Evaluation of the first Ergocalciferol-derived, non hypercalcemic anti-cancer agent MT19c in ovarian cancer SKOV-3 cell lines.
In human trials calcitriol and its analogs displayed unacceptable systemic toxicities including hypercalcemia. This study was designed to evaluate a novel non-hypercalcemic vitamin-D derivative (MT19c) and its anticancer effects in cultured ovarian cancer cell model. We modified the Ergocalciferol structure to generate MT19c, a heterocyclic vitamin-D derivative. Hypercalcemic liabilities of MT19c were assessed by estimating the blood calcium levels in drug treated animals. VDR agonistic or antagonistic properties of MT19c were determined via a VDR-coactivator binding assay. The anticancer effects of MT19c were evaluated by (i) cytotoxicity studies in cancer cell lines and the National Cancer Institute (NCI(60)) cell lines, (ii) identification of apoptosis markers by microscopy and western blots, (iii) cell cycle analysis, and (iv) by studying the insulin receptor substrate-1/2 (IRS1/2) signaling in ovarian cancer cells (SKOV-3) by western blotting. MT19c treatment did not cause hypercalcemia in mice and showed minor VDR antagonistic activity. In a NCI(60) screen MT19c revealed cell-type specific growth inhibition. MT19c displayed superior cytotoxicity to cisplatin, calcitriol, EB1089 and Iressa in SKOV-3 cell-lines and was comparable to Taxol in our in vitro assays. In SKOV-3 cells MT19c showed caspase dependent apoptosis, DNA fragmentation and cell cycle arrest. MT19c did not alter VDR but downregulated the IGFR/IRS-1/2-MEK-ras-ERK1/2-pathway via activated TNFα-receptor/SAPK/JNK component. Our results demonstrate how structural optimization of the vitamin-D scaffold leads to identification of a non-hypercalcemic compound MT19c which exerts cytotoxicity in vitro based on a VDR-independent signaling pathway and displays potent anti-cancer activity in ovarian cancer cell models.


Oxygen insufflation through the bronchoscope channel for sedation-induced hypoxia: safe and effective.
To evaluate both efficacy and safety parameters for insufflation through the bronchoscope as a method of recovery from sedation-induced hypoxia. To explore parameters applicable to use in human beings using an animal model. Two adult pigs were sedated enough to depress respiratory drive. The effects of insufflation at 15 l/min (the upper limits of flow that might be used clinically) were then evaluated. Pressure and volume responses to bronchoscopy during intubation and without an endotracheal tube in place were recorded. Several assays were performed for each scenario, with each animal acting as its own control. Recovery from hypoxemia using insufflation was compared with recovery using mechanical ventilation. Insufflation was effective, with rapid increases in fraction of inspired oxygen (FIO2), saturation, and partial pressure of arterial oxygen (PaO2). The rate of recovery using insufflation was faster than that from institution of mechanical ventilation. Insufflation in an intubated animal with cuff inflated led to a rapid and dangerous rise in pressure. With balloon deflated, there were no adverse pressure consequences from insufflation via the endotracheal tube at a rate of 15 l/min. Insufflation through the bronchoscope for episodes of sedation-induced hypoxia should be safe and effective as long as not delivered within a closed system.


Dynamic characteristics and fractal representations of crack propagation of rock with different fissures under multiple impact loadings.
To investigate the influence of the fissure morphology on the dynamic mechanical properties of the rock and the crack propagation, a drop hammer impact test device was used to conduct impact failure tests on sandstones with different fissure numbers and fissure dips, simultaneously recorded the crack growth after each impact. The box fractal dimension is used to quantitatively analyze the dynamic change in the sandstone cracks and a fractal model of crack growth over time is established based on fractal theory. The results demonstrate that under impact test conditions of the same mass and different heights, the energy absorbed by sandstone accounts for about 26.7% of the gravitational potential energy. But at the same height and different mass, the energy absorbed by the sandstone accounts for about 68.6% of the total energy. As the fissure dip increases and the number of fissures increases, the dynamic peak stress and dynamic elastic modulus of the fractured sandstone gradually decrease. The fractal dimensions of crack evolution tend to increase with time as a whole and assume as a parabolic. Except for one fissure, 60° and 90° specimens, with the extension of time, the increase rate of fractal dimension is decreasing correspondingly.


Immobilization of a lactase onto a magnetic support by covalent attachment to polyethyleneimine-glutaraldehyde-activated magnetite.
A magnetic immobilized lactase has been prepared using magnetite as the magnetic material. Magnetite was functionalized by treatment with polyethyleneimine and crosslinked with glutaraldehyde. Lactase was then covalently coupled to the activated magnetic matrix via the aldehyde groups. The conditions for optimal immobilization of enzyme are described. Eighty percent of the lactase activity was lost on immobilization and is thought to be owing to the orientation of enzyme binding to the matrix. The amount of protein coupled was 80% of that applied. The maximum lactase activity retained on the matrix following immobilization was 360 U/g matrix. The immobilized lactase showed optimal activity at pH 4.5 and 65 degrees C. The immobilized lactase was more heat stable than the free enzyme, and retained 83% of its original activity after 14 d at 55 degrees C. Galactose competitively inhibited the immobilized lactase preparation (Ki 20 m/M). The presence of high initial concentrations of galactose (10% w/v) did not prevent total hydrolysis of lactose. Glucose and calcium ions were activators of the immobilized enzyme. The immobilized enzyme hydrolyzed high concentrations of lactose (up to 25% w/v) to completion within 4-6 h in a stirred batch reactor at 55 degrees C. There was no evidence of substrate inhibition at high substrate concentrations. The efficiency of hydrolysis of lactose by the immobilized lactase was better than that of the free enzyme. The magnetic immobilized lactase was demonstrated to be suitable for use in the enzymatic hydrolysis of both pure, and cheese whey permeate, lactose.


Practice Patterns and Patient Outcomes After Widespread Adoption of Remote Heart Failure Care.
An unprecedented shift to remote heart failure outpatient care occurred during the coronavirus disease 2019 (COVID-19) pandemic. Given challenges inherent to remote care, we studied whether remote visits (video or telephone) were associated with different patient usage, clinician practice patterns, and outcomes. We included all ambulatory cardiology visits for heart failure at a multisite health system from April 1, 2019, to December 31, 2019 (pre-COVID) or April 1, 2020, to December 31, 2020 (COVID era), resulting in 10 591 pre-COVID in-person, 7775 COVID-era in-person, 1009 COVID-era video, and 2322 COVID-era telephone visits. We used multivariable logistic and Cox proportional hazards regressions with propensity weighting and patient clustering to study ordering practices and outcomes. Compared with in-person visits, video visits were used more often by younger (mean 64.7 years [SD 14.5] versus 74.2 [14.1]), male (68.3% versus 61.4%), and privately insured (45.9% versus 28.9%) individuals (P<0.05 for all). Remote visits were more frequently used by non-White patients (35.8% video, 37.0% telephone versus 33.2% in-person). During remote visits, clinicians were less likely to order diagnostic testing (odds ratio, 0.20 [0.18-0.22] video versus in-person, 0.18 [0.17-0.19] telephone versus in-person) or prescribe β-blockers (0.82 [0.68-0.99], 0.35 [0.26-0.47]), mineralocorticoid receptor antagonists (0.69 [0.50-0.96], 0.48 [0.35-0.66]), or loop diuretics (0.67 [0.53-0.85], 0.45 [0.37-0.55]). During telephone visits, clinicians were less likely to prescribe ACE (angiotensin-converting enzyme) inhibitor/ARB (angiotensin receptor blockers)/ARNIs (angiotensin receptor-neprilysin inhibitors; 0.54 [0.40-0.72]). Telephone visits but not video visits were associated with higher rates of 90-day mortality (1.82 [1.14-2.90]) and nonsignificant trends towards higher rates of 90-day heart failure emergency department visits (1.34 [0.97-1.86]) and hospitalizations (1.36 [0.98-1.89]). Remote visits for heart failure care were associated with reduced diagnostic testing and guideline-directed medical therapy prescription. Telephone but not video visits were associated with increased 90-day mortality.


Respiratory Fluctuation of Peak Systolic Velocities in the Carotid Doppler Waveforms of Patients With Obstructive Airway Disease: Evidence of Pulsus Paradoxus With Experimental Validation.
To characterize fluctuations in peak systolic velocities (PSVs) in Doppler waveforms of the carotid artery in patients with and without obstructive airway disease and in volunteers subjected to incremental levels of airway resistance in an experimental model. The PSV variation in common carotid waveforms was measured in 100 patients who had had a carotid ultrasound examination and no respiratory or carotid disease. This was compared to that of patients who had this study during an admission for acute exacerbation of chronic obstructive pulmonary disease (COPD). The PSV variation was correlated with pulmonary function testing. In addition, 14 healthy volunteers were asked to breathe through 5 resistors. Simultaneous recordings were made of Doppler waveforms in the common carotid artery, cardiac activity, and respiration. Peak systolic velocity changes from inspiration to expiration were calculated. Of the 100 patients without respiratory disease, the magnitude of the PSV variation averaged 6.3 cm/s. Of the 33 patients with COPD, the PSV variation averaged 16.5 cm/s. Nineteen of the 33 patients with COPD had concurrent pulmonary function testing; there was a statistically significant correlation between the PSV variation and forced vital capacity and forced expiratory volume indices. For the volunteers, mean velocity changes were 7.1, 6.6, 8.3, 15.1, and 16.1 cm/s for 0.00-, 2.15-, 3.27-, 3.58-, and 5.77-cm H2 O/L/s levels of breathing resistance, respectively. There was a statistically significant relationship between an increasing airway load and the decline in PSV during inspiration (P = .02). The PSV variation is greater in patients with increased airway resistance. Similar changes are evident in volunteers breathing into resistors. These findings likely reflect pulsus paradoxus.


Light-dependent segregation of begomoviruses in Asystasia gangetica leaves.
Asystasia gangetica (Acanthaceae) from tropical Africa and Asia is used as source of food and for medical applications. Plants collected in West Africa in the 1980s with typical geminivirus symptoms showed an unusual symptom segregation that included vein yellowing, curling and mosaic, which were present simultaneously or separately on different leaves of the same plant or on different plants propagated as cuttings from a single plant. Rolling-circle amplification in combination with restriction fragment length polymorphism analysis followed by deep sequencing of the RCA products identified two geminiviruses in these plants. One with a bipartite genome, Asystasia begomovirus 1, and the other with a monopartite genome together with its defective DNA, Asystasia begomovirus 2. The relationship between leaf symptoms and virus distribution under different light regimes was investigated, and showed for the first time an unusual segregation of symptoms and viruses, either within a single plant, or even within a leaf.


Clinical experience and patch testing using colophony (rosin) from different sources.
Patients with suspected allergy to colophony were patch-tested with colophony (rosin) of different kinds (gum rosin, tall oil rosin). More cases of allergy were detected by testing with more than one type of colophony. Tall oil rosin produced a smaller number of positive reactions than the gum rosins tested, which suggests a lower allergenic activity. Venice turpentine was a useful additional screening substance. When different test concentrations were compared (20% and 5%) the lower concentration failed to reveal four of 30 cases. The patients' eczema had been caused chiefly by contact with colophony in their work.


The fine structure of lipofuscin in the human inner ear.
Lipofuscin inclusions in the human membranous labyrinth were studied by electron microscopy. Lipofuscin is morphologically an irregularly shaped, membrane-bound inclusion consisting of an electron-dense structure. The most common component was a fine, granular, osmiophilic substance which was always associated with a homogenous, spherical structure resembling a lipid droplet. The combination of these two components was frequently observed in the human inner ear. Distended inclusions containing lipofuscin components were also observed within the supporting cells, saccular, utricular and ampullar wall, the epithelial cells of the transitional zone and in the dark cells. Lipofuscin is closely associated with lysosome and is known to accumulate in the tissue as a result of aging. The high lysosomal activity possibly may result in lipofuscin formation in the human inner ears. Also some other unknown metabolic conditions may provide the deposits of lipofuscin.


Effects of β-glucan on Salmonella enterica serovar Typhimurium swine colonization and microbiota alterations.
The 2017 Veterinary Feed Directive eliminated the use of medically important antibiotics for growth promotion of food animals; thus, alternative growth promoters are highly desirable by food animal producers to enhance animal health and reduce pathogen colonization, including the human foodborne pathogen Salmonella. β(1-3)(1-6)-D-glucan (β-glucan) is a soluble fiber with prebiotic characteristics; it has been shown to modulate immune and intestinal functions that strengthen swine resistance to health challenges such as bacterial infections when supplemented in the diets of growing pigs. The current study evaluated the effects of a β-glucan product on gut microbial community structure as well as Salmonella shedding and intestinal colonization. Five-week-old pigs were fed a β-glucan amended diet at 500 g/ton (n = 13) or a non-amended control diet (n = 14) for three weeks, followed by inoculation of the 27 pigs with 1 × 109 colony forming units of Salmonella enterica serovar Typhimurium strain UK1. While remaining on the respective diets, fecal samples collected at 2, 4, 7, and 16 days post-inoculation (dpi) were similar for Salmonella shedding counts between the two diets. At 16 dpi, Salmonella counts were significantly lower in the cecal contents of the β-glucan-fed pigs (P = 0.0339) and a trend towards a reduction was observed in the Peyer's patches region of the ileum (P = 0.0790) compared to the control pigs. Pigs fed β-glucan for three weeks exhibited an increase in members of the Clostridia class in their fecal microbial communities, and after inoculation with Salmonella, several potentially beneficial microorganisms were enriched in the microbiota of β-glucan-fed pigs (Lactobacillus, Ruminococcaceae, Prevotellaceae, Veillonellaceae, Bifidobacterium and Olsenella). Administration of β-glucan altered the swine gut microbiome and reduced Salmonella colonization in the cecal contents.


How has the pandemic lockdown changed our daily facial skincare habits?
During the COVID-19 pandemic, Poland implemented widespread closure of beauty and cosmetic services to control the virus spread. The aim of this study was to investigate the impact of the SARS-CoV-2 pandemic on home face care of women and to analyze changes that have occurred in their daily habits. An online survey was completed by 412 women living in Poland during the spring lockdown. Questions addressed changes in face care during the COVID-19 pandemic. Our questionnaire showed that during the lockdown, women were more interested in face skincare, more often followed the procedure of full home skincare. And after implementing the changes in skincare, they saw a good impact on their skin. The significance of the Internet also increased considerably, not only as a source of knowledge in the field of cosmetology but also as a thriving market selling cosmetic products.


Utility of indium-111-antimyosin scintigraphy for diagnosis of myocardial damage in systemic sclerosis.
The diagnosis of myocardial disease related to systemic sclerosis is often difficult, but it is clinically relevant since the occurrence of a specific ventricular dysfunction is of poor prognosis. This article reports a case of systemic sclerosis with a subacute episode of myocardial disease assessed by 111In-antimyosin antibody, a specific marker of the necrotic myocardial fiber.


Monoclonal antibodies to phenobarbital-induced rat liver cytochrome P-450.
Somatic cell hybrids were made between mouse myeloma cells and spleen cells derived from BALB/c female mice immunized with purified phenobarbital-induced rat liver cytochrome P-450 (PB-P-450). Hybridomas were selected in HAT medium, and the monoclonal antibodies (MAbs) produced were screened for binding to the PB-P-450 by radioimmunoassay, for immunoprecipitation of the PB-P-450, and for inhibition of PB-P-450-catalyzed enzyme activity. In two experiments, MAbs of the IgM and IgG1 were produced that bound and, in certain cases, precipitated PB-P-450. None of these MAbs, however, inhibited the PB-P-450-dependent aryl hydrocarbon hydroxylase (AHH) activity. In two other experiments, MAbs to PB-P-450 were produced that bound, precipitated and, in several cases, strongly or completely inhibited the AHH and 7-ethoxycoumarin deethylase (ECD) activities PB-P-450. These MAbs showed no activity toward the purified 3-methylcholanthrene-induced cytochrome P-450 (MC-P-450), beta-naphthoflavone-induced cytochrome P-450 (BNF-P-450) or pregnenolone 16-alpha-carbonitrile-induced cytochrome P-450 (PCN-P-450) in respect to RIA determined binding, immunoprecipitation, or inhibition of AHH activity. One of the monoclonal antibodies, MAb 2-66-3, inhibited the AHH activity of liver microsomes from PB-treated rats by 43% but did not inhibit the AHH activity of liver microsomes from control, BNF-, or MC-treated rats. The MAb 2-66-3 also inhibited ECD in microsomes from PB-treated rats by 22%. The MAb 2-66-3 showed high cross-reactivity for binding, immuno-precipitation and inhibition of enzyme activity of PB-induced cytochrome P-450 from rabbit liver (PB-P-450LM2). Two other MAbs, 4-7-1 and 4-29-5, completely inhibited the AHH of the purified PB-P-450. MAbs to different cytochromes P-450 will be of extraordinary usefulness for a variety of studies including phenotyping of individuals, species, and tissues and for the genetic analysis of P-450s as well as for the direct assay, purification, and structure determination of various cytochromes P-450.


The model of Kermack and McKendrick for the plague epidemic in Bombay and the type reproduction number with seasonality.
The figure showing how the model of Kermack and McKendrick fits the data from the 1906 plague epidemic in Bombay is the most reproduced figure in books discussing mathematical epidemiology. In this paper we show that the assumption of constant parameters in the model leads to quite unrealistic numerical values for these parameters. Moreover the reports published at the time show that plague epidemics in Bombay occurred in fact with a remarkable seasonal pattern every year since 1897 and at least until 1911. So the 1906 epidemic is clearly not a good example of epidemic stopping because the number of susceptible humans has decreased under a threshold, as suggested by Kermack and McKendrick, but an example of epidemic driven by seasonality. We present a seasonal model for the plague in Bombay and compute the type reproduction numbers associated with rats and fleas, thereby extending to periodic models the notion introduced by Roberts and Heesterbeek.


Molecular structure of 2-(hydroxyimino)propanohydroxamic acid in solid state and DMSO solution.
The 1H and 13C NMR spectra of 2-(hydroxyimino)propanohydroxamic acid (hpha) were measured in DMSO-d6 solution. The set of several monomeric structures along with the cluster of H-bonded hpha with three DMSO molecules were proposed to fit the experimental data. The calculated chemical shifts [B3LYP/6-311++G(d,p)] strongly suggested the formation of the cluster in which all the labile protons were H-bonded to the solvent molecules. The comparison between experimental and calculated Raman spectra of hpha in DMSO also suggested that in these conditions the investigated compound forms the proposed cluster rather than dimers. According to our calculations [B3LYP/6-31+G(d)] this cluster was energetically stabilized (84-106 kJ mol-1) compared to postulated dimeric structures. On the other hand, formation of dimers was proposed to be present for hpha in solid state. The comparison of the vibrational data (IR, RS) with the computed harmonic frequencies of three most probable dimers [B3LYP/6-31+G(d)] suggested that the dimer in which molecules adopted the zEe-keto form and were linked by two symmetric, almost linear H-bonds between the carbonyl oxygen atoms and the hydroxamic O-H protons was the predominant species of hpha in the solid state. Thus, the structures of hpha in solid state and DMSO solution appeared to be different.


Studies on new dehydropeptidase inhibitors. III. Biological properties of WS1358A1.
WS1358A1, a novel inhibitor of renal dehydropeptidase (DHP), augmented the urinary recovery of a carbapenem antibiotic imipenem and improved its protective effect in experimental infections when simultaneously administered to mice with the antibiotic. WS1358A1 was a competitive DHP inhibitor with a Ki value of 1.6 x 10(-7) M.


[Cell wall polysaccharide structure in the food protein yeast, Candida spec. H. II. Characterization of phosphate binding to the mannan-protein-phosphate complex and identification of phosphodiester-bound mono- oligosaccharides].
The proteophosphomannan (PPM) obtained by extraction with citrate buffer, purification by the cetavlon method and gel filtration contains a high proportion of diesterified phosphate groups between the C-6 of a side chain mannose and another glycosidically bound carbohydrate. Mild acid hydrolysis cleaved the phosphate diester linkages to yield mono- and oligosaccharide fractions. Chemical analysis and 1H-NMR studies demonstrated the heterogeneity of the oligosaccharide fractions containing alpha(1,2)-, alpha(1,3)- and alpha(1,6)-linked manno-oligosaccharides. All repeated PPM preparations contained mono-, tri- and heptasaccharides as the phosphate bound main compounds. Galactose, arabinose, fucose, and rhamnose of the monosaccharide fraction and tetra-, penta- and hexasaccharides were not found in all preparations.


Evaluation of reproductive toxicity in rats caused by organic extracts of Jialing River water of Chongqing, China.
OECD 421 screening test protocol was used to evaluate the reproductive toxicity of organic extracts of river water. These extracts, at doses of 0, 2, 16, or 80 equivalent L/kgbody weight(bw), were administered to rats daily by oral gavage. Vacuole degeneration of seminiferous epithelium was observed in the dosed groups. The caudal sperm counts/epididymis weight and the percentages of sperm with abnormal heads were increased in the group dosed with 80L/kgbw/day compared to the control group. Exposure of rats to organic extracts at the high dose resulted in a decrease in testosterone levels. The serum level of follicle-stimulating hormone increased in the groups dosed with 16 or 80L/kgbw/day compared to the control group. The number of apoptotic spermatid increased in the dosed groups. The results suggest that the extracts cause pathological damage to testicular tissue and disruption of spermatogenesis.


Exposure-Response Relationship Between Aircraft Noise and Sleep Quality: A Community-based Cross-sectional Study.
Exposure to aircraft noise has been shown to have adverse health effects, causing annoyance and affecting the health-related quality of life, sleep, and mental states of those exposed to it. This study aimed to determine sleep quality in participants residing near an airfield and to evaluate the relationship between the levels of aircraft noise and sleep quality. NEIGHBORING REGIONS OF A MILITARY AIRFIELD WERE DIVIDED INTO THREE GROUPS: a high exposure group, a low exposure group, and a control group. A total of 1082 participants (aged 30-79 years) completed a comprehensive self-administered questionnaire requesting information about demographics, medical history, lifestyle, and the Pittsburgh Sleep Quality Index. Of the 1082 participants, 1005 qualified for this study. The prevalence of sleep disturbance was 45.5% in the control group, 71.8% in the low exposure group, and 77.1% in the high exposure group (p for trend < 0.001). After adjusting for potential confounding factors, we determined the exposure-response relationship between the degree of aircraft noise and sleep quality. Of the participants with a normal mental status, the prevalence of sleep disturbance was 2.61-fold higher in the low exposure group and 3.52-fold higher in the high exposure group than in the control group. The relationship between aircraft noise and health should be further evaluated through a large-scale follow-up study.


A case of recurrent endometrial cancer with long-term complete remission following pembrolizumab-induced severe immune-related adverse event colitis.
Endometrial cancer is generally diagnosed at an early stage and has a good prognosis, although once it recurs, the prognosis is poor because of few therapeutic options. Since endometrial cancer has a high frequency of microsatellite instability-high/mismatch repair deficiency, the anti-PD-1 antibody pembrolizumab is expected to be one of the key therapeutic agents for recurrent endometrial cancer. Immune-related adverse events (irAEs) are autoimmune-like unique and occasionally life-threatening side effects of immune checkpoint inhibitors. Here, we report a rare case of recurrent endometrial cancer that showed long-term complete remission after developing relapsing severe irAE colitis following the introduction of pembrolizumab.


[Role of enterosorbents in treatment of complicated varicose disease].
Results of treatment of 43 patients, suffering varicose disease, complicated by trophic disorders, were analyzed. To the patients a complex was prescribed, including sorpents, angioprotectors, locally - ointments. There were operated 14 patients.


Valorization of Pumpkin Peel as a Source of Bioactive Compounds: Optimization of Heat- and Ultrasound-Assisted Extraction.
The peels from three pumpkin genotypes cultivated in Greece were assessed for their phenolic content and bioactive properties to obtain extracts with a high preservative capacity. The optimization of the extraction was performed through response surface methodology (RSM) based on a Box-Behnken experimental design after applying two extraction techniques: heat-assisted (HAE) and ultrasound-assisted (UAE) extraction. The implemented independent variables were time, solvent concentration, and temperature/power (for HAE/UAE), while as dependent variables the dry residue (DR), reducing power (RP), and total phenolic content (TP) were considered. In general, HAE was the most effective technique for 'TL' (75 min; 30 °C; 24% ethanol) and 'Voutirato' (15 min; 30 °C; 10% ethanol), while UAE was more effective for 'Leuka Melitis' (5 min; 400 W; 0% ethanol). The extracts obtained in the global optimum conditions for each genotype peel were then assessed for their phenolic profile, by HPLC-DAD-ESI/MS, and bioactive potential. Seven phenolic compounds were detected, including four flavonoids, two phenolic acids, and one flavan-3-ol. The extracts presented high antioxidant, antibacterial, and antifungal potential, with no cytotoxicity for non-tumor cells. The optimized conditions for the extraction of preservative compounds from bioresidues were defined, allowing the acquisition of antioxidant and antimicrobial extracts and proving their potential for food application.


Benefits of implementing an academic training of trainers program to promote knowledge and clarity in work with psychiatric suicidal patients.
A 200-hour academic, postgraduate training-of-trainers program in suicide prevention at Karolinska Institute for key mental healthcare staff, designed to enable them to enhance their co-workers' knowledge and job clarity, was evaluated in a panel study by means of questionnaires. Psychiatric staff working regularly with suicidal patients in clinics where key persons attended the course (n = 134, intervention group) were compared with staff working in clinics without participants (n = 166, control group). Perceptions of being sufficiently trained (p < .01) improved significantly among staff working in intervention clinics. Compared with the control group, the intervention group had a better understanding of essentials (p < .05); found instructions clearer (p < .01) and experienced fewer problems with superiors' differing views (p < .05) at follow up. Assistant nurses working in intervention clinics seem to have benefited most.


Characteristics of adult- compared to childhood-onset type 1 diabetes.
To compare diagnosis characteristics, diabetes management and comorbidities in a population diagnosed with type 1 diabetes in childhood with those in a similar population diagnosed in adulthood to identify disease differences related to the age of diabetes onset. This analysis was performed using the T1D Exchange Clinic Registry, a cross-sectional survivor cohort. Retrospectively collected characteristics were compared across the following age-at-diagnosis groups: <10, 10-17, 18-24, 25-39 and ≥40 years. The entire cohort included 20 660 participants [51% female, median (interquartile range) age 18 (14-36) years, 82% non-Hispanic white]. Diabetic ketoacidosis at diagnosis was more common among those with onset in childhood. Participants diagnosed as adults were more likely to be overweight/obese at diagnosis and to have used oral agents preceding type 1 diabetes diagnosis (57%). Current insulin pump use was less frequent in participants diagnosed at older ages. Current glycaemic control, measured by HbA1c , insulin requirements and use of a continuous glucose monitor were not different by age at diagnosis. Coeliac disease was the only comorbidity that was observed to have a different frequency by age at diagnosis, being more common in the participants diagnosed at a younger age. These results show differences and similarities between type 1 diabetes diagnosed in childhood vs adulthood; notably, there was a tendency for there was a higher frequency of diabetic ketoacidosis at onset in children and a higher frequency of use of oral antidiabetes agents in adults. The data indicate that there is little distinction between the clinical characteristics and outcomes of type 1 diabetes diagnosed in childhood vs adulthood. Optimizing glycaemic control remains a challenge in all age groups, with lower use of insulin pumps impacting those diagnosed as adults.


Proliferative response of human and animal tumours to surgical wounding of normal tissues: onset, duration and inhibition.
Acceleration of secondary tumour growth and metastases following excision of a primary tumour has been attributed to the consequent removal of primary tumour-generated inhibitory factors. However, our studies have shown that surgical wounding of normal tissues significantly stimulated the growth of malignant tissues without the concomitant presence or excision of a tumour mass. A humoral stimulating component was indicated by the proliferative response of tumours and metastases distant from the surgical wound. All 16 human and murine tumours, of nine different histologies, showed a measurable acceleration of growth when implanted in surgically treated animals, suggesting that the ability of malignant tissue to respond to surgical wounding of normal tissue was not histologically or species specific. The proliferative surge of malignant tissues was detectable soon after wounding and had a duration of 2-3 days. The surgical wound as the source of the tumour-stimulating factor(s) was affirmed by the significant inhibition of tumour proliferative responses when a somatostatin analogue was applied topically to the surgical wound within 1 h of wounding, and/or during the critical tumour-stimulatory period of 1-2 days after wounding. A potential therapeutic window for reducing a risk factor that may be inadvertently imposed upon every surgical/oncology patient is indicated.


Complete robotic-assistance during laparoscopic living donor nephrectomies: an evaluation of 38 procedures at a single site.
To evaluate our initial experience with entirely robot-assisted laparoscopic live donor (RALD) nephrectomies. From January 2002 to April 2006, we carried out 38 RALD nephrectomies at our institution, using four ports (three for the robotic arms and one for the assistant). The collateral veins were ligated, and the renal arteries and veins clipped, after completion of ureteral and renal dissection. The kidney was removed via a suprapubic Pfannenstiel incision. A complementary running suture was carried out on the arterial stump to secure the hemostasis. Mean donor age was 43 years. All nephrectomies were carried out entirely laparoscopically, without complications and with minimal blood loss. Mean surgery time was 181 min. Average warm ischemia and cold ischemia times were 5.84 min and 180 min, respectively. Average donor hospital stay was 5.5 days. None of the transplant recipients had delayed graft function. Robot-assisted laparoscopic live donor nephrectomy can be safely carried out. Robotics enhances the laparoscopist's skills, enables the surgeon to dissect meticulously and to prevent problematic bleeding more easily. Donor morbidity and hospitalization are reduced by the laparoscopic approach and the use of robotics allows the surgeon to work under better ergonomic conditions.


Influence of vanadate on electrophysiological and contractile parameters of atrial myocardium.
Whereas vanadate increases isometric force of contraction in stimulated rat left atria (EC50: 36.6 mumol/1), it decreases force of contraction in guinea-pigs (EC50: 4.7 mumol/1). Action potential duration at 90 and 30% repolarisation is decreased in guinea-pig atria by 70 and 60%, but in rat atria by only 40 and 7% respectively. Whereas the time course of the negative inotropic action is rapid and correlates with that of the shortening of the action potential, there is no relationship between action potential changes and the slowly developing positive intropic effect. Negative and positive inotropic actions seem to be the result of two superimposed processes, whose kinetics suggest an extra- and intracellular site of action. Na+, K+-ATPase prepared from rat and guinea-pig atria and ventricle is inhibited by vanadate to a similar extent: IC50 (mumol/1) rat: atria 1.05, ventricle 0.49; guinea-pig: atria 0.75, ventricle 0.62. This indicates that the discrepancy in inotropy cannot be explained by the different sensitivity of the Na+, K+-ATPase to vanadate.


Secukinumab responses vary across the spectrum of congenital ichthyosis in adults.
Treatment of congenital ichthyoses primarily focuses on reversing skin scaling and is not pathogenesis based. Recent studies showed Th17 immune skewing, as in psoriasis, across the spectrum of ichthyosis, suggesting that targeting this pathway might broadly reduce disease severity. To determine whether secukinumab, an IL-17A inhibitor, can improve ichthyosis across several congenital ichthyosis subtypes. Exploratory 16-week double-blind, randomized, placebo-controlled trial comparing secukinumab 300 mg every 4wks to placebo (1:1 randomization) in adults with the four major congenital ichthyosis subtypes (NCT03041038), followed by a 16-week open-label phase to evaluate response of the placebo-first group and a 20-week extension for safety. Significant differences in secukinumab- vs. placebo-treated subjects at Wk16 in the Ichthyosis Area Severity Index (IASI) score and lack of increased mucocutaneous bacterial and/or fungal infections were the co-primary efficacy and safety endpoints, respectively. Two tertiary referral centers: Northwestern University Feinberg School of Medicine, Chicago, and Mount Sinai Icahn School of Medicine, New York. Twenty subjects ≥ 18 yo with genotype-confirmed epidermolytic ichthyosis, Netherton syndrome, lamellar ichthyosis, or congenital ichthyosiform erythroderma with at least moderate erythroderma. IL-17A inhibition did not significantly reduce severity or increase mucocutaneous infections among the 18 who completed the 16-week double-blind phase. Five patients with 29-50% clinical improvement at Wk32 requested drug continuation. Th17-related biomarkers were not significantly reduced vs. baseline or placebo-treated levels. Small sample size; heterogeneous ichthyosis subsets. IL-17 inhibition with secukinumab is safe, but not efficacious across the spectrum of adult ichthyoses. NCT03041038; first posted on 02/02/2017.


Fixation of microsporidian spores for electron microscopy.
Fresh and frozen spores of the microsporidia Nosema apis and Nosema bombi were fixed using various fixatives at different times and temperatures. Paraformaldehyde and technical formaldehyde gave results comparable to or better than glutaraldehyde. Increased fixation temperature improved the fixation of spores from terrestrial hosts. Freezing did not destroy the cytology of the spore.


A Novel Application of a Bivariate Regression Model for Binary and Continuous Outcomes to Studies of Fetal Toxicity.
Public health concerns over the occurrence of birth defects and developmental abnormalities that may occur as a result of prenatal exposure to drugs, chemicals, and other environmental factors has led to an increasing number of developmental toxicity studies. Because fetal pups are commonly evaluated for multiple outcomes, data analysis frequently involves a joint modeling approach. In this paper, we focus on modelling clustered binary and continuous outcomes in the setting where both outcomes are potentially observable in all offspring but, due to practical limitations, the continuous outcome is only observed in a subset of offspring. The subset is not a simple random sample (SRS) but is selected by the experimenter under a prespecified probability model.While joint models for binary and continuous outcomes have been developed when both outcomes are available for every fetus, many existing approaches are not directly applicable when the continuous outcome is not observed in a SRS. We adapt a likelihood-based approach for jointly modelling clustered binary and continuous outcomes when the continuous response is missing by design and missingness depends on the binary trait. The approach takes into account the probability that a fetus is selected in the subset. Through the use of a partial likelihood, valid estimates can be obtained by a simple modification to the partial likelihood score. Data involving the herbicide 2,4,5-T are analyzed. Simulation results confirm the approach.


Evolving concepts of stability and intramedullary fixation of intertrochanteric fractures--a review.
Intramedullary nailing is gradually emerging as the treatment of choice for pertrochanteric femoral fractures. Nevertheless, prospective randomised trials have failed to demonstrate the assumed superiority of cephalomedullary nails over the traditional treatment with the sliding hip screw. On the contrary, the gamma nail has been implicated in predisposing to secondary femoral fractures, although this seems to be rectified by newer techniques and nail designs. Sliding hip screw fixation remains the gold standard but can lead certain unstable pertrochanteric fracture subgroups to failure. Amongst these are transverse or reverse obliquity but also multifragmentary fractures, that suffer intra- or postoperative shattering of the lateral trochanteric wall. Nails seem to prevent failure by opposing the uncontrollable medialisation, and eventual failure, that occurs under these circumstances. The importance of the size of the proximal fracture fragment has not yet been elucidated. Nail fixation is, thus, mandatory in a small percentage of grossly unstable fractures, whose characteristics are still undergoing definition.


Immunohistochemical reaction to human milk fat globule antibodies and breast cancer differentiation.
Immunohistochemical studies of human breast cancers using human milk fat globule (HMFG) antibodies are divergent regarding the association with histologic differentiation. To clarify this association 392 tumors were assessed using two antibodies, HMFG-1 and HMFG-2. In half the tumors studied the tissue reaction to both antibodies was the same and in 63% the site of reaction was identical. Using both univariate and multivariate statistics, a highly significant association was recorded between membrane staining and well differentiated cancers and cytoplasmic staining and poor differentiation. Well differentiated tumors contained significantly more reactive cells. Complementing these findings was the association between age at diagnosis, tumor stage, and estrogen receptor status and differentiation. It is possible that immunohistochemical analysis with HMFG antibodies will provide better characterization of tumor differentiation than morphologic interpretation.


Dietary fiber modulates abdominal fat deposition associated with cecal microbiota and metabolites in yellow chickens.
Excessive deposition of abdominal fat is a public concern in the yellow chicken industry related to human nutrition. The common practice of nutritionists is to increase the fiber content in feed to control abdominal fat deposition of chickens. Corncob meal (CCM) is the cheapest ingredient widely used in animal diets. The possible effects of CCM on chicken abdominal fat deposition and the possible mechanism involving cecal microbiota remain unknown. The objectives of this study were to investigate the effects of CCM in modulating abdominal fat deposition and the role of the cecal microbiota and their metabolites. A total of 200 ninety-day-old Huxu female chickens were divided into 2 dietary treatments, each with 10 replicates of 10 birds, and were fed two finisher diets, from 90 to 135 d. The diets were a typical corn-soybean control diet (CON) and that diet with CCM partially replacing corn and corn gluten meal. Results showed that the CCM diet markedly decreased live weight and abdominal fat percentage (P < 0.05); chickens fed the CCM diet exhibited lower (P < 0.01) expression in abdominal fat of fatty acid binding protein 4 (FABP4), stearoyl-CoA desaturase (SCD), fatty acid synthase (FAS), and peroxisome proliferator-activated receptor γ (PPARγ) but higher (P < 0.05) expression of estrogen receptor alpha (ESR1). The CCM increased the abundance of Akkermansia (P < 0.05) and markedly reduced the relative cecal abundance of Phascolarctobacterium (P < 0.01), Rikenellaceae (P < 0.05), and Faecalibacterium (P < 0.01). The metabolomic and biochemical analyses demonstrated that the CCM diet increased (P < 0.05) the concentrations of butyrate in cecal contents. The majority of the metabolites in cecal digesta with differences in abundance were organic acids. The CCM diet increased (P < 0.05) contents of (R)-5-diphosphomevalote, pantothenic acid, 2-epi-5-epi-valiolone 7-phosphate, D-ribose 5-diphosphate, arbutin 6-phosphate, D-ribitol 5-phosphate, undecanoic acid, nicotinic acid, 4-methyl-2-oxovaleric acid, while decreasing (P < 0.05) those of oleic acid, glutaric acid, adipic acid, suberic acid, and L-fuculose 1-phosphate. In conclusion, these findings demonstrated that the dietary CCM treatment significantly decreased abdominal fat and altered the cecal microbiota and metabolite profiles of the yellow chickens.


Long-term clinical outcomes of Amplatzer cardiac plug versus Amulet occluders for left atrial appendage closure.
To compare long-term clinical outcomes after left atrial appendage closure with the Amplatzer Cardiac Plug (ACP) and Amulet. The Amulet was designed to improve clinical outcomes of first-generation ACP. Three Amplatzer registries (Bern, Coburg, Zurich), with enrollment of patients from 2009 to 2018, were retrospectively analyzed. The primary safety endpoint was a composite of major peri-procedural complications and major bleedings, the primary efficacy endpoint included stroke, systemic embolism, and cardiovascular/unexplained death. The net clinical benefit was a combination of all above-mentioned hazards. A total of consecutive 563 patients (344 ACP vs. 219 Amulet) with a mean follow-up of 2.9 ± 1.6 and 1.9 ± 0.9 years were included. Mean age (74.4 ± 9.9 [ACP] vs. 74.4 ± 9.1 [Amulet] years), stroke (CHA2 DS2 -VASc score 4.4 ± 1.6 vs. 4.6 ± 1.7), and bleeding risk (HAS-BLED score 3.2 ± 1.1 vs. 3.2 ± 0.9) were comparable. The primary endpoints of efficacy (72/998, 7.2% [ACP] vs. 43/417, 10.3% [Amulet]; hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.44-1.02, p = .062), safety (40/998, 4.0% vs. 18/417, 4.3%; HR, 1.15; 95% CI, 0.53-2.51, p = .72), and the net clinical benefit (101/998, 10.1% vs. 55/417, 13.4%; HR, 0.73; 95% CI, 0.49-1.07, p = .11) were similar. In the long term, left atrial appendage closure with first and second-generation Amplatzer devices provided similar efficacy, safety, and net clinical benefit. Clinical outcomes may be rather determined by implantation technique and hemodynamics, but not by the design modifications of the Amulet.


Boosting Hydrogen Production by Selective Anodic Electrooxidation of Ethanol over Trimetallic PdSbBi Nanoparticles: Composition Matters.
The conventional hydrogen evolution from water electrolysis is severely impeded by the sluggish kinetics of oxygen evolution reaction (OER). In this work, an integrated electrolysis system of replacing the anodic OER with a thermodynamically favorable ethanol oxidation reaction (EOR) has been developed by using PdSbBi/C as an electrocatalyst. To maximize the EOR performance, the composition of PdSbBi nanoparticles is tuned by varying the ratio of Sb and Bi precursors. Ternary PdSbBi-based electrocatalysts exhibit enhanced activity and stability toward EOR compared to commercial Pd/C and binary catalysts. In particular, the Pd76Sb17Bi7/C catalyst delivers a very high specific activity up to 52.4 mA cm-2 and mass activity of 2.66 A mg-1Pd. Besides, this EOR process is demonstrated to have high selectivity with acetic acid as the oxidation product in the electrolyte. When coupled with a cathodic platinum mash, the two-electrode electrolyzer cell requires a voltage input of merely 0.61 V to afford a current density of 10 mA cm-2. Density functional theory calculations reveal that the presence of Sb and Bi can promote the adsorption of hydroxide ions and facilitate the removal of reaction intermediates in the EOR pathway. This work provides a novel catalyst for the energy-efficient coproduction of acetic acid and hydrogen fuel.


Robotic assistive and rehabilitation devices leading to motor recovery in upper limb: a systematic review.
Stroke, spinal cord injury and other neuromuscular disorders lead to impairments in the human body. Upper limb impairments, especially hand impairments affect activities of daily living (ADL) and reduce the quality of life. The purpose of this review is to compare and evaluate the available robotic rehabilitation and assistive devices that can lead to motor recovery or maintain the current motor functional level. A systematic review was conducted of the literature published in the years from 2016-2021, to focus on the most recent rehabilitation and assistive devices available in the market or research environments. A total of 230 studies published between 2016 and 2021 were identified from various databases. 107 were excluded with various reasons. Twenty-eight studies were taken into detailed review, to determine the efficacy of robotic devices in improving upper limb impairments or maintaining the current level from getting worse. It was concluded that with a good strategy and treatment plan; appropriate and regular use of these robotic rehabilitation and assistive devices do lead to improvements in current conditions of most of the subjects and prolonged use may lead to motor recovery.Implications for RehabilitationStroke, accidents, spinal cord injuries and other neuromuscular disorders lead to impairments. Upper limb impairments have a tremendous adverse affect on ADL and reduces quality of life drastically.Advancement in technology has led to the designing of many robotic assistive and rehabilitation devices to assist in motor recovery or aid in ADL.This review analyses different available devices for rehabilitation and assistance and points out that use of these devices in time does help in motor recovery. Most of the studies reviewed showed improvements for the user.Future devices should be more portable and easier to use from home.


An integrated proteomics and genomics analysis to unravel a heterogeneous platelet secretion defect.
Eight patients with clinical bleeding problems have evidence for platelet storage pool disease as they present with impaired platelet aggregation and secretion with low concentrations of ADP and collagen and an absence of second phase aggregation with epinephrine. Electron microscopy analysis further showed a reduced but not absent amount of platelet dense granules, and CD63 staining was decreased compared to healthy controls. The presence of alpha granules and CD62P expression after platelet activation was normal. This work aimed at identifying differentially expressed proteins in the platelet releasate and its remaining pellet after activation with A23187 and TRAP in patients and controls using DIGE-based proteomic technology. We identified 44 differentially expressed proteins in patients and the altered expression for some of them was confirmed by immunoblot analysis. Most of these proteins belong to the class of cytoskeleton-related proteins. In addition, 29 cytoskeleton-related genes showed an altered expression in platelet mRNA from patients using a real-time PCR array. In conclusion, our study shows that the dense granule secretion defect in patients with platelet storage pool disease is highly heterogeneous with evidence of an underlying cytoskeleton defect.


Behavioral measurement of axonal thresholds.
A behavioral method for measuring the electrical sensitivity of directly stimulated elements in the brain is described and applied to the medial forebrain bundle (MFB) reward path and the tectospinal circling path. Equations are derived from which threshold current densities may be calculated from knowledge of the electrode tip dimensions and the current required to produce criterion behavior, which is a function of electrode size. Four different sizes of electrode were implanted in the MFB of rats and self-stimulation rates plotted against stimulating current. The mean currents for criterion bar-pressing rates of 25% and 55% of maximum rate were determined for each electrode size and the values used to calculate average threshold current densities. Two sizes of electrode were implanted in the tectospinal tract of rats and the average currents to produce circling at 0.2 and 0.4 turns/s were measured. The threshold current densities for self-stimulation axons were about 5 times as large as those for circling, in accordance with other evidence that tectal circling path axons are larger than those of the MFB reward path.


High-pressure liquid chromatography of amino acids and dipeptides on a tripeptide bonded stationary phase.
A bonded tripeptide (L-valyl-L-phenylalanyl-L-valine) phase has been used as a stationary phase in liquid chromatography. Unique retention orders and retention variations are shown for phenylthiohydantoin (PTH) derivatives of amino acids and isomeric dipeptides using acidic and basic mobile phases. It is shown that the 25 PTH-amino acids studied here have different capacity ratios when 1% citric acid in water (ca. pH 2.5) is used as the mobile phase. The analysis time for these amino acid derivatives could be shortened without a loss in the resolution by adding 5% methanol to the above mobile phase. Of particular importance is the fact that the basic amino acids are eluted first. Isomeric dipeptides have been resolved by using deionized water (pH 5.5), and 1% sodium citrate in water (pH 7.9), as mobile phases. The data show that the nature of the mobile phases, the pH, and the ionic strength are the important factors affecting the selectivity and efficiency of the separations of amino acids and dipeptides.


Socioeconomic disparities and COVID-19 vaccination acceptance: a nationwide ecologic study.
To analyse the correlation between COVID-19 vaccination percentage and socioeconomic status (SES). A nationwide ecologic study based on open-sourced, anonymized, aggregated data provided by the Israel Ministry of Health. The correlations between municipal SES, vaccination percentage and active COVID-19 cases during the vaccination campaign were analysed by using weighted Pearson correlations. To assess the adequacy of first dose vaccination rollout relative to the municipality COVID-19 disease burden, a metric termed the vaccination need ratio was devised by dividing the total number of active cases (per 10 000 people) by the vaccination percentage of the population over 60 in each municipality, and its correlation with the SES was examined. 23 days after initiation of the vaccination campaign, 760 916 (56.8%) individuals over the age of 60 were vaccinated in Israel with the first dose of the BNT162b2 COVID-19 vaccine. A negative correlation was found between the COVID-19 active case burden and the vaccination percentage of the study population in each municipality (r = -0.47, 95% CI -0.59 to -0.30). The vaccination percentage significantly correlated with the municipal SES (r = 0.83, 95% CI 0.79 to 0.87). This finding persisted but was attenuated over a 5-week period. A negative correlation between the vaccination need ratio and municipal SES (r = -0.80, 95% CI -0.88 to -0.66) was found. Lower COVID-19 vaccination percentage was associated with lower SES and high active disease burden. Vaccination efforts should focus on areas with lower SES and high disease burden to assure equality of vaccine allocation and potentially provide a more diligent disease mitigation.


Adapting ACMG/AMP sequence variant classification guidelines for single-gene copy number variants.
The ability of a single technology, next-generation sequencing, to provide both sequence and copy number variant (CNV) results has driven the merger of clinical cytogenetics and molecular genetics. Consequently, the distinction between the definition of a sequence variant and a CNV is blurry. As the 2015 American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) standards and guidelines for interpretation of sequence variants address CNV classification only sparingly, this study focused on adapting ACMG/AMP criteria for single-gene CNV interpretation. CNV-specific modifications of the 2015 ACMG/AMP criteria were developed and their utility was independently tested by three diagnostic laboratories. Each laboratory team interpreted the same 12 single-gene CNVs using three systems: (1) without ACMG/AMP guidance, (2) with ACMG/AMP criteria, and (3) with new modifications. A replication study of 12 different CNVs validated the modified criteria. The adapted criteria system presented here showed improved concordance and usability for single-gene CNVs compared with using the ACMG/AMP interpretation guidelines focused on sequence variants. These single-gene CNV criteria modifications could be used as a supplement to the ACMG/AMP guidelines for sequence variants, allowing for a streamlined workflow and a step toward a uniform classification system for both sequence and copy number alterations.


Clean Air, Smart Cities, Healthy Hearts: Action on Air Pollution for Cardiovascular Health.
More than twenty percent of all cardiovascular disease (CVD) deaths are caused by air pollution - more than three million deaths every year - and these numbers will continue to rise unless the global community takes action. Nine out of ten people worldwide breathe polluted air, which disproportionately affects those living in low-resource settings. The World Heart Federation (WHF) is committed to reducing the impact of air pollution on people's health and has made this a priority area of its global advocacy efforts. In pursuit of this goal, WHF has formed an Air Pollution Expert Group to inform action on air pollution for CVD health and recommend changes to public health policy. This policy paper lays out the health impacts of air pollution, examines its position on the global policy agenda, demonstrates its relevance to the cardiovascular community, and proposes actionable policy measures to mitigate this deadly risk factor to health. The paper considers the important roles to be played by the Members of WHF, including scientific societies and the physicians that constitute them, heart health foundations, and patient advocacy groups. The paper concludes with a detailed table of recommendations for the various sub-target groups at the global, national, local, and patient level.


Elevated glucose alters A23187-induced release of arachidonic acid from porcine aortic endothelial cells by enhancing reacylation.
Cultured porcine aortic endothelial cells were conditioned in normal (5.2 mM) and elevated (15.6 mM) glucose, prelabeled with [14C]arachidonic acid and stimulated with ionophore A23187. Elevated glucose cultures released less radiolabeled products and less [14C]arachidonic acid. Analysis of cellular lipids revealed that elevated glucose reduced net loss of radiolabel from diacylphosphatidylethanolamine, did not affect early phosphatidylinositol hydrolysis, and increased net loss from diacylphosphatidylcholine and alkenylacylphosphatidylethanolamine. Uptake of radiolabel upon stimulation was examined to measure the role of reacylation on the diminished net release of radiolabel in elevated glucose cultures. Enhanced acylation of [3H]arachidonic acid into cellular lipids, especially PI, was observed in stimulated and resting cultures with elevated glucose. Further, pretreatment of the cultures with an acyltransferase inhibitor, thimerosal, prior to A23187 stimulation in radiolabeled cultures, abolished the effects of glucose on eicosanoid and arachidonic acid release. Differences in the ionophore-induced net loss of radiolabel from diacylphosphatidylethanolamine and phosphatidylinositol of the two glucose treatments were diminished by thimerosal exposure, while net loss of radiolabel from diacylphosphatidylcholine and alkenylacylphosphatidylethanolamine were unaffected. The data indicate that elevated glucose alters deacylation and enhances reacylation of arachidonic acid into endothelial cells and particularly into phosphatidylinositol. Enhanced reacylation may explain some of the altered lipid pathways that have been observed in experiments that elevate glucose concentrations or involve diabetes.


The ultrastructure of the accessory sex organs of the male rat. XI. Nuclear alterations of prostatic epithelial cells induced by castration.
The fine structure of the nuclei of epithelial cells of the dorsal lobe of the rat prostate were studied 2, 3, 5, 7 and 21 days after castration. The nucleolus appears to undergo a progressive disorganisation with partial fragmentation and dispersion of its normal components. Changes in the nucleoplasm were primarily reflected by a condensation of chromatin, particularly along the nuclear membrane and adjacent to the nucleolus. Later, different types of intranuclear inclusions were observed. After 21 days, the nuclei were characterized by an irregular outline with large indentation. Within the nucleoplasm aggregates of coarse granular chromatin were found. No cell necrosis was observed, indicating that androgen deprivation results in a remodeling of the cell to a less active state with marked cellular alterations and cessation of secretion, but apparently with some of their basic functions still intact. Injections of testosterone completely reverse the castrated-induced alterations. The changes observed are assumed to be due to the withdrawal of the androgenic stimulus, with a direct influence on the secretory function of the cell. The findings support the view that the stimulating secretory effect of androgen is mediated via an intranuclear androgen receptor, probably located in the nucleolus-associated-chromatin. It is also proposed that the secretory function of the epithelial cells of the prostatic complex, initiated by androgens, may be regulated by an intranuclear secretory center.


A common variant of the pregnancy-associated plasma protein-A (PAPPA) gene encodes a protein with reduced proteolytic activity towards IGF-binding proteins.
Pregnancy-associated plasma protein-A (PAPP-A) is a key regulator of insulin-like growth factor (IGF) bioactivity, by releasing the IGFs from their corresponding IGF-binding proteins (IGFBPs). The minor allele of the single nucleotide polymorphism (SNP), rs7020782 (serine < tyrosine), in PAPPA has previously been associated with recurrent pregnancy loss as well as with significant reduced levels of PAPP-A protein in human ovarian follicles. The aim of the present study was to reveal a possible functional effect of the rs7020782 SNP in PAPPA by comparing recombinant PAPP-A proteins from transfected human embryonic kidney 293 T cells. The proteolytic cleavage of IGFBP-4 was shown to be affected by the rs7020782 SNP in PAPPA, showing a significantly reduced cleavage rate for the serine variant compared to the tyrosine variant (p-value < 0.001). The serine variant also showed a trend towards reduced cleavage rates, that was not significant, towards IGFBP-2 and IGFBP-5 compared to the tyrosine variant. No differences were found when analysing cell surface binding, complex formation between PAPP-A and STC2 or proMBP, nor when analysing STC1 inhibition of PAPP-A-mediated IGFBP-4 cleavage. Regulation of IGF bioactivity in reproductive tissues is important and the rs7020782 SNP in PAPPA may disturb this regulation by altering the specific activity of PAPP-A.


[Fatal outcome of a cervical nerve block].
A patient with brachialgia was admitted to a surgical clinic and a cervical nerve block was performed under fluoroscopic guidance. Acute severe cervical pain prevented completion of the procedure. On the following day the patient developed incomplete paralysis of both legs and arms and was transferred to a neurosurgical department for further diagnosis and therapy. The CT scan showed a space-occupying cervical intraspinal haematoma, which was removed immediately as far as possible by a dorsal approach. Postoperatively little improvement of neurologic function was noticed, and 11 days after the event the patient died from a massive pulmonary embolism despite intense resuscitation efforts.


Protein A-independent tumoricidal responses in dogs after extracorporeal perfusion of plasma over Staphylococcus aureus.
Protein A-positive or -negative Staphylococcus aureus preparations were used in an extracorporeal system to treat dogs with spontaneously occurring cancers. Tumor regression was seen in 4 of 7 dogs treated by reinfusion of plasma that had been incubated with protein A-positive S. aureus Cowan I strain (SAC). Therapy was associated with fever, liver enzyme abnormalities, and hypocomplementemia. Tumor response and toxicity could be diminished by more extensive washing of the SAC preparation. Tumor regression was also seen in 2 of 2 animals treated with protein A-negative S. aureus Wood strain 46. In addition, tumors regressed in 3 of 4 dogs treated with infusions of protein A-free saline extracts from S. aureus. These results suggest that the release of a non-protein A bacterial product contributes to tumor regression following incubation of plasma with S. aureus.


Peripheral afferents with common function cluster in the median nerve and somatotopically innervate the human palm.
Concentric needle electrodes with a central core diameter of 20-30 microm were used to explore median nerve fascicles in man. Such electrodes can simultaneously monitor subtle electrophysiological and topographical features even within parts of a fascicle. Single-unit recordings from myelinated fibres were more easily obtained at some intrafascicular sites than others. Typically, groups of identified myelinated fibres in these regions, possibly corresponding to a cluster of Ranvier nodes, tended to be fibres responding to stimuli of the same modality. These afferents innervated the glabrous skin of the human hand and fingers in a somatotopic manner. In particular, the somatotopy even seemed to be present at the receptor level in the skin. This novel aspect of peripheral nerve organisation is probably of fundamental importance for the interplay between peripheral and central processes involved in somatosensation both under normal conditions and in disease. Some clinical implications of the findings are discussed.


Tackling the cytotoxicity and genotoxicity of cellulose nanofibers from the banana rachis: A new food packaging alternative.
Cellulose nanofibrils from the banana rachis are a good alternative as packaging materials, food packaging, stabilizing agents, and functional food ingredients. To address the potential effects of ingested banana rachis cellulose nanofibrils (BR-CNFs), their toxicity in vitro and in vivo was evaluated using Caco-2 intestinal cells and mice, respectively. The results showed that BR-CNFs did not cause cytotoxic effects at the concentrations evaluated on Caco-2 cells. In addition to cytotoxicity tests, genotoxicity assays using comet assay indicated that Caco-2 cells showed no DNA damage at the concentrations of CNFs tested. Finally, acute in vivo cytotoxicity assays indicated that mice showed no sign of pathogenesis or lesions in the liver, kidney, or small intestine when treated with a single dose of BR-CNFs. Moreover, when the mice were treated daily for a month with BR-CNFs no hyperplasia or hypertrophy was observed in any of the organs evaluated. Additionally, biochemical parameters such as blood chemistry, creatinine, liver enzymes, and renal function showed that the BR-CNFs do not cause organ damage. Overall, this study shows that BR-CNFs are neither cytotoxic nor genotoxic. In conclusion, these studies are essential to guarantee the safety of this high value-added product in the food industry.


The segmental distribution and clinical significance of colorectal fluorodeoxyglucose uptake incidentally detected on PET-CT.
Unexpected focal colorectal fluorodeoxyglucose (FDG) uptake is becoming a common clinical dilemma with the increasing utilization of positron emission tomography (PET). These findings may subsequently reveal malignant or premalignant pathology. In addition to reporting the prevalence of clinically significant colonic pathology associated with unexpected focal FDG uptake, this study analysed the correlation between pathological colonic segments with those reported on the FDG-PET scan. The reports of 2071 consecutive PET-computed tomography (PET-CT) scans performed in a calendar year were reviewed. Information regarding subsequent patient investigation and management was collected from medical records. The segments harbouring foci of unexpected bowel FDG uptake were compared against the eventual outcome(s) of the endoscopic and pathological investigations. Among the 62 individual patients represented, 37 (60%) were investigated further. Clinically unsuspected neoplasms were found in 68% of those investigated, including 10 diagnosed with carcinoma. In addition, an unknown bowel lymphoma and 19 colonic adenomas were discovered. The positive predictive value for pathology was higher in the proximal colon than the distal colon. The segments in which the pathological findings were identified correlated well with those reported as abnormal on PET-CT. Unexpected bowel FDG uptake on PET-CT is associated with a high incidence of neoplastic pathology. In particular, focal FDG uptake in the proximal colon is associated with a high positive predictive value for neoplasm. The location of pathology is strongly concordant with endoscopic findings.


gEL DNA: A Cloning- and Polymerase Chain Reaction-Free Method for CRISPR-Based Multiplexed Genome Editing.
Even for the genetically accessible yeast Saccharomyces cerevisiae, the CRISPR-Cas DNA editing technology has strongly accelerated and facilitated strain construction. Several methods have been validated for fast and highly efficient single editing events, and diverse approaches for multiplex genome editing have been described in the literature by means of SpCas9 or FnCas12a endonucleases and their associated guide RNAs (gRNAs). The gRNAs used to guide the Cas endonuclease to the editing site are typically expressed from plasmids using native Pol II or Pol III RNA polymerases. These gRNA expression plasmids require laborious, time-consuming cloning steps, which hampers their implementation for academic and applied purposes. In this study, we explore the potential of expressing gRNA from linear DNA fragments using the T7 RNA polymerase (T7RNAP) for single and multiplex genome editing in Saccharomyces cerevisiae. Using FnCas12a, this work demonstrates that transforming short, linear DNA fragments encoding gRNAs in yeast strains expressing T7RNAP promotes highly efficient single and duplex DNA editing. These DNA fragments can be custom ordered, which makes this approach highly suitable for high-throughput strain construction. This work expands the CRISPR toolbox for large-scale strain construction programs in S. cerevisiae and promises to be relevant for other less genetically accessible yeast species.


Requirement for Crk and CrkL during postnatal lens development.
The Crk and CrkL adaptor proteins have SH2 and SH3 domains and play essential overlapping, as well as distinct, roles in many biological processes, ranging from cell structure and motility to proliferation. Conditional ablation of both Crk and CrkL in neuronal progenitor cells, using a Nestin-Cre transgene, resulted in severe defects in postnatal eye development, including progressive eye closure, lens rupture, and retinal malformation. These phenotypes were not observed in the presence of a single wild-type allele of either Crk or CrkL. We found that the lens in knockout mice started to rupture and disintegrate between postnatal days 7 and 12, although the structure of the retina was relatively well maintained. As the lens deteriorated further, the outer nuclear layer in the posterior of the retina enlarged and developed ruffles. Cre recombination occurred in the lens and retina of the knockout mice. Furthermore, the posterior lens capsule of the knockout mouse was thinner at postnatal days 0.5 and 3, suggesting that the defective lens capsule caused rupturing of the lens near the posterior pole. These results indicate that Crk and CrkL play essential overlapping roles in postnatal lens development.


Early infant diagnosis of HIV in Myanmar: call for innovative interventions to improve uptake and reduce turnaround time.
In collaboration with the national AIDS program, early infant diagnosis (EID) is implemented by Integrated HIV Care (IHC) program through its anti-retroviral therapy (ART) centers across 10 cities in five states and regions of Myanmar. Blood samples from the ART centers are sent using public transport to a centralized PCR facility. Among HIV-exposed babies <9 months at enrolment into IHC program (2013-15), to describe the EID cascade (enrolment, sample collection for PCR, result receipt by mother, HIV diagnosis and ART initiation) and factors associated with delayed (>8 weeks of age) or no blood sample collection for EID. Retrospective cohort study involving record review. A predictive poisson regression model with robust variance estimates was fitted for risk factors of delayed or no sample collection. Of 1349 babies, 523 (39%) of the babies' mothers were on ART before pregnancy. Timely uptake of EID (<8 weeks of age) was 47% (633/1349); sample collection was delayed in 27% (367/1349) and not done in 26% (349/1349) babies. Among samples collected (n = 1000), 667 results were received by the mother; 52 (5%) were HIV-infected; among them 42 (81%) were initiated on ART. Median (IQR) turnaround time from sample collection to result receipt by mother and time to initiate ART from result receipt by mother was 7 (4,12) and 8.5 (6,16) weeks, respectively. Mothers not on ART before pregnancy and distance of ART center from PCR facility (more than 128 km) were the risk factors of delayed or no sample collection. Improving provision of ART to mothers (through universal 'test and treat') is urgently required, which has the potential to improve the timely uptake of EID as well. Interventions to reduce turnaround times, like point of care EID testing and/or systematic use of mobile technology to communicate results, are needed.


Atmospheric chlorinated polyfluorinated ether sulfonate and ionic perfluoroalkyl acids in 2006 to 2014 in Dalian, China.
Chlorinated polyfluorinated ether sulfonate (Cl-PFESA; trade name F-53B) is an alternative product for perfluorooctane sulfonate (PFOS) used in metal plating; little is known about its levels in the environment and its risks. To our knowledge, the present study constitutes the first report of Cl-PFESA in the atmosphere. In 2006 to 2014, C8 Cl-PFESA, along with ionic perfluoroalkyl acids (PFAAs), was detected in atmospheric particulate matter in Dalian, China. Concentrations of C8 Cl-PFESA increased from 140 pg/m3 in 2007 to 722 pg/m3 in 2014. Levels of 11 (total) ionic PFAAs increased in 2006 to 2008 and decreased afterward, with a range of 35.7 to 860 pg/m3 . The PFAAs in the particulate matter were dominated by perfluorocarboxylates, with perfluorooctanoate detected at the highest concentration at a mean level of 71.7 pg/m3 , followed by perfluoroheptanoate and perfluorohexanoate. Perfluorosulfonates were detected at lower levels, with mean concentrations of PFOS, perfluorobutanesulfonate, and perfluorohexane sulfonate of 5.73, 1.64, and 1.24 pg/m3 , respectively. Back-trajectory analysis suggested that the air mass approaching Dalian during the sampling originated from the northwest, where fluorochemical industry parks and metal plating industries are densely located. No significant correlation was observed between Cl-PFESA and the ionic PFAAs. The relatively high Cl-PFESA concentrations suggested that it possibly contributed largely to the previously reported exposure to undefined organic fluorine compounds, for which further research on emission and environmental risks is needed. Environ Toxicol Chem 2017;36:2581-2586. © 2017 SETAC.


Nutrients and trace elements content of wood decay fungi isolated from oak (Quercus ilex).
The presence of chemical elements and the differences in their concentration in the fruiting bodies of wood decay fungi may reflect their activity either as saprobes or parasites and the intimate physiological relation with the substrate from which they extract their nutrients. In order to test this hypothesis, we carried out a systematic sampling of eight species of wood decay fungi on oak (Quercus ilex). The data show that the concentration of some elements exhibits a very wide range of values for the species tested, which could mean that the relative content of some elements may provide clues about the nature of the substrate and, moreover, about the nutritional physiology. The comparison between the foliar analysis (FA) and the elemental content of fungi may shed light on the specific physiological behaviour of the species. Potassium is an element accumulated in fungal biomass in higher quantities than in the FA. By contrast, calcium appears in foliar analysis in much higher quantities than in fungal fruiting bodies' biomass. Concerning this element, we have also found profound differences between the two species phylogenetic groups and lifestyle. Of all elements measured, we believe that the relative accumulation of K and Ca may be related to the close connection between fungi and the substrate on which they live and may also explain their physiological role as saprobes or parasites. When the lifestyle and the systematic position of the different species sampled were compared, differences also emerged in the content of Na and Ca.


Mass spectrometric analysis of digesta does not improve the allergenicity assessment of GM crops.
An investigation of the potential allergenicity of newly expressed proteins in genetically modified (GM) crops comprises part of the assessment of GM crop safety. However, allergenicity is not completely predictable from a definitive assay result or set of protein characteristics, and scientific opinions regarding the data that should be used to assess allergenicity are continuously evolving. Early studies supported a correlation between the stability of a protein exposed to digestive enzymes such as pepsin and the protein's status as a potential allergen, but over time the conclusions of these earlier studies were not confirmed. Nonetheless, many regulatory authorities, including the European Food Safety Authority (EFSA), continue to require digestibility analyses as a component of GM crop risk assessments. Moreover, EFSA has recently investigated the use of mass spectrometry (MS), to make digestion assays more predictive of allergy risk, because it can detect and identify small undigested peptides. However, the utility of MS is questionable in this context, since known allergenic peptides are unlikely to exist in protein candidates intended for commercial development. These protein candidates are pre-screened by the same bioinformatics processes that are normally used to identify MS targets. Therefore, MS is not a standalone allergen identification method and also cannot be used to predict previously unknown allergenic epitopes. Thus, the suggested application of MS for analysis of digesta does not improve the poor predictive power of digestion assays in identifying allergenic risk.


Impact of Increased End-Tidal Carbon Dioxide on Continuous Noninvasive Hemoglobin Monitoring during Laparoscopic Gastrectomy: A Randomized Controlled Study.
The pulse CO-Oximetry allows continuous, noninvasive monitoring of hemoglobin (SpHb). We assessed the impact of increased end-tidal carbon dioxide (EtCO2) on the accuracy and trending ability of SpHb in laparoscopic surgery. Participants (n = 64) were randomly allocated to the low carbon dioxide (CO2) group (EtCO2: 30-35 mmHg) or the high CO2 group (EtCO2: 40-45 mmHg). The SpHb and laboratory hemoglobin (tHb) were obtained during surgery. The correlation coefficient (r) between SpHb and tHb showed greater tendency in the low CO2 group (r = 0.68) than in the high CO2 group (r = 0.43). The bias (precision) was -1.18 (1.09) with a limit of agreement (LOA) of -3.31 to 0.95 in low CO2 group and -1.02 (1.24) with a LOA of -3.45 to 1.42 in high CO2 group; they did not differ significantly between the groups (p = 0.246). The low CO2 group showed a high concordance rate of 95.9% and a moderate correlation between ΔSpHb and ΔtHb (r = 0.53). However, the high CO2 group showed a concordance rate of 77.8% and no correlation between ΔSpHb and ΔtHb (r = 0.11). In conclusion, increased EtCO2 significantly reduced the trending ability of SpHb during laparoscopic surgery. Caution should be executed when interpreting SpHb values during laparoscopic surgery in patients with hypercapnia.


Protect European green agricultural policies for future food security.
European green agricultural policies have been relaxed to allow cultivation of fallow land to produce animal feed and meet shortfalls in exports from Ukraine and Russia. However, conversion of semi-natural habitats will disproportionately impact long term biodiversity and food security.


The critical role of caspases activation in hypoxia/reoxygenation induced apoptosis.
Hypoxia/reoxygenation insult can be found in many tissues, including heart, brain, and tumor. It is believed that cell death may be resulted after cells were subjected to chronic hypoxia or reoxygenation after chronic hypoxia. The molecular mechanism for reoxygenation induced cell death is so far not clear and will require further study, in particular, to be distinguished from the pathways associated only with chronic hypoxia. In this study, the cell death mechanism in human squamous carcinoma A431 cells after hypoxia/reoxygenation insult is examined. It is demonstrated that although caspase-9 and -3 were activated during both hypoxia and reoxygenation, only those caspases activated during reoxygenation were responsible for reoxygenation induced apoptosis. Activation of caspase-9 and -3 during reoxygenation is believed to be triggered by the ROS formation at the time of reoxygenation. Addition of catalase during reoxygenation was found to attenuate reoxygenation induced apoptosis and caspase activation.


The role of forest type in the variability of DOC in atmospheric deposition at forest plots in Italy.
Dissolved organic carbon (DOC) was studied in atmospheric deposition samples collected on a weekly basis in 2005-2009 at 10 forest plots in Italy. The plots covered a wide range of geographical attributes and were representative of the main forest types in Italy. Both spatial and temporal variations in DOC concentrations and fluxes are discussed, with the aim of identifying the main factors affecting DOC variability. DOC concentration increased from bulk to throughfall and stemflow water samples at all sites, as an effect of leaching from leaves and branches, going from 0.7-1.7 mg C L(-1) in bulk samples to 1.8-15.8 mg C L(-1) in throughfall and 4.2-10.7 mg C L(-1) in stemflow, with striking differences among the various plots. Low concentrations were found in runoff (0.5-2.0 mg C L(-1)), showing that the export of DOC via running waters was limited. The seasonality of DOC in throughfall samples was evident, with the highest concentration in summer when biological activity is at a maximum, and minima in winter due to limited DOC production and leaching. Statistical analysis revealed that DOC had a close relationship with organic and total nitrogen, and with nutrient ions, and a negative correlation with precipitation amount. Forest type proved to be a major factor affecting DOC variability: concentration and, to a lesser extent, fluxes were lower in stands dominated by deciduous species. The character of evergreens, and the size and shape of their leaves and needles, which regulate the interception mechanism of dry deposition, are mainly responsible for this.


Performance-based hospital contracting for quality improvement.
A carefully negotiated process that ties improvements in performance to additional compensation can align incentives and support efforts to improve care. Such a process needs to be objective, data-driven, and focused on issues that are important both to the purchaser and to the provider.


The Conceptualization of Everyday Racism in Research on the Mental and Physical Health of Ethnic and Racial Groups: a Systematic Review.
Research on the influence of everyday racism and discrimination on the mental and physical health of ethnic and racial groups is on the rise. Scholars use self-reported experiences of racism and discrimination scales to study the relationship between everyday racism/discrimination and health. Throughout the years, these scales have been tested for psychometric measures, validity, and reliability of the items. However, less attention is paid to how the concept of everyday racism and discrimination is defined in the first place. Based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic review perusing 106 papers is conducted of studies investigating the relationship of everyday racism/discrimination and the physical and mental health of ethnic and/or racial groups. This review allows to synthesize how everyday racism is conceptualized, interpreted, and operationalized. A meta-analysis was not possible due to the heterogeneity in research designs, methodologies, and populations. Following the original conceptualization of everyday racism, results indicate that research pays attention to the repeatability of everyday racism. However, racism was only defined in 7% of the papers and in different ways varying from individual to institutional racism. In 86% of the papers did they measure everyday racism/discrimination through the Everyday Discrimination Scale. This influenced the way in which everyday discrimination was defined taking on a more individual perspective paying less attention to the micro-macro link of everyday racism.


A fluorescent metal-organic framework for highly selective detection of nitro explosives in the aqueous phase.
Selective and sensitive nitro explosive detection by a porous luminescent metal-organic framework has been reported. For the first time MOF based selective explosive detection in the presence of other nitro analytes in aqueous media is demonstrated.


Attribute nonattendance in COVID-19 vaccine choice: A discrete choice experiment based on Chinese public preference.
The global coronavirus disease 2019 (COVID-19) pandemic has not been well controlled, and vaccination could be an effective way to prevent this pandemic. By accommodating attribute nonattendance (ANA) in a discrete choice experiment (DCE), this paper aimed to examine Chinese public preferences and willingness to pay (WTP) for COVID-19 vaccine attributes, especially the influence of ANA on the estimated results. A DCE was designed with four attributes: effectiveness, protection period, adverse reactions and price. A random parameter logit model with an error component (RPL-EC) was used to analyse the heterogeneity of respondents' preferences for COVID-19 vaccine attributes. Two equality constraint latent class (ECLC) models were used to consider the influence of ANA on the estimated results in which the ECLC-homogeneity model considered only ANA and the ECLC-heterogeneity model considered both ANA and preference heterogeneity. Data from 1,576 samples were included in the analyses. Effectiveness had the highest relative importance, followed by adverse reactions and protection period, which were determined by the attributes and levels presented in this study. The ECLC-heterogeneity model improved the goodness of fit of the model and obtained a lower probability of ANA. In the ECLC-heterogeneity model, only a small number of respondents (29.09%) considered all attributes, and price was the most easily ignored attribute (64.23%). Compared with the RPL-EC model, the ECLC-homogeneity model obtained lower WTPs for COVID-19 vaccine attributes, and the ECLC-heterogeneity model obtained mixed WTP results. In the ECLC-heterogeneity model, preference group 1 obtained higher WTPs, and preference groups 2 and 3 obtained lower WTPs. The RPL-EC, ECLC-homogeneity and ECLC-heterogeneity models obtained inconsistent WTPs for COVID-19 vaccine attributes. The study found that the results of the ECLC-heterogeneity model considering both ANA and preference heterogeneity may be more plausible because ANA and low preference may be confused in the ECLC-homogeneity model and the RPL-EC model. The results showed that the probability of ANA was still high in the ECLC-heterogeneity model, although it was lower than that in the ECLC-homogeneity model. Therefore, in future research on DCE (such as the field of vaccines), ANA should be considered as an essential issue. Chinese adults from 31 provinces in mainland China participated in the study. All participants completed the COVID-19 vaccine choice questions generated through the DCE design.


Azorean wild rabbits as reservoirs of antimicrobial resistant Escherichia coli.
Antibiotic resistance in bacteria is an increasing problem that is not only constrained to the clinical setting but also to other environments that can lodge antibiotic resistant bacteria and therefore they may serve as reservoirs of genetic determinants of antibiotic resistance. One hundred and thirty-six faecal samples from European wild rabbits (Oryctolagus cuniculus algirus) were collected on São Jorge Island in Azores Archipelago, and analysed for Escherichia coli isolates. Seventy-seven isolates (56.6%) were recovered and studied for antimicrobial resistance, one isolate per positive sample. Thirteen (16.9%), 19 (24.7%), 25 (32.4%) and 20 (26%) isolates were ascribed to A, B1, B2 and D phylogenetic groups, respectively, by specific primer polymerase chain reaction. Different E. coli isolates were found to be resistant to ampicillin (16.9%), tetracycline (1.3%), streptomycin (42.9%), sulfamethoxazole-trimethoprim (1.3%), amikacin (1.3%), tobramycin (2.6%) and nalidixic acid (1.3%). Additionally, the blaTEM, tetA, strA/strB, aadA, sul1, intI, intI2 and qacEΔ+sul1 genes were found in most resistant isolates. This study showed that E. coli from the intestinal tract of wild rabbits from Azores Archipelago are resistant to widely prescribed antibiotics in medicine and they constitute a reservoir of antimicrobial resistant genes, which may play a significant role in the spread of antimicrobial resistance. Therefore, antibiotic resistant E. coli from Azorean wild rabbits may represent an ecological and public health problem.


MALDI-TOF-MS analysis in low molecular weight serum peptidome biomarkers for NSCLC.
Lung cancer is one of the leading causes of death from cancer in the world. Screening new serum biomarkers is important for the early detection of lung cancer. The purpose of this study was to investigate the serum peptide model between non-small cell lung cancer (NSCLC) patients and healthy controls, as well as between paired pre- and postoperative NSCLC patients, and to find the low molecular weight (LMW) potential tumor markers for NSCLC. 56 serum samples from NSCLC patients, 56 controls, and 20 matched pre- and postoperative patients were analyzed using magnetic-bead (MB)-based purification technique combined with MALDI-TOF-MS. To distinguish NSCLC from cancer-free controls, three models were established. Finally, comparing the three groups of serum protein fingerprints, nano-liquid chromatography-electrospray ionization tandem mass spectrometry was used to further identify the differential peptides. Among the three models constructed, the GA model had the best diagnostic efficacy. Five differential peaks were screened by combining the case group, healthy controls, and postoperative group analysis, which were up-regulated in the case group and showed a tendency to return to healthy control values after surgery. The protein matching the mass spectrometry peak m/z 2953.73 was identified as fibrinogen α chain. This study shows that the application of MALDI-TOF-MS is a promising approach for the identification of potential serum biomarkers for NSCLC, which is potentially valuable for establishing a new diagnostic method for lung cancer. In addition, we found that fibrinogen α chain may be an auxiliary diagnostic indicator for NSCLC.


Ultrastructural observations of host-cell invasion by sporozoites of Eimeria papillata in vivo.
Scanning and transmission electron microscopy were used to study the invasion of mouse small-intestinal epithelium by sporozoites of Eimeria papillata. Some mice received oocysts by gavage and others received either sporocysts or sporozoites by direct injection into the small intestine. The highest concentration of invaded cells were found in ligated intestinal tissues studied at 5-45 min after the inoculation of sporozoites. Sporozoites actively invaded anterior end first, which resulted in extensive damage to the host cell. Such cells showed disrupted microvilli; protuberances of cytoplasm into the lumen, apparently the result of a disrupted plasma membrane; vacuolization of the cytoplasm; and damage to the mitochondria. These damaged cells were rapidly vacated as the sporozoite moved laterally into one or more adjacent intact host cells without entering the lumen. It is suggested that the host cell initially entered from the lumen becomes so severely traumatized that the parasite of necessity enters an adjacent cell as a prelude to further development. Various aspects of host-cell invasion by coccidia and malarial parasites are reviewed.


Acute ingestion of different dietary fatty acid species modulates postprandial lipid responses in New Zealand white rabbits.
Although several investigations have linked the degree of fatty acid saturation to plasma lipid responses in the postprandial state, further evaluation is necessary. In this study, we compared the effect of saturated (SFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acids on postprandial lipid metabolism using complementary in vivo and in vitro approaches. Fat (10 g) cholesterol (0.5 g) test meals that provided either lard (SFA), olive oil (MUFA), or sunflower oil (PUFA) were ingested by chow-fed New Zealand white rabbits (n = 8). In addition, hepatic uptake of triglyceride-cholesterol-rich lipoproteins (TCRL) isolated from rabbits chronically ingesting SFA, MUFA, or PUFA diets was measured using freshly isolated chow-fed rabbit hepatocytes. Whatever dietary fatty acids ingested, postprandial triglyceridemia and occurrence of radiolabelled dietary lipids in plasma were not markedly different. Conversely, SFA induced higher postprandial cholesterolemia and phospholipemia than MUFA (P < 0.05) whereas PUFA prevented postprandial cholesterol increase. TCRL disappearance from cultured liver cell media was delayed with SFA-rich TCRL and faster with PUFA whereas MUFA-rich TCRL showed an intermediate figure. From these data, we conclude that SFA, MUFA, and PUFA elicited different postprandial plasma and lipoprotein lipid responses. The fatty acid composition of TCRL had a major impact on their subsequent metabolism, especially uptake by cultured hepatocytes. The SFA-induced hypercholesterolemia could be related to an altered hepatic uptake whereas a faster clearance and hepatic uptake could explain the cholesterol-lowering effect of PUFA in rabbits. MUFA, like PUFA, accelerate uptake by hepatocytes but favor cholesterol ester enrichment of TCRL.


Echo patterns of benign cystic teratomas by transvaginal ultrasound.
The transvaginal ultrasound echo patterns of 39 surgically proven cystic teratomas were retrospectively reviewed. Six different ultrasound echo patterns could be differentiated, ranging from purely cystic to densely echogenic. Importantly, in 82% of the tumors, areas of dense echogenicity were noted. Although the transvaginal appearance of cystic teratomas may allow correct preoperative prediction, the variable nature of the echo patterns makes differentiation from malignant tumors difficult.


Camera-computer systems for rapid dynamic imaging studies.
The extraction of valuable diagnostic information from rapid, dynamic studies performed on a gamma camera requires that the data be recorded for latter analysis. If these data are to be available rapidly and if quantitative analysis is to be performed, it is imperative that a computer be used in conjuction with the gamma camera. This review describes the more important features of a nuclear medicine computer system both from the point of view of hardware and software. The various aspects that cause some limitations to be imposed on the capability of the system in order to carry out fast, dynamic studies are described and some possible solutions are suggested.


Action spectra for photoinduced inactivation of bacteriophage T7 sensitized by 8-methoxypsoralen and angelicin.
The action spectrum (240-300 nm) for photoinactivation of unsensitized phage T7 and the action spectra (310-380 nm) for photoinactivation of phage T7 sensitized with 8-methoxypsoralen (8-MOP) and angelicin were measured by an automated method. For unsensitized phage T7 the action spectrum is in good agreement with the absorption spectrum. For sensitization with angelicin the action spectrum is similar to the absorption spectrum, but for sensitization with 8-MOP the spectra are different. The agreement between the T7 absorption and action spectra in the far-UV region is due to photodamage of DNA, leading to phage inactivation. The similarity in the action and absorption spectra in the near-UV region for sensitization with angelicin seems to be in accordance with the monofunctional photobinding of angelicin to DNA. The action spectrum for sensitization with 8-MOP has a maximum at about 320 nm and this suggests that, in addition to the monoadducts, the biadducts play a role in the inactivation of phage T7. Taking the number of bound furocoumarin molecules into consideration, the quantum efficiencies were estimated. Furocoumarin increases the quantum efficiency in the near-UV region and the values are similar to those obtained in far-UV light without psoralens.