Putting your best face forward: How instructor emoji use influences students' impressions of credibility, immediacy, and liking.
This project explores the impacts of emojis on students' impressions when used in a course welcome email. We adopt a 4 × 3 factorial design to determine how different emojis (i.e., , , ) impact students' impressions of credibility, immediacy, and liking. Data from students (N = 368) indicates emoji choice does impact impressions. Consistently, instructors' emoji use resulted in decreased perceived competence and trustworthiness but increased perceived caring, immediacy, and liking. Findings have implications for instructors who engage in technologically-mediated out-of-class communication and want to strengthen early student-instructor relationships. Limitations and future directions are also discussed.


Antibodies to mycobacteria in healthy and tuberculous badgers from two English counties.
Sera obtained from 2 groups of badgers removed in bovine tuberculosis control operations have been examined for antibodies to 11 species of mycobacteria. From animals without post mortem evidence of tuberculosis, levels of antibodies to mycobacteria were found to increase with age, and different patterns of antibodies were found in animals coming from 2 different places. Some animals (5 out of 60) without evidence of progressive infection had antibodies suggesting contact with tubercle bacilli. Animals found to have tuberculosis at post mortem had increased levels of antibody to common mycobacterial antigen, as do humans with that disease. Only 2 of the 12 tuberculous animals had markedly more antibody binding to Tuberculin than to the other reagents. There was no evidence of greater specificity of antibody binding than was shown by sera of healthy badgers. The suggestion is made that contact with environmental mycobacteria might be a major factor determining distribution of tuberculosis amongst badgers.


Genome profiling of melanocytic tumors using multiplex ligation-dependent probe amplification (MLPA): Its usefulness as an adjunctive diagnostic tool for melanocytic tumors.
The histopathology of melanocytic tumors sometimes presents diagnostic problems. Applicable parameters other than routine pathology are needed. We assessed the feasibility of multiplex ligation-dependent probe amplification (MLPA), a novel PCR-based genome profiling method, in the classification of melanocytic tumors. We extracted DNA from paraffin-embedded tissue sections of 24 primary melanomas, 14 Spitz nevi and 17 common melanocytic nevi. We analyzed the copy number gains or losses of a total of 76 genes spanning almost all chromosome arms using commercially available MLPA kits. Although four melanocytic nevi and three Spitz nevi did not yield sufficient DNA for reliable analysis due to small tumor size, the MLPA analysis was feasible and applicable to the remaining 88% of samples. We found multiple genetic aberrations in primary melanomas. The total number of aberrations in each tumor ranged from 1 to 32 (average, 12.04). All but two melanomas showed aberrations at more than three genetic loci. Seventeen (70.8%) of the 24 melanomas showed a copy number loss of either the CDKN2A or CDKN2B gene on chromosome 9p21. All the Spitz nevi and 7 (50%) of 14 common melanocytic nevi had copy number changes at one or two gene loci (average, 1.04). The receiver operator characteristic curve analysis showed that the threshold value of copy number aberrations corresponding to 98% specificity for melanoma was 2.42 and the sensitivity using this threshold value was 92.5%. MLPA could be used as an adjunctive diagnostic tool for melanocytic tumors.


Multimodality imaging results of TAP versus novel modified TAP stenting in coronary bifurcation: From bench testing to first-in-man investigation.
We investigated the results of T and small protrusion (TAP) versus a novel modification of TAP (mTAP) stenting by multimodality imaging in bench testing and in patients with coronary bifurcation lesions (CBL). TAP stenting is a suboptimal technique for bailout side branch (SB) stenting. In a bench model, optical coherence tomography (OCT), microscopic examinations (ME), and computational fluid dynamics (CFD) were performed after TAP and mTAP stenting. In 20 patients with CBL, 80 intravascular ultrasound (IVUS) examinations were performed during mTAP stenting in which the SB stent was pulled-back to indent the inflated main vessel (MV) balloon and deployed while deflating it. For TAP stenting, the tip of the SB stent was positioned in the MV and deployed. In bench testing, OCT showed neocarina length (NL) was shorter and minimum stent area (MSA) was larger after mTAP versus TAP stenting (2.84 ± 0.70 vs. 4.80 ± 020 mm; 6.75 ± 1.50 vs. 4.5 ± 2.2 mm2 ; respectively; p < 0.05). By ME, NL was shorter and shear rate trended lower after mTAP versus TAP stenting. In patients, IVUS showed MSA was larger after versus before mTAP stenting (6.32 ± 0.58 vs. 5.21 ± 0.56 mm2 ; p < 0.01); NL was 1.43 ± 0.22 mm with SB ostium coverage. The Seattle Angina questionnaire (SAQ) score was higher at 6 months versus baseline (85 ± 4.0 vs. 48 ± 6.0, respectively; p < 0.001). This multimodality imaging study showed, for the first time, mTAP stenting resulted in larger stent area and shorter neocarina than TAP stenting in bench testing. In patients with CBL, mTAP stenting led to larger stent area, short neocarina with complete SB ostium coverage, and improved the SAQ score at follow-up.


Nematode CDC-37 and DNJ-13 form complexes and can interact with HSP-90.
The molecular chaperones Hsc70 and Hsp90 are required for proteostasis control and specific folding of client proteins in eukaryotic and prokaryotic organisms. Especially in eukaryotes these ATP-driven molecular chaperones are interacting with cofactors that specify the client spectrum and coordinate the ATPase cycles. Here we find that a Hsc70-cofactor of the Hsp40 family from nematodes, DNJ-13, directly interacts with the kinase-specific Hsp90-cofactor CDC-37. The interaction is specific for DNJ-13, while DNJ-12 another DnaJ-like protein of C. elegans, does not bind to CDC-37 in a similar manner. Analytical ultracentrifugation is employed to show that one CDC-37 molecule binds to a dimeric DNJ-13 protein with low micromolar affinity. We perform cross-linking studies with mass spectrometry to identify the interaction site and obtain specific cross-links connecting the N-terminal J-domain of DNJ-13 with the N-terminal domain of CDC-37. Further AUC experiments reveal that both, the N-terminal part of CDC-37 and the C-terminal domain of CDC-37, are required for efficient interaction. Furthermore, the presence of DNJ-13 strengthens the complex formation between CDC-37 and HSP-90 and modulates the nucleotide-dependent effects. These findings on the interaction between Hsp40 proteins and Hsp90-cofactors provide evidence for a more intricate interaction between the two chaperone systems during client processing.


Alginate/chitosan microparticles for tamoxifen delivery to the lymphatic system.
Oral administration of the nonsteroidal anti-estrogen tamoxifen (TMX) is the treatment of choice for metastatic estrogen receptor-positive breast cancer. With the aim to improve TMX oral bioavailability and decrease its side effects, crosslinked alginate microparticles for the targeting to the lymphatic system by Peyer's patch (PP) uptake were developed and in vitro characterized. TMX was molecularly dispersed inside the microparticles and an electrostatic interaction involving the TMX tertiary amine was detected by rheological and FT-IR assays. Microparticles showed a size less than 3mum, then suitability to be taken up by M cells in PP and a positive surface charge. Moreover, TMX loading level as well as in vitro release behaviour was affected by the polymer network connected with the mannuronic/guluronic ratio of the alginate chains.


The use of dipeptide-p-nitranilides for the study of aminopeptidase specificity.
The use of dipeptide-p-nitranilides for the study of 2 placental aminopeptidases separated on Sephadex G200 helped in establishing some regular features of their specifities. The high-molecular (320,000 daltons) one prefers Phe in position P'1 to Leu, whereas the lower-molecular aminopeptidase (145,000 daltons) prefers Leu. The high-molecular aminopeptidase splits very slowly the N-terminal Leu when Gly is in adjacent position. Leu-Gly-p-NA is therefore an inhibitor of this AP.


Cost-effectiveness acceptability curves revisited.
Since the introduction of the cost-effectiveness acceptability curve (CEAC) in 1994, its use as a method to describe uncertainty around incremental cost-effectiveness ratios (ICERs) has steadily increased. In this paper, first the construction and interpretation of the CEAC is explained, both in the context of modelling studies and in the context of cost-effectiveness (CE) studies alongside clinical trials. Additionally, this paper reviews the advantages and limitations of the CEAC. Many of the perceived limitations can be attributed to the practice of interpreting the CEAC as a decision rule while it was not developed as such. It is argued that the CEAC is still a useful tool in describing and quantifying uncertainty around the ICER, especially in combination with other tools such as plots on the CE plane and value-of-information analysis.


Changes in the numbers of retinal ganglion cells and optic nerve axons in the developing albino rabbit.
In albino rabbits aged from the 16th postconceptional day (16PCD) to adulthood, the number of axons in the optic nerves were estimated from sample areas totalling 1-12% of the cross-sectional area of the nerve. On the 16PCD there are about 20,000 axons in the optic stalk. The number of axons in the retrobulbar part of the optic nerve reaches a peak value of 766,000 on the 23PCD, and then decreases to about 350,000 by the 32PCD (the day of birth). The number of axons does not change between the 32PCD and 50PCD, but thereafter it slowly decreases, reaching the adult number (294,000) by the 84PCD. A similar trend is apparent in pigmented animals. Thus, on the 25PCD there are 736,000 axons in the retrobulbar part of the optic nerve and the number decreases to 428,000 by the 31PCD. In the adult pigmented rabbit there are 280,000 axons in the optic nerve. In animals younger than the 32PCD, growth cones are present, and the number of axons in the prechiasmal part of the optic nerve was 8-22% lower than in the retrobulbar part of the same nerve. These observations suggest that there is a continued outgrowth of axons from the eye towards the target nuclei. By the 32PCD, the numbers of axons in the retrobulbar and prechiasmal parts of the nerve were very similar, suggesting that by this age all axons had reached the chiasm. The numbers of retinal ganglion cells (RGCs) labelled by massive injections of horseradish peroxidase into the retino-recipient nuclei were estimated in albino rabbits aged from the 24PCD to adulthood. RGCs were counted in evenly spaced sample areas totalling 4-11% of the retinal area. On the 24PCD, the number of labelled RGCs (500,000) was lower than the number of axons in the optic nerve (probably because not all RGC axons had reached their target nuclei by this age). However, by the 27PCD the number of labelled RGCs (550,000) was very similar to the number of prechiasmal axons (568,000). At all ages thereafter, the numbers of both RGCs and axons were very similar, with adult RGC numbers (about 291,000) being reached by the 85PCD. We conclude that axon loss in the rabbit optic nerve after the 27PCD is almost certainly due to the elimination (presumably death) of the parent RGCs, and we suggest that RGC death is also the most likely cause of axon loss prior to the 27PCD.(ABSTRACT TRUNCATED AT 400 WORDS)


Exploring the genetic correlation of cardiovascular diseases and mood disorders in the UK Biobank.
Cardiovascular diseases (CVDs) are the leading cause of deaths globally. Mortality and incidence of CVDs are significantly higher in people with mood disorders. About 81.1% of CVD patients were reported with comorbidities in 2019, where the second most common comorbidity was due to major depressive disorder (MDD). This study, therefore, aimed to evaluate the genetic correlation between CVDs and mood disorders by using data from the UK Biobank towards understanding the influence of genetic factors on the comorbidity due to CVDs and mood disorders. The UK Biobank database provides genetic and health information from half a million adults, aged 40-69 years, recruited between 2006 and 2010. A total of 117,925 participants and 6,128,294 variants were included for analysis after applying exclusion criteria and quality control steps. This study focused on two CVD phenotypes, two mood disorders and 12 cardiometabolic-related traits to conduct association studies. The results indicated a significant positive genetic correlation between CVDs and overall mood disorders and MDD specifically, showing substantial genetic overlap. Genetic correlation between CVDs and bipolar disorder was not significant. Furthermore, significant genetic correlation between mood disorders and cardiometabolic traits was also reported. The results of this study can be used to understand that CVDs and mood disorders share a great deal of genetic liability in individuals of European ancestry.


Radiomics features from 3D-MPRAGE imaging can differentiate temporal-plus epilepsy from temporal lobe epilepsy.
This study aimed to differentiate temporal-plus epilepsy (TPE) from temporal lobe epilepsy (TLE) using extraction of radiomics features from three-dimensional magnetization-prepared rapid acquisition gradient echo (3D-MPRAGE) imaging data. Data from patients with TLE or TPE who underwent epilepsy surgery between January 2019 and January 2021 were retrospectively analyzed. Thirty-three regions of interest in the affected hemisphere of each patient were defined on 3D-MPRAGE images. A total of 3531 image features were extracted from each patient. Four feature selection methods and 10 machine learning algorithms were used to build 40 differentiation models. Model performance was evaluated using receiver operating characteristic analysis. Eighty-two patients were included for analysis, 47 with TLE and 35 with TPE. The model combining logistic regression and the relief selection method had the best performance (area under the receiver operating characteristic curve, .779; accuracy, .875; sensitivity, .800; specificity, .929; positive predictive value, .889; negative predictive value, .867). Radiomics analysis can differentiate TPE from TLE. The logistic regression classifier trained with radiomics features extracted from 3D-MPRAGE images had the highest accuracy and best performance.


An independent effect of parental lipids on the offspring lipid levels in a cohort of adolescents with type 1 diabetes.
Genetic factors modulate lipid levels and an intrafamilial aggregation of abnormal lipid profiles has been reported in the general population. As dyslipidemia is common among people with diabetes and has been related to diabetic nephropathy, we investigated whether parental lipid levels were related to lipids and albumin excretion in young offspring with childhood-onset type 1 diabetes (T1D). Non-fasting blood samples were collected from 895 offspring, 808 mothers and 582 fathers. Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and non-HDL-C were measured. Three early morning urinary albumin-creatinine ratios (ACR), hemoglobin A1C (HbA1c) and anthropometric parameters were also assessed. The offspring's mean age (±SD) was 14.5 ± 2.2 yr, mean diabetes duration 5.5 ± 3.7 yr; the fathers' age was 45.7 ± 6.1 yr and the mothers' age was 42.8 ± 5.5 yr. After adjusting for the offspring age, gender, body mass index, HbA1c, maternal (TC: β = 0.242; TG: β = 0.152; HDL-C: β = 0.285; LDL-C: β = 0.278; non-HDL-C: β = 0.253; all p < 0.001) and paternal lipid levels (TC: β = 0.188; TG: β = 0.108; HDL-C: β = 0.253; LDL-C: β = 0.187; non-HDL-C: β = 0.173; all p < 0.001) were significantly associated with the offspring's lipid parameters. In contrast, no significant association was found between parental lipid levels and the offspring's ACR. In the present study, parental lipid levels were independently associated with the same traits in the offspring, suggesting a role of genetic influences and/or shared environmental factors in modulating the metabolic profile of adolescents with T1D. In contrast, there was no significant association between parental lipid levels and the offspring's albumin excretion.


Screening for psychiatric morbidity. The pattern of psychological illness and premorbid characteristics in four chronic pain populations.
Three hundred and seventy-eight patients from 4 chronic pain populations have been examined by self-assessment questionnaire methods to estimate the amount of psychiatric morbidity present. Using the General Health Questionnaire-28 scaled version (GHQ-28) the findings for probable psychiatric illness by clinic were: for anaesthetists' pain clinics serving a mixed urban and rural population--37%; for an oral medicine facial pain clinic--30%; for a rural hospital pain clinic--37%; and for a psychiatrists' pain assessment and treatment service--51%. These findings demonstrate the effects of selection upon the psychiatric characteristics of different pain populations. On the subscales of the General Health Questionnaire the psychiatric clinic patients were significantly more depressed than those in the other 3 groups (P less than 0.001) and also showed more social dysfunction (P less than 0.001). On the Irritability/Depression and Anxiety Questionnaire (IDA), depression and inward irritability were higher in the psychiatric clinic patients (P less than 0.001) but the amount of anxiety did not differ by clinic or by diagnosis (P greater than 0.05). These findings are taken to indicate that the extent of somatic complaints and anxiety does not differentiate the majority of pain patients in pain services with psychological illness from others attending for treatment. However, in the patients who have definite psychological symptoms, depression, social dysfunction and irritability provide a characteristic pattern. The psychiatric clinic patients were demonstrably more introverted or obessional on the Hysteroid/Obsessoid Questionnaire (HOQ) than those in other clinics. Childhood experience as seen by the patients did not differ by clinic or diagnosis and did not correlate significantly with personality as measured by the HOQ. It did correlate very significantly with measures of the current mood represented by the IDA. This effect was relatively weak, permitting the inference that the major portion of those psychological abnormalities which were found to be present was related to other factors such as the occurrence of painful lesions.


Gen-ecology of capsella bursa-pastoris from an altitudinal transsect in the Alps.
Seeds were collected in wild populations of Capsella bursa-pastoris growing along a cline from low elevations to the high mountain region in Switzerland. Progeny were grown in open field random block experiments and a number of relevant characters was measured. Germination behaviour showed no relationsship to the place of origin and exhibits considerable phenotypic plasticity. Flowering, plant height, rosette diameter and leaf forms displayed genotypic variations that were correlated with altitude. Along the considered altitude gradient phenotypic plasticity was overruled by genetic variation. Later flowering genotypes replaced the earlier flowering genotypes along the topocline which indicates retarded maturity and prolongation of the life cycle at high altitude.


Unilateral linear basal cell nevus associated with diffuse osteoma cutis, unilateral anodontia, and abnormal bone mineralization.
A case of unilateral linear basal cell nevus, diffuse osteoma cutis, unilateral anodontia, and abnormal bone mineralization is reported. Unlike the anodontia, the unilateral linear basal cell nevus and osteoma cutis began to appear in adulthood. A hamartomatous process is suggested to explain these conditions. This complex syndrome has not been reported in the literature.


Computer-aided detection of early Barrett's neoplasia using volumetric laser endomicroscopy.
Volumetric laser endomicroscopy (VLE) is an advanced imaging system that provides a near-microscopic resolution scan of the esophageal wall layers up to 3-mm deep. VLE has the potential to improve detection of early neoplasia in Barrett's esophagus (BE). However, interpretation of VLE images is complex because of the large amount of data that need to be interpreted in real time. The aim of this study was to investigate the feasibility of a computer algorithm to identify early BE neoplasia on ex vivo VLE images. We used 60 VLE images from a database of high-quality ex vivo VLE-histology correlations, obtained from BE patients ± neoplasia (30 nondysplastic BE [NDBE] and 30 high-grade dysplasia/early adenocarcinoma images). VLE features from a recently developed clinical VLE prediction score for BE neoplasia served as input for the algorithm: (1) higher VLE surface than subsurface signal and (2) lack of layering. With this input, novel clinically inspired algorithm features were developed, based on signal intensity statistics and grayscale correlations. For comparison, generic image analysis methods were examined for their performance to detect neoplasia. For classification of the images in the NDBE or neoplastic group, several machine learning methods were evaluated. Leave-1-out cross-validation was used for algorithm validation. Three novel clinically inspired algorithm features were developed. The feature "layering and signal decay statistics" showed the optimal performance compared with the other clinically features ("layering" and "signal intensity distribution") and generic image analyses methods, with an area under the receiver operating characteristic curve (AUC) of .95. Corresponding sensitivity and specificity were 90% and 93%, respectively. In addition, the algorithm showed a better performance than the clinical VLE prediction score (AUC .81). This is the first study in which a computer algorithm for BE neoplasia was developed based on VLE images with direct histologic correlates. The algorithm showed good performance to detect BE neoplasia in ex vivo VLE images compared with the performance of a recently developed clinical VLE prediction score. This study suggests that an automatic detection algorithm has the potential to assist endoscopists in detecting early neoplasia on VLE. Future studies on in vivo VLE scans are needed to further validate the algorithm.


Usefulness of a "puzzle" flap; more than an advancement flap for surgical reconstruction of nasal ala defects: Review of 10 cases.
Reconstructive surgery in nasal pyramid can be a challenge for surgeons. Moreover this anatomic area is one the most common sites for non-melanoma skin cancer. The "puzzle" flap was described to repair surgical defects located just on the nasal ala affecting melolabial sulcus. We have seen this flap can be also very useful to repair defects located on nasal sidewall and cheek without dysfunctional effects and with a good cosmetic result.


Biocompatibility of magnetic nanoparticles synthesized through green routed with a focus on hematological and histological analysis.
The interaction of metal nanoparticles (MNPs) with blood cells and tissues is essential from the perspectives of biocompatibility and the production of novel drug delivery systems. In the present study, biosynthesized-Fe3O4 nanoparticles (bio-Fe3O4 NPs) were prepared and bio-modified using Daphne mucronata Royle leaf extracts. The physicochemical properties of bio-Fe3O4 NPs were determined using UV-Visible spectroscopy, Energy-dispersive X-ray spectroscopy (EDX), X-ray powder diffraction (XRD), dynamic light scattering (DLS), and Fourier transform infrared (FT-IR) analyses. According to the SEM analysis, the bio-Fe3O4 NPs are spherical-shaped with a size range of 10-30 nm. Antibacterial effects of bio-Fe3O4 NPs against Staphylococcus aureus ATCC 43300 and Pseudomonas aeruginosa ATCC 27853 bacteria were measured by minimum inhibition/bactericidal concentrations (MIC and MBC tests). Result showed that the bio-Fe3O4 NPs (300 ppm) revealed highest antibacterial effect on S. aureus ATCC 43300. Also, bio-Fe3O4 NPs have different cell viability in the human breast cancer cell line (MCF-7) and mouse embryonic fibroblast (MEF). The interaction of bio-Fe3O4 NPs with blood cells and the complete blood count (CBC) factor illustrated that the morphology of blood cells and platelet clumping did not influence by nanoparticles. Furthermore, histological analysis of the liver, spleen, and kidney did not show any abnormality upon exposure to 100 mg kg-1 bio-Fe3O4 NPs treated samples. Hence, the biosynthesized Fe3O4 NPs are a good candidate for applications in medical fields.


Enzyme-mediated nitric oxide production in vasoactive erythrocyte membrane-enclosed coacervate protocells.
The design and construction of synthetic therapeutic protocells capable of establishing cognate chemical communication channels with living cells is an important challenge for synthetic biology and bio-engineering. Here we develop a step towards protocell-mediated nitric-oxide-induced vasodilation by constructing a new synthetic cell model based on bio-derived coacervate vesicles with high haemocompatibility and increased blood circulation times. The hybrid protocells are prepared by the spontaneous self-assembly of haemoglobin-containing erythrocyte membrane fragments on the surface of preformed polysaccharide-polynucleotide coacervate micro-droplets containing glucose oxidase. We use the sequestered enzymes to program a spatially coupled glucose oxidase/haemoglobin reaction cascade, which in the presence of glucose and hydroxyurea generates a protocell-mediated flux of nitric oxide that we exploit for in vitro and in vivo blood vessel vasodilation. Taken together, our results provide new opportunities for the development of endogenously organized cell-like entities (biocompatible micro-bots) geared specifically towards active interfacing with individual living cells and cell communities.


Eating disorders revisited. II: Bulimia nervosa and related syndromes.
Bulimia nervosa and related syndromes are common, and occur in up to 5% of women who attend general practitioners. Young women in First World countries, particularly those who "diet", are at increased risk. Behaviours, such as binge eating and induced vomiting, are typically kept well hidden. Only a minority of those with these disorders present for treatment. General practitioners play a key role in primary and secondary prevention. Effective treatments include psychotherapies that focus on the patient's attitudes and relationships, not just the binge eating behaviour. About 50% of patients make a complete recovery, but the long term outcome is unknown.


Wildlife Emergency and Critical Care.
Wildlife patients often present as emergencies. For veterinarians who do not typically treat wildlife, it is important to be able to stabilize and determine the underlying cause of the animal's signs. This article discusses initial assessment, stabilization, and treatment of common emergency presentations in wild birds, reptiles, and mammals.


[Image-guided radiation therapy].
Radiotherapy technology has improved rapidly over the past two decades. New imaging modalities, such as positron emission (computed) tomography (PET, PET-CT) and high-resolution morphological and functional magnetic resonance imaging (MRI) have been introduced into the treatment planning process. Image-guided radiation therapy (IGRT) with 3D soft tissue depiction directly imaging target and normal structures, is currently replacing patient positioning based on patient surface markers, frame-based intracranial and extracranial stereotactic treatment and partially also 2D field verification methods. On-line 3D soft tissue-based position correction unlocked the full potential of new delivery techniques, such as intensity-modulated radiotherapy, by safely delivering highly conformal dose distributions that facilitate dose escalation and hypofractionation. These strategies have already resulted in better clinical outcomes, e.g. in prostate and lung cancer and are expected to further improve radiotherapy results.


Prostaglandin-endoperoxide synthase (PTGS2) and Defensin beta 1 (DEFB1) gene polymorphisms are not associated with periodontitis in Malays.
In line with the association of prostaglandin-endoperoxide synthase 2 (PTGS2) and defensin beta 1 (DEFB1) single nucleotide polymorphisms (SNPs) with periodontitis among the Chinese and European populations, the current study was aimed to assess the same association among the Malays in Malaysia. Blood samples of individuals with periodontitis (PD) (n=72) and periodontally healthy (PH) (n=62) donors were obtained from Malaysian Periodontal Database and Biobanking system (MPDBS). Genomic DNA samples were analyzed for three PTGS2 SNPs (rs5275, rs20417, rs689466,) and one DEFB1 SNP (rs1047031) using Taqman SNP genotyping assays. Notably, rs20417 and rs689466 were located in the promoter region while rs5275 and rs1047031 were located in the 3' untranslated region of the transcript. Association between the SNPs and PD were then analyzed using genotypic association analysis (additive, dominant and recessive models). The allelic frequency for the rs689466-G was higher in PD group (35.2%) compared that in PH group (29.0%). However, the association of rs689466-G and other SNPs with PD was not statistically significant (at 95% CI). No associations were observed for genotypic associations between the PTGS2 and DEFB1 SNPs with PD susceptibility. PTGS2 (rs5275, rs20417, and rs689466) and DEFB1 (rs1047031) polymorphism was not associated with PD in Malays, unlike the Chinese, Taiwanese & European population. This suggests that other causal variants might be involved in the development and progression of PD among Malays.


DRD2 C957T genotype modulates the time-on-task effect during total sleep deprivation.
Total sleep deprivation (TSD) and time-on-task (TOT), especially in combination, increase cognitive instability and cause performance impairment. There are large inter-individual differences in TSD and TOT effects which, in part, have a genetic basis. Here, we show that the dopamine receptor D2 C957T genetic polymorphism predicts the magnitude of the TOT effect on a psychomotor vigilance test (PVT) during 38 h of TSD. This finding indicates that dopamine availability in the striatum, where the dopamine receptor D2 is most prevalent, influences the TOT effect, suggesting a role for dopaminergic pathways in sustained attention deficits during sleep loss.


Clinical Investigation of Burn Patients Transported by Helicopter Based on the Japan Trauma Data Bank.
We retrospectively investigated the actual conditions of burn patients evacuated by helicopter in comparison to those evacuated by ground ambulance using the Japan Trauma Data Bank. This study was a retrospective analysis of the data recorded in the Japan Trauma Data Bank between January 2004 and May 2019. After propensity score matching for the method of transportation, the survival rate was compared between the 2 groups. During the investigation period, there were 4,627 burn patients (helicopter group, n = 276; ambulance group, n = 4,351). After propensity score matching, there were no significant differences between the 2 groups in any of the assessed variables, and the survival rate did not differ to a statistically significant extent. After propensity score matching, the survival rate of the helicopter group did not appear to be superior to the ambulance group. Further prospective studies are needed to explore the proper indications for air transportation of burn patients, which could potentially improve outcomes.


Peripheral lymphocyte signaling pathway deficiencies predict treatment response in first-onset drug-naïve schizophrenia.
Despite being a major cause of disability worldwide, the pathophysiology of schizophrenia and molecular basis of treatment response heterogeneity continue to be unresolved. Recent evidence suggests that multiple aspects of pathophysiology, including genetic risk factors, converge on key cell signaling pathways and that exploration of peripheral blood cells might represent a practical window into cell signaling alterations in the disease state. We employed multiplexed phospho-specific flow cytometry to examine cell signaling epitope expression in peripheral blood mononuclear cell (PBMC) subtypes in drug-naïve schizophrenia patients (n = 49) relative to controls (n = 61) and relate these changes to serum immune response proteins, schizophrenia polygenic risk scores and clinical effects of treatment, including drug response and side effects, over the longitudinal course of antipsychotic treatment. This revealed both previously characterized (Akt1) and novel cell signaling epitopes (IRF-7 (pS477/pS479), CrkL (pY207), Stat3 (pS727), Stat3 (pY705) and Stat5 (pY694)) across PBMC subtypes which were associated with schizophrenia at disease onset, and correlated with type I interferon-related serum molecules CD40 and CXCL11. Alterations in Akt1 and IRF-7 (pS477/pS479) were additionally associated with polygenic risk of schizophrenia. Finally, changes in Akt1, IRF-7 (pS477/pS479) and Stat3 (pS727) predicted development of metabolic and cardiovascular side effects following antipsychotic treatment, while IRF-7 (pS477/pS479) and Stat3 (pS727) predicted early improvements in general psychopathology scores measured using the Brief Psychiatric Rating Scale (BPRS). These findings suggest that peripheral blood cells can provide an accessible surrogate model for intracellular signaling alterations in schizophrenia and have the potential to stratify subgroups of patients with different clinical outcomes or a greater risk of developing metabolic and cardiovascular side effects following antipsychotic therapy.


Kinetic studies on mammalian cytochrome c modified with 2-hydroxy-5-hydroxy-5-nitrobenzyl bromide.
The reduction of 2-hydroxy-5-nitrobenzyl tryptophyl cytochrome c by the chromous ion was studied by stopped-flow techniques. At pH6.5 the reduction of 2-hydroxy-5-nitrobenzyl tryptophyl cytochrome c is complex, showing the presence of three distinct phases. Two chromium concentration-dependent phases are observed (1.1 X 10(5) M-1-S-1, phase 1; 1.25 X 10(4)M-1-S-1, phase 2) and one slow first-order process (0.25S-1, phase 3). A comparison of the static and kinetic difference spectra, along with the data from the reduction of the reoxidized reduced protein, suggests that the slow chromium concentration-independent phase is due to a slow conformational event after fast reduction of the NO2 group. The rates of the chromium concentration-dependent phases show a marked variation with pH above 7.5. The activation energies for the three processes were also measured at 33.2, 38.6 and 69.7 kJ-mol-1 for phases 1, 2 and 3 respectively. The reaction of reduced 2-hydroxy-5-nitrobenzyl tryptophyl cytochrome c with CO was foollowed by means of both stopped-flow and flash photolysis. The combination with CO at pH 6.8 as measured in stopped-flow experiments showed two phases, one CO-dependent phase (phase 2, 2.4 X 10(2)M-1-S-1) and one CO-independent phase (phase 1, 0.015S-1). Investigation of the pH-dependence of the phases showed both the rates and amounts of each phase to be pH-invariant. CO recombination, after photolytic removal, was found to be biphasic; a CO-dependent phase (phase 2, 2.4 X 10(2)M-1-S-1) and a CO-independent phase (phase 1, 1.0s-1) were observed. A tentative model which can accommodate these observations is proposed.


Development of an ion-pair liquid chromatography-high resolution mass spectrometry method for determination of organophosphate pesticide metabolites in large-scale biomonitoring studies.
Organophosphate based pesticides are widely used in the agricultural sector, and exposure to these chemicals is common for the general population. Pesticides are toxic due to the inhibition of acetylcholinesterases, and the potential for adverse health effects have been investigated in past and recent studies. Human biomonitoring of organophosphate pesticide exposure is carried out through the determination of the metabolites in urine (dialkylphosphates, DAPs). Hereby we present a new method for determination of the 6 non-specific metabolites dimethyl phosphate (DMP), diethyl phosphate (DEP), dimethyl thiophosphate (DMTP), diethyl thiophosphate (DETP), dimethyl dithiophosphate (DMDTP), and diethyl dithiophosphate (DEDTP) in urine based on off-line solid phase extraction (anion exchange, 96-well plates) followed by ion-pair ultra-performance liquid chromatography time-of-flight mass spectrometry. Recoveries and accuracies in control urine spiked at 5ng/mL ranged from 48% to109% and from 91% to 115%, respectively. The method limits of detection for the DAPs were 1.2ng/mL for DMP, 0.38ng/mL for DEP, 0.20ng/mL for DMTP, 0.33ng/mL for DETP, 0.64ng/mL for DMDTP, and 0.15ng/mL for DEDTP. The method was applied to samples from a Norwegian mother/child study group (n=48/56) and the DAPs detection frequencies in urine from mothers and children were about: 40% for DMP, 95% for DEP, 96% for DMTP, 50% for DETP, 15% for DMDTP, and 1% for DEDTP. In both mothers and children, the most abundant DAPs were DMTP (median 2.4/5.2ng/mL) and DEP (median 2.6/3.4ng/mL) followed by DMP (median 1.5/2.1ng/mL). The SG corrected concentrations of DEP and DETP in mothers were statistically higher than in children (p-value<0.05; Mann-Whitney test) which might suggest a higher exposure to pesticides in these mothers, or significant differences in toxicokinetics between adults and children. The method was proven robust and suitable for large-scale biomonitoring studies.


Reliability of pediatric ventricular function analysis by short-axis "single-cycle-stack-advance" single-shot compressed-sensing cines in minimal breath-hold time.
Cardiovascular magnetic resonance (CMR) cine imaging by compressed sensing (CS) is promising for patients unable to tolerate long breath-holding. However, the need for a steady-state free-precession (SSFP) preparation cardiac cycle for each slice extends the breath-hold duration (e.g. for 10 slices, 20 cardiac cycles) to an impractical length. We investigated a method reducing breath-hold duration by half and assessed its reliability for biventricular volume analysis in a pediatric population. Fifty-five consecutive pediatric patients (median age 12 years, range 7-17) referred for assessment of congenital heart disease or cardiomyopathy were included. Conventional multiple breath-hold SSFP short-axis (SAX) stack cines served as the reference. Real-time CS SSFP cines were applied without the steady-state preparation cycle preceding each SAX cine slice, accepting the limitation of omitting late diastole. The total acquisition time was 1 RR interval/slice. Volumetric analysis was performed for conventional and "single-cycle-stack-advance" (SCSA) cine stacks. Bland-Altman analyses [bias (limits of agreement)] showed good agreement in left ventricular (LV) end-diastolic volume (EDV) [3.6 mL (- 5.8, 12.9)], LV end-systolic volume (ESV) [1.3 mL (- 6.0, 8.6)], LV ejection fraction (EF) [0.1% (- 4.9, 5.1)], right ventricular (RV) EDV [3.5 mL (- 3.34, 10.0)], RV ESV [- 0.23 mL (- 7.4, 6.9)], and RV EF [1.70%, (- 3.7, 7.1)] with a trend toward underestimating LV and RV EDVs with the SCSA method. Image quality was comparable for both methods (p = 0.37). LV and RV volumetric parameters agreed well between the SCSA and the conventional sequences. The SCSA method halves the breath-hold duration of the commercially available CS sequence and is a reliable alternative for volumetric analysis in a pediatric population. • Compressed sensing is a promising accelerated cardiovascular magnetic resonance imaging technique. • We omitted the steady-state preparation cardiac cycle preceding each cine slice in compressed sensing and achieved an acquisition speed of 1 RR interval/slice. • This modification called "single-cycle-stack-advance" enabled the acquisition of an entire short-axis cine stack in a single short breath hold. • When tested in a pediatric patient group, the left and right ventricular volumetric parameters agreed well between the "single-cycle-stack-advance" and the conventional sequences.


B1-3,5-diiodotyrosine insulin: a valid tracer for insulin.
Insulin, specifically substituted at the PheB1 position with 3,5-diiodotyrosine, has been tested in several biological and immunological systems. Immunoreactivity was assessed using antisera specific for different parts of the insulin molecule. Biological activity in vitro was estimated on isolated rat fat cells. In vivo bioactivity (hypoglycaemia) and metabolism (metabolic and urinary clearance rates, half-life, apparent distribution space) were measured by infusion of the material into greyhounds. The results indicated that this B1-labelled insulin preparation was biologically fully active and, unlike randomly labelled preparations of iodoinsulin, was metabolised with kinetics indistinguishable from those of the unlabelled hormone. We suggest that this material is a valid tracer for insulin, fulfilling the criteria of high specific activity and biological identity to the native hormone.


Monday and non-Monday concentrations of lifestyle-related blood components in the Oslo Diet and Exercise Study.
We hypothesized that participants of intervention studies have an unfavourable lifestyle at the weekend compared with the rest of the week, thus affecting the concentrations of components in samples drawn on Mondays. The hypothesis was examined using data from the Oslo Diet and Exercise Study, a 2 x 2 randomized intervention trial on diet and exercise involving 209 participants. Each person chose which day of the week to attend for blood sampling, both before and after the 1 year of intervention. Comparison of mean concentrations of the components measured, in samples drawn on Mondays vs. non-Mondays, both at the start and at the end of intervention. At the start, nine components, from haemostasis, carbohydrate and lipid metabolism, showed a difference of more than 10% between Monday and non-Monday values, all Monday values differing from the non-Monday values in a cardiovascularly unfavourable direction. Participants starting and ending on a Monday showed the unfavourable profile both times, and those who were examined both times on a non-Monday showed a consistently favourable profile, whereas those who changed the day of examination at the start and end changed profile accordingly. The lifestyle-related components examined here showed differences between Monday and non-Monday values, which were not due to a selection bias. We suggest they may be related to a different lifestyle at the weekend compared with ordinary working days. If such effects are not recognized and properly taken into account, they may markedly affect the outcome of intervention studies.


Clinical evaluation of a new anti-aliasing technique for ultrasound pulsed Doppler analysis.
Clinical evaluation of a new method of Doppler spectral analysis is discussed in this paper. According to this method, which basically involves a proper reformatting of the data provided by a conventional spectrum analyser, the frequency range usually considered in pulsed systems is considerably extended. This has been demonstrated even in extreme clinical conditions, corresponding to tight stenosis in major arteries. Details of materials and methods employed in this evaluation are included. Examples of experimental results are reported, along with a discussion about some possible applications of the new technique.


Forebrain and brainstem afferents to the arcuate nucleus in the rat: potential pathways for the modulation of hypophyseal secretions.
Doxorubicin, an anti-oncogenic agent, was used as a retrograde marker to identify arcuate nucleus afferent projections. Injections of this tracer into the arcuate nucleus indicated that the subfornical organ, the organum vasculosum of the lamina terminalis, the nucleus raphe dorsalis and median raphe send projections to the arcuate nucleus. Immunocytochemical procedures were used to demonstrate that the raphe projections to the arcuate nucleus are serotoninergic. This anatomical investigation provides evidence that neural pathways exist between forebrain body fluid and mineral nuclei, mesencephalic serotonin nuclei and the arcuate nuclei.


Recurrent dorsal root potentials and motoneuron morphology in the frog spinal cord.
About one third of motoneurons stimulated intracellularly evoked dorsal root potentials (DRP) in the lumbar segments of the isolated and perfused frog spinal cord. Axon collaterals were found in one of the 22 motoneurons filled with HRP (horseradish peroxidase) through the stimulating electrode. In further experiments injecting individual motoneurons with cobalt, and filling the ventral roots with HRP or cobalt, the frequency of occurrence of axon collaterals was about 2% of the number of labelled motor cells. It is suggested that the presence of motor axon collaterals is not indispensable in the generation of the DRP evoked by ventral root or motor cell stimulation.


BDNF protects neurons following injury by modulation of caspase activity.
Neurotrophins can protect against apoptotic death following neuronal injury. In a previous article, we showed that activation of the trk receptor is required, but the subsequent mechanisms of action remain unclear. Because the caspase family of cysteine proteases plays a central role in the apoptotic process, we examined the effect of the neurotrophins on caspase activation. Primary neuronal cultures from the embryonic rat cortex were injured with radiation, oxygen deprivation, or oxygen-glucose deprivation. Neurons were treated with brain-derived growth factor (BDNF) or caspase inhibitors. The level of injury was assayed by measuring lactate dehydrogenase release. Western blots were used to note the presence and activation of the caspases 1, 2, 3, 8, and 9--with and without treatment with BDNF. Proenzymes for caspases 1, 2, and 3--but not for caspases 8 or 9 were expressed. With radiation or oxygen deprivation, but not oxygen-glucose deprivation, caspase 3 was activated. Treatment with BDNF was protective against radiation and oxygen deprivation only. Treatment with BDNF also blocked the activation of caspase 3. A similar effect was achieved by directly blocking caspase 1 or 3 activation using an inhibitor. In this study, we showed that BDNF treatment inhibits caspase 3 activation following neuronal injury. This is a central event: when injury did not lead to caspase 3 activation, BDNF treatment was not protective. These results suggest one mechanism by which the neurotrophins protect neurons following injury.


Increased HLA- A*11 in Chinese children with steroid-responsive nephrotic syndrome.
Human leukocyte antigen (HLA) associations have been frequently reported in childhood steroid-responsive nephrotic syndrome (SRNS) in other populations. The aim of this study was to characterize the immunogenetic background of Singaporean Chinese patients with childhood SRNS. We determined the HLA class I (HLA- A* and HLA-B*) as well as class II (HLA- DRB1*, HLA- DQB1*) gene polymorphisms using the polymerase chain reaction-sequence specific oligonucleotide (PCR-SSO) technique, in patients with SRNS (n=64) and normal controls (n=236 for HLA- A*, n=80 for HLA- B*, HLA- DRB1* and HLA- DQB1*). The frequency of HLA- A*11 allele was significantly higher in the SRNS patients compared to controls (78.1% vs 54.2%, respectively; relative risk, RR=3.01, Pc=0.011). However, there was no significant difference in the allele frequencies of HLA- B*, HLA- DRB1* and HLA- DQB1* between the SRNS patients and controls, unlike that in previous studies. Our data suggest that the immunogenetic background of Singaporean Chinese with childhood SRNS was different from that in other populations. As HLA- A*11 has been strongly associated with other autoimmune diseases, it is conceivable that the HLA- A*11-specific motif may play a role in the development of the abnormal T-cell-mediated immune response that may be responsible for triggering the proteinuria seen in SRNS.


Comparison of three methods to assess individual skeletal maturity.
The knowledge of facial growth and development is fundamental to determine the optimal timing for different treatment procedures in the growing patient. To analyze the reproducibility of three methods in assessing individual skeletal maturity, and to evaluate any degree of concordance among them. In all, 100 growing subjects were enrolled to test three methods: the hand-wrist, cervical vertebral maturation (CVM), and medial phalanges of the third finger method (MP3). Four operators determined the skeletal maturity of the subjects to evaluate the reproducibility of each method. After 30 days the operators repeated the analysis to assess the repeatability of each method. Finally, one operator examined all subjects' radiographs to detect any concordance among the three methods. The weighted kappa values for inter-operator variability were 0.94, 0.91, and 0.90, for the WRI, CVM, and MP3 methods, respectively. The weighted kappa values for intra-operator variability were 0.92, 0.91, and 0.92, for the WRI, CVM, and MP3 methods, respectively. The three methods revealed a high degree of repeatability and reproducibility. Complete agreement among the three methods was observed in 70% of the analyzed samples. The CVM method has the advantage of not necessitating an additional radiograph. The MP3 method is a simple and practical alternative as it requires only a standard dental x-ray device.


Is Platelet Expiring Out of Date? A Systematic Review.
Current platelet concentrates are perishable blood products with short shelf lives. Combined with often unpredictable demand, this results in platelet inventory management problems, manifested by high rates of outdating frequently reported at 10% to 20%, and sometimes inadequate clinical supply. The objective of this study was to critically review the published methodologies on measures to reduce platelet outdating rates, in order to determine how platelet outdating and availability can be improved. We performed a systematic review of journal articles published in English to May 2019 identified from MEDLINE, with reported methods to improve platelet inventory outdating rates and availability. The complexity of each methodology was scored based on whether a typical blood bank manager could design, implement and run a platelet outdating program based on the methodology. Twenty-four relevant citations were found-these included 8 citations employing operational research (OR) methodologies, 7 evaluation/best practice, 6 simulation and 3 forecasting. Over half the included studies have been published within the last decade. The citations reporting the lowest predicted outdating were also the most complex methods. Overall predicted outdating and shortages were less than 4% based on the available data. In conclusion, we found that research interest in platelet inventory management problems has increased in line with platelet demand and methods to assist in reducing outdating rates without increased shortages have been available now for 4 decades; high rates of platelet outdating do however continue to be reported around the world. Developments in platelet preparation and storage, and other new approaches, may assist in addressing this problem.


A case of pituitary adrenocorticotropin-dependent Cushing's syndrome in the horse.
In the horse, a syndrome of hirsutism, hyperglycemia, glucosuria, polydipsia, polyuria, polyphagia, and progressive debilitation has been recognized. Most often the syndrome has been associated with adenomas of the pars intermedia of the pituitary and bilateral adrenal hyperplasia or nodular hyperplasia involving primarily the zona fasciculata. Previously, the syndrome has been ascribed to compression of the hypothalamus by an expanding but functionally inactive pituitary neoplasm. In the present case, with RIA determination of plasma ACTH concentrations, the syndrome was ascribed to pituitary ACTH-dependent hyperadrenocorticism and likened to human Cushing's disease.


Assessment of voice and speech symptoms in early Parkinson's disease by the Robertson dysarthria profile.
Changes in voice and speech are thought to involve 75-90% of people with PD, but the impact of PD progression on voice/speech parameters is not well defined. In this study, we assessed voice/speech symptoms in 48 parkinsonian patients staging <3 on the modified Hoehn and Yahr scale and 37 healthy subjects using the Robertson dysarthria profile (a clinical-perceptual method exploring all components potentially involved in speech difficulties), the Voice handicap index (a validated measure of the impact of voice symptoms on quality of life) and the speech evaluation parameter contained in the Unified Parkinson's Disease Rating Scale part III (UPDRS-III). Accuracy and metric properties of the Robertson dysarthria profile were also measured. On Robertson dysarthria profile, all parkinsonian patients yielded lower scores than healthy control subjects. Differently, the Voice Handicap Index and the speech evaluation parameter contained in the UPDRS-III could detect speech/voice disturbances in 10 and 75% of PD patients, respectively. Validation procedure in Parkinson's disease patients showed that the Robertson dysarthria profile has acceptable reliability, satisfactory internal consistency and scaling assumptions, lack of floor and ceiling effects, and partial correlations with UPDRS-III and Voice Handicap Index. We concluded that speech/voice disturbances are widely identified by the Robertson dysarthria profile in early parkinsonian patients, even when the disturbances do not carry a significant level of disability. Robertson dysarthria profile may be a valuable tool to detect speech/voice disturbances in Parkinson's disease.


Primary subacute hematogenous osteomyelitis of navicular bone: A rare case report in 7-year-old child.
Navicular bone location of primary subacute hematogenous osteomyelitis uncommon. There are few cases reported in literature. We aim to describe the clinico-radiological features of primary subacute hematogenous osteomyelitis of the navicular bone in a 7-year-old child, to explain our management of this rare disease and demonstrate that medical treatment without surgery is enough. A 7-year-old child presented to emergency department. His chief complaint was fever, left limping and foot pain. The positive examination features of were painful palpation of the dorsal side of the foot and a swelling of the homolateral ankle. The erythrocyte sedimentation rate was high. The x-ray revealed a lytic lesion of the left navicular bone. The MRI findings led to the diagnosis of subacute osteomyelitis. Pain relief and normalization of inflammatory markers were obtained after 8 weeks of antibiotic therapy. Complete radiological healing was obtained after 9 months. One year after treatment, the patient was able to practice sports as previously. Subacute osteomyelitis of the navicular bone in pediatric population is a rare condition. This case shows the importance of early diagnosis thanks to MRI findings and appropriate antibiotic therapy based on the endemic bacteriological profile. The navicular bone may develop primary subacute osteomyelitis in immunocompetent child. Early diagnosis is important for prescribing effective conservative treatment.


Prediction of Pseudoprogression versus Progression using Machine Learning Algorithm in Glioblastoma.
We aimed to investigate the feasibility of machine learning (ML) algorithm to distinguish pseudoprogression (PsPD) from progression (PD) in patients with glioblastoma (GBM). We recruited the patients diagnosed as primary GBM who received gross total resection (GTR) and concurrent chemoradiotherapy in two institutions from April 2010 to April 2017 and presented suspicious contrast-enhanced lesion on brain magnetic resonance imaging (MRI) during follow-up. Patients from two institutions were allocated to training (N = 59) and testing (N = 19) datasets, respectively. We developed a convolutional neural network combined with a long short-term memory ML structure. MRI data, which was 9 axial post-contrast T1-weighted images in our study, and clinical features were incorporated (Model 1). In the testing set, the trained Model 1 resulted in AUC of 0.83, AUPRC of 0.87, and F1-score of 0.74 using optimal threshold. The performance was superior to that of Model 2 (CNN-LSTM model with MRI data alone) and Model 3 (random forest model with clinical feature alone). The developed algorithm involving MRI data and clinical features could help making decision during follow-up of patients with GBM treated with GTR and concurrent CCRT.


Advanced gastric cancer successfully resected following cisplatin therapy: report of a case.
A case of unresectable advanced gastric cancer was treated with cis-dichlorodiammine platinum (CDDP) at a dosage of 30 mg/day for 5 days every month after operation. After three courses of administration, examinations revealed that the tumor had disappeared, and an evaluation of complete response was made. Four months later, a second-look operation was performed; and it was found that the cancer was smaller than a thumb and could be resected radically. No significant side effects were observed during CDDP therapy.


Effect of activators and blockers of ligand-regulated ion channels on the activity of the Cl-stimulated Mg2+-ATPase of the plasma membrane fraction from bream (Abramis brama L.) brain.
Effects of GABA, glycine, acetylcholine, and glutamate (agonists of the GABAa/benzodiazepine, glycine, choline, and glutamate receptors, respectively) at concentrations in the range 10(-8)-10(-4) M on the activity of "basal" Mg(2+)-ATPase of the plasma membrane fraction from bream brain and on its activation by Cl(-) were investigated. GABA and glycine activated "basal" Mg(2+)-ATPase activity and suppressed its activation by Cl(-). Acetylcholine and glutamate activated "basal" Mg(2+)-ATPase to a lesser extent and did not suppress the activation of the enzyme by Cl(-). The activation of "basal" Mg(2+)-ATPase by neuromediators was decreased by blockers of the corresponding receptors (picrotoxin, strychnine, benztropine mesylate, and D-2-amino-5-phosphonovaleric acid). In addition, picrotoxin and strychnine eliminated the inhibiting effect of GABA and glycine, respectively, on the Cl(-)-stimulated Mg(2+)-ATPase activity. Agonists of the GABAa/benzodiazepine receptor--phenazepam (10(-8)-10(-4) M) and pentobarbital (10(-6)-10(-3) M)--activated the "basal" Mg(2+)-ATPase activity and decreased the Cl(-)-stimulated Mg(2+)-ATPase activity. The dependence of both enzyme activities on ligand concentration is bell-shaped. Moreover, phenazepam and pentobarbital increased the "basal" Mg(2+)-ATPase activity in the presence of 10(-7) M GABA and did not influence it in the presence of 10(-4) M GABA and 10(-6) M glycine. The data suggest that in the fish brain membranes the Cl(-)-stimulated Mg(2+)-ATPase interacts with GABAa/benzodiazepine and glycine receptors but not with m-choline and glutamate receptors.


[Validation of a gender awareness scale in health sciences students].
Given the need to promote gender equity in healthcare, this research aimed to adapt and validate a short version of the Nijmegen Gender Awareness Scale (N-GAMN), that assesses attitudes and gender stereotyping of health sciences students. A cross-sectional study was carried out using a questionnaire among health sciences students from the universities of Barcelona, Cantabria, Cartagena de Indias and the National Autonomous University of Nicaragua. Nine hundred fifty-six students filled out the questionary. A confirmatory factor analysis was performed to establish the relationship between the observed variables and the latent dimensions. The factorial analysis evaluated the validity of the scale and confirmed the existence of a three-dimensional structure composed of: (F1) gender stereotypes towards patients, (F2) gender stereotypes towards professionals and (F3) gender sensitivity in the healthcare (fit data: CFI=0.917, TFI=0.899, RMSEA=0.08 and SRMEA=0.06). Descriptive statistics showed relatively high levels of gender awareness among the participants. Fewer stereotypes were observed towards professionals than towards patients. Women and students from Spanish universities showed a higher level of awareness. However, the significance values of the Mann-Whitney U test allow us to infer the existence of differences based on geographical area, but not based on gender. The results suggest the potential application of the scale to assess the attitudes of students and professionals towards gender stereotypes and biases associated with clinical practice, as well as to assess the impact of gender awareness actions.


Pulmonary Manifestations of Renal Disorders in Children.
The causes of kidney disease in pediatric patients are evenly divided between congenital abnormalities of the kidney and urinary tract and acquired disorders. Nearly 10% to 15% of adults in the United States have chronic kidney disease (CKD); there are no comparable data in children. Regardless of patient age, CKD is a systemic problem that affects every organ system, including the lung. We review the tests used to diagnose and evaluate kidney disease and the main clinical syndromes that are likely to be encountered to aid the pulmonology consultant who is asked to evaluate patients with kidney disease.


Nondisease-specific problems and all-cause mortality in the REasons for Geographic and Racial Differences in Stroke study.
To evaluate the association between six nondisease-specific problems (problems that cross multiple domains of health) and mortality in middle-aged and older adults. Prospective, observational cohort. U.S. population sample. Participants included 23,669 black and white U.S. adults aged 45 and older enrolled in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. Nondisease-specific problems included cognitive impairment, depressive symptoms, exhaustion, falls, impaired mobility, and polypharmacy. Age-stratified (<65, 65-74, ≥ 75) hazard ratios for all-cause mortality were calculated for each problem individually and according to number of problems. One or more nondisease-specific problems occurred in 40% of participants younger than 65, 45% of those aged 65 to 74, and 55% of those aged 75 and older. Compared with participants with none of these problems, the multivariable adjusted hazard ratio for all-cause mortality associated with each additional nondisease-specific problem was 1.34 (95% confidence interval (CI) = 1.23-1.46) for participants younger than 65, 1.24 (95% CI = 1.15-1.35) for those aged 65 to 74, and 1.30 (95% CI = 1.21-1.39) for those aged 75 and older. Nondisease-specific problems were associated with mortality across a wide age spectrum. Future studies should explore whether treating these problems will improve survival and identify innovative healthcare models to address multiple nondisease-specific problems simultaneously.


Expirograms of O2, CO2 and intravenously infused C2H2 and Freon-22 during panting in dogs.
To study pulmonary gas transport in panting, expirograms of several inert and respiratory gases were simultaneously measured in panting dogs. The experiments were performed on 5 conscious dogs (mean body weight 34.4 kg) provided with a chronic tracheostomy. Panting at a mean frequency of 312/min (5.2 Hz) was induced by elevated room temperature (mean 28.1 degrees C). Isotonic saline equilibrated with 50% acetylene and 50% Freon-22 was infused intravenously at a constant rate (4 ml/min). Fractional concentrations in the tracheostomy tube were measured by a respiratory mass spectrometer, using a special sampling system designed for quasi-continuous analysis of rapidly changing gas concentrations. Air flow was monitored by an ultrasonic transit-time flowmeter. A tracing of expired gas concentrations versus expired volume showed no alveolar plateau, displaying a steep increase of Freon-22, acetylene and CO2 (decrease of O2) up to the onset of inspiration. The small but statistically highly significant differences between the expirograms of CO2 and O2, and of Freon-22 and acetylene, could be qualitatively explained by ventilation-perfusion inequalities with sequential emptying, by Taylor dispersion and by reversible solution in airway mucosa in the course of the respiratory cycle.


Tumor necrosis factor-α-activated mesenchymal stem cells promote endothelial progenitor cell homing and angiogenesis.
Mesenchymal stem cells (MSCs) accelerate regeneration of ischemic or injured tissues by stimulation of angiogenesis through a paracrine mechanism. Tumor necrosis factor-α (TNF-α)-activated MSCs secrete pro-angiogenic cytokines, including IL-6 and IL-8. In the present study, using an ischemic hindlimb animal model, we explored the role of IL-6 and IL-8 in the paracrine stimulation of angiogenesis and tissue regeneration by TNF-α-activated MSCs. Intramuscular injection of conditioned medium derived from TNF-α-treated MSCs (TNF-α CM) into the ischemic hindlimb resulted in attenuated severe limb loss and stimulated blood perfusion and angiogenesis in the ischemic limb. Immunodepletion of IL-6 and IL-8 resulted in attenuated TNF-α CM-stimulated tissue repair, blood perfusion, and angiogenesis. In addition, TNF-α CM induced migration of human cord blood-derived endothelial progenitor cells (EPCs) through IL-6- and IL-8-dependent mechanisms in vitro. Intramuscular injection of TNF-α CM into the ischemic limb led to augmented homing of tail vein-injected EPCs into the ischemic limb in vivo and immunodepletion of IL-6 or IL-8 from TNF-α CM attenuated TNF-α CM-stimulated homing of EPCs. In addition, intramuscular injection of recombinant IL-6 and IL-8 proteins resulted in increased homing of intravenously transplanted EPCs into the ischemic limb and improved blood perfusion in vivo. These results suggest that TNF-α CM stimulates angiogenesis and tissue repair through an increase in homing of EPCs through paracrine mechanisms involving IL-6 and IL-8.


Prevalence and Factors of Urinary Incontinence among Postmenopausal Women Attending the Obstetrics and Gynecology Outpatient Service in a Tertiary Health Care Center in Kochi, Kerala.
Urinary incontinence has an immense impact on the social and mental health, and the quality of life of a person. Women neither come forward seeking medical consultation nor do they discuss about their incontinence openly, and the condition remains underestimated in the society. Hence, this study was undertaken to assess the type of urinary incontinence in postmenopausal women visiting obstetrics and gynecology (OBG) outpatient in a tertiary health care sector and to determine the risk factors of urinary incontinence. All postmenopausal women of age 45-90 years visiting the OBG Department of Amrita Institute of Medical Sciences in the months of May and June 2018 were assessed for urinary incontinence. QUID questionnaire - a six item urinary incontinence diagnostic questionnaire to diagnose and differentiate stress, urge and mixed incontinence - was used. The prevalence of urinary incontinence was 26.47%, stress urinary incontinence contributing 13.9%, mixed urinary incontinence 7.2%, and urge urinary incontinence 5.4%. Chronic cough, recurrent urinary tract infections (UTI), and prolonged duration of labor were independent risk factors associated with urinary incontinence in postmenopausal women. Stress incontinence was found to be the major type of urinary incontinence in the postmenopausal women. Those having history of chronic cough, prolonged duration of labor, and recurrent UTI should be screened regularly for urinary incontinence.


Complement receptor 3 mediates NADPH oxidase activation and dopaminergic neurodegeneration through a Src-Erk-dependent pathway.
Microglial NADPH oxidase (Nox2) plays a key role in chronic neuroinflammation and related dopaminergic neurodegeneration in Parkinson's disease (PD). However, the mechanisms behind Nox2 activation remain unclear. Here, we revealed the critical role of complement receptor 3 (CR3), a microglia-specific pattern recognition receptor, in Nox2 activation and subsequent dopaminergic neurodegeneration by using paraquat and maneb-induced PD model. Suppression or genetic deletion of CR3 impeded paraquat and maneb-induced activation of microglial Nox2, which was associated with attenuation of dopaminergic neurodegeneration. Mechanistic inquiry revealed that blocking CR3 reduced paraquat and maneb-induced membrane translocation of Nox2 cytosolic subunit p47phox, an essential step for Nox2 activation. Src and Erk (extracellular regulated protein kinases) were subsequently recognized as the downstream signals of CR3. Moreover, inhibition of Src or Erk impaired Nox2 activation in response to paraquat and maneb co-exposure. Finally, we found that CR3-deficient mice were more resistant to paraquat and maneb-induced Nox2 activation and nigral dopaminergic neurodegeneration as well as motor dysfunction than the wild type controls. Taken together, our results showed that CR3 regulated Nox2 activation and dopaminergic neurodegeneration through a Src-Erk-dependent pathway in a two pesticide-induced PD model, providing novel insights into the immune pathogenesis of PD.


Epidemiology and screening of colorectal cancer.
Knowledge of the descriptive epidemiology of colorectal cancer is essential to a better understanding of the aetiology of the disease and the development of screening strategies. Considerable research efforts have been launched over the last 15 years to evaluate the ability of screening tests to decrease the incidence and mortality of colorectal cancer. This chapter provides a worldwide update of the incidence of colorectal cancer and reviews the evidence for screening for colorectal cancer based on published studies.


Primigravida with Bernard-Soulier Syndrome: a case report.
Bernard-Soulier Syndrome is a rare congenital bleeding disorder, mainly inherited in an autosomal recessive pattern. It is characterized by a genetic defect on one of the four genes encoding the subunits of the transmembrane protein complex GPIb-V-IX, physiologically expressed only in platelets. The exact phenotype varies widely from individual to individual depending on the particular mutation presented. Currently, there is no consensus about ideal management of affected pregnant women, in face of the scarcity of cases. We report on a 28-year-old Black Brazilian primigravida who was referred to our maternity hospital, a tertiary care center, for decision about the most adequate mode of delivery. She was admitted with a platelet count of 43.000 plt/μL, and hemoglobin of 13.6 g/dL. Platelet transfusion was regarded as a necessary prophylactic measure prior to delivery. Ten units of random donor platelets were administered on the course of three days, after which the patient was submitted to an elective cesarean section delivery under general anesthesia at 40 weeks of gestational age. A healthy male baby with a normal birthweight of 3.615 kg was delivered. After the delivery, the mother's state continued being assessed daily, with special attention taken to lochia and surgical wound healing. At one week postpartum, a complete blood count revealed a platelet count of 41.000 plt/μL, and hemoglobin of 13.3 g/dL. As there were no signs of neither evident nor occult hemorrhage, and surgical wound was healing accordingly, the patient was discharged, after being oriented about bleeding preventive measures. The peripartum period is regarded as the most crucial moment of pregnancy in women with Bernard-Soulier Syndrome, hence the importance of a judiciously planned mode of delivery, and of careful prophylaxis against bleeding beforehand. Furthermore, absence of complications during the peripartum period does not predict how the woman will do subsequently. Strict vigilance is warranted at least until six weeks postpartum, due to the virtual risk of secondary postpartum hemorrhage.


MSU Crystals induce sterile IL-1β secretion via P2X7 receptor activation and HMGB1 release.
The mechanism by which monosodium urate (MSU) crystals induce inflammation is not completely understood. Few studies have shown that MSU is capable of stimulating the release of IL-1β in the absence of LPS treatment. The purinergic P2X7 receptor is involved in the release of IL-1β in inflammatory settings caused by crystals, as is the case in silicosis. We investigated the role of P2X7 receptor in sterile MSU-induced inflammation by evaluating peritonitis and paw edema. In in vitro models, we performed the experiments using peritoneal macrophages and THP-1 cells. We measured inflammatory parameters using ELISA and immunoblotting. We measured cell recruitment using cell phenotypic identification and hemocytometer counts. Our in vivo data showed that animals without P2X7 receptors generated less paw edema, less cell recruitment, and lower levels of IL-1β release in a peritonitis model. In the in vitro model, we observed that MSU induced dye uptake by the P2X7 receptor. In the absence of the receptor, or when it was blocked, MSU crystals induced less IL-1β release and this effect corresponded to the concentration of extracellular ATP. Moreover, MSU treatment induced HMGB1 release; pre-treatment with P2X7 antagonist reduced the amount of HMGB1 in cell supernatants. IL-1β secretion induced by MSU depends on P2X7 receptor activation and involves HMGB1 release. We propose that cell activation caused by MSU crystals induces peritoneal macrophages and THP-1 cells to release ATP and HMGB1, causing IL-1β secretion via P2X7 receptor activation.


Tacrine and physostigmine block nicotinic receptors in Xenopus oocytes injected with Torpedo electroplaque membranes.
Tacrine and physostigmine were tested for direct nicotinic actions on Xenopus oocytes microinjected with Torpedo electroplaque membranes. In this preparation, responses to acetylcholine arise 6-8 h after microinjection, due to the incorporation of nicotinic receptors into the plasma membrane by a process not involving protein synthesis. Currents elicited by acetylcholine (100-1000 microM) were recorded by two-electrode voltage clamping. Tacrine (1-1000 microM) and physostigmine (1-100 microM) exerted a potent, reversible block of the nicotinic receptors. The concentration-dependence curves fitted simple hyperbolas, suggesting a stoichiometry of 1:1 in the drug-channel interactions. Currents elicited by the highest acetylcholine concentration were inhibited by tacrine with maximal affinity, indicating an action at a site other than the ligand-binding domain. Inhibition was reduced at depolarising potentials, which is consistent with a preferential interaction with the ligand-bound form of the receptor. Blockade by tacrine or physostigmine was accompanied by a concentration-dependent slowing of the desensitisation, resembling the action of local anaesthetics. These results could indicate a modulatory effect of these drugs on neurosecretion through nicotinic receptors.


Roles of RNA-binding Proteins and Post-transcriptional Regulation in Driving Male Germ Cell Development in the Mouse.
Tissue development and homeostasis are dependent on highly regulated gene expression programs in which cell-specific combinations of regulatory factors determine which genes are expressed and the post-transcriptional fate of the resulting RNA transcripts. Post-transcriptional regulation of gene expression by RNA-binding proteins has critical roles in tissue development-allowing individual genes to generate multiple RNA and protein products, and the timing, location, and abundance of protein synthesis to be finely controlled. Extensive post-transcriptional regulation occurs during mammalian gametogenesis, including high levels of alternative mRNA expression, stage-specific expression of mRNA variants, broad translational repression, and stage-specific activation of mRNA translation. In this chapter, an overview of the roles of RNA-binding proteins and the importance of post-transcriptional regulation in male germ cell development in the mouse is presented.


Control of pain with meclofenamate sodium following removal of an impacted molar.
The analgesic effectiveness of meclofenamate sodium (Meclomen) at two dose levels, 200 mg and 100 mg, was compared with the effectiveness of a placebo and aspirin, 600 mg, in a double-blind study of 174 adult outpatients who had undergone removal of impacted third molars. When compared with the placebo, meclofenamate sodium at either dose level produced a significantly greater reduction in pain intensity, greater pain relief, fewer withdrawals for inefficacy, greater percentage of patients who considered their medication effective, and greater percentage of patients considered by the investigator to have received drug-attributable benefits. In comparison with aspirin, 600 mg, meclofenamate sodium at either 200 mg or 100 mg produced significantly greater reduction in pain intensity and greater pain relief. The other measures of efficacy showed no significant differences between the two drugs. Side effects were minimal in all treatment groups. Meclofenamate sodium appears to be a safe and effective analgesic for the control of pain.


Time between milestone events in the Alzheimer's disease amyloid cascade.
Estimate the time-course of the spread of key pathological markers and the onset of cognitive dysfunction in Alzheimer's disease. In a cohort of 335 older adults, ranging in cognitive functioning, we estimated the time of initial changes of Aβ, tau, and decreases in cognition with respect to the time of Aβ-positivity. Small effect sizes of change in CSF Aβ42 and regional Aβ PET were estimated to occur several decades before Aβ-positivity. Increases in CSF tau occurred 7-8 years before Aβ-positivity. Temporoparietal tau PET showed increases 4-5 years before Aβ-positivity. Subtle cognitive dysfunction was observed 4-6 years before Aβ-positivity. Increases in tau and cognitive dysfunction occur years before commonly used thresholds for Aβ-positivity. Explicit estimates of the time for these events provide a clearer picture of the time-course of the amyloid cascade and identify potential windows for specific treatments.


Association between preoperative serum Cystatin-C levels and postsurgical oncological prognosis in patients with PRCC: A retrospective cohort study.
Cystatin-C (Cys-C) is a predictor of several malignancies. However, whether Cys-C levels predict prognosis in patients with papillary renal cell carcinoma (PRCC) remains uncertain. The aim of this study was to assess the correlation between Cys-C and clinical outcomes in patients with PRCC. The medical records of 137 patients with PRCC who underwent surgery at our institution from January 2008 to December 2020 were retrospectively analyzed. Data were divided into two subgroups based on cutoff values and the relationship between the Cys-C group and their clinical outcomes was assessed. By the last follow-up, 62 patients had died of various causes, 53 of whom died from PRCC. Sixty patients suffered recurrence or metastasis during follow-up. Based on the cutoff value, the patients were divided into two groups: low Cys-C group (Cys-C < 1.25 mg/L, n = 92) and high Cys-C group (Cys-C ≥ 1.25 mg/L, n = 45). Pathological classification and serum Cys-C levels were shown to be independent prognostic factors affecting clinical outcomes, according to multivariate Cox regression analysis (p < 0.05). After adjusting the Cox proportional hazards model, the risk of death was elevated in the high Cys-C group. The results of the area under the curve for time-dependent receiver operating characteristics analysis indicated that Cys-C is a stable and reliable prognostic biomarker for predicting survival in patients with PRCC. Forest plots, constructed to better reflect the comparison of hazard ratios between the two groups, confirmed that Cys-C levels were significantly associated with worsening overall survival. This study is the first to examine the relationship between preoperative serum Cys-C levels and prognostic overall survival in patients with PRCC. Cys-C may be a useful biomarker for preoperative screening of high-risk patients who may require adjuvant therapy.


Publisher Correction: Vacuum induced transparency and photon number resolved Autler-Townes splitting in a three-level system.
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.


Elevated intraspinal pressure drives edema progression after acute compression spinal cord injury in rabbits.
Elevated intraspinal pressure (ISP) following traumatic spinal cord injury (tSCI) can be an important factor for secondary SCI that may result in greater tissue damage and functional deficits. Our present study aimed to investigate the dynamic changes in ISP after different degrees of acute compression SCI in rabbits with closed canals and explore its influence on spinal cord pathophysiology. Closed balloon compression injuries were induced with different inflated volumes (40 μl, 50 μl or no inflation) at the T7/8 level in rabbits. ISP was monitored by a SOPHYSA probe at the epicenter within 7 days post-SCI. Edema progression, spinal cord perfusion and damage severity were evaluated by serial multisequence MRI scans, somatosensory evoked potentials (SEPs) and behavioral scores. Histological and blood spinal cord barrier (BSCB) permeability results were subsequently analyzed. The results showed that the ISP waveforms comprised three peaks, significantly increased after tSCI, peaked at 72 h (21.86 ± 3.13 mmHg) in the moderate group or 48 h (31.71 ± 6.02 mmHg) in the severe group and exhibited "slow elevated and fast decreased" or "fast elevated and slow decreased" dynamic changes in both injured groups. Elevated ISP after injury was correlated with spinal cord perfusion and edema progression, leading to secondary lesion enlargement. The secondary damage aggravation can be visualized by diffusion tensor tractography (DTT). Moreover, the BSCB permeability was significantly increased at the epicenter and rostrocaudal segments at 72 h after SCI; by 14 days, notable permeability was still observed at the caudal segment in the severely injured rabbits. Our results suggest that the ISP of rabbits with closed canals increased after acute compression SCI and exhibited different dynamic change patterns in moderately and severely injured rabbits. Elevated ISP exacerbated spinal cord perfusion, drove edema progression and led to secondary lesion enlargement that was strongly associated with BSCB disruption. For severe tSCI, early intervention targeting elevated ISP may be an indispensable choice to rescue spinal cord function.


Medial Orbitofrontal Cortex Mediates Outcome Retrieval in Partially Observable Task Situations.
Choice between actions often requires the ability to retrieve action consequences in circumstances where they are only partially observable. This capacity has recently been argued to depend on orbitofrontal cortex; however, no direct evidence for this hypothesis has been reported. Here, we examined whether activity in the medial orbitofrontal cortex (mOFC) underlies this critical determinant of decision-making in rats. First, we simulated predictions from this hypothesis for various tests of goal-directed action by removing the assumption that rats could retrieve partially observable outcomes and then tested those predictions experimentally using manipulations of the mOFC. The results closely followed predictions; consistent deficits only emerged when action consequences had to be retrieved. Finally, we put action selection based on observable and unobservable outcomes into conflict and found that whereas intact rats selected actions based on the value of retrieved outcomes, mOFC rats relied solely on the value of observable outcomes.


Amlodipine versus chlorthalidone versus placebo in the treatment of stage I isolated systolic hypertension.
The study was to compare the effects of amlodipine (calcium channel antagonist), chlorthalidone (diuretic), and placebo in adults more than 50 years of age with stage 1 isolated systolic hypertension (ISH). After a 4-week placebo run-in phase, 150 patients were randomly assigned in a double-blind fashion to treatment with 5 mg of amlodipine (n = 48), 15 mg of chlorthalidone (n = 50), or placebo (n = 52). Patients who failed to meet the systolic blood pressure (BP) reduction goal by week 4 had their dose increased to 10 mg of amlodipine or 30 mg of chlorthalidone, and maintained at this increased dose for 12 weeks. Results showed a mean reduction (mean +/- SD) in sitting systolic BP from baseline to the last treatment visit of -14.6+/-12.2 mm Hg (95% confidence interval [CI] -18.2, -11.0), -14.0+/-13.46 mm Hg (95% CI -17.8, -10.2), and -3.4+/-11.83 mm Hg (95% CI -6.7, -0.1) for the amlodipine, chlorthalidone, and the placebo treatment groups, respectively. Both active treatments showed significantly greater reductions than the placebo group (P < or = .001), but were not significantly different from each other. Sixty-seven percent of the amlodipine, 69% of the chlorthalidone, and 25% of the placebo-treated patients reached the protocol defined systolic BP goal (P = .001). Both active treatment groups showed a trend of better systolic BP response in older patients (> or =65 years). Secondary efficacy measures including pulse pressure, standing systolic, diastolic, and the 24-h ambulatory BP were also statistically significantly improved for both active treatments at the end of treatment, except for chlorthalidone in standing diastolic BP. Adverse events that occurred during the study were as expected and were well tolerated. The results of this study support the efficacy and safety of amlodipine and chlorthalidone for the treatment of stage 1 ISH during 20 weeks of treatment.


Carbon Nanotube Mode-Locked Thulium Fiber Laser With 200 nm Tuning Range.
We demonstrated a mode-locked thulium/holmium (Tm/Ho) fiber laser continuously tunable across 200 nm (from 1860 nm to 2060 nm), which to the best of our knowledge represents the widest tuning range ever achieved for a passively mode-locked fiber laser oscillator. The combined use of a broadband carbon nanotube (CNT) saturable absorber and a diffraction grating mirror ensures ultra-broad tuning range, superb stability and repeatability, and makes the demonstrated laser a highly practical source for spectroscopy, imaging and optical communications. The laser emits <5 ps pulses with an optical spectral bandwidth of ∼3 nm across the full tuning range. Our results indicate that carbon nanotubes can be an excellent saturable absorber for achieving gain-bandwidth-limited tunable operation for 2 μm thulium fiber lasers.


Association of Sex or Race With the Effect of Weight Loss on Physical Function: A Secondary Analysis of 8 Randomized Clinical Trials.
Consideration of differential treatment effects among subgroups in clinical trial research is a topic of increasing interest. This is an especially salient issue for weight loss trials. To determine whether stratification by sex and race is associated with meaningful differences in physical function response to weight loss among older adults. This pooled analysis used individual-level data from 8 completed randomized clinical trials of weight loss conducted at Wake Forest University or Wake Forest School of Medicine, Winston-Salem, North Carolina. Data were housed within the Wake Forest Older Americans Independence Center data repository and provided complete exposure, outcome, and covariate information. Data were collected from November 1996 to March 30, 2017, and analyzed from August 15, 2019, to June 10, 2020. Treatment arms within each study were collapsed into caloric restriction (CR [n = 734]) and non-CR (n = 583) categories based on whether caloric restriction was specified in the original study protocol. Objectively measured 6-month change in weight, fast-paced gait speed (meters per second), and Short Physical Performance Battery (SPPB) score. A total of 1317 adults (mean [SD] age, 67.7 [5.4] years; 920 [69.9%] female; 275 [20.9%] Black) with overweight or obesity (mean [SD] body mass index [calculated as weight in kilograms divided by height in meters squared], 33.9 [4.4]) were included at baseline. Six-month weight change achieved among those randomized to CR was -7.7% (95% CI, -8.3% to -7.2%), with no difference noted by sex; however, White individuals lost more weight than Black individuals assigned to CR (-9.0% [95% CI, -9.6% to -8.4%] vs -6.0% [95% CI, -6.9% to 5.2%]; P < .001), and all CR groups lost a significantly greater amount from baseline compared with non-CR groups (Black participants in CR vs non-CR groups, -5.3% [95% CI, -6.4% to -4.1%; P < .001]; White participants in CR vs non-CR groups, -7.2% [95% CI, -7.8% to -6.6%; P < .001]). Women experienced greater weight loss-associated improvement in SPPB score (CR group, 0.35 [95% CI, 0.18-0.52]; non-CR group, 0.08 [95% CI, -0.11 to 0.27]) compared with men (CR group, 0.23 [95% CI, 0.00-0.46]; non-CR group, 0.34 [95% CI, 0.09-0.58]; P = .03). Black participants experienced greater weight loss-associated improvement in gait speed (CR group, 0.08 [95% CI, 0.05-0.10] m/s; non-CR group, 0.02 [95% CI, -0.01 to 0.05] m/s) compared with White participants (CR group, 0.07 [95% CI, 0.06-0.09] m/s; non-CR group, 0.06 [95% CI, 0.04-0.08] m/s; P = .02). The association of weight loss on physical function in older adults appears to differ by sex and race. These findings affirm the need to consider biological variables in clinical trial design.


Virgin olive oil ortho-phenols--electroanalytical quantification.
An electroanalytical methodology was developed for the determination of the total ortho-phenol content of virgin olive oil (VOO) with high sensitivity and reproducibility. The VOO ortho-phenol content depends on its freshness and is normally expressed as HT equivalent. Screen-printed electrodes were used with cyclic voltammetry to investigate the oxidation of catechol, phenol, hydroxytyrosol (HT), tyrosol, caffeic acid and ferulic acid. The oxidation of ortho-phenols and mono-phenols occurs following different mechanisms, and at different potentials. Using screen-printed electrodes and square wave voltammetry, an HT detection limit of 0.40 μM, was obtained. The electroanalytical methodology developed was applied to the determination of ortho-phenol content in fresh and old VOO. The HT equivalent determined for a two-year-old VOO sample was 3mg/kg, for one-year-old samples was 6-7 mg/kg, and for a fresh VOO sample 30 mg/kg, recoveries in the range of 78-93% of HT standard being obtained. The effect of VOO matrix components on the HT standard response was investigated.


Purification and characterization of Bacillus thuringiensis var. tenebrionis insecticidal proteins produced in E. coli.
Native and single amino acid variants of the Bacillus thuringiensis var. tenebrionis insecticidal proteins were expressed in Escherichia coli, purified and examined for biological and biochemical properties. A novel, pH dependent, preferential precipitation method was implemented to purify Escherichia coli produced Bacillus thuringiensis var. tenebrionis proteins, which are active against Colorado potato beetle (Leptinotarsa decemlineata) larvae. Cysteine residues of the native Bacillus thuringiensis var. tenebrionis protein were replaced by serine residues by site-directed mutagenesis to investigate the biological and structural importance of the individual cysteine residues. Sulfhydryl determination of the native and amino acid variant Bacillus thuringiensis var. tenebrionis proteins revealed that the native protein contains no disulfide bonds. Modification of the carboxyl terminal cysteine residue (amino acid 540) caused complete inactivation of the protein. Native, truncated and single amino acid variants (other than at amino acid 540) exhibited insecticidal activities comparable to each other and to solubilized crystals from the original strain.


Equilibrium, kinetic, and footprinting studies of the Tus-Ter protein-DNA interaction.
Arrest of DNA replication in the terminus region of the Escherichia coli chromosome is mediated by protein-DNA complexes composed of the Tus protein and 23 base pair sequences generically called Ter sites. We have characterized the in vitro binding of purified Tus protein to a 37-base pair oligodeoxyribonucleotide containing the TerB sequence. The measured equilibrium binding constant (KD) for the chromosomal TerB site in KG buffer (50 mM Tris-Cl, 150 mM potassium glutamate, 25 degrees C, pH 7.5, 0.1 mM dithiothreitol, 0.1 mM EDTA, and 100 micrograms/ml bovine serum albumin) was 3.4 x 10(-13) M. Kinetic measurements in the same buffer revealed that the Tus-TerB complex was very stable, with a half-life of 550 min, a dissociation rate constant of 2.1 x 10(-5) s-1, and an association rate constant of 1.4 x 10(8) M-1 s-1. Similar measurements of Tus protein binding to the TerR2 site of the plasmid R6K showed an affinity 30-fold lower than the Tus-TerB interaction. This difference was due primarily to a more rapid dissociation of the Tus-TerR2 complex. Using standard chemical modification techniques, we also examined the DNA-protein contacts of the Tus-TerB interaction. Extensive contacts between the Tus protein and the TerB sequence were observed in the highly conserved 11 base-pair "core" sequence common to all identified Ter sites. In addition, protein-DNA contact sites were observed in the region of the Ter site where DNA replication is arrested. Projection of the footprinting data onto B-form DNA indicated that the majority of the alkylation interference and hydroxyl radical-protected sites were arranged on one face of the DNA helix. We also observed dimethyl sulfate protection of 2 guanine residues on the opposite side of the helix, suggesting that part of the Tus protein extends around the double helix. The distribution of contacts along the TerB sequence was consistent with the functional polarity of the Tus-Ter complex and suggested possible mechanisms for the impediment of protein translocation along DNA.


Immunolike growth hormone substance in tissues from human embryos/fetuses and adults.
GH immunolike reactivity was measured by RIA and IRMA tests in the extracts of tissues from human fetuses (8-32 weeks) and adults. For some fetal tissues a comparison was made with the T4 values obtained in a previous study. Both hormones were already measurable in peripheral tissues at 8 weeks of gestation. The increase in GH was faster than for T4 and it reached the zenith at approximately 20 weeks; thereafter, the GH concentration declined until delivery. In contrast, T4 progressively increased until term. Thirteen tissues were studied both in fetuses and in adults: the GH concentration was about 10 times higher in fetal tissues, with the exception of the brain and the pancreas. The brain showed the lowest GH concentration throughout fetal life and adulthood, whereas the highest GH levels were recorded in adults' pancreas, but they resulted to be artifacts since the RIA values were not confirmed by the IRMA test. In both groups of subjects the highest GH concentrations were found in kidneys, liver and small intestine; the lowest, beyond the brain, in red muscle and cartilage. Thus, the pattern of the quantitative distribution of GH in fetal tissues is the same as in adults, suggesting a functional role of the hormone in the developing human during the prenatal period, in contrast with the concept that high tissue levels of GH are a mere reflection of high GH blood levels. Moreover, in all tissues examined no correlation was found between GH and T4 concentration.


Positive feedback action of pituitary beta-endorphin on acupuncture analgesia afferent pathway.
Potentials in the final sector of the afferent pathway from the acupuncture point (AP) were enhanced by intraperitoneal 0.5 mg/kg morphine without changing the threshold of AP stimulation and greatly decreased by hypophysectomy. The decreased potentials were restored to the control level by morphine (0.5 mg/kg, IP). Potentials evoked in the final sector of the afferent pathway from the nonacupuncture point (NAP) by NAP stimulation after lesion of the analgesia inhibitory system were greatly enhanced by corticotropin (ACTH) (0.25 mg/kg, IP) and greatly decreased by hypophysectomy. Diminished potentials were restored to the control level by ACTH (0.25 mg/kg, IP). Both morphine (0.5 mg/kg, IP) and ACTH (0.25 mg/kg, IP) produced analgesia, but morphine did not affect acupuncture analgesia (AA) and ACTH did not affect nonacupuncture point stimulation-produced analgesia (NAA). All analgesia, that due to 0.5 mg/kg morphine or 0.25 mg/kg ACTH, AA, and NAA were abolished by hypophysectomy. The abolished AA and NAA were restored by 0.5 mg/kg morphine and 0.25 mg/kg ACTH, respectively. Hence, beta-E and ACTH liberated from the pituitary gland by stimulation of an AP and NAP may act as positive feedback on the AA and NAA afferent pathways, respectively.