Exercise first-pass radionuclide assessment of left and right ventricular function and valvular regurgitation in symptomatic mitral valve prolapse.
The changes in right ventricular (RV) and left ventricular (LV) function and in regurgitant fractions on first-pass exercise radionuclide angiography (RNA) were assessed in 29 consecutive patients with symptomatic mitral valve prolapse (MVP). The mean right ventricular ejection fraction (RVEF) was 35 +/- 8% at rest and 46 +/- 15% after exercise (p less than 0.001). The mean left ventricular ejection fraction (LVEF) was 62 +/- 11% at rest and 74 +/- 13% after exercise (p less than 0.001). Seven of 29 patients had an abnormal RV response and 6 had an abnormal LV response. Eight had abnormal wall motion after exercise. A total of 12/29 patients (41%) had one or more abnormalities. The mean left-sided regurgitant fraction before exercise was 27 +/- 17% in 21/29 patients (72%) and 31 +/- 21% after exercise (p = ns). An additional 5 patients (17%) developed left-sided regurgitation after exercise. These findings indicate that wall motion abnormalities and abnormal RVEF and LVEF responses to exercise occur in symptomatic MVP patients. In addition, 26/29 (89.6%) had left-sided regurgitation after exercise. Since the presence of a murmur did not correlate with the presence of mitral regurgitation by RNA, then symptomatic patients with MVP should have first-pass exercise RNA to assess the presence of regurgitation at rest and after exercise. Antibiotic prophylaxis is recommended in MVP patients with systolic murmurs or with regurgitation. Since patients without murmurs can have regurgitation, further study is necessary to determine the need for endocarditis prophylaxis in these patients.


Fate of urinary calculi in children and teenagers.
Urinary calculi are more common in children and teenagers in the Middle East than in other parts of the world. The fate of 45 cases is discussed in this work. Twenty-one passed their stones, three with renal calculi were kept under observation, and 21 cases had different types of surgical intervention. There were only two bladder stones treated by cystolithotomy and only one nephrectomy was done. The low incidence of bladder stones and the high percentage of radio-opaque stones, inspite of the relatively high incidence of stone disease in this age group, are probably due to the changing socio-economic conditions in Jordan.


A light microscope attachment for isolating small specific areas from slide embedded monolayers: an aid in electron microscopy.
Based on the idea of a spring-loaded microscope objective, a boring attachment has been designed and constructed to fit a standard revolving multi-objective holder. It enables many small specific areas of a slide embedded specimen to be selected, ringed and bored out without removing the slide from the microscope stage.


Dexamethasone prevents TACE-induced adverse events: A meta-analysis.
While dexamethasone has been applied following transcatheter arterial chemoembolization (TACE) for years, its clinical effects have not been determined. In the current study, we aimed to evaluate the efficacy of dexamethasone in preventing adverse events induced by TACE. Literature retrieval was conducted using globally recognized online databases, namely MEDLINE, EMBASE, and Cochrane Central, to identify randomized controlled trials (RCTs) of dexamethasone application in patients undergoing TACE. The relative odds ratios (ORs) of incidence rates of three adverse events, namely, fever, abdominal pain and nausea/vomiting, were calculated. The value of I was applied to evaluate the heterogeneity of the trials, and the overall publication bias was assessed with Egger test. Four RCTs containing 350 subjects were included for the pooled estimation. Dexamethasone significantly reduced the incidence rate of TACE-induced adverse events (OR = 1.237, 95% CI: 1.170-1.308, P < .001) with moderate heterogeneity (I = 46.0%). The result of Egger test revealed a publication bias for the included studies. The current meta-analysis confirmed the efficacy of dexamethasone in preventing TACE-induced adverse events. To confirm the practicality of dexamethasone use with TACE, further studies with large sample sizes are warranted to update the evidence-based analyses.


Risk of monoclonal gammopathy of undetermined significance (MGUS) and subsequent multiple myeloma among African American and white veterans in the United States.
The age-adjusted incidence of multiple myeloma (MM) is 2-fold higher in African Americans than in whites. A few small studies have reported a higher prevalence of monoclonal gammopathy of undetermined significance (MGUS) in African Americans versus whites. Etiologic factors for MGUS and determinants for transformation of MGUS to MM are unknown. We quantified the prevalence of MGUS and subsequent risk of MM among 4 million African American and white male veterans admitted to Veterans Affairs (VA) hospitals. The age-adjusted prevalence ratio of MGUS in African Americans compared with whites was 3.0 (2.7-3.3 95% confidence interval). Among 2046 MGUS cases, the estimated cumulative risk of MM during the first 10 years of follow-up was similar (P = .37) for African Americans (17%) and whites (15%). In the largest study to date, we suggest that the excess risk of MM in African Americans results from an increase in risk of MGUS rather than an increased risk of progression from MGUS to MM.


The Caledonian face test: A new test of face discrimination.
This study aimed to develop a clinical test of face perception which is applicable to a wide range of patients and can capture normal variability. The Caledonian face test utilises synthetic faces which combine simplicity with sufficient realism to permit individual identification. Face discrimination thresholds (i.e. minimum difference between faces required for accurate discrimination) were determined in an "odd-one-out" task. The difference between faces was controlled by an adaptive QUEST procedure. A broad range of face discrimination sensitivity was determined from a group (N=52) of young adults (mean 5.75%; SD 1.18; range 3.33-8.84%). The test is fast (3-4 min), repeatable (test-re-test r(2)=0.795) and demonstrates a significant inversion effect. The potential to identify impairments of face discrimination was evaluated by testing LM who reported a lifelong difficulty with face perception. While LM's impairment for two established face tests was close to the criterion for significance (Z-scores of -2.20 and -2.27) for the Caledonian face test, her Z-score was -7.26, implying a more than threefold higher sensitivity. The new face test provides a quantifiable and repeatable assessment of face discrimination ability. The enhanced sensitivity suggests that the Caledonian face test may be capable of detecting more subtle impairments of face perception than available tests.


[A new experimental procedure of intraamniotic application of substances in multiparous experimental animals (author's transl)].
In order to proof the distribution and metabolizing of various substances experimental operation models in animals were developed. The placental transfer was examined in guinea pigs and rabbits; while metabolism was studied in the Göttinger miniature pig. The presented model enables us to examine the following compartments: maternal organism, placenta, amniotic fluid and fetus.


Elevation of tricuspid regurgitant jet velocity, a marker for pulmonary hypertension in children with sickle cell disease.
Pulmonary hypertension (PHTN) is a potentially life-threatening complication, detected by echocardiographic evidence of elevated tricuspid regurgitant velocity (TRV). This condition has been described in adults with sickle cell disease (SCD) and other hemolytic disorders; however, there is little information on the occurrence of this condition in pediatric patients. Records for pediatric SCD patients were retrospectively reviewed to determine clinical characteristics and co-morbidities of patients with elevated TRV on echocardiograms obtained under steady state conditions as an outpatient. Correlation of TRV > or =2.5 m/sec with age, sex, type of SCD, number of outpatient echocardiograms per patient, episodes of vasoocclusive crisis (VOC) and acute chest syndrome (ACS), mean hemoglobin and reticulocyte count, asthma, obstructive sleep apnea, cerebrovascular disease (CVD), and hydroxyurea therapy was determined. Of 224 SCD patients, 44 had outpatient echocardiographic measurement of TRV. Patients (11 of 44) (26.2%) with TRV > or =2.5 m/sec were compared to 31 patients without elevated TRV. Significant differences were noted for percent with HbSS disease (P = 0.041), CVD (P = 0.021), hemoglobin (P = 0.003), % reticulocytes (P = 0.037), and number of echocardiograms performed (P < 0.001). No significant differences were observed for gender, age, asthma, or frequency of VOC and ACS. Elevated TRV, a surrogate marker for PHTN, occurs in children with SCD and is associated with low hemoglobin, elevated reticulocyte count, and cerebral vasculopathy. Appropriate screening by echocardiography can lead to detection and treatment that may reduce TRV and potentially reverse the disease process, prevent the increased morbidity and mortality associated with PHTN.


Coronary vasoactivity of adenosine in the conscious dog.
Intracoronary adenosine infusions in conscious dogs produced half-maximal coronary vasodilation at 0.57 +/- 0.18 (SD) microns and at 1.01 +/- 0.25 microns in open-chest dogs. In both preparations, adenosine at concentrations in the range found in cardiac muscle by direct analysis produced coronary vasodilation equal to that attained during a maximum reactive hyperemic response. The quantitative structure-activity relationship technique was applied to data on the coronary vasoactivity of 68 adenosine analogs to identify the chemical features of this molecule that determine its vasoactivity. These are: (1) the size of the purine base; (2) the inductive effect of C-2 substituent; (3) the electron-withdrawing effect of the C-6 substituent; (4) the glycosylic torsion angle; (5) the ability of the C-2' and C-3' hydroxyls to participate in hydrogen bonding; (7) the absence of sterically hindering groups in the vicinity of C-2' and, more importantly, C-3'; and (8) the inductive effect of the C-5' substituent. The hydrophobicity of these analogs did not correlate with vasoactivity, suggesting that the hydrophilicity of the ribose moiety overshadows any hydrophobic influence of the very weakly aromatic purine base.


Response of a phage modification factor to enhanced production of its target molecule.
Escherichia coli cells with plasmids bearing the valS gene were constructed from the Clark-Carbon collection. Their increased valyl-tRNA synthetase (EC 188.8.131.52) activity was not matched by commensurate production of a modifying peptide during T4 infection. Thus, phage vs gene expression is set to modify the normal amount of valyl-tRNA synthetase activity.


A phenome-wide association study (PheWAS) to identify the health impacts of 4-cresol sulfate in the Nagahama Study.
Gut-microbiota derived metabolites are important regulators of host biology and metabolism. To understand the impacts of the microbial metabolite 4-cresol sulfate (4-CS) on four chronic diseases [type 2 diabetes mellitus, metabolic syndrome (MetS), non-alcoholic fatty liver disease, and chronic kidney disease (CKD)], we conducted association analyses of plasma 4-CS quantified by liquid chromatography coupled to mass spectrometry (LC-MS) in 3641 participants of the Nagahama study. Our results validated the elevation of 4-CS in CKD and identified a reducing trend in MetS. To delineate the holistic effects of 4-CS, we performed a phenome-wide association analysis (PheWAS) with 937 intermediate biological and behavioral traits. We detected associations between 4-CS and 39 phenotypes related to blood pressure regulation, hepatic and renal functions, hematology, sleep quality, intraocular pressure, ion regulation, ketone and fatty acid metabolisms, disease history and dietary habits. Among them, 19 PheWAS significant traits, including fatty acids and 14 blood pressure indices, were correlated with MetS, suggesting that 4-CS is a potential biomarker for MetS. Consistent associations of this gut microbial-derived metabolite on multiple endophenotypes underlying distinct etiopathogenesis support its role in the overall host health, with prospects of probiotic-based therapeutic solutions in chronic diseases.


Endoscopic sclerosis of the cardia affects gastroesophageal reflux.
Gastroesophageal reflux disease remains a disorder of unknown etiology associated with abnormal function of the lower esophageal sphincter (LES) and other physiological co-factors of the pathologic reflux. Effective operations for reflux are designed to reinforce the anti-reflux barrier and alter the tendency towards abnormal reflux. We have postulated that the most important component of these procedures is the prevention of distraction of the lowermost components of the LES at the onset of a potential reflux episode. Distraction of the LES causes shortening of the effective sphincter mechanism and can initiate experimental reflux events. In this study we used endoscopic sclerosis of the submucosal space at the cardia as a means of reducing distraction of the cardia in the hope that this would reduce abnormal reflux events. Canine gastroesophageal reflux was induced by intravenous atropine and monitored by continuous esophageal pH monitoring. Sclerosis of the cardia prevented gastroesophageal reflux, without measurable effect on the LES pressure or length. Endoscopic sclerosis of the cardia may be a useful technique in the control of human gastroesophageal reflux.


Efficient synthesis of maleimides and carbazoles via Zn(OTf)(2)-catalyzed tandem annulations of isonitriles and allenic esters.
Lewis acid Zn(OTf)(2)-catalyzed tandem annulations of isonitriles and allenic esters which lead to efficient and flexible syntheses of a range of biologically significant maleimides and carbazoles and related compounds are reported. A mechanistic rationale is proposed to account for the observed reactivity.


Sleep fragmentation increases blood pressure and is associated with alterations in the gut microbiome and fecal metabolome in rats.
The gut microbiota, via the production of metabolites entering the circulation, plays a role in blood pressure regulation. Blood pressure is also affected by the characteristics of sleep. To date, no studies have examined relationships among the gut microbiota/metabolites, blood pressure, and sleep. We hypothesized that fragmented sleep is associated with elevated mean arterial pressure, an altered and dysbiotic gut microbial community, and changes in fecal metabolites. In our model system, rats were randomized to 8 h of sleep fragmentation during the rest phase (light phase) or were undisturbed (controls) for 28 consecutive days. Rats underwent sleep and blood pressure recordings, and fecal samples were analyzed during: baseline (days -4 to -1), early sleep fragmentation (days 0-3), midsleep fragmentation (days 6-13), late sleep fragmentation (days 20-27), and recovery/rest (days 28-34). Less sleep per hour during the sleep fragmentation period was associated with increased mean arterial pressure. Analyses of gut microbial communities and metabolites revealed that putative short chain fatty acid-producing bacteria were differentially abundant between control and intervention animals during mid-/late sleep fragmentation and recovery. Midsleep fragmentation was also characterized by lower alpha diversity, lower Firmicutes:Bacteroidetes ratio, and higher Proteobacteria in intervention rats. Elevated putative succinate-producing bacteria and acetate-producing bacteria were associated with lower and higher mean arterial pressure, respectively, and untargeted metabolomics analysis demonstrates that certain fecal metabolites are significantly correlated with blood pressure. These data reveal associations between sleep fragmentation, mean arterial pressure, and the gut microbiome/fecal metabolome and provide insight to links between disrupted sleep and cardiovascular pathology.


Sickle cell disease in North London.
We have examined our experience of sickle cell disease in the London Borough of Haringey over the past 20 years. There are currently (1986) 145 patients on the Haringey Sickle Cell Register and when comparison is made with other centres, admission for painful crises in Hb SS disease is more frequent than in Jamaica, but the acute chest syndrome appears to be less common in the United Kingdom than in Jamaica. Splenomegaly is less frequent in Hb SC patients in this country and there is also a lower incidence of leg ulceration in both Hb SS and Hb SC disease in the United Kingdom than in Jamaica. The incidence of alloimmunization among transfused sickle cell disease individuals in Haringey is 21%, the most frequently encountered antibodies being anti-E and anti-Kell. All pregnant patients with sickle cell disease were managed with regular blood transfusion throughout pregnancy starting at 12 weeks of gestation. There were no fetal or maternal mortalities, although three babies born were 'small for dates' despite uneventful antenatal courses and adequate Hb A levels being achieved in the mother. Examination of the effect of seasonal variation on the incidence of hospital admissions for painful crises reveals no significant clustering of cases in a particular month or season of the year.


Importance of resectability status in neoadjuvant treatment for pancreatic cancer.
Much attention has been paid to neoadjuvant treatment (NAT) as a new strategy especially for borderline resectable pancreatic cancer (BRPC). However, the optimal indication of NAT remains undetermined. We analyzed 248 patients with pancreatic cancer (PC). One hundred resectable tumors were classified as R group. Sixty-nine tumors with venous involvement were classified as BR-P group, while 31 tumors with arterial involvement were classified as BR-A group. Ninety-nine patients received NAT. Furthermore, 48 unresectable locally advanced PC served as controls (LAPC group). Among them, 11 patients received adjuvant surgery afterwards (Ad-surg group). The overall median survival time in the R, BR-P and BR-A groups was 45.3, 24.8 and 16.8 months. In the R and BR-P groups, patients treated with NAT had a better prognosis than those without. In contrast, NAT had no impact on prognosis in the BR-A group. Patients treated with NAT in the BR-P, but not BR-A group, had a better prognosis than patients in the LAPC group. Furthermore, patients in the Ad-surg group had a significantly better prognosis than patients in the BR-A group. Borderline resectable pancreatic cancer with venous involvement, but without arterial involvement, may be a good indication for NAT. Our data highlight the importance of preoperative resectability assessment to evaluate the indication and efficacy of NAT.


Phenotypic variation in the breeding phenology of the woodlouse Armadillidium vulgare.
The breeding phenology of temperate wood-lice is strongly seasonal, the result of physiological constraints and precise environmental cues for reproduction. The adaptive value of such mechanisms is that the release of offspring coincides with favourable conditions for growth and survival (Willows 1984). We recorded the breeding phenology of Armadillidium vulgare (Latreille) on two grassland sites in Great Britain and found between-site and between-year variation in the onset of reproduction, the duration of reproductive activity, the release of offspring, the size of reproductive females and the number of broods per female. Between 82.7 and 97.7% of gravid females sampled were semelparous at 23 months, with the remainder iteroparous, producing a second brood after 35 months. On one site (Weeting Health) improved growth conditions during 1984 allowed some females (19.3% of gravid females sampled in that year) to produce a brood after 11 months. There was also an increase in the number of 3-year-old females found to be gravid. An experimental manipulation of the same habitat confirmed that such changes in life history tactics could be phenotypic responses. The observed phenotypic variation was sufficient to produce a range of life history tactics within a population. Mixtures of life history tactics within a population may be typical of invasive species and populations at the edge of the species range. Our results support the idea that phenotypic plasticity can be an appropriate tactic to maximise fitness in a fluctuating environment (Caswell 1983, 1989).


Elevated circulating Hsp70 levels are correlative for malignancies in different mammalian species.
Circulating Hsp70 levels were determined in feline and porcine cohorts using two different ELISA systems. These comparative animal models of larger organisms often reflect diseases, and especially malignant tumors, better than conventional rodent models. It is therefore essential to investigate the biology and utility of tumor biomarkers in animals such as cats and pigs. In this study, levels of free Hsp70 in the blood of cats with spontaneously occurring tumors were detected using a commercial Hsp70 ELISA (R&D Systems). Sub-analysis of different tumor groups revealed that animals with tumors of epithelial origin presented with significantly elevated circulating Hsp70 concentrations. In addition to free Hsp70 levels measured with the R&D Systems Hsp70 ELISA, levels of exosomal Hsp70 were determined using the compHsp70 ELISA in pigs. Both ELISA systems detected significantly elevated Hsp70 levels (R&D Systems: median 24.9 ng/mL; compHsp70: median 44.2 ng/mL) in the blood of a cohort of APC1311/+ pigs diagnosed with high-grade adenoma polyps, and the R&D Systems Hsp70 ELISA detected also elevated Hsp70 levels in animals with low-grade polyps. In contrast, in flTP53R167H pigs, suffering from malignant osteosarcoma, the compHsp70 ELISA (median 674.32 ng/mL), but not the R&D Systems Hsp70 ELISA (median 4.78 ng/mL), determined significantly elevated Hsp70 concentrations, indicating that in tumor-bearing animals, the dominant form of Hsp70 is of exosomal origin. Our data suggest that both ELISA systems are suitable for detecting free circulating Hsp70 levels in pigs with high-grade adenoma, but only the compHsp70 ELISA can measure elevated, tumor-derived exosomal Hsp70 levels in tumor-bearing animals.


New Paradigms for CKD Management in Patients With T2D.
At the end of the activity, participants will be able to: Identify the risks of kidney disease and their consequences in patients with type 2 diabetes (T2D). Appropriately screen for the presence of chronic kidney disease (CKD) in patients with T2D. Initiate evidence-based therapy to slow the progression of kidney disease in patients with T2D and CKD. Become familiar with the novel nonsteroidal mineralocorticoid receptor antagonist finerenone and its role in the treatment of patients with T2D and CKD.


Phyto-mediated metallic nano-architectures via Melissa officinalis L.: synthesis, characterization and biological properties.
The development of methods for obtaining new materials with antimicrobial properties, based on green chemistry principles has been a target of research over the past few years. The present paper describes the phyto-mediated synthesis of metallic nano-architectures (gold and silver) via an ethanolic extract of Melissa officinalis L. (obtained by accelerated solvent extraction). Different analytic methods were applied for the evaluation of the extract composition, as well as for the characterization of the phyto-synthesized materials. The cytogenotoxicity of the synthesized materials was evaluated by Allium cepa assay, while the antimicrobial activity was examined by applying both qualitative and quantitative methods. The results demonstrate the synthesis of silver nanoparticles (average diameter 13 nm) and gold nanoparticles (diameter of ca. 10 nm); the bi-metallic nanoparticles proved to have a core-shell flower-like structure, composed of smaller particles (ca. 8 nm). The Ag nanoparticles were found not active on nuclear DNA damage. The Au nanoparticles appeared nucleoprotective, but were aggressive in generating clastogenic aberrations in A. cepa root meristematic cells. Results of the antimicrobial assays show that silver nanoparticles were active against most of the tested strains, as the lowest MIC value being obtained against B. cereus (approx. 0.0015 mM).


[Granular cell tumor (Abrikossoff's tumor). A review and our experience].
The low incidence of these tumors compelled the AA., after diagnosis of one of laryngeal sitting, to a review of the theme and its literature as well, particularly under the viewpoint of its histogenesis, which has been debatable up to lately. The report is complemented with the study of immunohistochemical tests for NHK, S-100 and specific neural enolase of the specimen.


Dense Bicoid hubs accentuate binding along the morphogen gradient.
Morphogen gradients direct the spatial patterning of developing embryos; however, the mechanisms by which these gradients are interpreted remain elusive. Here we used lattice light-sheet microscopy to perform in vivo single-molecule imaging in early Drosophila melanogaster embryos of the transcription factor Bicoid that forms a gradient and initiates patterning along the anteroposterior axis. In contrast to canonical models, we observed that Bicoid binds to DNA with a rapid off rate throughout the embryo such that its average occupancy at target loci is on-rate-dependent. We further observed Bicoid forming transient "hubs" of locally high density that facilitate binding as factor levels drop, including in the posterior, where we observed Bicoid binding despite vanishingly low protein levels. We propose that localized modulation of transcription factor on rates via clustering provides a general mechanism to facilitate binding to low-affinity targets and that this may be a prevalent feature of other developmental transcription factors.


Intranasal immunisation with a 62 kDa proteinase combined with cholera toxin or CpG adjuvant protects against Trichomonas vaginalis genital tract infections in mice.
Trichomonosis, caused by the protozoan parasite Trichomonas vaginalis, is one of the most frequent sexually transmitted diseases and is widely spread in all continents. Trichomonas vaginalis as well as other protozoan organisms have high levels of proteolitic activity mainly of the cysteine-proteinase type. This activity is necessary for recognition and adhesion of the parasite to the superficial epithelial cells of the host. In the present study, we show that intranasal immunisation with a 62 kDa cysteine-proteinase purified from T. vaginalis excretion-secretion products in combination with cholera toxin or with synthetic oligodeoxynucleotides (ODN) that contain unmethylated CpG motifs (CpG-ODN) elicits 62kDa specific IgG and IgA in vaginal lavage fluid and specific IgG in serum. This immunisation protocol resulted in enhanced elimination of parasites following intravaginal challenge of BALB/c mice.


Nationwide prevalence and trends in cigarette smoking among adult men with and without disabilities in South Korea between 2009 and 2017.
Current smoking rates for people with and without disabilities vary among countries. This study analyzed smoking behavior over 9 years in adult South Korean men with disabilities, according to disability severity and type, and in those without disabilities. This was a cross-sectional study. This analysis was conducted using national disability registration data and national general health checkup data for 2009-2017. Age-standardized smoking behaviors were analyzed for each year according to the presence, severity, and type of disability. The odds of current smoking were determined by multivariate logistic regression after adjusting for sociodemographic and clinical variables. The age-standardized smoking rate and average number of cigarettes for men with mild disabilities in the younger age group were 1.16 (43.0 vs 36.8%) and 1.05 (16.1 vs 15.3 cigarettes) times higher than in non-disabled men as of 2017. The highest smoking rate was observed in men with physical disabilities in the younger age. In the older age group, the highest smoking rate was that of men with intellectual or psychological disabilities. Smoking behaviors remained poorest in men with disabilities, especially those with mild, physical, and intellectual/psychological disabilities. Public health policies should focus on people with disabilities to promote health, prevent secondary conditions, and reduce health disparities by implementing antismoking health policies.


Efficacy and Safety of 12-week Monotherapy With Once Daily 5 mg Tadalafil for Lower Urinary Tract Symptoms of Benign Prostatic Hyperplasia: Evidence-based Analysis.
Background: Tadalafil has been approved for the treatment of benign prostatic hyperplasia (BPH) for nearly 10 years. However, there are insufficient evidence-based studies of the efficacy and safety of tadalafil in treating lower urinary tract symptoms of BPH (LUTS/BPH). Objective: To evaluate the therapeutic effect and clinical safety of tadalafil monotherapy (5 mg once daily for 12 weeks) for LUTS/BPH. Methods: A total of 13 studies (15 randomized clinical trials [RCTs]) were extracted from the following databases: PubMed, Cochrane Central Register of Controlled Trials, Embase, and Web of Science for the period up to July 2021. The quality of the included RCTs was evaluated independently by two authors, who, respectively, extracted data according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses principles. Conflicts were settled by a discussion with two-third of senior authors. All data analyses were conducted by the Review Manager, version 5.4. Results: Regarding efficacy, 12-week trials indicated that 5 mg once daily tadalafil showed a significantly lower and, consequently, better total International Prostate Symptom Score (IPSS) than the placebo did (mean difference [MD]: -1.97, 95% CI: -2.24 to -1.70; P < 0.00001). In addition, significant differences were found between the tadalafil regimen and the placebo in the IPSS voiding subscore (MD: -1.30, 95% CI: -1.48 to -1.11; P < 0.00001), the IPSS storage subscore (MD: -0.70, 95% CI: -0.82 to -0.58; P < 0.00001), the IPSS quality of life (MD: -0.29, 95% CI: -0.35 to -0.22; P < 0.00001), and BPH impact index (MD: -0.58, 95% CI: -0.76 to -0.40; P < 0.00001). The safety analysis did not show a significant difference in serious adverse events between the two groups (risk ratio: 1.27, 95% CI: 0.80-2.01; P = 0.31), although the adverse events occurred at a higher incidence in the tadalafil group than in the placebo. Conclusions: This study demonstrates that once daily 5 mg tadalafil is a potentially effective and safe treatment choice with excellent tolerability for patients with LUTS/BPH. Systematic Review Registration: Identifier (CRD42021228840).


Insights into the synthesis strategies of plant-derived cyclotides.
Cyclotides are plant peptides characterized with a head-to-tail cyclized backbone and three interlocking disulfide bonds, known as a cyclic cysteine knot. Despite the variations in cyclotides peptide sequences, this core structure is conserved, underlying their most useful feature: stability against thermal and chemical breakdown. Cyclotides are the only natural peptides known to date that are orally bioavailable and able to cross cell membranes. Cyclotides also display bioactivities that have been exploited and expanded to develop as potential therapeutic reagents for a wide range of conditions (e.g., HIV, inflammatory conditions, multiple sclerosis, etc.). As such, in vitro production of cyclotides is of the utmost importance since it could assist further research on this peptide class, specifically the structure-activity relationship and its mechanism of action. The information obtained could be utilized to assist drug development and optimization. Here, we discuss several strategies for the synthesis of cyclotides using both chemical and biological routes.


New Developments in Anti-Angiogenic Therapy of Cancer, Review and Update.
Angiogenesis is one of the critical physiological processes, by which the new blood vessels are generated from the pre-existing vessels in the early stage of vasculogenesis. While normal angiogenesis is critical for development and tissue growth, pathologic angiogenesis is important for the growth and spread of cancers by supplying nutrients and oxygen as well as providing a conduit for distant metastasis. In the last two decades, angiogenesis has been the area of extensive researches, indicating antiangiogenic target therapy as an effective strategy for cancer therapy. At present, this field has become a major avenue for research and development of novel therapeutics. This review is dedicated to an updated review of the most prominent antiangiogenic agents, emphasizing the novel advancements and their applications, in particular, in the fields of antibodies, peptides, vaccines, endogenous inhibitors, Nanoparticles (NPs), antiangiogenic oligonucleotides and small molecules. Also, the potential role of 3D microfluidic models as an affordable and time-saving tool for angiogenesis investigations are discussed. Firstly, we collected and summarized new developments that have occurred in all review and research articles in databases. Then, we used important keywords related to antiangiogenic target therapy and their applications for retrieval of most relevant data. This review is based on recent research and review articles and intended to cover all newly discovered agents inhibiting tumor angiogenesis and in particular, VEGF. New research studies have shown that anti-angiogenesis agents especially, in the form of combination therapy are effective in various cancers treatment.


Bromination of selected pharmaceuticals in water matrices.
The bromination of five selected pharmaceuticals (metoprolol, naproxen, amoxicillin, phenacetin, and hydrochlorothiazide) was studied with these compounds individually dissolved in ultra-pure water. The apparent rate constants for the bromination reaction were determined as a function of the pH, obtaining the sequence amoxicillin>naproxen>>hydrochlorothiazide≈phenacetin≈metoprolol. A kinetic mechanism specifying the dissociation reactions and the species formed for each compound according to its pK(a) value and the pH allowed the intrinsic rate constants to be determined for each elementary reaction. There was fairly good agreement between the experimental and calculated values of the apparent rate constants, confirming the goodness of the proposed reaction mechanism. In a second stage, the bromination of the selected pharmaceuticals simultaneously dissolved in three water matrices (a groundwater, a surface water from a public reservoir, and a secondary effluent from a WWTP) was investigated. The pharmaceutical elimination trend agreed with the previously determined rate constants. The influence of the main operating conditions (pH, initial bromine dose, and characteristics of the water matrix) on the degradation of the pharmaceuticals was established. An elimination concentration profile for each pharmaceutical in the water matrices was proposed based on the use of the previously evaluated apparent rate constants, and the theoretical results agreed satisfactorily with experiment. Finally, chlorination experiments performed in the presence of bromide showed that low bromide concentrations slightly accelerate the oxidation of the selected pharmaceuticals during chlorine disinfection.


Differential functions of G protein and Baz-aPKC signaling pathways in Drosophila neuroblast asymmetric division.
Drosophila melanogaster neuroblasts (NBs) undergo asymmetric divisions during which cell-fate determinants localize asymmetrically, mitotic spindles orient along the apical-basal axis, and unequal-sized daughter cells appear. We identified here the first Drosophila mutant in the Ggamma1 subunit of heterotrimeric G protein, which produces Ggamma1 lacking its membrane anchor site and exhibits phenotypes identical to those of Gbeta13F, including abnormal spindle asymmetry and spindle orientation in NB divisions. This mutant fails to bind Gbeta13F to the membrane, indicating an essential role of cortical Ggamma1-Gbeta13F signaling in asymmetric divisions. In Ggamma1 and Gbeta13F mutant NBs, Pins-Galphai, which normally localize in the apical cortex, no longer distribute asymmetrically. However, the other apical components, Bazooka-atypical PKC-Par6-Inscuteable, still remain polarized and responsible for asymmetric Miranda localization, suggesting their dominant role in localizing cell-fate determinants. Further analysis of Gbetagamma and other mutants indicates a predominant role of Partner of Inscuteable-Galphai in spindle orientation. We thus suggest that the two apical signaling pathways have overlapping but different roles in asymmetric NB division.


Synthesis and Nonlinear Optical Behavior of Thermally Stable Chromophores Based on 9,9-Dimethyl-9H-fluoren-2-amine: Improving Intrinsic Hyperpolarizability through Modulation of "Push-Pull".
Improvement in the first hyperpolarizability (βHRS) as well as intrinsic hyperpolarizability (βint) of chromophores based on 9,9-dimethyl-9H-fluoren-2-amine through modulation of the conjugation pathway is described. A series of six novel chromophores with "linear" conjugation showed significant enhancement of βHRS as well as βint compared to the counterparts lacking a "linear" conjugation but having an identical combination of donor, acceptor, and the intervening π-conjugated linker. The hyperpolarizability (βHRS as well as βint) values of the new series measured using hyper-Rayleigh scattering exceeded the apparent limit set by the latter set of fluorene-based chromophores. The experimental results are analyzed and interpreted in the context of linear optical properties, single-crystal X-ray analysis, electrochemistry, etc. and corroborated by theoretical studies. We find that modulation of the "push-pull" of the conjugation pathway in these donor-acceptor chromophores compares favourably with the corresponding changes in the optical gaps, transition dipole moments, and dipole moment difference between the ground and excited states.


Relation between coronary artery stenosis and myocardial purine metabolism, histology and regional function in humans.
In 54 patients undergoing elective or emergency aortocoronary bypass grafting, angiographic and electrocardiographic changes were studied. Five patients with unstable angina and five patients with evolving myocardial infarction were included. High energy phosphate metabolism and the histologic appearance of the myocardium were analyzed in transmural biopsy specimens acquired at the time of surgery. In patients without anterior infarction on the electrocardiogram, severe stenosis of the left anterior descending coronary artery resulted in a reduction of anterior wall motion that was associated with a partial depletion of the adenylate pool. Mitochondrial function, however, remained intact: the adenosine diphosphate/adenosine triphosphate ratio, the energy charge and the creatine phosphate/adenosine triphosphate ratio were in the normal range. Histologic assessment demonstrated viable myocardium with a high incidence of atrophic cells. In evolving myocardial infarction, 170 minutes of acute coronary artery obstruction resulted in anterior wall akinesia associated with a decrease of the sum of the adenylates to 52% and of creatine phosphate to 16% of their normal value (p less than 0.05). The nucleosides accumulated; their major fraction (91%) was inosine. The adenosine diphosphate/adenosine triphosphate ratio increased from 0.14 +/- 0.04 to 0.49 +/- 0.20 (p less than 0.01) and the energy charge decreased from 0.924 +/- 0.021 to 0.660 +/- 0.169 (p less than 0.01). Ultrastructure examination revealed irreversible cell damage in at least the subendocardial layer. These results suggest that the energetic base of reduced contractility due to severe coronary artery stenosis is different from that in acute coronary obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)


Long-term effects of lanreotide SR and octreotide LAR on tumour shrinkage and GH hypersecretion in patients with previously untreated acromegaly.
The therapeutic efficacy of lanreotide SR and octreotide LAR has been studied widely in patients treated previously with neurosurgery and/or radiotherapy. These therapies limit the evaluation of the long-term effects of somatostatin analogues on tumour shrinkage. Neurosurgical and radiotherapy treatments cause irreversible anatomical changes in pituitary morphology, which can make accurate evaluation of tumour shrinkage difficult. The aim of this study was to investigate the therapeutic efficacy of lanreotide SR and octreotide LAR in previously untreated patients with acromegaly. We aimed to investigate the long-term effects of these drugs on tumour shrinkage and growth hormone (GH) hypersecretion without the confounding influences of previous therapy. Twenty-three newly diagnosed patients with acromegaly (14 women, nine men) with active disease began the study; of these, three were lost for follow-up, leaving a total of 20 patients to complete the study. Patients were assigned randomly to lanreotide SR (12 patients) and octreotide LAR (eight patients), and the randomization stratified patients to assure a balance between the groups with respect to baseline tumour dimension, age and sex. Tumour volume was evaluated by magnetic resonance imaging of the sella, and calculated with the rotating ellipsoid formula. A morphological and biochemical evaluation was performed at baseline, 12 and 24 months after beginning lanreotide SR and octreotide LAR treatment. A reduction of tumour volume of at least 10% was considered significant. Biochemical control increased progressively throughout the study in patients with microadenomas more than in patients with macroadenomas (70% vs. 10%; P < 0.05) and without a difference between lanreotide SR and octreotide LAR (41.0% vs. 37.5%; P not significant). After 12 months of treatment, mean tumour shrinkage was 28.3 +/- 18.0%. A greater reduction was observed in macro- vs. microadenomas (40.5 +/- 17.0% vs. 16.1 +/- 8.0%, respectively; P < 0.05). No statistical difference in the tumour shrinking effects of lanreotide SR vs. octreotide LAR was observed (26.5 +/- 17.3% vs. 31.1 +/- 16.1%, respectively). At the 24th month of therapy, no further overall shrinkage was observed, compared to the 12-month evaluation (31.9 +/- 17.2% vs. 28.3 +/- 18.0%) at which there was no difference between lanreotide SR and octreotide LAR (30.0 +/- 17.2% vs. 34.8 +/- 16.5%, respectively). This study showed that the new long-acting somatostatin analogues, lanreotide SR and octreotide LAR, cause significant shrinkage of pituitary GH-secreting adenomas in previously untreated patients with acromegaly. This effect was more marked in macroadenomas than microadenomas, and did not correlate with control of GH hypersecretion.


An ultrasonographic study of liver fibrosis in patients infected with Schistosoma mansoni in north-east Brazil.
Between August 1988 and July 1990, 176 patients with Schistosoma mansoni infection attending the University Hospital, Recife, Brazil received a complete clinical examination including stool examination for intestinal parasites, liver function tests, and ultrasonography. The majority were also examined by upper digestive tract endoscopy. The clinical distribution of their disease was as follows: 26.7% intestinal, 13.6% hepato-intestinal, 53.4% compensated hepatosplenic and 6.3% decompensated hepatosplenic. Infection intensity was high, with a median of 360 eggs/g of faeces. Ultrasonography showed a good correlation between the degree of hepatic periportal fibrosis and the clinical stage of disease (P < 0.0001). Of the patients with the intestinal form of schistosomiasis, 12.8% had grade I fibrosis and the others had no fibrosis; 33.3% of patients with hepatointestinal schistosomiasis had grade I fibrosis, 8.3% had grade II fibrosis, and 58.4% had no fibrosis; all the patients with hepatosplenic disease had grade II or grade III fibrosis. The degree of liver fibrosis detected by ultrasonography correlated with the degree of oesophageal varices detected by endoscopy (P = 0.0001). The degree of oesophageal varices also correlated with the presence of haemorrhage (P < 0.0001). Ultrasonography is considered superior to liver biopsy, permitting a dynamic approach to the study of schistosomiasis morbidity with precise diagnosis and simple sequential follow-up of post-treatment results.


Magnetization transfer weighted laminar fMRI with multi-echo FLASH.
Laminar functional magnetic resonance imaging (fMRI) using the gradient echo (GRE) blood oxygenation level dependent (BOLD) contrast is prone to signal changes arising from large unspecific venous vessels. Alternatives based on changes of cerebral blood volume (CBV) become more popular since it is expected that this hemodynamic response is dominant in microvasculature. One approach to sensitize the signal toward changes in CBV, and to simultaneously reduce unwanted extravascular (EV) BOLD blurring, is to selectively reduce gray matter (GM) signal via magnetization transfer (MT). In this work, we use off-resonant MT-pulses with a 3D FLASH readout to perform MT-prepared (MT-prep) laminar fMRI of the primary visual cortex (V1) at multiple echo times at 7 T. With a GRE-BOLD contrast without additional MT-weighting as reference, we investigated the influence of the MT-preparation on the shape and the echo time dependency of laminar profiles. Through numerical simulations, we optimized the sequence parameters to increase the sensitivity toward signal changes induced by changes in arterial CBV and to delineate the contributions of different compartments to the signal. We show that at 7 T, GM signals can be reduced by 30 %. Our laminar fMRI responses exhibit an increased signal change in the parenchyma at very short TE compared to a BOLD-only reference as a result of reduced EV signal intensity. By varying echo times, we could show that MT-prep results in less sensitivity toward unwanted signal changes based on changes in T2*. We conclude that when accounting for nuclear overhauser enhancement effects in blood, off-resonant MT-prep combined with efficient short TE readouts can become a promising method to reduce unwanted EV venous contributions in GRE-BOLD and/or to allow scanning at much shorter echo times without incurring a sensitivity penalty in laminar fMRI.


"This snack is too small - I'll take a different one": Quantifying 'norm' and 'choice' boundaries to inform effective portion-reduction strategies.
Previous research suggests that portion sizes can be categorised as 'normal' or 'abnormal' and that reduced portions which are still categorised as normal do not promote compensatory responses in intake. However, a critical question remains - will consumers choose a reduced portion product from among standard portion competitors? For the first time, we explore the effects of portion reduction on food choice. Participants (N = 45) categorised 20 different portions (range 40-420 kcal) of five snacks as normal or abnormal (to quantify individual 'norm boundaries' for each food) and rated their desire to eat each snack. Using a 2-alternative forced choice hypothetical task, we then calculated a 'choice boundary' by offering smaller portions of their most-desired snack (range 40-240 kcal) alongside standardised portions (240 kcal) of the less-desired foods. Boundaries were derived using probit analysis (choice boundary mean = 185.8 kcal, SD = 54, norm boundary mean = 127.3 kcal, SD = 49.5) and these deviated significantly (p < .01, d = 0.98, mean difference = 58.0 kcal, SD = 59.1). Critically, this shows that only a small reduction - where the product is still considered normal - can nudge a consumer to select an alternative. Choice boundaries were also affected by differences in desire to eat; when two foods were desired to a similar degree, only minor reductions in the size of the favourite food elicited a switch in choice. Together, these findings indicate that portion reduction can also influence food choice, highlighting the importance of measuring choice boundaries before reformulating commercial products.


Enhanced arsenite removal in aqueous with Fe-Ce-Cu ternary oxide nanoparticle.
Arsenite is both more harmful and challenging to get out of water than arsenate. For enhanced As (III) removal, a ternary oxide nanoparticle (FCCTO) mainly composed of iron(Fe), with a small proportion of cerium(Ce) and copper(Cu) was created using a coprecipitation-calcination process. FCCTO was found to be effective in removing As (III) from water, with factors such as adsorbent dose, pH, temperature, and coexisting anions influencing its efficiency. The surface area of FCCTO reached 180.2 m2/g and the doping significantly increased its pore volume and diameter. The adsorption process on FCCTO was endothermic and spontaneous. Ce and Cu in FCCTO were able to efficiently oxidize 81.3% As (III) to As(V). Abundant sites were provided by surface hydroxyl groups for arsenic adsorption. The maximal As(III) adsorption capacity of this adsorbent under the synergistic impact of oxidation and adsorption was 101.5 mg/g. After five cycles, the FCCTO's As(III) adsorption rate dropped to 60% as a result of tetravalent Ce consumption. Surface complexation, redox, and adsorption all had a significant impact on the adsorption process. Overall, FCCTO was an excellent adsorbent with benefits of being facile fabrication, environmentally, recyclable, and having a high As(III) adsorption capacity.


Results of a technique of pancreaticojejunostomy that optimizes blood supply to the pancreas.
Anastomotic failure after pancreaticojejunostomy is still a common problem. Failure rates have not decreased perceptibly in the past 3 decades. The neck of the pancreas is a vascular watershed between celiac and superior mesenteric arterial systems. Prior attempts to reduce anastomotic failure at pancreaticojejunostomy have not focused on issues related to blood supply of the pancreas. The aim of this study was to determine whether pancreaticojejunostomy performed using a technique that included optimization of blood supply to the pancreas, would result in a low anastomotic failure rate. The technique was prospectively evaluated in 40 patients having pancreaticojejunostomy, 39 during pancreaticoduodenectomy and 1 after traumatic transection of the neck of the pancreas. Blood supply to the pancreatic neck was evaluated clinically and by Doppler techniques. When blood supply was considered marginal, the pancreas was re-resected 1.5-2.0 cm to the left, away from the vascular watershed. Blood supply at the cut margin of pancreas was judged as brisk in 24 patients and marginal in 16 patients. Resecting a segment of pancreas in these 16 patients resulted in brisk bleeding from the new cut margin in all but 1 patient who had an anomalous artery that had to be sacrificed for oncologic reasons. The only fistula in the series occurred in this patient. There were no intraabdominal abscesses. A technique that includes ensuring adequate blood supply to the pancreas can result in a very low rate of anastomotic failure.


How do we measure quality in primary dental care?
In the second paper of a series exploring quality in primary dental care a way to measure quality in dentistry is considered. Unless there are valid and reliable tools to measure quality then quality can never be improved. Measurement tools need to be acceptable to patients if they are to be employed, as well as to busy practices in terms of practicality and costs. Examples such as the General Medical Practitioner's Quality Outcome Framework need to be understood to see if they can be translated to dentistry.


Endoscopy-assisted surgery of the petrous apex.
Five large petrous apex lesions, 4 cholesterol granulomas and 1 cholesteatoma, were managed with a combination of microsurgical and endoscopic techniques. Retrospective review of clinical experience in an academic medical center. Traditional microsurgical approaches, infracochlear and/or retrofacial, were used in all cases, followed by endoscopic examination and debridement of the interior of the cysts. In all cases residual disease or fibrous septae within the cysts were found endoscopically that were not evident through use of the operating microscope. In all cases, the lesions were successfully managed without operative complications. The addition of endoscopic visualization to traditional microsurgical approaches allowed exposure of recesses within the lesions, removal of debris and inspissated secretions, and identification and removal of septae and fibrous bands within the petrous apex lesions that would not have been identified with the operating microscope alone. No surgical or postsurgical complications occurred in any of the cases, including facial weakness, hearing loss, or cerebrospinal fluid (CSF) leak.


Lifting the fog in store-operated Ca2+ entry.
Immunoreceptor signalling leads to Ca2+ release from intracellular stores, which is followed by the entry of external Ca2+ into the cell through mysterious store-operated Ca2+ (SOC) channels. Recent studies have identified stromal interaction molecules (STIMs) as having an essential role in SOC influx. Remarkably, Ca2+ store depletion induces a rapid redistribution of the endoplasmic reticulum STIM1 into puncta that accumulate near the plasma membrane. The combined data suggest that STIM1 functions as a Ca2+ sensor in the signalling pathways connecting Ca2+ store depletion to SOC entry.


Is Telemental Health Services a Viable Alternative to Traditional Psychotherapy for Deaf Individuals?
Access to mental health treatment is a vital part of a comprehensive health care plan. Deaf individuals often have difficulty accessing mental health services. Four-hundred twenty-two participants completed an anonymous questionnaire about their perspectives of telemental health services for deaf individuals. Results showed that several variables, such as if the participant was unable to receive another type of psychotherapy and whether the therapist was ASL-fluent, were significantly related to whether the respondent would use TMH. The participants reported that TMH services are a viable option for treating a variety of mental health issues. Telemental health services can act as a bridge between consumers of mental health care and their providers allowing accessible and equitable healthcare opportunities.


Management of complications relating to complex traumatic hand injuries.
Complex hand injuries result in local trauma to osseous, neurovascular, and soft tissue structures. The large amount of energy imparted to these tissues may result in complex regional pain syndrome, stiffness, or infection. Unfortunately, a good outcome may not only depend on the technical aspects of the procedure but on the expectations, occupation, age, and other factors that are out of the surgeon's control. The best treatment for these complications is prevention; however, this review offers strategies to combat the complications once they arise.


Induction of Ca2+-activated K+ current and transient outward currents in human capillary endothelial cells.
Human capillary endothelial cells (HCEC) in normal media contain noninactivating outwardly rectifying chloride currents, TEA-sensitive delayed rectifier K+ currents and an inward rectifier K+ current. Two additional ionic currents are induced in HCEC when the media are allowed to become conditioned: A Ca2+-activated K+ current (BKCA) that is sensitive to iberiotoxin is induced in 23.5% of the cells, a transient 4-AP-sensitive K+ current (A current) is induced in 24.7% of the cells, and in 22.3% of the cells both the transient and BKCA currents are coinduced. The EC50 for Ca2+ activation of the BKCA current in HCEC from conditioned media is 213 nM. RNA message for BKCA (hSlo clone) is undetecable after PCR amplification in control cells but is seen in those from conditioned cells. The induction of BKCA current is not blocked by conditioning with inhibitors of nitric oxide synthase, cyclo-oxgenase or lypo-oxygenase pathways. Apparently the characteristics of human endothelial cells are highly malleable and can be easily modified by their local environment.


K562 human leukemia cell passages differ in embryonic globin gene expression.
K562 is a human leukemia cell line inducible by a variety of agents for the synthesis of embryonic and fetal hemoglobins. We compared early and late passages to determine whether a change has occurred in globin synthetic pattern. Clone LA4, derived from passage 199 which had been frozen by Lozzio in 1973, was compared with clone RA6, derived from a line received from Rutherford in 1979. Globin synthetic pattern was determined by incubation with [3]leucine, separation of globins by Triton-X100 polyacrylamide gel electrophoresis, and analysis by fluorography. For RA6, hemin-induced synthesis was greatest for zeta globin but minimal for epsilon globin, whereas for LA4 it was greatest for epsilon globin but minimal for zeta globin. Both lines are pseudotriploid with three No. 11 and three No. 16 chromosomes. However only RA6 has a translocation involving the short arm of chromosome 11 which contains the locus of the beta globin gene cluster. However, translocation-associated deletion does not simply explain the deficient inducibility of epsilon synthesis because G gamma and A gamma globins, whose genes are linked to the epsilon gene, are similarly inducible in the two lines.


Association of mental health and negative life events with weight change in patients with overweight: A cohort study.
It is unclear to what extent mental health and negative life events (NLEs) contribute to weight change in patients with overweight. This study aimed to evaluate the association of anxiety, depression, NLEs and quality of life (QoL) with weight change over ten years in middle-aged individuals with overweight. Population-based cohort study of 2889 middle-aged men and women with a body mass index ≥27 kg/m2. Relative weight change over ten years was defined as weight loss (≤- 5 %), stable weight (between >- 5 % and <5 %) or weight gain (≥5 %). At baseline, participants reported anxiety symptoms, depressive symptoms, recent (last year) and distant (lifetime) NLEs, and a mental component summary of QoL. With multinomial logistic regression adjusting for potential confounding, we examined the association of mental health and NLEs with weight change after a median (25th, 75th percentiles) follow-up of 9.7 (9.0-10.5) years. In 51 % participants weight was stable, 33 % participants lost weight and 17 % gained weight. Mild (odds ratio 1.36; 95 % confidence interval 1.05-1.75), and moderate to very severe depressive symptoms (1.43; 0.97-2.12) and four or more distant NLEs (1.35; 1.10-1.67) were associated with weight gain. Anxiety symptoms, the mental component summary of QoL were not associated with either weight gain or weight loss. Due to the observational design residual confounding cannot be excluded. Our study suggests that depressive symptoms or having experienced distant NLEs are associated with weight gain over time in middle-aged individuals with overweight. These subgroups might benefit from proactive attention from their health care providers.


Evidence for risk reduction among amphetamine-injecting men who have sex with men; results from national HIV behavioral surveillance surveys in the Seattle area 2008-2012.
In the Seattle area men who have sex with men and also inject amphetamines (amphetamine-injecting MSM/IDU) are disproportionately likely to be infected with HIV. To characterize their distinctive characteristics, we combined data from two Seattle-area surveys of men who have sex with men (MSM) and two surveys of injection drug users (IDU). Amphetamine-injecting MSM/IDU were compared with: male IDU, MSM and other MSM/IDU. Amphetamine-injecting MSM/IDU were older than MSM but younger than IDU, more likely to be white than either group, and had an educational level higher than IDU but below MSM. They had the highest HIV prevalence (56 vs. 4-19 %). However, reported HIV cases among them fell from 92 in 1990 to 25 in 2012. They were most likely to report ten or more sex partners (49 vs. 4-26 %), an STD diagnosis (22 vs. 1-7 %) and be tested for HIV (odds ratio 1.00 vs. 0.34-0.52), and least likely to share needles (odds ratio 1.00 vs. 6.80-10.50). While sexual risk remains high, these data suggest measurable and effective risk reduction with respect to sharing injection equipment and HIV testing among Seattle-area amphetamine-injecting MSM/IDU.


A convolutional network and attention mechanism-based approach to predict protein-RNA binding residues.
Protein-RNA interactions play a key role in various biological cellular processes, and many experimental and computational studies have been initiated to analyze their interactions. However, experimental determination is quite complex and expensive. Therefore, researchers have worked to develop efficient computational tools to detect protein-RNA binding residues. The accuracy of existing methods is limited by the features of the target and the performance of the computational models; there remains room for improvement. To solve the problem of the accurate detection of protein-RNA binding residues, we propose a convolutional network model named PBRPre based on improved MobileNet. First, by extracting the position information of the target complex and the 3-mer amino acid feature data, the position-specific scoring matrix (PSSM) is improved by using spatial neighbor smoothing processing and discrete wavelet transform to fully exploit the spatial structure information of the target and enrich the feature dataset. Second, the deep learning model MobileNet is used to integrate and optimize the potential features in the target complexes; then, by introducing the Vision Transformer (ViT) network classification layer, the deep-level information of the target is mined to enhance the processing ability of the model for global information and to improve the detection accuracy of the classifiers. The results show that the AUC value of the model can reach 0.866 in the independent testing dataset, which shows that PBRPre can effectively realize the detection of protein-RNA binding residues. All datasets and resource codes of PBRPre are available at https://github.com/linglewu/PBRPre for academic use.


Exercise pre-conditioning reduces brain damage in ischemic rats that may be associated with regional angiogenesis and cellular overexpression of neurotrophin.
There is increasing evidence that physical activity is associated with a decreased stroke risk. The purpose of this study was to determine if exercise could also reduce brain damage in rats subjected to transient middle cerebral artery (MCA) occlusion, and if the reduced brain injury is associated with angiogenesis as well as cellular expression of the nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in regions supplied by the MCA. Adult male Sprague Dawley rats (n=36) exercised 30 min each day for 3 weeks on a treadmill on which repetitive locomotor movement was required. Then, stroke was induced by a 2-h MCA occlusion using an intraluminal filament, followed by 48 h of reperfusion. In addition to the two exercised groups of animals with or without MCA occlusion, there were two other groups of animals, with or without MCA occlusion, housed for the same duration and used as non-exercised controls. Brain damage in ischemic rats was evaluated by neurologic deficits and infarct volume. Exercise preconditioned and non-exercised brains were processed for immunocytochemistry to quantify the number of microvessels or NGF- and BDNF-labeled cells. Pre-ischemic motor activity significantly (P<0.01) reduced neurologic deficits and infarct volume in the frontoparietal cortex and dorsolateral striatum. Cellular expressions of NGF and BDNF were significantly (P<0.01) increased in cortex (neuron) and striatum (glia) of rats under the exercise condition. Significant (P<0.01) increases in microvessel density were found in striatum. Physical activity reduced stroke damage. The reduced brain damage may be attributable to angiogenesis and neurotrophin overexpression in brain regions supplied by the MCA following exercise.


Identification of the site of phosphorylation on the osmosensor, EnvZ, of Escherichia coli.
EnvZ is a membrane-bound histidine kinase that functions as an osmotic sensor capable of phosphorylating the regulator protein OmpR in Escherichia coli. To characterize the site of phosphorylation biochemically, we overexpressed a 36-kDa truncated EnvZ protein (Glu-106 to Gly-450) that formed inclusion bodies in the cell. After solubilization, the inclusion body form of EnvZ was cleaved into two major fragments with molecular weights of 25,000 and 10,000. The 25-kDa fragment, EnvZc, was purified and found to exist as a dimer. N-terminal sequence analysis established that cleavage had occurred at Arg-214, indicating that EnvZc contained most of the cytoplasmic domain of EnvZ. After labeling EnvZc with [gamma-32P]ATP, the protein was proteolytically digested, and the resulting peptides were separated by reverse phase chromatography using high performance liquid chromatography. One major radioactive peptide containing greater than 90% of the recovered peptide-associated radioactivity was isolated. Amino acid analysis of this purified peptide indicated that the composition was consistent with a peptide that contained His-243. The amino acid sequence of this peptide was determined to be MAGVSHDLRTP (residues 238-248). These results indicate that His-243 is the major site of phosphorylation on EnvZ and represents the first biochemical characterization of the site of phosphorylation of a membrane histidine kinase of the two-component regulatory family of molecules in bacteria.


Trinucleotide repeat disorders.
Trinucleotide repeat disorders comprise a variable group of inherited neurodegenerative diseases, with a large range in prevalence figures. There is a broad range in clinical presentations, but many of these diseases lead to some form of ataxia or other movement disorders, which are frequently combined with cognitive or psychiatric disturbances. This group can be divided into CAG- versus non-CAG-repeat diseases. Apart from spinocerebellar ataxia type 6 and 12 (SCA6 and SCA12), these CAG-repeat diseases, as well as Huntington disease-like 2 (HDL2) and SCA8, can be neuropathologically identified using 1C2 polyglutamine antibodies. In fragile X-associated tremor and ataxia, SCA6 and SCA12 ubiquitin/p62-positive and 1C2-negative inclusion bodies can be observed. In the other diseases proteinaceous inclusions are not found. For definite diagnosis genetic analysis is necessary.


Feasibility of an adaptive riding pilot study and acceptability to dementia care partners: "Your spirits are lifted".
We sought to assess the feasibility and acceptability of an adaptive riding program with dyads (persons living with dementia, family care partners) and a gardening comparison condition. This is a two-arm (adaptive riding and adaptive gardening), mixed methods, convergent, feasibility study that occurred February 2019-June 2019. Upon enrollment, dyads (n=9) self-selected into either community-based adaptive riding (n=5) or adaptive gardening (n=4), two complementary interventions in Northern Colorado. Interventions occurred for hour-long, weekly sessions for eight weeks. Feasibility was measured with recruitment (actual/planned, response rate, participants enrolled/month) retention, adherence to study procedures (attendance, retention, fidelity), and data collection processes (planned versus collected); and analyzed with descriptive statistics. Acceptability of adaptive riding was measured with pre/post care partner interviews and analyzed using thematic analysis. Afterwards, findings were converged. We recruited n=10/24 dyads (6 dyads per month), with the highest response rates for referrals and in-person events, n=9 dyads enrolled. We adhered to study procedures with attendance (6/8 gardening, 8/8 riding), retention (100%), fidelity (100%) and data collected (98%). Care partners (n=5) found the adaptive riding intervention acceptable with two themes Overall hopes: "Joy in the present moment" and "Experience as a Whole: "Your spirits are lifted," affirming quantitative attendance and retention data. Findings underscore the feasibility and acceptability of including care partners of persons living with dementia in complementary interventions involving horsemanship activities. Feasibility data can guide study designs and implementation processes for other nature-based complementary interventions for this population.


Fabrication of high-strength, flexible, porous collagen-based scaffolds to promote tissue regeneration.
Collagen-based scaffolds lack mechanical strength, flexibility, and tunable pore structure, affecting tissue repair outcomes and restricting their wide clinical application. Here, two kinds of scaffolds were prepared by a combination of vacuum homogenization, natural air drying, water soaking, lyophilization, and crosslinking. Compared with the scaffolds made of collagen molecules (Col-M), the scaffolds made of collagen aggregates (Col-A) exhibited higher mechanical strength (ultimate tensile strength: 1.38 ± 0.26 MPa vs 15.46 ± 1.55 MPa), stronger flexibility, advanced cell adhesion, survival, and proliferation. Subcutaneous implantation in rats showed that Col-A scaffolds promoted cell infiltration, macrophage polarization, and vascularization. Furthermore, the Col-A scaffolds inhibited abdominal bulges due to their adequate mechanical support, and they also promoted vascularized muscle regeneration in a rat abdominal hernia defect model. Our study provides a novel strategy for generating high-strength, flexible, porous collagen-based scaffolds, which can be applied to tissue repair with mechanical strength requirements. It broadens their application range in the field of regenerative medicine.


Photodynamic therapy for Barrett's esophagus: follow-up in 100 patients.
This report presents clinical results of photodynamic therapy in patients with Barrett's esophagus and dysplasia or superficial esophageal cancer. One hundred patients including 13 with superficial cancers were treated. Light (630 nm) was endoscopically delivered to the esophageal mucosa by a diffuser or a windowed esophageal centering balloon. Nd:YAG laser was required to ablate small residual areas of Barrett's mucosa during-long-term follow-up. Patients were maintained on omeprazole and were followed for 4 to 84 months (mean 19 months). Conversion of approximately 75% to 80% of treated Barrett's mucosa to normal squamous epithelium was found in all patients; complete elimination of Barrett's mucosa was noted in 43 patients. Dysplasia was eliminated in 78 patients. Dysplasia developed during follow-up in 11 of 48 patients in untreated Barrett's mucosa requiring additional therapy. Ten of the 13 malignancies were ablated. Esophageal strictures occurred in 34%. Use of longer centering balloons reduced the incidence of strictures. Photodynamic therapy alone or with Nd:YAG laser thermal ablation combined with long-term acid inhibition provides an effective endoscopic therapy to (1) eliminate Barrett's mucosal dysplasia and superficial esophageal cancer and (2) reduce the extent of and, in some cases, eliminate Barrett's mucosa.


In vitro fertilization in women with "frozen pelvis": clinical outcome of treatment.
The outcome of 93 consecutive cycles of in vitro fertilization (IVF) and embryo transfer (ET) treatment in 52 women with "frozen pelvis" is reported. The treatment termination rate due to inadequate ovarian stimulation was 20%. The mean +/- standard deviation of the number of follicles of mean diameter greater than or equal to 15 mm, oocytes recovered and fertilized per operation, and embryos replaced per cycle were 4.80 +/- 2.07, 4.02 +/- 2.32, 2.54 +/- 2.06, and 2.57 +/- 1.30, respectively. The pregnancy rate per ET was 29.6%. These data compare with those of other treated women with adhesion-free ovaries over the same period, suggesting that pelvic adhesive disease has no adverse effect on outcome of IVF-ET.


GABAA antagonists reveal binding sites for [35S]TBPS in cerebellar granular cell layer.
Autoradiography revealed picrotoxin-sensitive [35S]TBPS ([35S]t-butylbicyclophosphorothionate) binding sites in the cerebellar granule cell layer only in the presence of GABAA receptor antagonists. However, under the same conditions, the binding was decreased in other brain regions, including the cerebellar molecular cell layer. Thus, the convulsant binding sites at GABAA receptors in the granule cell layer are highly sensitive to down-regulation by GABA, which may be due to a unique combination of receptor subunits.


Recent diagnostic procedures for colorectal cancer screening: Are they cost-effective?
Colorectal cancer (CRC) is the third most common cancer worldwide and the fourth most common cause of death. Reduction in mortality rates in some countries worldwide are most likely ascribed to CRC screening and/or improved treatments. We reviewed the most relevant articles which discuss the cost-effectiveness of colorectal cancer screening procedures, in particular, the recent ones through the last eight years. The effectiveness of screening estimated by discounted life years gained (LYGs) compared to no screening, differed considerably between the studies. Despite these differences, all studies consistently emphasized that screening for CRC was cost-effective compared with no screening for each of the recognized screening strategies. Newer technologies for colorectal cancer screening, including computed tomographic colonography (CTC), faecal DNA test, and Pillcam Colon are less invasive and accurate, however, they are not cost-effective, as their cost was higher than all other established screening strategies. When compliance and adherence to such new techniques are increased more than the established strategies they would be more cost-effective particularly CTC.


Identification of a 94-bp GC-rich element in the smooth muscle myosin heavy-chain promoter controlling vascular smooth muscle cell-specific gene expression.
The previously described rabbit 2.3-kilobase smooth muscle myosin heavy-chain (SMHCwt) promoter targets gene expression in transgenic animals to vascular smooth muscle cells (SMCs), including coronary arteries. Therefore, SMHCwt is thought to provide a promising tool for human gene therapy. In the present study, we examined tissue specificity and expression levels of wild-type and mutated SMHC promoters within the system of high-capacity adenoviral (hcAd) vectors. SMHCwt and a series of SMHC promoter deletion mutants, a triple promoter as well as a cytomegalovirus-SMHC hybrid promoter driving the enhanced green fluorescence protein (EGFP) reporter gene were transiently transfected into aortic SMCs. Fluorescence intensity was measured by flow cytometric analysis. Consecutively, hcAd vectors were constructed with the SMHCwt and the mutant promoter with the highest fluorescence activity. Levels of EGFP expression were determined after transduction of SMCs derived from human coronary arteries. For analysis of tissue specificity, embryonic stem (ES) cell-derived SMCs (ESdSMHCs) and cardiomyocytes (ESdCMs) were used. In comparison with SMHCwt, only the SMHCdel94 mutant lacking a 94-bp GC-rich element revealed a 1.5-fold increased fluorescence activity. Transduction of primary SMCs of human coronary arteries with hcAd vectors confirmed an increased EGFP expression driven by the SMHCdel94 promoter. In ES-cell-derived embryoid bodies, SMHCwt was exclusively active in transduced ESdSMCs. In contrast, expression of SMHCdel94 was also found in ESdCMs and other nontarget cells of the embryoid body. The tissue-specific rabbit SMHCwt promoter seems to be suitable for adenoviral gene transfer in SMCs of human coronary arteries and deletion of a 94-bp negative cis-acting GC-rich element results in loss of specificity.


Shepherding a flock of different fleece: a historical and social analysis of the unique attributes of the African American pastoral caregiver.
Scholars researching and writing on the roles of pastor-caregivers in predominantly black congregations have done so using models originally designed to examine the roles of pastor-caregivers in primarily white churches. This study offers a revised model based on the historical development and present reality of black churches that more closely matches the historical and present roles of the black pastor who can trace his or her roots back to African spiritual traditions.


The effect of age on protein synthesis by isolated liver parenchymal cells.
The protein synthesizing capacity of liver parenchymal cells isolated from 3-, 12-, 24-, 31- and 36-month-old rats was determined by the incorporation of 14C-leucine. Conditions for optimum protein synthesis included the use of an enriched medium (modified Waymouth's MB 752/1) and cell suspension concentrations ranging from 0.25 to 4 X 10(6) cells/ml medium. The cells were incubated with a dose of 6 micronmol leucine/ml medium for 2 h at 37 degrees C under an atmosphere of 95% O2 and 5% CO2. With parenchymal cells isolated from 3-month-old rats, a leucine incorporation rate of 14.4 nmol leucine/h/10(6) cells was found. The capacity of the parenchymal cells to synthesize protein decreased between 3 and 12 months, remained constant between 12 and 24 months and increased between 24 and 26 months. Degradation of newly synthesized proteins or reutilization of 14C-leucine did not occur during the incubation period. The ratio between albumin and total protein synthesis as a function of age was determined. This ratio did not change between 3 and 24 months but there was a significant increase between 24 and 36 months. The increase in total protein synthesis in late age may be due to a compensation by the liver for a more pronounced proteinuria, increased proteolysis or an accumulation of "altered" proteins.


Impairment in psychosocial functioning in patients with different subtypes of eating disorders.
To examine psychosocial functioning in eating disorder (ED) patients with restrictive and purgative subtypes. Forty-four adult female patients with a diagnosis of ED were divided into restrictive (RP) and purgative (PP) groups according the presence of purgative symptoms. Functioning was assessed using the Functioning Assessment Short Test (FAST) and the Global Assessment of Functioning Scale (GAF). No differences were found in total FAST scores or in specific domains between the RP (39.58±11.92) and PP (45.75±11.75) groups (p = 0.19). However, PP showed more severe functional impairment than RP in the financial domain (p < 0.01). There were no differences in comorbidity with mood disorders, depressive symptoms, or general psychiatric symptoms between the two ED subtypes. The similarities found between PP and PR in overall functioning and in autonomy, cognition, work, interpersonal relationships, and leisure seem to reflect the use of an objective scale that corresponds to the clinical impression. In fact, the assessment of psychosocial functioning in ED patients using self-report instruments requires careful consideration because results may reflect the egosyntonic nature of symptoms commonly observed in these patients, particularly in the restrictive subtype.


The effects of sodium fluoride, calcium phosphate, and vitamin D2 for one to two years on calcium and phosphorus metabolism in postmenopausal women with spinal crush fracture osteoporosis.
Calcium and phosphorus balances and 47Ca turnover studies were performed before and after 12-27 months of daily treatment with sodium fluoride (60 mg), calcium (30-45 mmol), phosphate (29-44 mmol), and vitamin D2 (18,000 IU) in 20 postmenopausal women with spinal crush fracture osteoporosis. Before treatment the mean calcium balance (-1.6 mmol Ca/day) was negative (P less than 0.05), whereas the mean phosphorus balance (-1.6 mmol P/day) did not differ from zero (P greater than 0.10). The treatment induced an increase in calcium absorption (P less than 0.01) with an unchanged renal excretion and dermal loss of calcium and an increase (P less than 0.02) in calcium balance, which became positive (P less than 0.01) (+3.3 mmol Ca/day). This enhancement in calcium balance was obtained by the combined effects of an increase (P less than 0.05) in bone mineralization rate and a decrease (P less than 0.05) in bone resorption rate. The observed increase in net phosphorus absorption (P less than 0.001) was more pronounced than the increase in renal excretion of phosphorus (P less than 0.001), and the phosphorus balance therefore increased (P less than 0.001) and became positive (P less than 0.001). A positive correlation was observed between net calcium and net phosphorus absorption (r = 0.065; (P less than 0.001) in the 32 studies where both calcium and phosphorus balance data were available. Furthermore, a positive correlation (r = 0.61; P less than 0.05) was found between the changes in net calcium and net phosphorus absorption during treatment.(ABSTRACT TRUNCATED AT 250 WORDS)


Long-term skin-resident memory T cells proliferate in situ and are involved in human graft-versus-host disease.
The skin contains a population of tissue-resident memory T cells (Trm) that is thought to contribute to local tissue homeostasis and protection against environmental injuries. Although information about the regulation, survival program, and pathophysiological roles of Trm has been obtained from murine studies, little is known about the biology of human cutaneous Trm Here, we showed that host-derived CD69+ αβ memory T cell clones in the epidermis and dermis remain stable and functionally competent for at least 10 years in patients with allogeneic hematopoietic stem cell transplantation. Single-cell RNA sequencing revealed low expression of genes encoding tissue egress molecules by long-term persisting Trm in the skin, whereas tissue retention molecules and stem cell markers were displayed by Trm The transcription factor RUNX3 and the surface molecule galectin-3 were preferentially expressed by host T cells at the RNA and protein levels, suggesting two new markers for human skin Trm Furthermore, skin lesions from patients developing graft-versus-host disease (GVHD) showed a large number of cytokine-producing host-derived Trm, suggesting a contribution of these cells to the pathogenesis of GVHD. Together, our studies highlighted the relationship between the local human skin environment and long-term persisting Trm, which differs from murine skin. Our results also indicated that local tissue inflammation occurs through host-derived Trm after allogeneic hematopoietic stem cell transplantation.


Molecular characterization and expression analysis of extracellular copper-zinc superoxide dismutase gene from swimming crab Portunus trituberculatus.
An extracellular CuZnSOD cDNA was cloned from the haemocytes of swimming crab Portunus trituberculatus by a reverse-transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA end (RACE) method. Analysis of the nucleotide sequence revealed that the ecCuZnSOD full-length cDNA consisted of 965 bp with an open reading frame of 579 bp. It encoded a polypeptide of 192 amino acids which had a predicted molecular weight of 20.0 kDa and with an estimated pI of 6.23. The deduced amino acid sequence contained a putative signal peptide of 31 amino acids. It is predicted to possess all the expected features of CuZnSOD members, including amino acids responsible for binding Cu and Zn, two putative CuZnSOD signatures, two cysteines and one N-linked glycosylation site. Sequence comparison showed that the CuZnSOD deduced amino acid sequence of P. trituberculatus has similarity of 80%, 76%, 55% and 50% to that of blue crab Callinectes sapidus, mud crab Scylla serrata, crayfish Pacifastacus leniusculus and freshwater prawn Macrobrachium rosenbergii, respectively. The ecCuZnSOD transcripts expressed in all examined tissues, including haemocytes, hepatopancreas, heart, stomach, intestine, gill, ovary and muscle. RT-PCR analysis indicated that ecCuZnSOD transcripts both in haemocytes and hepatopancreas increased in the first 3 h after Vibrio alginolyticus challenging, as the bacterial infection progressed, the challenged crabs decreased to levels significantly lower than control by 96 h post-infection. These facts indicated that ecCuZnSOD was potentially involved in the acute response against invading bacteria in P. trituberculatus.


Spontaneous ureteral rupture in a patient with systemic lupus erythematosus.
A patient with known systemic lupus erythematosus had fever and symptoms of a lower urinary tract infection. Bone scintigraphy showed left ureteral perforation and necrosis with no demonstrable nephrolithiasis. It is speculated that this episode was due to lupus vasculitis.


A manganese-superoxide dismutase/catalase mimetic extends survival in a mouse model of human prion disease.
Animal models, and human postmortem studies, of prion disease have demonstrated the presence of heightened oxidative stress in the brain, with additional findings supporting the likelihood that the normal isoform of prion protein directly contributes to neuronal antioxidant defences. Although such data are consistent with the postulate that oxidative stress plays a salient pathogenic role in prion disease, it remains possible that oxidative damage represents a secondary or relatively less important phenomenon in neurons already rendered dysfunctional from other primary insults. To provide further insights into the relative pathogenic importance of oxidative stress, we employed a potent manganese-superoxide dismutase/catalase mimetic, EUK-189, as a therapeutic in our mouse model of human prion disease. A significant but relatively modest prolongation of survival in EUK-189-treated mice was observed, which correlated with reductions in oxidative, especially nitrative, damage to proteins when compared to untreated disease controls. Lesion profiling also revealed reductions in spongiform change in specific brain regions of terminally sick EUK-189-treated mice. Our results are consistent with heightened oxidative stress playing a pathogenic role in prion disease but underscore the need for more biologically potent and, most likely, broader spectrum antioxidant treatments if more successful amelioration is to be achieved.


Evaluation of silicon influence on the mitigation of cadmium-stress in the development of Arabidopsis thaliana through total metal content, proteomic and enzymatic approaches.
The mitigation of Cd-stress through Si addition to Arabidopsis thaliana cultivation is evaluated in terms of total metal content, proteomic and enzymatic approaches. Four different treatment are evaluated: TC (control, without Si or Cd addition), T1 (with Si addition), T2 (with Cd addition), and T3 (with Si and Cd addition). Through the total determination of Cd and Si in Arabidopsis leaves, the Cd concentration decreased by half when T2 is compared with T3 treatment. In terms of proteomic approach, some differential protein species are achieved by comparative proteomics through 2-D DIGE of all treatments evaluated. Fifty six differential abundant proteins spots (abundance factor ≥1.5) are detected, and 32 of them accurately characterized and identified through nESI-LC-MS/MS. These proteins are differentially produced due to Cd and/or Si treatments, which mainly include proteins associated with disease/defense, energy and metabolism. The most difference in the abundance of proteins is found due to the presence or absence of Si in plants treated with Cd. Regarding the enzymatic approaches, a major increase is found on APX, CAT and GR activities (5.0, 3.5, and 1.5-fold, respectively). The same is observed for the MDA concentration because an increase of 3-fold is found when TC are compared to those treated with T2. However, when T3 plants are evaluated, the enzymes activities are similar to TC plants. Differences ranging from 6.5 to 21% are detected considering the activity of SOD in the treatments (T1-T3 x TC). The decreased activities of CAT, APX and GR and lower MDA concentration indicate a lower reactive oxygen species production in plants treated with Cd and Si. Based on a proteomics point of view it is possible to conclude that Si-Cd interactions occur at protein level and allow plants to respond effectively to the Cd toxicity, revealing the active involvement of Si on mechanisms involved in Si-induced Cd tolerance in Arabidopsis plants. Additionally, from an enzymatic point of view, it is possible to conclude that Si positively interferes diminishing the negative effects of Cd in Arabidopsis by decreasing the reactive oxygen species generation and increasing the antioxidative enzyme activity.


Effect of pertussis toxin and N-ethylmaleimide on voltage-dependent and -independent calcium current modulation in serotonergic neurons.
Introduction of GTP-gamma-S into a neuronal cell spontaneously results in G-protein activation. A possible contribution to this mechanism is that some receptors have a constitutive activity that stimulates GDP/GTP exchange resulting in increased GTPase activity of G-protein alpha subunits, leading to a facilitation of GTP-gamma-S binding. It follows that partial or complete uncoupling of receptors and G-proteins could inhibit Ca(2+) current modulation by GTP-gamma-S. This possibility was tested in acutely isolated rat dorsal raphe neurons by uncoupling the receptor and G-protein using N-ethylmaleimide and pertussis toxin. Since these compounds have been suggested to differentially block voltage-dependent inhibition, relative to voltage-independent, we investigated whether the apparent voltage-independent component of Ca(2+) channel modulation by 5-hydroxytryptamine (5-HT) shares the same mechanism as the voltage-dependent component. N-ethylmaleimide inhibited the response to 5-HT by about 50% but had no effect on the response to GTP-gamma-S. In dorsal raphe neurons 28.9% of the total response to 5-HT was voltage-independent. N-ethylmaleimide had identical effects on the voltage-dependent and -independent components as measured by tail current inhibition. The response to 5-HT was completely sensitive to pertussis toxin, and completely uncoupling the receptors and G-proteins did not affect the maximal response to GTP-gamma-S. Our results suggest that the apparent voltage-independent component of Ca(2+) channel modulation by 5-HT in dorsal raphe neurons might share the same mechanism as does the voltage-dependent component. In addition, these experiments provided evidence that partial or even complete uncoupling of receptors and G-proteins did not affect Ca(2+) current modulation by direct activators of G-proteins.


Oral berberine ameliorates high-fat diet-induced obesity by activating TAS2Rs in tuft and endocrine cells in the gut.
Although oral berberine, a natural compound extracted from the Chinese herbal medicine curcumin, has low bioavailability, it is still effective in suppressing obesity; however, the underlying mechanism is unclear. Berberine can bind to bitter-taste receptors (TAS2Rs) in intestinal endocrine secretin tumor (STC-1) cells to promote glucagon-like peptide-1 (GLP-1) secretion. Notably, TAS2Rs also exist in the tuft cells of the gut. Therefore, this study aimed to explore whether the beneficial effect of oral berberine on obesity is dependent on bitter-taste signaling in the tuft cells of the gut. Standard chow diet (SCD) or high-fat diet (HFD) was administered to C57BL/6 mice, with or without berberine (100 mg/kg, 200 mg/kg, p. o.). The PLCβ2 inhibitor U73122 was used to verify whether the anti-obesity effect of berberine was dependent on the bitter-taste signaling pathway. In this study, we observed that the oral administration of berberine alleviated HFD-induced obesity in mice that U73122 partially inhibited. Both in vivo and ex vivo, berberine upregulated the release of GLP-1, promoted the proliferation of tuft cells and secretion of IL-25 in obesity via the TAS2R signaling pathway. Oral berberine ameliorated HFD-induced obesity through the TAS2R-IL-25 signaling pathway in tuft cells in the gut. We identified and functionally characterized the TAS2Rs and Gα-gustducin/Gβ1γ13 signaling pathway utilized by tuft cells in response to oral berberine in obese mice and proposed a new mechanism underlying the anti-obesity effect of berberine.


Factors associated with antibody titer levels among an occupational cohort of fully vaccinated individuals and subsequent risk of COVID-19 infection: A cohort study.
This study (1) determined the association of time since initial vaccine regimen, booster dose receipt, and COVID-19 history with antibody titer, as well as change in titer levels over a defined period, and (2) determined risk of COVID-19 associated with low titer levels. This observational study used data from staff participating in the National Football League COVID-19 Monitoring Program. A cohort of staff consented to antibody-focused sub-study, during which detailed longitudinal data were collected. Among all staff in the program who received antibody testing, COVID-19 incidence following antibody testing was determined. Five hundred eighty-six sub-study participants completed initial antibody testing; 80% (469) completed follow-up testing 50-101 days later. Among 389 individuals who were not boosted at initial testing, the odds of titer < 1000 AU/mL (vs. ≥1000 AU/mL) increased 44% (odds ratio [OR] = 1.44, 95% confidence interval [CI]: 1.18-1.75) for every 30 days since final dose. Among 126 participants boosted before initial testing with no COVID-19 history, 125 (99%) had a value > 2500 AU/ml; 86 (96%) of 90 tested at follow-up and did not develop COVID-19 in the interim remained at that value. One thousand fifty-seven fully vaccinated (330 [29%] boosted at antibody test) individuals participating in the monitoring program were followed to determine COVID-19 status. Individuals with titer value < 1000 AU/mL had twice the risk of COVID-19 as those with >2500 AU/mL (HR = 2.02, 95% CI: 1.28-3.18). Antibody levels decrease postvaccination; boosting increases titer values. While antibody level is not a clear proxy for infection immunity, lower titer values are associated with higher COVID-19 incidence, suggesting increased protection from boosters.


Endometrial stromal sarcoma mimicking a myoma.
Uterine malignancies are not uncommonly misdiagnosed for the more ubiquitous leiomyoma. A case of endometrial stromal sarcoma with ultrasound and color Doppler imaging is described.


A Comparative Study of Amide Proton Transfer Weighted Imaging and Intravoxel Incoherent Motion MRI Techniques Versus (18) F-FDG PET to Distinguish Solitary Pulmonary Lesions and Their Subtypes.
Amide proton transfer weighted imaging (APTw), intravoxel incoherent motion (IVIM), and positron emission tomography (PET) imaging all have the potential to characterize solitary pulmonary lesions (SPLs). To compare APTw and IVIM with PET imaging for distinguishing between benign and malignant SPLs and their subtypes. Prospective. Ninety-five patients, 78 with malignant SPLs (including 48 with adenocarcinoma [AC] and 17 with squamous cell carcinoma [SCC]), and 17 with benign SPLs. Fast spin-echo (FSE) T2WI, FSE APTw and echo-planar imaging IVIM, MR-base attenuation correction (MRAC), and PET imaging on a 3-T whole-body PET/MR system. The magnetization transfer ratio asymmetry (MTRasym) at 3.5 ppm, diffusion coefficient (D), pseudo diffusion coefficient (D*), perfusion fraction (f), and the maximum standardized uptake value (SUVmax) were analyzed. Individual sample t-test, Delong test, Pearson's correlation analysis, and area under the receiver operating characteristic curve (AUC). P < 0.05 indicated statistical significance. The MTRasym and SUVmax were significantly higher, and D was significantly lower in the malignant group (3.3 ± 2.6 [%], 7.8 ± 5, and 1.2 ± 0.3 [×10-3 mm2 /second]) compared to the benign group (-0.3 ± 1.6 [%], 3.1 ± 3.8, and 1.6 ± 0.3 [×10-3 mm2 /second]). The MTRasym and D were significantly lower, and SUVmax was significantly higher in the SCC group (0.8 ± 1.0 [%], 1.0 ± 0.2 [×10-3 mm2 /second] than in the AC group (4.1 ± 2.6 [%], 1.3 ± 0.3 [×10-3 mm2 /second], 6.7 ± 4.6). Besides, the combination (AUC = 0.964) of these three methods showed higher diagnostic efficacy than any individual method (AUC = 0.917, 0.851, 0.82, respectively) in identifying malignant and benign SPLs. However, APTw showed better diagnostic efficacy than the combination of three methods or PET imaging alone in distinguishing SCC and AC groups (AUC = 0.934, 0.781, 0.725, respectively). APTw, IVIM, and PET imaging are all effective methods to distinguish benign and malignant SPLs and their subtypes. APTw is potentially more capable than PET imaging of distinguishing lung SCC from AC. 2 TECHNICAL EFFICACY: Stage 2.


Modified Bedside Index for severity in acute pancreatitis (BISAP) score validation in the national inpatient sample database.
The aim of this study was to build and validate modified score to be used in the healthcare cost and utilization project databases for further classification of acute pancreatitis (AP). The National Inpatient Sample database for the years 2016-2019 was queried for all primary adult discharge diagnoses of AP. An mBISAP score system was created utilizing the ICD-10CM codes for pleural effusion, encephalopathy, acute kidney injury, systemic inflammatory response, and age >60. Each was assigned a 1-point score. A multivariable regression analysis was built to test for mortality. Sensitivity and specificity analyses were performed for mortality. A total of 1,160,869 primary discharges for AP were identified between 2016 and 2019. The pooled mortality rate was: 0.1%, 0.5%, 2.9%, 12.7%, 30.9% and 17.8% (P < 0.01), respectively for scores 0 to 5. Multivariable regression analysis showed increasing odds of mortality with each one-point increment: mBISAP score of 1 (adjusted odds ratio [aOR] 6.67; 95% confidence interval [CI] 4.69-9.48), score of 2 (aOR 37.87; 95% CI 26.05- 55.03), score of 3 (aOR 189.38; 95% CI 127.47-281.38), score of 4 (aOR 535.38; 95% CI 331.74-864.02), score of 5 (aOR 184.38; 95% CI 53.91-630.60). Using a cut-off of ≥3, sensitivity and specificity analyses reported 27.0% and 97.7%, respectively, with an area under the curve (AUC) of 0.811. In this 4-year retrospective study of a US representative database, an mBISAP score was constructed showing increasing odds of mortality with each 1-point increase and a specificity of 97.7% for a cut-off of ≥3.