermore discuss how the mathematical model could be extended in future works. In summary, this is a first approach to improve the adaptation of artificial devices to plants, advance their performance, and to counteract damage by mathematical modelling in the device design phase.


Fetal ECG extraction via Type-2 adaptive neuro-fuzzy inference systems.
We proposed a noninvasive method for separating the fetal ECG (FECG) from maternal ECG (MECG) by using Type-2 adaptive neuro-fuzzy inference systems. The method can extract FECG components from abdominal signal by using one abdominal channel, including maternal and fetal cardiac signals and other environmental noise signals, and one chest channel. The proposed algorithm detects the nonlinear dynamics of the mother's body. So, the components of the MECG are estimated from the abdominal signal. By subtracting estimated mother cardiac signal from abdominal signal, fetal cardiac signal can be extracted. This algorithm was applied on synthetic ECG signals generated based on the models developed by McSharry et al. and Behar et al. and also on DaISy real database. In environments with high uncertainty, our method performs better than the Type-1 fuzzy method. Specifically, in evaluation of the algorithm with the synthetic data based on McSharry model, for input signals with SNR of -5dB, the SNR of the extracted FECG was improved by 38.38% in comparison with the Type-1 fuzzy method. Also, the results show that increasing the uncertainty or decreasing the input SNR leads to increasing the percentage of the improvement in SNR of the extracted FECG. For instance, when the SNR of the input signal decreases to -30dB, our proposed algorithm improves the SNR of the extracted FECG by 71.06% with respect to the Type-1 fuzzy method. The same results were obtained on synthetic data based on Behar model. Our results on real database reflect the success of the proposed method to separate the maternal and fetal heart signals even if their waves overlap in time. Moreover, the proposed algorithm was applied to the simulated fetal ECG with ectopic beats and achieved good results in separating FECG from MECG. The results show the superiority of the proposed Type-2 neuro-fuzzy inference method over the Type-1 neuro-fuzzy inference and the polynomial networks methods, which is due to its capability to capture the nonlinearities of the model better.


Prognostic value of phase analysis on gated single photon emission computed tomography in patients with cardiac sarcoidosis.
We aimed to determine the correlation between phase analysis, reflecting the heterogeneity of perfusion defects, and the dyssynchrony of the left ventricle wall motion, and adverse cardiac events in cardiac sarcoidosis (CS) patients. Fifty-seven consecutive patients with diagnosed CS (64 [IQR 55-71] years old, 14 males), who underwent 18F-FDG PET/CT and ECG-gated SPECT, were studied. FDG PET was analysed to measure cardiac metabolic volume (CMV), and total lesion glycolysis (TLG). The SPECT findings, such as LVEF, Summed Rest Score (SRS), bandwidth (BW) were evaluated. The median of BW was 56° (IQR 40-95). BW showed a strong inverse correlation with LVEF (r = - 0.60, P < 0.0001), and positive correlation with SRS (r = 0.82, P < 0.0001). However, there were no significant correlations between BW and CMV or TLG. The Kaplan-Meier curves revealed a significantly higher rate of MACE in the high BW group (BW > 56°) than the low BW group (BW ≤ 56°) (15.1%/years vs. 4.4%/years, P = 0.025). In multivariable analysis, BW was a significant independent predictor of MACE (P = 0.015). Phase analysis on gated SPECT was a significant and independent predictor of MACE in patients with CS.


Failure of cAMP agonists to activate rescued deltaF508 CFTR in CFBE41o- airway epithelial monolayers.
The cystic fibrosis transmembrane conductance regulator (CFTR) is a cyclic AMP-regulated chloride channel. Mutations in the CFTR gene result in cystic fibrosis (CF). The most common mutation, deltaF508, results in endoplasmic reticulum-associated degradation (ERAD) of CFTR. DeltaF508 CFTR has been described as a temperature-sensitive mutation that can be rescued following growth at 27 degrees C. In order to study the processing and function of wild-type and rescued deltaF508 CFTR at the cell surface under non-polarized and polarized conditions, we developed stable cell lines expressing deltaF508 or wild-type CFTR. CFBE41o- is a human airway epithelial cell line capable of forming high resistance, polarized monolayers when cultured on permeable supports, while HeLa cells are normally grown under non-polarizing conditions. Immunoprecipitation, cell surface biotinylation, immunofluorescence, and functional assays confirmed the presence of deltaF508 CFTR at the cell surface in both cell lines after incubating the cells for 48 h at 27 degrees C. However, stimulators of wild-type CFTR such as forskolin, beta2-adrenergic or A2B-adenosine receptor agonists failed to activate rescued deltaF508 CFTR in CFBE41o- monolayers. Rescued deltaF508 CFTR could be stimulated with genistein independent of pretreatment with cAMP signalling agonists. Interestingly, rescued deltaF508 CFTR in HeLa cells could be efficiently stimulated with either forskolin or genistein to promote Cl- transport. These results indicate that deltaF508 CFTR, when rescued in CFBE41o- human airway epithelial cells, is poorly responsive to signalling pathways known to regulate wild-type CFTR. Furthermore, the differences in rescue and activation of deltaF508 CFTR in the two cell lines suggest that cell-type specific differences in deltaF508 CFTR processing are likely to complicate efforts to identify potentiators and/or correctors of the deltaF508 defect.


Insufficient measles antibody protection in 6-month-old Malawian infants: Reconsider vaccination schedule?
Measles vaccination is currently recommended at 9 months, since maternal antibodies are supposed to protect infants until that age. In this study of 6-month-old Malawian infants 98.3% (58/59) had non-protective IgG levels against measles, irrespective of HIV exposure. Anticipating the first dose at 6 months could be considered.


Prevalence of adverse events in pronated intubated adult COVID-19 patients: A systematic review with meta-analysis.
To present the pooled estimated prevalence of adverse events in pronated intubated adult COVID-19 patients. A systematic review and meta-analysis. This study used the Cochrane Library, CINAHL, Embase, LILACS, Livivo, PubMed, Scopus, and Web of Science databases as data sources. The studies were meta-analysed using JAMOVI 1.6.15 software. A random-effects model was used to identify the global prevalence of adverse events, confidence intervals and the heterogeneity data. Risk of bias was assessed using the Joanna Briggs Institute tool, and the certainty of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. Of the 7904 studies identified, 169 were included for full reading, and 10 were included in the review. The most prevalent adverse events were pressure injuries (59%), haemodynamic instability (23%), death (17%) and device loss or traction (9%). The most prevalent adverse events in mechanically ventilated pronated patients with COVID-19 are pressure injuries, presence of haemodynamic instability, death and device loss or traction. The evidence identified in this review can help improve the quality and safety of patient care by helping to design care protocols to avoid the development of adverse events that can cause permanent sequelae in these patients. This systematic review addressed the adverse events related to prone position in intubated adult COVID-19 patients. We identified that the most prevalent adverse events in these patients were pressure injuries, haemodynamic instability, device loss or traction and death. The results of this review may influence the clinical practice of nurses who work in intensive care units and, consequently, the nursing care provided not only to COVID-19 patients but for all intubated patients due to other reasons in intensive care units. This systematic review adhered to the PRISMA reporting guideline. As this is a systematic review, we analysed data from primary studies conducted by many researchers. Thus, there was no patient or public contribution in this review.


Beneficial regulation of type I collagen and matrixmetalloproteinase-1 expression by estrogen, progesterone, and its combination in skin fibroblasts.
There is impaired wound healing and loss of type I collagen in skin aging, which can be improved by topical estrogen in vivo. The goal of this study was to determine the effects of estrogen, and progesterone and a combination of estrogen and progesterone as well, on the proliferation and the expression of type I collagen and matrixmetalloprotienase-1 (MMP-1, degrades collagen) in dermal fibroblasts (cells that synthesize collagen and MMP-1) in-vitro. Estrogen, progesterone, and its combination similarly and significantly inhibited cell proliferation and MMP-1 protein levels, and simultaneously stimulated type I collagen expression in the fibroblasts, indicating beneficial modulation.


Textbook outcome as a composite outcome measure to compare hospital performances regarding cytoreductive surgery for ovarian cancer: A nationwide population-based study.
Textbook outcome (TO) is a composite outcome measure used in surgical oncology to compare hospital outcomes using multiple quality indicators. This study aimed to develop TO as an outcome measure to assess healthcare quality for patients undergoing cytoreductive surgery (CRS) for advanced-stage ovarian cancer. This population-based study included all CRS for FIGO IIIC-IVB primary ovarian cancer registered in the Netherlands between 2017 and 2020. The primary outcome was TO, defined as a complete CRS, combined with the absence of 30-day mortality, severe complications, and prolonged length of admission (≥ten days). Delayed start of adjuvant chemotherapy (≥six weeks) was not included in TO because of missing data. Logistic regressions were used to assess the association of case-mix factors with TO. Hospital variation was displayed using funnel plots. A total of 1909 CRS were included, of which 1434 were interval CRS and 475 were primary CRS. TO was achieved in 54% of the interval CRS cohort and 47% of the primary CRS cohort. Macroscopic residual disease after CRS was the most important factor for not achieving TO. Age ≥ 70 was associated with lower TO rates in multivariable logistic regressions. TO rates ranged from 40% to 69% between hospitals in the interval CRS cohort and 22% to 100% in the primary CRS cohort. In both analyses, one hospital had significantly lower TO rates (different hospitals). Case-mix adjustment significantly affected TO rates in the primary CRS analysis. TO is a suitable composite outcome measure to detect hospital variation in healthcare quality for patients with advanced-stage ovarian cancer undergoing CRS. Case-mix adjustment improves the accuracy of the hospital comparison.


Polythiophene as a sensor model for chlorofluorocarbon, fluorine, and oxygen gas using DFT calculations.
Adsorption of CCl3F, CCl2F2, CClF3, F2, and O2 has been investigated systematically on the polythiophene (PT) moieties using density functional theory (DFT) calculations at the B3LYP/6-31G (d) level. Here, geometry optimizations have been performed on some polythiophene (5PT and 7PT) complexes. Likewise, adsorption energies, dipole moments, HOMO-LUMO orbital analysis, density of states (DOSs), global indices, and UV-vis spectra are calculated using the DFT method. Energies of interaction and HOMO-LUMO gap show that polythiophene has the highest sensitivity toward O2 for B3LYP functional. According to our findings, CFCs, F2, and O2 molecules can be physically adsorbed on the moieties of polythiophene.


Effect of mandating vaccination on COVID-19 cases in colleges and universities.
With the introduction of COVID-19 vaccines, many colleges and universities decided to mandate vaccination for all students and employees. The objective of this paper is to empirically investigate the effect of the mandate policy on Fall 2021 COVID-19 cases in institutions of higher education. We construct a unique dataset of a sample of 94 colleges and universities in the east and southeast regions of the United States, 41 of which required vaccination prior to Fall 2021. A difference-in-differences analysis is conducted, considering vaccine requirement as a policy implemented only in a sub-group of these institutions. We control for several factors, including state-level case per capita and student population. Our analysis shows that mandatory vaccination substantially decreased cases in institutions of higher education by 1,473 cases per 100,000 student population (95 CI: 132, 2813). The results suggest that a COVID-19 vaccine requirement is an effective policy in decreasing cases in such institutions, leading to a safer educational experience.


Effects of neonatally administered low-dose diethylstilbestrol on the induction of mammary carcinomas and dysplasias induced by 7,12-dimethylbenz [a] anthracene in female rats.
The aim of this study was to investigate the effects of neonatal administration of diethylstilbestrol (DES) on the induction of mammary carcinomas (MCs) and dysplasias (MDs) induced by 7,12-dimethylbenz[a]anthracene (DMBA) in female rats. Three different methods of continuous administration of DES (1 microg) were used: 0-14, 0-5 and 6-14 days after birth, and all rats were given DMBA (10 mg) at 50 days after birth. All rats administered DES showed persistent estrus and anovulatory ovaries. In rats administered DES from 0-14 days after birth, neither MCs nor MDs were observed, and serum levels of both estrogen and progesterone were significantly lower than in controls at 100 days after birth. In rats administered DES from 0-5 days after birth, the incidence and number of MCs were significantly lower while the number ofMDs was slightly higher than in controls. In rats administered DES from 6-14 days after birth, the incidence of MCs was equal to that of the controls while the incidence and number ofMDs were significantly higher. These results suggest that neonatal periods of exposure and doses of endocrine disruptors, such as DES, could affect the incidence and progression of MCs and MDs.


Accuracy of annual erythema exposure estimation using different numbers of ambient exposure fractions in the human exposure model.
The aim was to determine the optimum number of ambient exposure fractions required in the human exposure model for accurate computation of annual erythema effective solar exposure. Ambient exposure fractions were determined on a daily basis over a period of a year in the Rockhampton region using ambient exposure measurements and erythema effective solar exposure measurements at selected body sites of Australia post mail delivery personnel (APMDP). Several values of annual erythema effective exposure for the same body sites were computed using different combinations of ambient exposure fractions on a monthly, seasonally and half-yearly basis in the human exposure model and compared with the measured values. This method enabled a check on the accuracy of annual erythema effective solar exposure estimation using the different combinations of ambient exposure fractions in the human exposure model. In the worst case there was approximately 35% difference between the measured value and the computed value. The best accuracy was obtained with the use of ambient exposure fractions on a monthly basis where most of the estimated values for the different body sites were within 20% of the measured values.


Questions Posed by Residents in the Operating Room: A Thematic Analysis.
Questioning behavior is a type of intraoperative communication for which little information exists on the types of questions that residents ask. The purpose of this study is to describe and identify themes of questions asked by residents in the operating room. Trained observers documented questions asked by residents during operations. Thematic analysis was applied. University of Utah Hospital (Salt Lake City, Utah) operating rooms; institutional. A total of 10 general surgical residents (postgraduate year 1 to 5) were observed along with 10 attending general surgeons. Cases were purposefully selected to be broadly representative of general surgery cases. Thematic saturation occurred following examination of 16 operative cases, which included 178 questions asked by residents. Two broad categories of questions emerged: case-related (71%) and noncase-related (29%), with multiple subcategories within the 2 groups. Case-related subcategories included operative techniques, logistics, patient care, and other. Questions unrelated to the case included subcategories of social, work-related but unrelated to case, other. Less than 1% of questions asked by residents during operations were reflective. Most questions related to the case were technical and most of those unrelated to the case were social; almost all questions were transactional in nature. Our identification of questioning themes by residents expands understanding of resident questioning behaviors, and therefore may enable residents and faculty to be more effective in establishing entrustment.


The impact of family violence, family functioning, and parental partner dynamics on Korean juvenile delinquency.
The present study was aimed at determining the family factors related to juvenile delinquency and identifying the effect of family violence, family functioning, parental partner dynamics, and adolescents' personality on delinquent behavior among Korean adolescents. A cross-sectional study was performed using an anonymous, self-reporting questionnaire. The subjects for this study consisted of 1,943 Korean adolescents, including 1,236 students and 707 juvenile delinquents, using a proportional stratified random sampling method. Compared to student adolescents, delinquent adolescents perceived their parents as having a higher level of dysfunctional parental partner dynamics, poorer family functioning, and a higher level of family violence. Furthermore, delinquent adolescents were more likely to report a greater incidence of antisocial personality tendencies, a higher level of psychosomatic symptoms and frustration, and higher frequencies of delinquent behavior compared to student adolescents. Antisocial personality tendency and gender had the largest significant total effects on delinquent behavior, followed by family violence, psychosomatic symptoms, family functioning, parental partner dynamics and need frustration. On the other hand, family functioning and parental partner dynamics had the largest indirect effect on delinquent behavior. Gender, antisocial personality tendency, and family violence, in that order, had the largest direct effects on delinquent behavior. In conclusion, it is apparent from the results of the present study that delinquent Korean adolescents perceived and experienced significantly more family dysfunction, family violence, and poor parental partner dynamics than did non-delinquents.


Properties of chlorophyllase from Capsicum annuum L. fruits.
The in vitro properties of semi-purified chlorophyllase (chlorophyll-chlorophyllido hydrolase, EC 184.108.40.206) from Capsicum annuum fruits have been studied. The enzyme showed an optimum of activity at pH 8.5 and 50 degrees C. Substrate specificity was studied for chlorophyll (Chl) a, Chl b, pheophytin (Phe) a and Phe b, with Km values of 10.70, 4.04, 2.67 and 6.37 microM respectively. Substrate inhibition was found for Phe b at concentrations higher than 5 microM. Chlorophyllase action on Chl a' and Chl b' was also studied but no hydrolysis was observed, suggesting that the mechanism of action depends on the configuration at C-13(2) in the chlorophyll molecule, with the enzyme acting only on compounds with R132 stereochemistry. The effect of various metals (Mg2+, Hg2+, Cu2+, Zn2+ Co2+, Fe2+ and Fe3+) was also investigated, and a general inhibitory effect was found, this being more marked for Hg2+ and Fe2+. Functional groups such as -SH and -S-S- seemed to participate in the formation of the enzyme-substrate complex. Chelating ion and the carbonyl group at C3 appeared to be important in substrate recognition by the enzyme. The method for measuring Chlase activity, including HPLC separation of substrate and product, has been optimized.


Effects of electroconvulsive therapy on EEG and cerebral blood flow in depression.
Changes in global EEG and global cerebral blood flow (CBF) and their relationship following electroconvulsive therapy (ECT) were studied in 21 depressed in-patients, examined before and after treatment during an ECT series and at follow-up. Two patterns of ECT action could be discerned: acute changes related to single ECT's. The effects on CBF were more marked at the beginning of the ECT series, while the EEG slowing became more pronounced towards the end; non-acute accumulating ECT effects which were insignificant for CBF, whereas the EEG slowing increased progressively during the ECT series. Thus acute and non-acute effects of ECT on EEG and CBF follow different patterns indicating independent seizure effects. They showed a different time course and few correlations were found, suggesting that CBF is more linked to cortical changes while EEG is probably more related to activity in deeper, subcortical structures.


Radiotherapy refusal in breast cancer with breast-conserving surgery.
Although radiotherapy after breast-conserving surgery has been the standard treatment for breast cancer, some people still refuse to undergo radiotherapy. The aim of this study is to identify risk factors for refusal of radiotherapy after breast-conserving surgery. To investigate the trend of refusing radiotherapy after breast-conserving surgery in patients with breast cancer using the Surveillance, Epidemiology, and End Results database. The patients were divided into radiotherapy group and radiotherapy refusal group. Survival results were compared using a multivariate Cox risk model adjusted for clinicopathological variables. Multivariate logistic regression was used to analyze the influencing factors of patients refusing radiotherapy after breast-conserving surgery and a nomogram model was established. The study included 87,100 women who underwent breast-conserving surgery for breast cancer between 2010 and 2015. There were 84,948 patients (97.5%) in the radiotherapy group and 2152 patients (2.5%) in the radiotherapy refusal group. The proportion of patients who refused radiotherapy after breast-conserving surgery increased from 2.1% in 2010 to 3.1% in 2015. The Kaplan-Meier survival curve showed that radiotherapy can improve overall survival (p < 0.001) and breast cancer specific survival (p < 0.001) in the patients with breast-conserving surgery. The results of multivariate logistic regression showed that age, income, marital status, race, grade, stage, subtype and chemotherapy were independent factors associated with the refusal of radiotherapy. Postoperative radiotherapy can improve the benefits of breast-conserving surgery. Patients with old age, low income, divorce, white race, advanced stage, and no chemotherapy were more likely to refuse radiotherapy.


Noxious stimulus-induced increase in spinal prostaglandin E2 is noradrenergic terminal-dependent.
Prostaglandins (PGs) were measured in perfusate from the lumbar intrathecal (IT) space of pentobarbital anaesthetized rats. The level of PGE2, but not of PGF2 alpha or 6-keto PGF1 alpha, was increased by immersion of a hindpaw in water at a noxious temperature (50 degrees C). No increase in PGE2 was produced by non-noxious thermal stimulation (35 degrees C water). The noxious stimulus-evoked increase in PGE2, and increases in PGE2 during norepinephrine infusion (10 micrograms/ml), were significantly decreased in rats pretreated with intrathecal 6-hydroxydopamine. These data suggest that noxious stimuli induce an increase in the production of spinal PGE2 and that this production derives from, or requires the presence of noradrenergic terminals in the spinal cord.


Sternum bone giant cell tumor resection and chest wall reconstruction after the excision of breast cancer.
Giant cell tumor (GCT) is generally treated with wide surgical excision, but the local bone tissue dysfunction is a major complication. Here, we report a sternum GCT patient who had previously undergone a mastectomy. The tumor was excised, and the patient accepted chest wall reconstruction. The patient recovered well and suffered no recurrence at the first year follow-up.


Serum melatonin levels in predicting mortality in patients with severe traumatic brain injury.
A secondary brain injury could appear after traumatic brain injury (TBI) due to neuroinflammation, oxidation and apoptosis. Higher levels of serum melatonin have been found on admission for TBI in non-surviving than in surviving patients. Thus, the objective of this study was to know serum melatonin levels during the first week of TBI in surviving and non-surviving patients, and to know if serum melatonin levels during the first week of TBI can be used to predict mortality. Patients with an isolated and severe TBI were included; that is, if they scored < 10 points in non-cranial aspects of Injury Severity Score and < 9 points in the Glasgow Coma Scale. We measured serum melatonin concentrations at days 1, 4 and 8 of TBI. Thirty-day mortality was the end-point study. Lower serum melatonin levels were found in the surviving patients (n = 90) than in the non-survivors (n = 34) on days 1 (p < 0.001), 4 (p < 0.001), and 8 (p = 0.02) of TBI. Serum melatonin concentrations on days 1, 4, and 8 of TBI had an area under curve (95% Confidence Interval) for the prediction of 30-day mortality of 0.85 (0.77-0.91; p < 0.001), 0.82 (0.74-0.89; p < 0.001) and 0.71 (0.61-0.79; p = 0.06) respectively. The new findings of this study were the presence of higher levels of serum melatonin on days 1, 4 and 8 of TBI in non-survivors than in survivors, and the ability to predict 30-day mortality for serum melatonin levels measured at these time points. However, more research is necessary to confirm our results.


Ethical permission for the publication of routinely collected data.
Data collected from undergraduate medical students for routine purposes on a non-consented basis, but subsequently perceived as being potentially valuable for research purposes, lie in an ethical grey area. Currently, such data appear to be used routinely without explicit consideration of ethical considerations. This paper proposes a consistent framework that would permit the use of such data. It also provides an advance on current practice with regard to ethical considerations around the absence of consent. We argue that students should be informed of generic possible uses of such data and given the opportunity to opt out, that researchers should be able to analyse such data retrospectively, but should then seek ethical permission for publication, and that an ethics committee should determine if ethical practices have been upheld before giving permission for any study incorporating such data to be submitted for publication. It is hoped that these proposals will stimulate debate, and that the results of such debate will inform practice in medical schools and medical education publishing.


Effects of resting membrane potential and intactness of the T-tubules on caffeine contractures in rat skeletal muscle.
We have studied the effects of changes in the resting membrane potential (Vm) and T-tubules on caffeine contracture (25 mM) elicited in rat soleus muscle in vitro at 34 degrees C. In high [K]o (30-140 mM, [K]o X [Cl]o constant) caffeine contractures were reduced by about 40-50% and had a faster time course than in normal Krebs ([K]o = 5 mM). Detubulation of the muscles by an osmotic treatment produces a reduction of about 30% in the caffeine contracture tension. Our results with high K solutions suggest a reduced sensitivity of the myofibrils to calcium released by caffeine. The effects of detubulation on caffeine contracture suggest that caffeine may have a direct effect on sarcolemma in addition to its well known action on the sarcoplasmic reticulum (SR). However, a depletion of the calcium content in the SR of depolarized muscle fibres as well as an anatomical damage produced by the osmotic treatment can not be ruled out as an explanation for the reduced caffeine contracture.