Do F-box proteins with a C-terminal domain homologous with the tobacco lectin play a role in protein degradation in plants?
Protein turnover is a key post-translational event that regulates numerous cellular processes. It enables cells to respond rapidly to intracellular signals and changing environmental conditions by adjusting the levels of pivotal proteins. A major proteolytic pathway involves the ubiquitination of target proteins and subsequent targeting to the 26S proteasome for degradation. Many F-box proteins play a determining role in the substrate specificity of this degradation pathway. In most cases, selective recognition of the target proteins relies on protein-protein interactions mediated by the C-terminal domain of the F-box proteins. In mammals, the occurrence of F-box proteins with a C-terminal SBD (sugar-binding domain) that specifically interacts with high-mannose N-glycans on target glycoproteins has been documented. The identification and characterization of these sugar-binding F-box proteins demonstrated that F-box proteins do not exclusively use protein-protein interactions but also protein-carbohydrate interactions in the Ub (ubiquitin)/proteasome pathway. Recently, putative sugar-binding F-box proteins have been identified in plants. Genome analyses in Arabidopsis and rice revealed the presence of F-box proteins with a C-terminal lectin-related domain homologous with Nictaba, a jasmonate-inducible lectin from tobacco that was shown to interact with the core structure of high-mannose and complex N-glycans. Owing to the high similarity in structure and specificity between Nictaba and the SBD of the mammalian Fbs proteins, a similar role for the plant F-box proteins with a Nictaba domain in nucleocytoplasmic protein degradation in plant cells is suggested.


Long-term follow-up of web-based and group-based behavioural intervention in NAFLD in a real world clinical setting.
The long-term results of web-based behavioural intervention in non-alcoholic fatty liver disease (NAFLD) have not been described in patients followed in specialised centres. To analyse the long-term effectiveness of web education compared with the results achieved by a group-based behavioural intervention in the same years 2012-2014. We followed 679 patients with NAFLD (web-based, n = 290; group-based, n = 389) for 5 years. Weight loss ≥10% was the primary outcome; secondary outcomes were attrition, changes in liver enzymes and in biomarkers of steatosis (Fatty liver Index) and fibrosis (Fibrosis-4 index). The cohorts differed in age, education, working status and presence of diabetes. Attrition was higher in the web-based cohort (hazard ratio: 1.53; 95% CI: 1.24-1.88), but not different after adjustment for confounders. Among patients in active follow-up, 50% lost ≥5% of initial body weight and 19% lost ≥10%, without difference between cohorts. Alanine aminotransferase levels fell to within the normal range in 51% and 45% of web- and group-based cohorts, respectively. Fatty Liver Index declined progressively and, by year 5, it ruled out steatosis in 4.8%, whereas 24.9% were in the indeterminate range. Fibrosis-4 index increased in both cohorts, driven by age, but the prevalence of cases ruling-in advanced fibrosis remained very low (around 1%). Improvements in the class of both surrogate biomarkers were associated with ≥5% weight loss. Although burdened by attrition, web-based behavioural intervention is feasible and effective in NAFLD, expanding the cohort involved in behavioural programs and reducing the risk of progressive disease.


The effect of segmental weight of prosthesis on hemodynamic responses and energy expenditure of lower extremity amputees.
[Purpose] The aim of this study was to investigate the effect of segmental weight of the prosthesis on hemodynamic responses and energy expenditure in lower extremity amputees. [Subjects and Methods] Thirteen patients with a mean age of 44 ± 15.84 years and with unilateral transtibial, transfemoral and Syme's amputation were included to the study. The difference between the lightest and the heaviest prosthesis, 250 g used as the weight. All the patients completed the measurements first without weight and then with 250 g weight on the ankle joint. The blood pressure and heart rate of the patients were recorded before and after Six Minute Walk Test (6MWT) and 10 stairs up & down stairs test. Physiological Cost Index was used to calculate the energy expenditure. [Results] Heart rate and energy expenditure increased significantly when without weight and with weight results compared. [Conclusion] We conclude that the segmental weight of the prosthetic limb has a significant effect on the heart rate and energy expenditure but has no effect on the systolic and diastolic blood pressure of lower limb amputees. In order to generalize our results to lower limb amputees, more patients need to be included in future studies.


Organization of choline acetyltransferase-containing structures in the forebrain of the rat.
The cholinergic structures in the forebrain of the rat were studied immunohistochemically with a monoclonal antibody to choline acetyltransferase (ChAT) which has proven to be particularly suited to reveal the trajectory of ChAT-positive fibers and their terminations. The habenulo-interpeduncular tract contained the most distinctly ChAT-positive fibers. Here, ChAT-positivity was demonstrated in the perikarya, fibers and terminal field. From the basal forebrain, ChAT-positive fiber bundles could be followed rostrally to the olfactory bulb, dorsomedially to the neocortex and hippocampus, and dorsocaudally to the hippocampus. Terminations of ChAT-positive fibers in these regions were either boutons terminaux (in the interpeduncular nucleus), finely granular (in the hippocampus) or a network of varicose fibers (in the olfactory bulb and neocortex). Cholinergic terminal fields were also demonstrated in the following regions: the nucleus of the lateral olfactory tract, the olfactory tubercle, the pyriform cortex, the lateral nucleus and part of the basal nucleus of the amygdala, the caudate-putamen, the nucleus accumbens, some thalamic nuclei, and the suprachiasmatic nucleus of the hypothalamus. In most of these regions, ChAT-positivity appeared as either fine granules or a meshwork of varicose fibers.


Hysterectomy on benign indication in Denmark 1988-1998. A register based trend analysis.
The aims of the study were to describe the trends in Danish hysterectomy rates from 1988 to 1998 for operations done on benign indication. Data from all women (n=67,096) undergoing hysterectomy from 1988 to 1998 were obtained from the Danish National Patient Register. Data on the female population distribution were obtained from the Danish National Population Register. During the last 11 years the incidence rate of hysterectomy performed for benign diseases has been stable. However, the rate of women treated surgically for benign diseases of the uterus has increased by 14%. During the study period the number of total abdominal hysterectomies has decreased by 38%, the number of subtotal abdominal hysterectomies has increased by 458%, the number of vaginal hysterectomies has increased by 107% and two new methods of surgical treatment for benign diseases of the uterus have been introduced. Abdominal hysterectomy still accounts for 80% of the total number of hysterectomies performed in Denmark in 1998. The age distribution for all hysterectomies has changed, from a maximum of 36-45 years in 1988 to 46-55 years in 1998. The age maximum for abdominal hysterectomy corresponds to that of all hysterectomies. For vaginal hysterectomy the age maximum is 56 years or older, while it is 36-45 years for laparoscopic hysterectomy. The incidence rate of hysterectomy was stable during the study period and the age distribution for all hysterectomies has changed. The study showed a change in the choice of surgical methods, although no evidence supports this practice.


Rationale for Immune Checkpoint Inhibitors Plus Targeted Therapy in Metastatic Melanoma: A Review.
In recent years, the management of metastatic melanoma has been transformed by the emergence of immune checkpoint inhibitors and targeted therapies that significantly improve patient survival. The complementary response kinetics of these treatment approaches, supported by mechanistic evidence that targeted therapy affects immune aspects of the tumor microenvironment, suggest that the optimal combination or sequencing of immune checkpoint inhibitors and targeted therapy may provide additional clinical benefit. Clinical responses to BRAF and/or MEK inhibitors are associated with immune changes within the tumor microenvironment that have the potential to increase the sensitivity of BRAF V600-mutant melanoma to immune checkpoint inhibitors. The combination of immune checkpoint inhibitors with targeted therapy may therefore increase duration of response, improve tumor control, extend survival, and increase the proportion of patients experiencing durable benefit. A targeted therapy-immune checkpoint inhibitor sequencing approach may also be supported by this evidence, but clinical questions regarding optimal timing, duration, and patient selection remain. This review outlines the rationale and preclinical evidence that support immune checkpoint inhibitor plus targeted therapy combination and sequencing strategies in melanoma and highlights the results available to date from clinical trials exploring these approaches to treatment. Several late-stage trials are under way looking to answer open questions in this field and address the continuing debate surrounding up-front combination vs sequencing. As phase 3 data have begun to emerge, trial designs and available data from key studies are discussed in the context of their resultant implications for clinical practice.


The Dienes phenomenon: identification of the determinants of compatibility.
Two hundred and four isolates of swarming strains of Proteus species which had been typed for their ability to produce bacteriocin (proticine) and also their proticine sensitivity (P/S typing) were tested in all combinations for their Dienes compatibility with each other. Ninety-eight distinct Dienes compatibility groups were found. Physiological and genetic experiments supported the evidence of typing results that, irrespective of species, both the type of proticine a strain produces (P type) and the sensitivity of the strain to proticine (S type) were determinants of Dienes compatibility. Strains showing compatibility in the Dienes test were of the same P/S type, whereas those of different P/S types were incompatible.


How many people in the USA have essential tremor? Deriving a population estimate based on epidemiological data.
Essential tremor (ET) is often reported to be among the most prevalent movement disorders, yet the precise number of cases in the USA is not known. The goal of the current analyses was to use published data from epidemiological studies to derive an estimate of the number of people currently residing in the USA who have ET. A PubMed search was conducted to identify population-based prevalence studies of ET. The methodology of 34 identified studies was assessed. Then the three most methodologically rigorous studies were selected, and age-specific prevalence data were abstracted. US census data from 2012 were used to determine the population in the USA by 10-year age categories. Using data from three studies, estimates of the number of ET cases (2012) ranged from 6.38 to 7.63 million (mean = 7.01 million). This corresponds to approximately 2.2% of the US population. Knowing the number of ET cases in the USA is important in terms of estimating the medical burden on communities and society, and providing an objective metric on which to base health resource planning.


Molecular determinants of the human α2C-adrenergic receptor temperature-sensitive intracellular traffic.
The human α2C-adrenergic receptor (α2C-AR) is localized intracellularly at physiologic temperature. Decreasing the environmental temperature strongly stimulates the receptor transport to the cell surface. In contrast, rat and mouse α2C-AR plasma membrane levels are less sensitive to decrease in temperature, whereas the opossum α2C-AR cell surface levels are not changed in these conditions. Structural analysis demonstrated that human α2C-AR has a high number of arginine residues in the third intracellular loop and in the C-terminus, organized as putative RXR motifs. Although these motifs do not affect the receptor subcellular localization at 37°C, deletion of the arginine clusters significantly enhanced receptor plasma membrane levels at reduced temperature. We found that this exaggerated transport of the human receptor is mediated by two functional arginine clusters, one in the third intracellular loop and one in the C-terminus. This effect is mediated by interactions with COPI vesicles, but not by 14-3-3 proteins. In rat α2C-AR, the arginine cluster from the third intracellular loop is shifted to the left due to three missing residues. Reinsertion of these residues in the rat α2C-AR restored the same temperature sensitivity as in the human receptor. Proteomic and coimmunoprecipitation experiments identified pontin as a molecule having stronger interactions with human α2C-AR compared with rat α2C-AR. Inhibition of pontin activity enhanced human receptor plasma membrane levels and signaling at 37°C. Our results demonstrate that human α2C-AR has a unique temperature-sensitive traffic pattern within the G protein-coupled receptor class due to interactions with different molecular chaperones, mediated in part by strict spatial localization of specific arginine residues.


The Evolution of Sex through the Baldwin Effect.
This article suggests that the fundamental haploid-diploid cycle of eukaryotic sex exploits a rudimentary form of the Baldwin effect. With this explanation for the basic cycle, the other associated phenomena can be explained as evolution tuning the amount and frequency of learning experienced by an organism. Using the well-known NK model of fitness landscapes, it is shown that varying landscape ruggedness varies the benefit of the haploid-diploid cycle, whether based upon endomitosis or syngamy. The utility of pre-meiotic doubling and recombination during the cycle are also shown to vary with landscape ruggedness. This view is suggested as underpinning, rather than contradicting, many existing explanations for sex.


Expression of ORF A1 of infectious bursal disease virus results in the formation of virus-like particles.
A recombinant vaccinia virus inducibly expressing ORF A1 of infectious bursal disease virus (IBDV) has been constructed and characterized. Cells infected with this recombinant virus express the IBDV polyprotein, which is proteolytically processed to give mature VP2, VP3, and VP4 polypeptides. An electron microscopy study revealed that the cytoplasm of cells infected with the recombinant virus contains abundant IBDV-like particles (VLP). These VLP form close-packed paracrystalline arrays that are specifically recognized by anti-IBDV antibodies. The size and morphology of purified VLP were found to be akin to those of authentic IBDV particles.


Are overall adiposity and abdominal adiposity separate or redundant determinants of blood viscosity?
In line with recent literature showing that both general adiposity and abdominal adiposity are independently associated with the risk of death, we recently reported that body mass index (BMI) and waist-to hip ratio (WHR) were independent predictors of blood viscosity, related to different determinants of viscosity (for BMI: plasma viscosity and red cell aggregation; for WHR: hematocrit). Since this report was challenged by a study showing that abdominal adiposity (as measured with waist circumference WC and not WHR) is the only independent determinant of viscosity, we re-assessed on our previous database correlations among viscosity factors, BMI, WHR and WC. Blood viscosity was correlated to BMI (r = 0.155 p = 0.004), WHR (r = 0.364; p = 0.027) and WC (r = 0.094; p = 0.05). Hematocrit was correlated to WHR (r = 0.524) but neither to BMI (r =-0.021) nor waist circumference (r = 0.053). WC was correlated with plasma viscosity (r = 0.154; p = 0.002) while WHR was not (r =-0.0102 NS). A stepwise regression analysis selected two determinants of whole blood viscosity at high shear rate: BMI (p = 0.0167) and WC (p = 0.0003) excluding WHR. Therefore, in this sample, abdominal fatness expressed by WC and whole body adiposity remain independent determinants of blood viscosity. WHR and WC have not the same meaning, WC measuring the size of abdominal fat while WHR measuring the shape of body distribution regardless the degree of fat excess. Interestingly, hematocrit is rather related to shape (even within a normal range of body size) than the extent of abdominal fatness, and is not related to whole body adiposity.


Spontaneous coupling of the beta-adrenergic receptor to Ns in mammalian cardiac membranes.
The beta-adrenergic receptor in membranes from cat, rat, and guinea pig hearts appears to undergo spontaneous coupling to the stimulatory nucleotide-regulatory protein, Ns. This was demonstrated by incubating cardiac membranes from acutely reserpinized animals with the alkylating reagent N-ethylmaleimide (NEM), which is known to "freeze" the beta-receptor Ns-complex. The concentration of norepinephrine in these membrane preparations was less than 0.1 nM. Cat heart membranes were preincubated for 10 min at 30 degrees with NEM (10(-7)-10(-3) M) and subsequently incubated with (-)-[125I]iodopindolol (IPIN) (18 min, 30 degrees). NEM caused a concentration-dependent decrease in specific IPIN binding with a maximal reduction of about 20% at 0.1 mM. This decrease occurred even in the absence of MgCl2 (0.5 mM EDTA added as well). A comparable reduction was also observed in myocardial membranes from rat and guinea pig. This fall reflects a decrease in the number of beta-adrenergic receptor sites, as demonstrated by saturation binding experiments with IPIN. The equilibrium dissociation constant of the radioligand for the remaining receptors was not affected. When increasing concentrations of GTP were included in the preincubation mixture, it resulted in a dose-dependent protection of NEM-induced decrease in IPIN binding. The protection was complete at 0.1 mM GTP. In addition, GTP reversed the NEM effect when added to the incubation mixture 10 min after NEM. The apparent reduction in cardiac beta-adrenergic receptor number by NEM (in the absence of beta-receptor agonist) is compatible with a model in which part of the receptor population is able to undergo spontaneous coupling to Ns.


Drug Discovery by Molecular Imaging and Monitoring Therapy Response in Lymphoma.
Molecular imaging allows a noninvasive assessment of biochemical and biological processes in living subjects. Treatment strategies for malignant lymphoma depend on histology and tumor stage. For the last two decades, molecular imaging has been the mainstay diagnostic test for the staging of malignant lymphoma and the assessment of response to treatment. This technology enhances our understanding of disease and drug activity during preclinical and clinical drug development. Here, we review molecular imaging applications in drug development, with an emphasis on oncology. Monitoring and assessing the efficacy of anti-cancer therapies in preclinical or clinical models are essential and the multimodal molecular imaging approach may represent a new stage for pharmacologic development in cancer. Monitoring the progress of lymphoma therapy with imaging modalities will help patients. Identifying and addressing key challenges is essential for successful integration of molecular imaging into the drug development process. In this review, we highlight the general usefulness of molecular imaging in drug development and radionuclide-based reporter genes. Further, we discuss the different molecular imaging modalities for lymphoma therapy and their preclinical and clinical applications.


Oral modafinil facilitates intracranial self-stimulation in rats: comparison with methylphenidate.
Modafinil is a low-potency inhibitor of dopamine transporters (DAT) approved clinically to promote wakefulness. In most procedures used for abuse-liability assessment, modafinil produces effects similar to those of abused DAT inhibitors such as cocaine and methylphenidate, although modafinil often shows lower effectiveness. However, modafinil has failed to maintain drug self-administration or produce conditioned place preferences in rats. The low potency and poor solubility of modafinil complicate its delivery by parenteral routes of administration commonly used in rats, and this may contribute toward negative results. This study evaluated the effects of orally administered modafinil in rats using an assay of intracranial self-stimulation (ICSS) that has been used to examine the effects of other DAT inhibitors. Adult male Sprague-Dawley rats equipped with electrodes in the medial forebrain bundle responded for pulses of brain stimulation that varied across a range of frequencies (158-56 Hz) during daily behavioral sessions. Modafinil (20-600 mg/kg, orally) and methylphenidate (1.0-10 mg/kg, intraperitoneally; 3.2-32 mg/kg, orally) produced dose-dependent and time-dependent facilitation of ICSS, an effect produced by abused DAT inhibitors and other classes of abused drugs. These results are in agreement with other evidence for stimulant-like abuse liability of modafinil and show the sensitivity of ICSS to orally administered drug.


Relationship of mitochondrial function and cellular adenosine triphosphate levels to hematoporphyrin derivative-induced photosensitization in R3230AC mammary tumors.
The effects of hematoporphyrin derivative-induced photosensitization on the levels of adenosine triphosphate (ATP) in R3230AC mammary adenocarcinomas were studied. Enzymatically dissociated tumor cells were exposed to various doses of hematoporphyrin derivative (HPD) in vitro plus photoradiation. A drug and light dose-dependent decrease in cellular ATP levels was observed; ATP levels were reduced by 60% after treatment with 7.0 micrograms HPD per ml plus 0.72 J total energy density per cm2. Cell viability, assessed by exclusion of trypan blue, displayed an apparently coordinate behavior to ATP levels. The effects of hematoporphyrin derivative plus photoradiation were examined in the presence of oligomycin, an inhibitor of mitochondrial oxidative phosphorylation, or iodoacetate, an inhibitor of glycolysis, experiments designed to elucidate the site of action leading to reduced ATP levels. The results indicated that HPD-induced photosensitization had little additive effects to oligomycin-sensitive ATP production, whereas significant further reduction in ATP levels was obtained by HPD-induced photosensitization in the presence of iodoacetate. Taken together, along with earlier studies of selected mitochondrial enzymes, we conclude that HPD plus photoradiation inhibits mitochondrial function leading to reduction in cellular ATP levels and loss of viability.


Are physicians creating a barrier to pre-conception care access? A qualitative study exploring patients' experiences and perspectives around pre-conception care.
The pre-conception period is an unmissable opportunity to introduce preventive measures before pregnancy to improve maternal and fetal outcomes. Despite the global pre-conception initiatives and the 2030 Saudi national vision to promote maternal, fetal health and safety, various barriers still exist. This study focuses on exploring pre-conception care extensively from the patients' perspectives and their experience in accessing this type of care in the primary care setting. A qualitative study using interpretive thematic analysis was used to explore patients' perspectives, and experiences in accessing pre-conception care in the city of Riyadh from January 2019 to January 2020. A semi-structured interview guide and field notes were used to collect data. A step wise interpretive and iterative process was used for data analysis and thematic extraction. Theme saturation was achieved by the eleventh interview. The participants' perspectives were influenced by their cultural beliefs, understanding of pre-conception, and their prevised barriers to approaching physicians. Three main themes emerged: A) Acceptance of pre-conception care; was heavily influenced by how they understood and defined per-conception care. B) Pre-conception health seeking behavior; demonstrated a clear disconnect between the patient and the physician. C) Expectation from health services; to raise awareness about pre-conception care and push physicians to initiate the conversation with their patients. An appreciable gap in the patient-physician relationship was revealed as a source of inconsistency in accessing pre-conception care. Physicians are encouraged to take the first step in demonstrating to their patients both the importance of pre-conception care and their intent to offer respectful, empathetic, and culturally appropriate care.


Aerogels and polymorphism of isotactic poly(4-methyl-pentene-1).
Monolithic and highly crystalline aerogels of isotactic poly(4-methyl-pentene-1) (i-P4MP1) have been prepared by sudden solvent extraction with supercritical carbon dioxide from thermoreversible gels. The cross-link junctions of i-P4MP1 gels, depending on the solvent, can be constituted by pure polymer crystalline phases (I or III or IV) or by polymer-solvent cocrystalline phases (for cyclohexane and carbon tetrachloride gels). Gels with cocrystalline phases lead to aerogels exhibiting the denser crystalline form II, whereas all the other considered gels lead to aerogels exhibiting the thermodynamically stable form I. Aerogels obtained from form I gels, which do not undergo a crystalline phase transition during the CO(2) extraction process present the high structural stability most suitable for the preparation of porous membranes. The effect of solvents on the aerogel pore structure and morphology has been also investigated by scanning electron microscopy and N(2) sorption measurements. In all cases, the aerogels present highly porous interconnected structures with macropores and mesopores presenting a large size distribution and a vanishing presence of micropores.


Binge drinking, poor mental health, and adherence to treatment among California adults with asthma.
Binge drinking and poor mental health may affect adherence to treatment for individuals with asthma. The purposes were to (a) examine the relationship of self-reported binge drinking and mental health to adherence to daily asthma control medications and (b) identify other demographic and health-related factors associated with asthma control medication adherence. Secondary analyses of 2003 adult California Health Interview Survey data were undertaken, and these analyses identified 3.2 million California adults who had been told by a physician they had asthma. Of these, approximately 1.7 million were symptomatic. Binge drinking significantly predicted medication nonadherence among California adults with symptomatic asthma (OR = .63, 95% CI = .45-.89), whereas poor mental health did not. Other predictors of nonadherence (odds ratios < 1, p < .05) included being overweight, younger age, having some college education, being a current smoker, and having no usual source of medical care. Predictors of adherence (odds ratios > 1, p < .05) were older age, more frequent asthma symptoms, more ER visits, more missed work days, being African American, and being a non-citizen. Intervention efforts could be directed toward improving medication adherence among adult asthma patients who engage in risky health behaviors such as binge drinking. Also at risk for medication nonadherence and therefore good targets for asthma control medication management interventions are adults who are overweight, younger (18-44 age range), have some college education, and no usual source of medical care.


Expression profiling in a mammalian host reveals the strong induction of genes encoding LysM domain-containing proteins in Enterococcus faecium.
Enterococcus faecium is an important health care-associated pathogen that is difficult to treat due to the high level of antibiotic resistance of clinical isolates. The identification of new potential therapeutic targets or vaccination strategies is therefore urgently needed. In this regard, we carried out a transcriptomic analysis of the E. faecium vancomycin-resistant strain AUS0004, comparing the gene expression of bacteria grown under laboratory conditions and bacteria isolated from an infection site. This analysis highlighted more than 360 genes potentially induced under infection conditions. Owing to their expression profiles, four LysM domain-containing proteins were characterized in more detail. The EFAU004_01059, 1150 and 494 proteins are highly homologous, whereas EFAU004_01209 has a unique domain-architecture and sequence. The analysis of corresponding mutants showed that all LysM proteins played relevant roles in the infection process of E. faecium in mice. The EFAU004_01209 mutant also displayed profound morphological modifications, suggesting it has a role in cell wall synthesis or cell division. Furthermore, the adhesion to kidney cells and growth of the mutant was affected in human urine. All these phenotypes and the surface exposure of EFAU004_01209 identify this protein as an interesting new drug target in E. faecium.


The Impact of COVID-19 on Psychological and Social Stigma for Indonesian Nurses: A Cross-Sectional Survey.
Nurses are on the front line and are at high risk of experiencing a mental health crisis during the pandemic due to the psychological impact and stigma. The aim of this study was to identify the role of psychological status and social stigma in anxiety, fear, depression, and mental health crises during the pandemic. A cross-sectional design during December 2020-August 2021. A total of 2,156 nurses who work in health facilities, either hospitals, or communities based on the criteria of nurses who interact directly with COVID-19 patients, work at least 3 months, age 20-54 years, are literate, have internet access, and have the ability to access the electronic form. The eligible participants filled in online questionnaires that were sent to them via WhatsApp. Data were analyzed using Spearman rho correlation test with statistically significant p value < 0.05. A total of 2,156 respondents responded to the questionnaire, and the response rate was 100%. The psychological status of nurses was 78.4% moderate, 18.5% experienced social stigma, 44.0% showed an anxiety response, 53.5% fear, 64.5% depression in the very severe category, and 63.5% fell into a mental health crisis. The results of the inferential analysis showed that all P < 0.05 which indicated that psychological status and social stigma had a significant relationship with anxiety, fear, depression, and mental health crisis in nurses. The psychological status and social stigma experienced by nurses during the COVID-19 pandemic indicate a bad situation and lead to a mental health emergency crisis.


Peripheral Serotonin 1B Receptor Transcription Predicts the Effect of Acute Tryptophan Depletion on Risky Decision-Making.
The effects of acute tryptophan depletion on human decision-making suggest that serotonin modulates the processing of rewards and punishments. However, few studies have assessed which of the many types of serotonin receptors are responsible. Using a within-subject, double-blind, sham-controlled design in 26 subjects, we examined whether individual differences in serotonin system gene transcription, measured in peripheral blood, predicted the effect of acute tryptophan depletion on decision-making. Participants performed a task in which they chose between successive pairs of fixed, lower-stakes (control) and variable, higher-stakes (experimental) gambles, each involving wins or losses. In 21 participants, mRNA from 9 serotonin system genes was measured in whole blood prior to acute tryptophan depletion: 5-HT1B, 5-HT1F, 5-HT2A, 5-HT2B, 5-HT3A, 5-HT3E, 5-HT7 (serotonin receptors), 5-HTT (the serotonin transporter), and tryptophan hydroxylase 1. Acute tryptophan depletion did not significantly influence participants' sensitivity to probability, wins, or losses, although there was a trend for a lower tendency to choose experimental gambles overall following depletion. Significant positive correlations, which survived correction for multiple comparisons, were detected between baseline 5-HT1B mRNA levels and acute tryptophan depletion-induced increases in both the overall tendency to choose the experimental gamble and sensitivity to wins. No significant relationship was observed with any other peripheral serotonin system markers. Computational analyses of decision-making data provided results consistent with these findings. These results suggest that the 5-HT1B receptor may modulate the effects of acute tryptophan depletion on risky decision-making. Peripheral levels of serotonin markers may predict response to treatments that act upon the serotonin system, such as selective serotonin reuptake inhibitors.


Single-step EUS-guided endoscopic treatment for sterile pancreatic collections: a single-center experience.
Endoscopic ultrasound (EUS) is useful for the treatment of sterile pancreatic fluid collections (PFC), either by means of transmural drainage or by complete aspiration. The aim of this study was to evaluate the efficacy and safety of single-step EUS-guided endoscopic approaches for treatment of sterile PFC. During a 3-year period, 77 consecutive patients with symptomatic, persistent sterile PFC were evaluated and treated with the linear EUS. We excluded patients with grossly purulent collections, chronic pseudocyst and those whose cytology diagnostic was neoplastic cyst of pancreas. 44 patients received a single 10-Fr plastic straight stent under EUS or fluoroscopic control (group I) and 33 of these underwent a single-step complete aspiration with a 19-gauge needle (group II). The mean size of the sterile PFC was 48 mm in group I and 28 mm in group II (p < 0.001). Overall, endoscopic treatment was successful in 70 (90.9%) patients. The mean volume aspirated was 25 (18-65) ml. The total number of procedures was 50 in group I and 41 punctures in group II. After a mean follow-up of 64 +/- 15.6 weeks there were 6 complications (13.6%): 2 recurrences (referred to surgery), 2 developing abscesses (submitted a new EUS-guided endoscopic drainage with success), 1 perforation that died (2.2%), and 1 case of bleeding (sent to surgery) in group I. In group II there were only 6 (18.1%) recurrences (submitted a new EUS-guided aspiration). None of the patients undergoing single-step aspiration developed infections, perforation or hemorrhage. The recurrence of pancreatic pseudocysts after endoscopic treatment was similar, either by means of plastic stents or by complete single-step aspiration.


Late complication rates after aortic coarctation repair in patients with or without a bicuspid aortic valve.
Patients with previously repaired aortic coarctation (CoA) are at risk of developing late surgical complications. Many patients with CoA also have a bicuspid aortic valve (BAV). We sought to determine in patients with repaired CoA whether the presence of BAV is associated with more cardiovascular reinterventions during follow-up. Adults with previously repaired simple CoA were recruited from our Adult Congenital Heart Disease database (Sydney, Australia). The incidence of complications relating to the 'CoA-site' (descending aortic aneurysm or dissection, or recoarctation) and the 'AV/AscAo' (aortic valve or ascending aortic pathology) that required intervention was compared between those with BAV ('CoA-BAV') and without BAV ('CoA-only'). Of 146 patients with repaired CoA, 101 (69%) had BAV. Age at CoA repair was similar (median 6.0 (IQR 0.5-14.0) years vs 5.0 (IQR 0.5-11.0) years, p=0.44), as was the distribution of repair types, with end-to-end repair the most common in both groups (45.9% vs 45.6%). At a median of 28 years following initial repair, a significantly higher proportion of patients with CoA-BAV required cardiovascular reintervention (45.5% vs 20.0%, p=0.003). Whereas 'CoA-site' complications were more common than 'AV/AscAo' complications in patients with CoA only (13.3% and 0%, respectively), patients with CoA-BAV had a high prevalence of both 'CoA-site' as well as 'AV/AscAo' complications (19.8% and 21.8%, respectively). Overall survival was similar (p=0.42). In adults with repaired CoA, patients with CoA-BAV are more than twice as likely to require cardiovascular reintervention by early-to-mid-adult life compared with those with CoA alone. Despite this, no difference in survival outcomes was observed.


The role of positive goal engagement in increased mental well-being among individuals with chronic non-cancer pain.
Individuals with chronic pain commonly report significant functional impairment and reduced quality of life. Despite this, little is known about psychological processes and mechanisms underpinning enhancements in well-being within this population. The study aimed to investigate whether (1) increased levels of pain intensity and interference were associated with lower levels of mental well-being, (2) increased positive goal engagement was associated with higher levels of mental well-being and (3) whether the relationships between pain characteristics and mental well-being were mediated by increased positive goal engagement. A total of 586 individuals with chronic pain participated in the cross-sectional, online study. Participants completed self-report measures to assess pain intensity and interference, mental well-being and goal motivation variables. Results showed that pain interference and positive goal engagement were associated with mental well-being. Moreover, the relationship between pain interference and mental well-being was partially mediated by positive goal engagement. The results provide tentative evidence for the protective role of positive goal engagement in enabling individuals with chronic pain to maintain a sense of mental well-being. The study develops the biopsychosocial model of chronic pain by examining the roles and relationships of relevant yet previously unexplored psychological constructs. The promotion of mental well-being through the enhancement of positive goal engagement is discussed, offering a platform for further research and clinical interventions.


Non-steroidal anti-inflammatory drug use and colorectal polyps in the Prostate, Lung, Colorectal, And Ovarian Cancer Screening Trial.
Non-steroidal anti-inflammatory drugs (NSAIDs) have been documented in animal and human studies to reduce risk for colorectal cancer and adenomatous polyps, but risk modification for subgroups of the population and effects on hyperplastic polyps have been less studied. Data on recent use of two frequently ingested NSAIDs, aspirin and ibuprofen, were collected at baseline from participants aged 55-74 years in the 10 centers of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). Participants randomized to the intervention arm of the trial received a flexible sigmoidoscopy during a baseline examination. Follow-up of detected polyps was accomplished outside the Trial setting and relevant records were sought and abstracted. Cases (n=4,017) included subjects with a biopsy-proven polyp in the left side of the colon (descending colon, sigmoid, and rectum) detected as a consequence of PLCO screening; controls (n=38,396) were subjects with no left-sided colon polyp. Regular use of aspirin (≥ 4 times/month) in the past year was inversely associated with hyperplastic polyps (odds ratios (OR)=0.8, 95% confidence interval (CI)=0.7-0.9), adenomatous polyps (OR=0.8, 95% CI=0.8-0.9), and advanced adenomas (OR=0.8, 95% CI=0.7-0.9). As frequency of aspirin use increased, the prevalence of polyps decreased significantly for each histological classification (P for trend ≤ 0.0004). Similar patterns were found for adenomas and ibuprofen. Overall protection was consistent in both the descending colon or sigmoid and the rectum, but more evident in males. In males, the OR for heavy use of combined aspirin and ibuprofen (≥ 2 times/day) was 0.6 (95% CI=0.5-0.8), as opposed to 0.9 (95% CI=0.8-1.1) in females. The protective effects of NSAIDs for females were apparent only among those with body mass index (BMI) <25 (OR=0.8, 95% CI=0.7-1.0 for regular use of NSAIDs; P interaction=0.04). We also found a slightly stronger protection of NSAIDs in the 70-74 years age group compared with those aged 55-69 years. This study of a large general risk population supports previous work that recent use of aspirin and ibuprofen is associated with a decreased risk of colorectal adenomas and demonstrates that this protective effect may be stronger in certain population subgroups and is also evident for aspirin and hyperplastic polyps.


Respectful Maternal Care Experience in Low- and Middle-Income Countries: A Systematic Review.
Background and Objectives: Respectful maternity care promotes practices that acknowledge women's preferences and women and newborns' needs. It is an individual-centered strategy founded on ethical and human rights principles. The objective of this systematic review is to identify the impact of income on maternal care and respectful maternity care in low- and middle-income countries. Materials and Methods: Data were searched from Google Scholar, PubMed, Web of Science, NCBI, CINAHL, National Library of Medicine, ResearchGate, MEDLINE, EMBASE database, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), and Maternity and Infant Care database. This review followed PRISMA guidelines. The initial search for publications comparing low- and middle-income countries with respectful maternity care yielded 6000 papers, from which 700 were selected. The review articles were further analyzed to ensure they were pertinent to the comparative impact of income on maternal care. A total of 24 articles were included, with preference given to those published from 2010 to 2023 during the last fourteen years. Results: Considering this study's findings, respectful maternity care is a crucial component of high-quality care and human rights. It can be estimated that there is a direct association between income and maternity care in LMICs, and maternity care is substandard compared to high-income countries. Moreover, it is determined that the evidence for medical tools that can enhance respectful maternity care is sparse. Conclusions: This review highlights the significance of improving maternal care experiences, emphasizing the importance of promoting respectful practices and addressing disparities in low- and middle-income countries.


The endolymphatic sac in patients with Ménière's disease: correlation between the MRI and the surgical findings.
The endolymphatic sac (ES) is thought to have close relations to pathogenesis of endolymphatic hydrops. Here is reported a retrospective study of 41 patients (42 ears) with Meniere's disease who underwent MRI prior to endolymphatic sac surgery. Based on proton-density weighted image (PDI) and T2-weighted image (T2), the ES including an endolymphatic duct (ED) were estimated whether it was detectable or not. Fourteen ESs were detected on both images (Group A), 14 ESs were detected only on PDI (Group B), and the remaining 14 ESs were not detected on either image (Group D). The actual shape of the sac, obtained from surgical findings, was classified into three (normoplastic, atrophic, invisible). Seventeen ears showed normoplastic ESs and 14 showed atrophic ESs. ES was not detected in 11 ears during surgery, and these findings were compared with image classification. From the study data, normoplastic ESs tend to be observed on both images whereas atrophic or invisible sacs were hardly observed on T2. This classification of ES on MRI was thought to correlate with surgical findings and this correlation was statistically significant (Spearman's rank correlation coefficient. r(s) = 0.58, p < 0.01).


Motivations and Constraints to Family Planning: A Qualitative Study in Rwanda's Southern Kayonza District.
While Rwanda has achieved impressive gains in contraceptive coverage, unmet need for family planning is high, and barriers to accessing quality reproductive health services remain. Few studies in Rwanda have qualitatively investigated factors that contribute to family planning use, barriers to care, and quality of services from the community perspective. We undertook a qualitative study of community perceptions of reproductive health and family planning in Rwanda's southern Kayonza district, which has the country's highest total fertility rate. From October 2011 to December 2012, we conducted interviews with randomly selected male and female community members (n = 96), community health workers (n = 48), and health facility nurses (n = 15), representing all 8 health centers' catchment areas in the overall catchment area of the district's Rwinkwavu Hospital. We then carried out a directed content analysis to identify key themes and triangulate findings across methods and informant groups. Key themes emerged across interviews surrounding: (1) fertility beliefs: participants recognized the benefits of family planning but often desired larger families for cultural and historical reasons; (2) social pressures and gender roles: young and unmarried women faced significant stigma and husbands exerted decision-making power, but many husbands did not have a good understanding of family planning because they perceived it as a woman's matter; (3) barriers to accessing high-quality services: out-of-pocket costs, stock-outs, limited method choice, and long waiting times but short consultations at facilities were common complaints; (4) side effects: poor management and rumors and fears of side effects affected contraceptive use. These themes recurred throughout many participant narratives and influenced reproductive health decision making, including enrollment and retention in family planning programs. As Rwanda continues to refine its family planning policies and programs, it will be critical to address community perceptions around fertility and desired family size, health worker shortages, and stock-outs, as well as to engage men and boys, improve training and mentorship of health workers to provide quality services, and clarify and enforce national policies about payment for services at the local level.


Association of TIMP3 expression with vessel density, macrophage infiltration and prognosis in human malignant melanoma.
Several anti-tumour properties have been ascribed to the tissue inhibitor of matrix metalloproteinases-3 (TIMP3) gene, including inhibition of neovascularisation in tumour xenografts. Reduced protein expression has been linked to promoter hypermethylation and allelic loss of heterozygosity in various human malignancies. In melanoma-positive lymph nodes from patients, we evaluated the association between TIMP3 expression, vessel density, macrophage infiltration and potential correlations with disease-free survival (DFS) and overall survival (OS). TIMP3 expression was analysed by immunohistochemistry (IHC) in melanoma lymph node biopsies of stage III melanoma patients (n = 43). Blood vessel density and macrophage infiltration were quantitatively assessed and correlation with TIMP3 expression was investigated. Methylation status of the gene promoter was determined using methylation-specific polymerase chain reaction (MSP). Protein expression and promoter methylation status were investigated for associations with DFS and OS. Reduced expression of TIMP3, as determined by IHC, was observed in 74% of the cases (32 in 43). A significant inverse correlation was observed between TIMP3 expression and vessel density (p = 0.031). Correlation between TIMP3 expression and macrophage infiltration was not statistically significant (p = 0.369). MSP analysis revealed methylation of the gene promoter in 18% (7 in 38) of the analysed cases. No differences in OS and DFS were observed between cases with high and low TIMP3 expression. Gene promoter methylation was significantly associated with both poor 5-year DFS (p = 0.024) and OS (p = 0.034). Our data indicate that TIMP3 is a dominant negative regulator of angiogenesis in cutaneous melanoma and gene silencing by promoter methylation is associated with poor outcome.


Recognition of Pediatric Congenital Heart Diseases by Using Phonocardiogram Signals and Transformer-Based Neural Networks.
The phonocardiogram (PCG) or heart sound auscultation is a low-cost and non-invasive method to diagnose Congenital Heart Disease (CHD). However, recognizing CHD in the pediatric population based on heart sounds is difficult because it requires high medical training and skills. Also, the dependency of PCG signal quality on sensor location and developing heart in children are challenging. This study proposed a deep learning model that classifies unprocessed or raw PCG signals to diagnose CHD using a one-dimensional Convolution Neural Network (1D-CNN) with an attention transformer. The model was built on the raw PCG data of 484 patients. The results showed that the attention transformer model had a good balance of accuracy of 0.923, a sensitivity of 0.973, and a specificity of 0.833. The Receiver Operating Characteristic (ROC) plot generated an Area Under Curve (AUC) value of 0.964, and the F1-score was 0.939. The suggested model could provide quick and appropriate real-time remote diagnosis application in classifying PCG of CHD from non-CHD subjects.Clinical Relevance- The suggested methodology can be utilized to analyze PCG signals more quickly and affordably for rural doctors as a first screening tool before sending the cases to experts.


Factors associated with current smoking in COPD patients:A cross-sectional study from the Eastern Black Sea region of Turkey.
Even though smoking is a major reason for the development and progression of chronic obstructive pulmonary disease (COPD)-and quitting smoking is the only way to stop its progression-a significant number of smokers still continue to smoke after being diagnosed with COPD. The aim of this study is to compare the clinical and demographic characteristics of COPD patients who are current and former smokers and to find factors associated with their current smoking status. For this study, data were collected between June 2015 and August 2016; COPD patients who had been regularly visiting Hopa State Hospital's outpatient clinic over the last year or longer were included. Their demographic, clinical and functional data were recorded. Patients completed a pulmonary function test, six-minute walk test (6-MWT), COPD assessment test (CAT), and modified Medical Research Council (mMRC) dyspnea scale. Comparisons were then made according to their smoking status. In total 100 patients were included in the study; with a mean age of 63.4±10.7 years and mostly males (94%). Regarding smoking status, 49% were current smokers and 51% were former smokers. Multivariate logistic regression analysis revealed that current smoking was negatively associated with age (odds ratio, OR=0.93, 95% confidence interval, CI=0.88-0.96) and Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage (OR=0.32, 95% CI=0.13- 0.79), and was positively associated with six-minute walk distance (OR =1.005, 95% CI=1.001-1.009) and CAT score (OR=1.07, 95% CI=1.009-1.13). Nearly half of the COPD patients in the study continued smoking even after having been diagnosed with COPD. The younger patients, with better lung function, better exercise capacity and poor quality of life were associated with current smoking.


Piezoelectric tuning fork probe for atomic force microscopy imaging and specific recognition force spectroscopy of an enzyme and its ligand.
Piezoelectric quartz tuning fork has drawn the attention of many researchers for the development of new atomic force microscopy (AFM) self-sensing probes. However, only few works have been done for soft biological materials imaging in air or aqueous conditions. The aim of this work was to demonstrate the efficiency of the AFM tuning fork probe to perform high-resolution imaging of proteins and to study the specific interaction between a ligand and its receptor in aqueous media. Thus, a new kind of self-sensing AFM sensor was introduced to realize imaging and biochemical specific recognition spectroscopy of glucose oxidase enzyme using a new chemical functionalization procedure of the metallic tips based on the electrochemical reduction of diazonium salt. This scanning probe as well as the functionalization strategy proved to be efficient respectively for the topography and force spectroscopy of soft biological materials in buffer conditions.


Clinical features and outcome of Streptococcus agalactiae bone and joint infections over a 6-year period in a French university hospital.
Bone and joint infections (BJIs) due to Streptococcus agalactiae are rare but has been described to increase in the past few years. The objective of this study was to describe clinical features and outcomes of cases of S. BJIs. We conducted a retrospective analysis of adult cases of S. agalactiae BJIs that occurred between January 2009 and June 2015 in a French university hospital. The treatment success was assessed until 24 months after the end of antibiotic treatment. Among the 26 patients included, 20 (77%) were male, mean age was 62 years ± 13 and mean Charlson comorbidity index score was 4.9 ± 3.2. Diabetes mellitus was the most common comorbidity (n = 14, 54%). Six had PJI (Prosthetic Joint Infections), five osteosynthesis-associated infections, 11 osteomyelitis and four native septic arthritis. Eleven patients had a delayed or late infection: six with a prosthetic joint infection and five with an internal fixation device infection. Sixteen patients (62%) had a polymicrobial BJI, most commonly with Gram-positive cocci (75%) notably Staphylococcus aureus (44%). Polymicrobial infections were more frequently found in foot infections (90% vs 44%, p = 0.0184). During the two-year follow-up, three patients died (3/25, 12%) and seven (7/25, 28%) had treatment failure. Diabetes mellitus was the most common comorbidity. We observed an heterogenous management and a high rate of relapse.


Design and Real-World Evaluation of Eyes-Free Yoga: An Exergame for Blind and Low-Vision Exercise.
People who are blind or low vision may have a harder time participating in exercise due to inaccessibility or lack of encouragement. To address this, we developed Eyes-Free Yoga using the Microsoft Kinect that acts as a yoga instructor and has personalized auditory feedback based on skeletal tracking. We conducted two different studies on two different versions of Eyes-Free Yoga: (1) a controlled study with 16 people who are blind or low vision to evaluate the feasibility of a proof-of-concept and (2) an 8-week in-home deployment study with 4 people who are blind or low vision, with a fully functioning exergame containing four full workouts and motivational techniques. We found that participants preferred the personalized feedback for yoga postures during the laboratory study. Therefore, the personalized feedback was used as a means to build the core components of the system used in the deployment study and was included in both study conditions. From the deployment study, we found that the participants practiced Yoga consistently throughout the 8-week period (Average hours = 17; Average days of practice = 24), almost reaching the American Heart Association recommended exercise guidelines. On average, motivational techniques increased participant's user experience and their frequency and exercise time. The findings of this work have implications for eyes-free exergame design, including engaging domain experts, piloting with inexperienced users, using musical metaphors, and designing for in-home use cases.


Managing shame and guilt in addiction: A pathway to recovery.
A dominant view of guilt and shame is that they have opposing action tendencies: guilt- prone people are more likely to avoid or overcome dysfunctional patterns of behaviour, making amends for past misdoings, whereas shame-prone people are more likely to persist in dysfunctional patterns of behaviour, avoiding responsibility for past misdoings and/or lashing out in defensive aggression. Some have suggested that addiction treatment should make use of these insights, tailoring therapy according to people's degree of guilt-proneness versus shame-proneness. In this paper, we challenge this dominant view, reviewing empirical findings from others as well as our own to question (1) whether shame and guilt can be so easily disentangled in the experience of people with addiction, and (2) whether shame and guilt have the opposing action tendencies standardly attributed to them. We recommend a shift in theoretical perspective that explains our main finding that both emotions can be either destructive or constructive for recovery, depending on how these emotions are managed. We argue such management depends in turn on a person's quality of self-blame (retributive or 'scaffolding'), impacting upon their attitude towards their own agency as someone with fixed and unchanging dispositions (shame and guilt destructive for recovery) or as someone capable of changing themselves (shame and guilt productive for recovery). With an eye to therapeutic intervention, we then explore how this shift in attitude towards the self can be accomplished. Specifically, we discuss empathy-driven affective and narratively-driven cognitive components of a process that allow individuals to move away from the register of retributive self-blame into a register of scaffolding 'reproach', thereby enabling them to manage their experiences of both shame and guilt in a more generative way.


[The comparative characteristics of the age-related changes in the rate of fast axonal transport in the vagus and hypoglossal nerves and in the ventral spinal cord roots of rats].
The study was undertaken on the fast axonal transport (FAT) of 3H- or 14C-leucine labelled substances along the n. vagus, n. hypoglossus and ventral roots of the spinal cord in adult (8-10 months) and old (26-28 months) male rats after the label administration into nucleus ambiguus, nucleus hypoglossus, and the area of the ventral horn of the spinal cord, respectively. It has been found that in old rats compared to adult animals the rate of FAT along the n. vagus decreased from 552 +/- 12.7 mm to 252 +/- 13 mm per 24 hours; along the n. hypoglossus--from 492 +/- 38 mm to 216 mm per 24 hours; and along the ventral L5 and L6 roots--from 408 +/- 10.9 mm to 217 +/- 11.3 mm per 24 hours. It is suggested that age-related functional shifts in n. vagus influencing the heart are, to some degree, determined by the most significant disturbances of FAT substances in it.


Hand-Grip Strength Is Associated With Serum Testosterone and Albumin Levels in Male Kidney Transplant Recipients.
In kidney transplant recipients, reduced muscle mass and hand-grip strength are associated with impaired nutritional status. Serum testosterone is highly associated with muscle strength in the general population. Here, we aimed to determine the associations among serum testosterone, hand-grip strength, and nutritional and inflammatory parameters, as well as graft function. Our study included 144 stable male kidney transplant recipients from our renal transplant outpatient clinic. All patients were evaluated for clinical parameters (age, duration of hemodialysis, and posttransplant time), biochemical parameters (calcium, phosphorus, parathyroid hormone, C-reactive protein, albumin, creatinine), and serum testosterone levels. Body composition was analyzed with the bioimpedance spectroscopy analysis technique using a body composition monitor that estimates body mass index and percent fat. Hand-grip strength was analyzed by using a dynamometer (ProHealthcareProducts.com, Park City, UT, USA). We calculated estimated glomerular filtration rate using the Modification of Diet in Renal Disease-4 equation. Demographic characteristics, duration of dialysis before transplant, biochemical parameters, and estimated glomerular filtration rates were similar among study patients. Mean (standard deviation) serum testosterone was 588.0 (55.5) ng/dL, mean body mass index was 26.8 (0.6) kg/m2, and mean hand-grip strength was 42.2 (1.7) mm2. Serum testosterone levels were positively correlated with hand-grip strength (r = 0.445; P = .033) and serum albumin (r = 0.399; P = .05) and negatively correlated with serum C-reactive protein (r = -0.454; P = .05) and age. In linear multiple regression analysis, serum albumin (P = .033) and testosterone levels (P = .038) were shown to be predictors of hand-grip strength. However, we could not show a significant correlation between graft function and testosterone. Serum testosterone level is correlated with hand-grip strength and C-reactive protein and albumin levels, which may indicate that testosterone affects nutritional status and inflammation in male renal transplant recipients.


Thyroid peroxidase autoantibody epitopic 'fingerprints' in juvenile Hashimoto's thyroiditis: evidence for conservation over time and in families.
In Hashimoto's thyroiditis, the humoral component is manifest by autoantibodies to thyroid peroxidase (TPO). Epitopic 'fingerprinting' of polyclonal serum TPO autoantibodies has been facilitated by the molecular cloning and expression as Fab of a repertoire of human TPO autoantibody genes. To investigate whether TPO autoantibody fingerprints are (i) stable over long periods of time (approximately 15 years), and (ii) inherited, we studied a cohort of nine patients with juvenile Hashimoto's thyroiditis and 21 first degree relatives of four of these patients. Fingerprints were determined by competition between four selected FAB and serum autoantibodies for binding to 125I-TPO. Regardless of titre, the TPO epitopic profile was stable in 10/12 individuals whose TPO autoantibody levels were sufficient for analysis on two or three occasions over 12-15 years. Although the TPO epitopic fingerprint profiles in two families raised the possibility of inheritance, overall the data from all four families did not reveal an obvious pattern of genetic control. In no family was the TPO epitopic fingerprint associated with HLA A, B or DR. In conclusion, TPO autoantibody epitopic fingerprints are frequently conserved over many years. Studies on additional families are necessary to establish whether or not the epitopic profiles of TPO autoantibodies are inherited.


Detoxification enzyme activities (CYP1A1 and GST) in the skin of humpback whales as a function of organochlorine burdens and migration status.
The activities of glutathione-s-transferase (GST) and cytochrome P-450 1A1 (CYP1A1) enzymes were measured in freshly extracted epidermis of live-biopsied, migrating, southern hemisphere humpback whales (Megaptera novaeangliae). The two quantified enzyme activities did not correlate strongly with each other. Similarly, neither correlated strongly with any of the organochlorine compound groups previously measured in the superficial blubber of the sample biopsy core, likely reflecting the anticipated low levels of typical aryl-hydrocarbon receptor ligands. GST activity did not differ significantly between genders or between northward (early migration) or southward (late migration) migrating cohorts. Indeed, the inter-individual variability in GST measurements was relatively low. This observation raises the possibility that measured activities were basal activities and that GST function was inherently impacted by the fasting state of the sampled animals, as seen in other species. These results do not support the implementation of CYP1A1 or GST as effective biomarkers of organochlorine contaminant burdens in southern hemisphere populations of humpback whales as advocated for other cetacean species. Further investigation of GST activity in feeding versus fasting cohorts may, however, provide some insight into the fasting metabolism of these behaviourally adapted populations.


[Fungemia after oral treatment with Saccharomyces boulardii in a patient with multiple comorbidities].
A 48-year-old diabetic with multiple co-morbidities presented with generalized micro- and macroangiopathy including peripheral artery disease stage IV with necroses in several digits of both feet. He was admitted to the department of surgery for the insertion of femoropopliteal bypasses. Infectious parameters were elevated (CRP 66.1 mg/l, sedimentation rate 90/96), accompanied by anemia (Hb 7.1 mmol/l), leukocytosis (14.8 Gpt/l) and thrombocytosis (514 Gpt/l). Body temperature was normal (36.8 degrees C). With insulin treatment the patient became nearly normoglycemic (HbA1c 6.8 %). After receiving different broad-spectrum antibiotics over seven weeks the patient developed Clostridium difficile toxin-positive diarrhea that resolved after administration of oral metronidazole and Saccharomyces boulardii (Perenterol ((R))). Three days after bypass insertion, both legs had to be amputated due to infection and beginning sepsis. The condition of the patient improved. However, eight days after bypass-insertion the patient developed a toxic megacolon and sepsis. Blood cultures yielded the growth of Saccharomyces cerevisae. Despite of intensive care treatment the patient died five days later from to multi-organ failure. S. boulardii (synonym: S. cerevisiae) is considered an non-pathogenic probiotic yeast, and live yeast cells are used for supportive therapy of diarrhea. The present case and a review of the literature demonstrate that fungemia and sepsis are rare complications of the administration of S. boulardii in immunocompromised patients. For this reason the therapeutic usage of probiotics should be carefully considered regarding its risk-benefit potential.


Attitudes towards vaccines and intention to vaccinate against COVID-19: Implications for public health communications.
Negative attitudes towards vaccines and an uncertainty or unwillingness to receive vaccinations are major barriers to managing the COVID-19 pandemic in the long-term. We estimate predictors of four domains of negative attitudes towards vaccines and identify groups most at risk of uncertainty and unwillingness to receive a COVID-19 vaccine in a large sample of UK adults. Data were cross-sectional and from 32,361 adults in the UCL COVID-19 Social Study. Ordinary least squares regression analyses examined the impact of socio-demographic and COVID-19 related factors on four types of negative vaccine attitudes: mistrust of vaccine benefit, worries about unforeseen effects, concerns about commercial profiteering, and preference for natural immunity. Multinomial regression examined the impact of socio-demographic and COVID-19 related factors, negative vaccine attitudes, and prior vaccine behaviour on uncertainty and unwillingness to be vaccinated for COVID-19. 16% of respondents displayed high levels of mistrust about vaccines across one or more domains. Distrustful attitudes towards vaccination were higher amongst individuals from ethnic minority backgrounds, with lower levels of education, lower annual income, poor knowledge of COVID-19, and poor compliance with government COVID-19 guidelines. Overall, 14% of respondents reported unwillingness to receive a vaccine for COVID-19, whilst 23% were unsure. The largest predictors of both COVID-19 vaccine uncertainty and refusal were low-income groups (< £16,000, a year), having not received a flu vaccine last year, poor adherence to COVID-19 government guidelines, female gender, and living with children. Amongst vaccine attitudes, intermediate to high levels of mistrust of vaccine benefit and concerns about future unforeseen side effects were the most important determinants of both uncertainty and unwillingness to vaccinate against COVID-19. Negative attitudes towards vaccines are a major public health concern in the UK. General mistrust in vaccines and concerns about future side effects in particular will be barriers to achieving population immunity to COVID-19 through vaccination. Public health messaging should be tailored to address these concerns and specifically to women, ethnic minorities, and people with lower levels of education and incomes. The Nuffield Foundation [WEL/FR-000022583], the MARCH Mental Health Network funded by the Cross-Disciplinary Mental Health Network Plus initiative supported by UK Research and Innovation [ES/S002588/1], and the Wellcome Trust [221400/Z/20/Z and 205407/Z/16/Z].


Purposeful Misalignment of Severed Nerve Stumps in a Standardized Transection Model Reveals Persistent Functional Deficit With Aberrant Neurofilament Distribution.
Functional recovery following primary nerve repair of a transected nerve is often poor even with advanced microsurgical techniques. Recently, we developed a novel sciatic nerve transection method where end-to-end apposition of the nerve endings with minimal gap was performed with fibrin glue. We demonstrated that transected nerve repair with gluing results in optimal functional recovery with improved axonal neurofilament distribution profile compared to the end-to-end micro-suture repair. However, the impact of axonal misdirection and misalignment of nerve fascicles remains largely unknown in nerve-injury recovery. We addressed this issue using a novel nerve repair model with gluing. In our complete "Flip and Transection with Glue" model, the nerve was "first" transected to 40% of its width from each side and distal stump was transversely flipped, then 20 µL of fibrin glue was applied around the transection site and the central 20% nerve was completely transected before fibrin glue clotting. Mice were followed for 28 days with weekly assessment of sciatic function. Immunohistochemistry analysis of both sciatic nerves was performed for neurofilament distribution and angiogenesis. Tibialis anterior muscles were analyzed for atrophy and histomorphometry. Functional recovery following misaligned repair remained persistently low throughout the postsurgical period. Immunohistochemistry of nerve sections revealed significantly increased aberrant axonal neurofilaments in injured and distal nerve segments compared to proximal segments. Increased aberrant neurofilament profiles in the injured and distal nerve segments were associated with significantly increased nerve blood-vessel density and branching index than in the proximal segment. Injured limbs had significant muscle atrophy, and muscle fiber distribution showed significantly increased numbers of smaller muscle fibers and decreased numbers of larger muscle fibers. These findings in a novel nerve transection mouse model with misaligned repair suggest that aberrant neurofilament distributions and axonal misdirections play an important role in functional recovery and muscle atrophy.


Thyroid hypoechogenicity after methimazole withdrawal in Graves' disease: a useful index for predicting recurrence?
A characteristic thyroid ultrasonographic picture with diffuse or scattered low echogenicity has been described in Graves' disease (GD). Thyroid hypoechogenicity in GD at onset has been considered a prognostic index of relapse after medical treatment; moreover, thyroid hypoechogenicity is regularly observed in GD at the onset, but not in patients with 'burned-out' disease. The aim of this study was to evaluate the usefulness of thyroid hypoechogenicity changes in predicting GD relapse. Longitudinal prospective study of previously untreated patients with GD. Thirty-nine consecutive patients aged 10-72 years were treated with methimazole (MMI) for 12-24 months on a titration regimen. Evaluation of patients in remission or with relapse was done 12 and 24 months after MMI withdrawal. Thyroid ultrasonography and TSH receptor antibodies (TRAb) were evaluated in basal conditions and then one month after MMI withdrawal. Thyroid hypoechogenicity score (assessed by the same observer with the same equipment) was graded as: 0 absent; 1 mild; 2 moderate; 3 marked. At the withdrawal evaluation a score < 2 and a TRAb value < 10 U/l were considered as normal. Twelve and 24 months after withdrawal, there were 10 (25.6%) and 17 (44.7%) relapses, respectively. Neither thyroid hypoechogenicity score nor TRAb values evaluated in basal conditions, showed significant differences between patients remaining euthyroid and those who became again hyperthyroid. In the whole group, the thyroid hypoechogenicity score was significantly lower at the withdrawal than in basal conditions (1.1 +/- 1.1 vs 2 +/- 0.8; P < 0.0001); it was significantly lower in patients in remission (P < 0.001), but not in those who relapsed. The thyroid hypoechogenicity score at withdrawal was normal in 23/29 (79.3%) of patients still euthyroid and in 4/10 (40%) of those who relapsed up to the 12th month (P < 0.05); it was normal in 19/21 (90.4%) of patients still euthyroid and in 7/17 (41.2%) of those who relapsed up to the 24th month (P < 0.05). A normal thyroid hypoechogenicity score at withdrawal of MMI had a higher specificity (0.95) and sensitivity (0.59) with respect to TRAb values (0.86 and 0.53, respectively) for the prediction of the relapse of hyperthyroidism at the 24th month. Basal thyroid hypoechogenicity cannot be used as an index of relapse of GD. MMI treatment induces evident changes in thyroid hypoechogenicity, mainly in patients who subsequently go into remission. The absence or a low grade of thyroid hypoechogenicity after MMI treatment seems to be a favourable prognostic index of remission of hyperthyroidism in GD.


114mIn, a candidate for radionuclide therapy: low-energy cyclotron production and labeling of DTPA-D-phe-octreotide.
A method for production of carrier-free (114m)In (half-life 49.5 days), which is a potential radionuclide for radionuclide therapy of slowly growing tumors, is presented. A target consisting of five enriched cadmium ((114)Cd) foils, each 50 microm thick, was irradiated by protons (from 12.6-6.5 MeV) giving a target yield of 0. 8 MBq/microAh. A simple and cost-efficient thermal diffusion method was used for the separation. The irradiated target foils were heated for 2 h at 306 degrees C and then etched in 0.05 M HCl. The obtained cadmium/indium solution was purified using a cation ion-exchange resin (AG 1 x 8, Bio-Rad Laboratories, Hercules, CA USA). An overall yield of approximately 60% was obtained, whereas the loss of the target material was <1% per separation cycle. The (114m)In production gave (114m)In with high specific radioactivity and was successfully used to label diethylenetriamine pentaacetic acid (DTPA)-D-Phe-octreotide. Furthermore, no difference in biodistribution between [(114m)In]- and [(111)In]-DTPA-D-Phe(1)-octreotide in tumor-bearing nude mice was seen. The high radionuclide uptake in the tumors indicates a good receptor binding of the labeled octreotide.


Oriented circular dichroism analysis of chiral surface-anchored metal-organic frameworks grown by liquid-phase epitaxy and upon loading with chiral guest compounds.
Oriented circular dichroism (OCD) is explored and successfully applied to investigate chiral surface-anchored metal-organic frameworks (SURMOFs) based on camphoric acid (D- and Lcam) with the composition [Cu2(Dcam)(2x)(Lcam)(2-2x)(dabco)]n (dabco = 1,4-diazabicyclo-[2.2.2]-octane). The three-dimensional chiral SURMOFs with high-quality orientation were grown on quartz glass plates by using a layer-by-layer liquid-phase epitaxy method. The growth orientation, as determined by X-ray diffraction (XRD), could be switched between the [001] and [110] direction by using either OH- or COOH-terminated substrates. These SURMOFs were characterized by using OCD, which confirmed the ratio as well as the orientation of the enantiomeric linker molecules. Theoretical computations demonstrate that the OCD band intensities of the enantiopure [Cu2(Dcam)2(dabco)]n grown in different orientations are a direct result of the anisotropic nature of the chiral SURMOFs. Finally, the enantiopure [Cu2(Dcam)2(dabco)]n and [Cu2(Lcam)2(dabco)]n SURMOFs were loaded with the two chiral forms of ethyl lactate [(+)-ethyl-D-lactate and (-)-ethyl-L-lactate)]. An enantioselective enrichment of >60 % was observed by OCD when the chiral host scaffold was loaded from the racemic mixture.


Homophilic complex formation of CDCP1 via the extracellular CUB2 domain facilitates SFK activation and promotes cancer cell migration.
CUB domain‑containing protein 1 (CDCP1) is phosphorylated by Src family kinases (SFK), and is thought to serve an important role in tumor metastasis through downstream signaling subsequent to its interaction with protein kinase C δ. The present study investigated the mechanisms of activation for CDCP1 signaling, and demonstrated that CDCP1 is able to activate SFK via a homophilic complex of the extracellular complement C1r/C1s, urchin embryonic growth factor, bone morphogenetic protein 1 (CUB) 2 domain. Deletion of the extracellular CDCP1 region abolished homophilic complex formation of CDCP1 and the ability to promote cancer cell migration. When the culture medium was supplemented with recombinant CUB2 domain protein fused with maltose binding protein (rMBP‑CUB2), CDCP1 homophilic complex formation was effectively inhibited. rMBP‑CUB2 also inhibited SFK activation and the migratory capacity of invasive human lung adenocarcinoma A549 cells, and human pancreatic BxPC3 cells. These findings demonstrated a novel function for the extracellular CUB2 domain of CDCP1, promoting cancer cell migration via SFK activation on the plasma membrane. It was also indicated that the region blocking the homophilic binding site may be a potential therapeutic target against CDCP1‑dependent tumor invasion.


Eupafolin ameliorates lipopolysaccharide-induced cardiomyocyte autophagy via PI3K/AKT/mTOR signaling pathway.
Eupafolin, a major active component of Eupatorium perfoliatum L., has anti-inflammatory and anti-oxidant properties. Lipopolysaccharide (LPS) is responsible for myocardial depression. A line of evidences revealed that LPS induces autophagy in cardiomyocytes injury. This study aims to evaluate the effects of eupafolin on LPS-induced cardiomyocyte autophagy. The effect of LPS on cell viability was examined by CCK-8. Autophagic protein 2 light chain 3 (LC3II), which was regulated by LPS and eupafolin, was examined using immunofluorescent staining. The expression levels of Beclin-1 and p62 were detected by western blotting. The effects of eupafolin on phosphatidylinositol-3-kinase/ protein kinase B/ mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway were also evaluated by western blotting and immunofluorescent staining. Eupafolin pretreatment reduced the expression of LC3II and Beclin-1, whereas p62 was significant increased. In addition, eupafolin promoted expression of PI3K/AKT/mTOR signaling pathway and mTOR inhibitor rapamycin reversed the inhibitory effects on LPS-induced cardiomyocyte autophagy. Eupafolin exerts anti-autophagy activity via activation of PI3K/AKT/mTOR signaling pathway.


[Method for the quantitative analysis of competitive antagonism in isolated organs].
It has been shown in experiments on smooth muscle strips of the rat stomach that quantitative criteria of competitive antagonism, based on the acting mass law are not adhered to in studying acetylcholine and atropine interaction in a large range of concentrations (10(-8)-10(-3) M): the effect of low concentrations of the agonist is inhibited to a larger degree than that of high ones.


Functional tricuspid regurgitation of degenerative mitral valve disease: a crucial determinant of survival.
To assess functional tricuspid regurgitation (FTR) determinants, consequences, and independent impact on outcome in degenerative mitral regurgitation (DMR). All patients diagnosed with isolated DMR 2003-2011, with structurally normal tricuspid leaflets, prospective FTR grading and systolic pulmonary artery pressure (sPAP) estimation by Doppler echocardiography at diagnosis were identified and long-term outcome analysed. The 5083 DMR eligible patients [63 ± 16 years, 47% female, ejection fraction (EF) 63 ± 7%, and sPAP 35 ± 13 mmHg] presented with FTR graded trivial in 45%, mild in 37%, moderate in 15%, and severe in 3%. While pulmonary hypertension (PHTN-sPAP ≥ 50 mmHg) was the most powerful FTR severity determinant, other strong FTR determinants were older age, female sex, lower left ventricle EF, DMR, and particularly atrial fibrillation (AFib) (all P ≤ 0.002). Functional tricuspid regurgitation moderate/severe was independently linked to more severe clinical presentation, more oedema, lower stroke volume, and impaired renal function (P ≤ 0.01). Survival (95% confidence interval) throughout follow-up [70% (69-72%) at 10 years] was strongly associated with FTR severity [82% (80-84%) for trivial, 69% (66-71%) for mild, 51% (47-57%) for moderate, and 26% (19-35%) for severe, P < 0.0001]. Excess mortality persisted after comprehensive adjustment [adjusted hazard ratio 1.40 (1.18-1.67) for moderate FTR and 2.10 (1.63-2.70) for severe FTR, P ≤ 0.01]. Excess mortality persisted adjusting for sPAP/right ventricular function (P < 0.0001), by matching [adjusted hazard ratios 2.08 (1.50-2.89), P < 0.0001] and vs. expected survival [risk ratio 1.79 (1.48-2.16), P < 0.0001]. Within 5-year of diagnosis valve surgery was performed in 73% (70-75%) and 15% (13-17%) of severe and moderate DMR and in only 26% (19-34%) and 6% (4-8%) of severe and moderate FTR. Valvular surgery improved outcome without alleviating completely higher mortality associated with FTR (P < 0.0001). In this large DMR cohort, FTR was frequent and causally, not only linked to PHTN but also to other factors, particularly AFib. Higher FTR severity is associated at diagnosis with more severe clinical presentation. Long term, FTR is independently of all confounders, associated with considerably worse mortality. Functional tricuspid regurgitation moderate and even severe is profoundly undertreated. Thus careful assessment, consideration for tricuspid surgery, and testing of new transcatheter therapy is warranted.


How to develop a successful DUE (drug usage evaluation) program: experience of a teaching medical center.
A drug usage evaluation (DUE) program was successfully implemented in a busy teaching medical center within 12 months of adding a full-time coordinator. The success of this program was due largely to its approval by hospital administration, the recruitment of a pharmacist with the necessary background, and the creation of a structure and process that encouraged participation by leaders of the medical staff. Although the primary objective of hiring the coordinator was to meet Joint Commission on Accreditation of Healthcare Organizations requirements for accreditation, another achievement was confirmed cost savings. Techniques used in selecting DUE subjects and the steps taken in implementing and managing the program are presented.


Lagrangian mass-flow investigations of inorganic contaminants in wastewater-impacted streams.
Understanding the potential effects of increased reliance on wastewater treatment plant (WWTP) effluents to meet municipal, agricultural, and environmental flow requires an understanding of the complex chemical loading characteristics of the WWTPs and the assimilative capacity of receiving waters. Stream ecosystem effects are linked to proportions of WWTP effluent under low-flow conditions as well as the nature of the effluent chemical mixtures. This study quantifies the loading of 58 inorganic constituents (nutrients to rare earth elements) from WWTP discharges relative to upstream landscape-based sources. Stream assimilation capacity was evaluated by Lagrangian sampling, using flow velocities determined from tracer experiments to track the same parcel of water as it moved downstream. Boulder Creek, Colorado and Fourmile Creek, Iowa, representing two different geologic and hydrologic landscapes, were sampled under low-flow conditions in the summer and spring. One-half of the constituents had greater loads from the WWTP effluents than the upstream drainages, and once introduced into the streams, dilution was the predominant assimilation mechanism. Only ammonium and bismuth had significant decreases in mass load downstream from the WWTPs during all samplings. The link between hydrology and water chemistry inherent in Lagrangian sampling allows quantitative assessment of chemical fate across different landscapes.


Combining Zn Ion Catalysis with Homogeneous Gold Catalysis: An Efficient Annulation Approach to N-Protected Indoles.
The Fischer indole synthesis is perhaps the most powerful method for indole preparation, but it often suffers from low regioselectivities with unsymmetric aliphatic ketone substrates and strong acidic conditions and is not suitable for α,β-unsaturated ketones. In this article, we disclose an efficient synthesis of N-protected indoles from N-arylhydroxamic acids/N-aryl-N-hydroxycarbamates and a variety of alkynes via a cooperative gold and zinc catalysis. The zinc catalysis is similar to the related zinc ion catalysis in metalloenzymes such as human carbonic anhydrase II and substantially enhances the O-nucleophilicity of N-acylated hydroxamines by forming the corresponding Zn chelates. The Zn chelates can attack gold-activated alkynes to form O-alkenyl-N-arylhydroxamates, which can undergo facile 3,3-sigmatropic rearrangements and subsequent cyclodehydrations to yield N-protected indole products. This new chemistry offers several important improvements over the Fischer indole synthesis: a) the reaction conditions are mildly acidic and can tolerate sensitive groups such as Boc; b) broader substrate scopes including substrates with pendant carbonyl groups (reactive in the Fischer chemistry) and alkyl chlorides (e.g., 3f); c) better regioselectivities for the formation of 2-substituted indoles under much milder conditions; d) 2-alkenylindoles can be prepared readily in good to excellent yields, but the Fischer chemistry could not; e) with internal alkynes both steric and electronic controls are available for achieving good regioselectivities, while the Fischer chemistry is in general problematic.


Kinetics of irreversible enzyme inhibition by an unstable inhibitor.
A mathematical treatment for the general case of enzyme inactivation by an inhibitor that breaks down in solution in a first-order reaction is presented. Cathepsin D was inactivated by fluorescein isothiocyanate with a K(i) of 4.47mum. Kinetic constants were also determined for the inactivation of cathepsin D by 1,1-bis(diazoacetyl)-2-phenylethane, and the inactivation of pepsin C by diazoacetyl-dl-norleucine methyl ester.


Adolescent Weight and Electronic Vapor Product Use: Comparing BMI-Based With Perceived Weight Status.
This study examined the associations of BMI-based and perceived body weight status with electronic vapor product use, cigarette smoking, and dual use among U.S. adolescents. A cross-sectional analysis was conducted in 2017 on data from 15,129 adolescents in the National Youth Risk Behavior Survey, 2015. Multiple logistic regression analyses were used to examine the associations of BMI-based and perceived weight status with electronic vapor product use, cigarette smoking, and dual use, after adjusting for all other covariates. The regression models were stratified by gender. Overall, 25.5% of males used electronic vapor products, 11.6% smoked cigarettes, and 8.1% used both; percentages among females were 22.6%, 9.8%, and 6.8%, respectively. Females who perceived themselves as overweight were more likely than those who perceived themselves as normal weight to be current electronic vapor product users (AOR=1.09, 95% CI=1.01, 1.19) and dual users (AOR=1.23, 95% CI=1.01, 1.49). When compared with normal BMI-based category, males with obese BMI status were more likely to be current cigarette smokers (AOR=1.61, 95% CI=1.06, 2.44), however, only females with overweight BMI status were more likely to be current smokers (AOR=1.89, 95% CI=1.25, 2.86). Findings suggest that the influence of adolescents' body weight perceptions and BMI-based status should be accounted for when developing nicotine-containing product use prevention programs for adolescents. Specific strategies for influencing female adolescents who perceive themselves as overweight should be included to prevent emerging electronic vapor product and dual use.


Pharmacokinetics of radiolabeled monoclonal antibody B6.2 in patients with metastatic breast cancer.
Thirteen patients with metastatic breast carcinoma were given injections of 50-1593 micrograms of 131I-monoclonal antibody (MAb) B6.2 immunoglobulin G and F(ab')2 for pharmacokinetic evaluation and radioimmunoimaging. Blood clearance of the 131I-MAb-B6.2 was biphasic. The mean half-times (t 1/2 alpha, t 1/2 beta) for the immunoglobulin G were 3.5 +/- 1.7 and 20.9 +/- 11.0 h, respectively. The t 1/2 alpha for the F(ab')2 was 1.7 +/- 1.3 h, and the t 1/2 beta was 31.0 +/- 5.7 h. The percentage of protein bound 131I for the immunoglobulin G and for the F(ab')2 at 72 h was 73.7 +/- 11.4% and 58.2 +/- 14.5%, respectively. In vitro reactivity of MAb B6.2 with granulocytes isolated from normal subjects and patients was demonstrated by cytofluorometric and radioimmunoassays. MAb B6.2 was shown to bind with normal cross-reacting antigen, a cell surface antigen known to be expressed on normal human granulocytes. Reactivity with normal cross-reacting antigen on granulocytes is consistent with the skeletal images obtained during immunoscintigraphy of all 13 patients. A specific tumor image was observed in one patient. No toxicity was encountered. In spite of extensive preclinical data suggesting that 131I-MAb B6.2 would be a useful agent for radioimmunoimaging, the clinical utility of this reagent is probably limited because of the reactivity with granulocytes.


Associations of chronic diarrhoea with non-alcoholic fatty liver disease and obesity-related disorders among US adults.
Mechanisms explaining observed associations between diarrhoea and obesity or increased body mass index (BMI) are unclear. To assess associations of bowel patterns with BMI, metabolic syndrome (MS), non-alcoholic fatty liver disease (NAFLD) and other obesity-related disorders. We performed a cross-sectional analysis of data from adults who completed bowel health questions for the 2005 to 2010 cycles of the National Health and Nutrition Examination Surveys. Relationships were examined using multinomial logistic regression. Confounding effects of demographics, smoking, alcohol and BMI were examined by sequential modelling. Among 13 413 adults, weighted prevalence rates of constipation and diarrhoea were 8.9% and 6.6%, respectively. Mean BMI was associated with bowel patterns (p<0.001), and was higher with diarrhoea (30.3 kg/m2) versus normal bowel patterns (28.6 kg/m2) and with diarrhoea versus constipation (27.8 kg/m2). NAFLD was more prevalent (ORs, 95% CI) in diarrhoea versus normal bowel patterns (OR=1.34, 95% CI 1.01 to 1.78) or constipation (OR=1.45, 95% CI 1.03, 2.03) in adjusted analyses. The higher prevalence of MS in diarrhoea versus constipation (OR=1.27, 95% CI 0.97 to 1.67) was not independent of BMI. These findings suggest an association between diarrhoea and NAFLD that is independent of BMI.


Impaired neuromuscular function by conjoint actions of organophosphorus insecticide metabolites omethoate and cyclohexanol with implications for treatment of respiratory failure.
Ingestion of agricultural organophosphorus insecticides is a significant cause of death in rural Asia. Patients often show acute respiratory failure and/or delayed, unexplained signs of neuromuscular paralysis, sometimes diagnosed as "Intermediate Syndrome". We tested the hypothesis that omethoate and cyclohexanol, circulating metabolites of one agricultural formulation, cause muscle weakness and paralysis. Acetylcholinesterase activity of insecticide components and metabolites was measured using purified enzyme from eel electroplaque or muscle homogenates. Mechanomyographic recording of pelvic limb responses to nerve stimulation was made in anaesthetized pigs and isometric force was recorded from isolated nerve-muscle preparations from mice. Omethoate and cyclohexanol were administered intravenously or added to physiological saline bathing isolated muscle. We also assessed the effect of MgSO4 and cooling on neuromuscular function. Omethoate caused tetanic fade in pig muscles and long-lasting contractions of the motor innervation zone in mouse muscle. Both effects were mitigated, either by i.v. administration of MgSO4 in vivo or by adding 5 mM Mg2+ to the medium bathing isolated preparations. Combination of omethoate and cyclohexanol initially potentiated muscle contractions but then rapidly blocked them. Cyclohexanol alone caused fade and block of muscle contractions in pigs and in isolated preparations. Similar effects were observed ex vivo with cyclohexanone and xylene. Cyclohexanol-induced neuromuscular block was temperature-sensitive and rapidly reversible. The data indicate a crucial role for organophosphorus and solvent metabolites in muscle weakness following ingestion of agricultural OP insecticide formulations. The metabolites omethoate and cyclohexanol acted conjointly to impair neuromuscular function but their effects were mitigated by elevating extracellular Mg2+ and decreasing core temperature, respectively. Clinical studies of MgSO4 therapy and targeted temperature management in insecticide-poisoned patients are required to determine whether they may be effective adjuncts to treatment.


Predictors of annual prostate-specific antigen (PSA) screening among black men: results from an urban community-based prostate cancer screening program.
Black men have an increased risk of prostate cancer mortality compared with any racial or ethnic group. Further, research on prostate cancer prevention and control messaging focusing on Black men is limited. Community screening events are successful in attracting members from high-risk groups, like Black men, and are a valuable source to collect cancer screening and health promotion data. Therefore, the authors examined data of Black men attending a community-based PCa screening event to evaluate predictors of annual PCa screening, and identify sub-populations of Black men needing targeted cancer prevention messaging. Black men attending PCa screening events in St. Louis, MO 2007-2017 were eligible. Participants completed either a mail-in or on-site survey at the time of their screening to collect information on annual screening history. We analyzed sociodemographic factors, having a first-degree relative with a history of PCa, healthcare utilization characteristics, and predictors of annual PSA screening. Logistic regression analysis was used to assess the association between predictors and annual PSA screening. Data was analyzed from 447 respondents. One-third of the residents did not know their cancer family history status. Older age and having a primary healthcare provider predicted an annual prostate cancer after attending the PCa community screening event. In the fully adjusted model, all ages older than 45 years were 2-4 times more likely to have an annual PCa screening. Having a healthcare provider also predicted an annual PCa screening (OR: 4.59, 95% CI: 2.30-9.14). Regardless of sociodemographic and family history factors, older Black men and those with a primary physician are more likely to have an annual PSA screening. Cancer prevention promotion efforts for Black men should target mechanisms that facilitate family cancer history conversations to engage younger Black men. Also, additional health promotions efforts are needed to educate Black men without a primary healthcare provider.


Associations between mental health and HIV status among sexual minority and heterosexual adolescents in Nigeria.
We aimed to determine associations between the mental health status of adolescents by self-reported sexual identity; and to determine associations between the mental health status of sexual minority adolescents living with and without HIV. This cross-sectional study collected data from Nigerians aged 13-19 years old using an online survey. We collected information on dependent (sexual identity) and independent (presence of depressive symptoms, generalised anxiety disorder, suicidal attempt/ideation, HIV status) study variables. A multivariate regression model determined associations between the dependent and independent variables. A second multivariate regression model was developed to establish associations between HIV status among sexual minority individuals and the dependent variables. All models were adjusted for age, sex assigned at birth and education level. Among 1247 respondents living in Nigeria, 497 (39.9%) identified as sexual minority individuals. Compared with their heterosexual peers, sexual minority adolescents had significantly higher odds of reporting depressive symptoms (adjusted OR (AOR): 5.54; 95% CI: 4.10 to 7.47; p<0.001), high general anxiety (AOR: 3.56; 95% CI: 2.64 to 4.79; p<0.001) and history of suicidal attempt/ideation (AOR: 2.95; 95% CI: 2.20 to 3.94; p<0.001). Sexual minority adolescents living with HIV had significantly higher odds of high general anxiety (AOR: 2.42; 95% CI: 1.21 to 4.84; p=0.013), while those with unknown HIV status had significantly higher odds of depressive symptoms (AOR: 3.82, 95% CI: 2.78 to 5.27; p<0.001), high general anxiety (AOR: 3.09; 95% CI: 2.29 to 4.17; p<0.001) and suicidal attempt/ideation (AOR: 1.65; 95% CI: 1.22 to 2.24; p=0.001). Sexual minority adolescents reported poorer mental health status than heterosexual adolescents. Although there was no significant difference in the mental health status of sexual minority adolescents living and not living with HIV, sexual minority adolescents with unknown HIV status reported worse mental health than their HIV-negative peers. Sexual minority adolescents in Nigeria need comprehensive rights-based care that improves access to mental health services, and those with unknown HIV status may need both HIV and mental health screening and care.