Eye-tracking IQ: Cognitive capacity and strategy use on a ratio-bias task.
This study tested the relationship between strategy use (assessed by eye-gaze patterns), cognitive ability (CA), and reasoning performance on a ratio-bias task. For the ratio-bias problems, participants (N = 125) chose which of two ratios was larger; each ratio was represented both as a fraction and as a picture. Problems were solved in two blocks: once under a deadline (Time1) and once in free time (Time2). Consistent with the assumption of dual process theories that CA is needed to overturn a pre-potent, initial response (Evans & Stanovich, 2013), CA was positively associated with correct performance at Time2, as well as the increase in performance from Time1 to Time2. However, strategy use predicted performance independently of CA at Time2, and accounted for the relationship between CA and improvement between Time1 and Time2: reasoners who attended to the fractions rather than to the misleading pictures performed better, regardless of CA. CA also predicted performance at Time1. Together, these findings suggest that the robust relationship between CA and reasoning (Stanovich, 1999) may arise because 1) high capacity reasoners are more likely to "intuit" the initial answer and 2) because CA is correlated with good strategy use, which, in turn, predicts performance.


The influence of clinical variables on patients' satisfaction with complete dentures.
The effect of the technical quality of complete dentures and the physical condition of the mouth on patients' satisfaction was investigated in 130 patients who received new complete dentures. A moderately positive correlation was found between satisfaction of the patient and quality of the dentures. However, no correlation was found between the satisfaction of the patient and the physical condition of the mouth.


Difficulties in psychosocial functioning due to current depressive symptoms: What can C-Reactive protein tell us?
Multiple empirical studies and meta-analyses have examined how inflammation may be associated with various aspects of major depression, with older adults being particularly at risk for the effects of inflammation-related depression. Despite this wide area of research, no study has examined how depression-related inflammation impacts psychosocial functioning. Data from the National Health and Nutrition Examination Survey, years 2007-2008, were utilized to examine whether adults over the age of 40 experienced difficulty in their work, taking care of things at home, or getting along with other people due to current depressive symptoms through a logistic regression analysis. We selected C-reactive protein (CRP), a common marker of immune system activation, as our primary predictor of interest while controlling for relevant covariates. Greater CRP was positively associated with a greater risk for individuals experiencing difficulties in psychosocial functioning due to depressive symptoms. While current number and severity of depressive symptoms was also found to be significant in the model, comparison of effect sizes identified that CRP appears to be a more relevant marker for experiencing difficulty than a number of relevant biopsychosocial covariates. Inflammation as measured by CRP may be a helpful tool in understanding how depressive symptoms are associated with an individual's ability to successfully navigate their social environment. Results here demonstrate the emerging utility of CRP in helping to assess the risk for negative outcomes in those experiencing depressive symptoms, especially as it pertains to older adults.


TMEM70 and TMEM242 help to assemble the rotor ring of human ATP synthase and interact with assembly factors for complex I.
Human mitochondrial ATP synthase is a molecular machine with a rotary action bound in the inner organellar membranes. Turning of the rotor, driven by a proton motive force, provides energy to make ATP from ADP and phosphate. Among the 29 component proteins of 18 kinds, ATP6 and ATP8 are mitochondrial gene products, and the rest are nuclear gene products that are imported into the organelle. The ATP synthase is assembled from them via intermediate modules representing the main structural elements of the enzyme. One such module is the c8-ring, which provides the membrane sector of the enzyme's rotor, and its assembly is influenced by another transmembrane (TMEM) protein, TMEM70. We have shown that subunit c interacts with TMEM70 and another hitherto unidentified mitochondrial transmembrane protein, TMEM242. Deletion of TMEM242, similar to deletion of TMEM70, affects but does not completely eliminate the assembly of ATP synthase, and to a lesser degree the assembly of respiratory enzyme complexes I, III, and IV. Deletion of TMEM70 and TMEM242 together prevents assembly of ATP synthase and the impact on complex I is enhanced. Removal of TMEM242, but not of TMEM70, also affects the introduction of subunits ATP6, ATP8, j, and k into the enzyme. TMEM70 and TMEM242 interact with the mitochondrial complex I assembly (the MCIA) complex that supports assembly of the membrane arm of complex I. The interactions of TMEM70 and TMEM242 with MCIA could be part of either the assembly of ATP synthase and complex I or the regulation of their levels.


Developing and Validating Tests of Reading and Listening Comprehension for Fifth and Sixth Grade Students in Portugal.
An efficient assessment of reading and linguistic abilities in school children requires reliable and valid measures. Moreover, measures which include specific test forms for different academic grade levels, that are vertically equated, allow the direct comparison of results across multiple time points and avoid floor and ceiling effects. Two studies were conducted to achieve these goals. The purpose of the first study was to develop tests of reading and listening comprehension in European Portuguese, with vertically scaled test forms for students in the fifth and sixth grades, using Rasch model analyses. The purpose of the second study was to collect evidence for the validity of these tests based on the relationships of test scores with other variables. The samples included 454 and 179 students for the first and second study, respectively. The data from both studies provided evidence for good psychometric characteristics for the test forms: unidimensionality and local independence, as well as adequate reliability and evidence of validity. The developed test forms are an important contribution in the Portuguese educational context as they allow for the assessment of students' performance in these skills across multiple time points and can be used both in research and practice.


Relationship between renal function and blood pressure dipping status in renal transplant recipients: a longitudinal study.
Hypertension (HT) is associated with adverse outcomes in kidney transplant (KTX) recipients. Blunting of physiological decrease in nighttime compared to daytime blood pressure (non-dipping status) is frequent in this setting. However, weather non-dipping is independently associated with renal function decline in KTX patients is unknown. We retrospectively screened KTX outpatients attending for a routine ambulatory blood pressure monitoring (ABPM) (T1) at a single tertiary hospital. Patients had two successive follow-up visits, 1 (T2) and 2 (T3) years later respectively. Routine clinical and laboratory data were collected at each visit. Mixed linear regression models were used with estimated glomerular filtration rate (eGFR) as the dependent variable. A total of 123 patients were included with a mean follow-up of 2.12 ± 0.45 years after ABPM. Mean age and eGFR at T1 were 56.0 ± 15.1 and 54.9 ± 20.0 mL/min/1.73m2 respectively. 61 patients (50.4%) had sustained HT and 81 (65.8%) were non-dippers. In multivariate analysis, systolic dipping status was positively associated with eGFR (p = 0.009) and compared to non-dippers, dippers had a 10.4 mL/min/1.73m2 higher eGFR. HT was negatively associated with eGFR (p = 0.003). We confirm a high prevalence of non-dippers in KTX recipients. We suggest that preserved systolic dipping is associated with improved renal function in this setting independently of potential confounders, including HT and proteinuria. Whether modification of dipping status by chronotherapy would preserve renal function remains to be tested in clinical trials.


Quantitative Differentiation of Left Atrial Performance in Hypertrophic Cardiomyopathy: Comparison Between Nonobstruction and Occult Obstruction With 4-dimensional Volume-strain.
The objective of this study was to describe the different components of left atrial (LA) dysfunction predictors in nonobstructive and occult obstructive hypertrophy cardiomyopathy (HCM) patients especially with preserved left ventricular (LV) ejection fraction, particularly using LA 4-dimensional (D) longitudinal and circumferential strains. Twenty-eight nonobstructive HCM patients and 30 occult obstructive HCM patients according to LV outflow tract gradient at rest and after exercise were prospectively enrolled. 4D echocardiographic evaluation was performed in 58 HCM patients, both nonobstructive and occult obstructive, and 38 control subjects. LA reservoir, conduit, contractile functions were performed by 4D volume-strain with volumes and longitudinal, circumferential strains. Optimal correlation coefficients obtained between LV 4D mass (index) and LA 4D longitudinal/circumferential strain (r=-0.860 to 0.518, all P<0.001). Both nonobstructive and occult obstructive HCM patients had increased volumes and significantly decreased longitudinal, circumferential strain values with lower reservoir, conduit, contractile functions than the controls (all P<0.001). Occult obstructive HCM patients presented incremented volumes compared with nonobstructive ones (P<0.001 to 0.003). Lower conduit function and higher contractile function indicated with lower reservoir function revealed by circumferential strain in occult obstructive HCM patients than nonobstructive ones (P<0.001 to 0.017). Interclass correlation coefficients of intraobserver and interobserver in the LV and LA 4D value evaluations were >0.75 and >0.85, respectively. LA volumes were significantly increased and LA reservoir, conduit, and contractile functions were significantly impaired in HCM patients. Furthermore, different performances of LA functional analyses in nonobstruction and occult obstruction patients with 4D volume-strain echocardiography may facilitate the recognition of subtle LA dysfunctional differentiation in HCM patients.


Vocational analysis of health care professions as a basis for innovative curricular planning. An analysis and prognosis of the development of the professional competencies of midwives--cornerstones of innovative curricula in tertiary education.
This article describes current and future tendencies in the development of curriculum planning for health care professions in Germany, using the example of midwifery education. In particular, it discusses 'output-based control' of curriculum planning giving consideration to issues related to German education, health policies and professional educational theories with a view to the general international development. The results of this analysis constitute the starting point for the conceptual planning of a dissertation at the medical faculty of the Berlin Charité with the goal of developing a competency model for the curriculum planning of midwifery education, thus creating a modern curriculum as a basis for a fundamental reform of German midwifery education.


[Action of benzohydrothiochromylium salts on bacterial membranes].
Cultivation of Staphylococcus 209-P and Micrococcus lysodeikticus cells on media containing new antibacterial preparations--iodide and trifluoroacetate derivatives of benzohydrothiochromylium resulted in a remarkable lesion of the membrane respiratory apparatus, i.e. the amounts of membrane polypeptides, the specific concentration of cytochromes, the activities of reductases and oxidases--NADH, malate and lactate decreased. Profound changes in the cell cytology were observed.


The isolated major homology region of the HIV capsid protein is mainly unfolded in solution and binds to the intact protein.
Assembly of the mature human immunodeficiency virus type 1 (HIV-1) capsid involves the oligomerization of the capsid protein, CA. During retroviral maturation, the CA protein undergoes structural changes and forms exclusive intermolecular interfaces in the mature capsid shell, different from those in the immature precursor. The most conserved region of CA, the major homology region (MHR), is located in the C-terminal domain of CA (CTD). The MHR is involved in both immature and mature virus assembly; however, its exact function during both assembly stages is unknown. To test its conformational preferences and to provide clues on its role during CA assembly, we have used a minimalist approach by designing a peptide comprising the whole MHR (MHRpep, residues Asp152 to Ala174). Isolated MHRpep is mainly unfolded in aqueous solution, with residual structure at its C terminus. MHRpep binds to monomeric CTD with an affinity of ~30μM (as shown by fluorescence and ITC); the CTD binding region comprises residues belonging to α-helices 10 and 11. In the immature virus capsid, the MHR and α-helix 11 regions of two CTD dimers also interact [Briggs JAG, Riches JD, Glass B, Baratonova V, Zanetti G and Kräusslich H-G (2009) Proc. Natl. Acad. Sci. USA 106, 11090-11095]. These results can be considered a proof-of-concept that the conformational preferences and binding features of isolated peptides derived from virus proteins could be used to mimic early stages of virus assembly.


"Spice"-related deaths in and around Munich, Germany: A retrospective look at the role of synthetic cannabinoid receptor agonists in our post-mortem cases over a seven-year period (2014-2020).
Synthetic cannabinoid receptor agonists (SCRAs, "Spice") are a diverse group of recreational drugs, with their structural and pharmacological variability still evolving. Forensic toxicologists often rely on previous reports to assess their role in intoxication cases. This work provides detailed information on the "Spice"-related fatalities around Munich, Germany, from 2014 to 2020. All cases underwent an autopsy. Pharmaceutical and illicit drugs were detected and quantified in post-mortem peripheral blood or liver by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Based on circumstantial evidence, only those cases for which a prior consumption was suspected underwent additional analyses for SCRAs and other new psychoactive substances in post-mortem blood, liver or antemortem specimens. Drug concentrations, pathological findings at autopsy and case histories were considered to assess and rank the SCRAs' involvement in each death. Concentration ranges for the individual substances in blood were defined and their distribution patterns over the investigated period were determined and correlated with their legal status and local police seizures. We identified 41 different SCRAs among 98 fatalities. 91.8% were male, at a median age of 36 years. SCRAs played a causative role in 51%, contributory role in 26%, and an insignificant role in 23% of cases. In correlation with local police seizures and legal status, 5F-ADB was the most prevalent in our cases, followed by 5F-MDMB-PICA and AB-CHMINACA. Cumyl-CBMICA and 5F-MDMB-P7AICA were among the least frequently detected SCRAs. "Spice"-related fatalities and SCRAs' causative role have significantly decreased among our cases since the German New Psychoactive Substances Act.


Influence of competition and intraguild predation between two candidate biocontrol parasitoids on their potential impact against Harrisia cactus mealybug, Hypogeococcus sp. (Hemiptera: Pseudococcidae).
When two or more parasitoid species, particularly candidates for biocontrol, share the same target in the same temporal window, a complex of behaviors can occur among them. We studied the type of interactions (competition and intraguild predation) that existed between the nymphal parasitoids Anagyrus cachamai and A. lapachosus (Hymenoptera: Encyrtidae), two candidate neoclassical biocontrol agents against the Puerto Rican cactus pest mealybug, Hypogeococcus sp. (Hemiptera: Pseudococcidae). The surrogate native congener host in Argentina, the cactus mealybug Hypogeococcus sp., was studied to predict which species should be released; in the case that both should be released, in which order, and their potential impact on host suppression. In the laboratory we conducted experiments where different densities of the host mealybug were exposed to naive females of A. cachamai and A. lapachosus sequentially in both directions. Experiments were analyzed by combining a series of competitive behavioral and functional response models. A fully Bayesian approach was used to select the best explaining models and calculate their parameters. Intraguild predation existed between A. cachamai, the species that had the greatest ability to exploit the resource, and A. lapachosus, the strongest species in the interference competition. The role that intraguild predation played in suppression of Hypogeococcus sp. indicated that a multiple release strategy for the two biocontrol agents would produce better control than a single release; as for the release order, A. lapachosus should be released first.


Silicon Naphthalocyanine Tetraimides: Cathode Interlayer Materials for Highly Efficient Organic Solar Cells.
Naphthalocyanine derivatives (SiNcTI-N and SiNcTI-Br) were firstly used as excellent cathode interlayer materials (CIMs) in organic solar cells, via introducing four electron-withdrawing imide groups and two hydrophilic alkyls. Both of them showed deep LUMO energy levels (below -3.90 eV), good thermal stability (Td >210 °C), and strong self-doping property. The SiNcTI-Br CIM displayed high conductivity (4.5×10-5 S cm-1 ) and electron mobility (7.81×10-5 cm2 V-1 s-1 ), which could boost the efficiencies of the PM6:Y6-based OSCs over a wide range of CIM layer thicknesses (4-25 nm), with maximum efficiency of 16.71 %.


Neuroblastoma.
Neuroblastoma is the most common solid malignant tumor in children. The prognosis is poor, and despite varying chemotherapy and radiation regimens, its status has not been altered much in the past 20 years. Seventy per cent of the patients have abdominal neuroblastomas, which carry the worst prognosis of all the possible sites for the disease. Seventy per cent of the patients have metastases at the time of diagnosis. Survival is best in children under one year of age and in those patients (8 per cent) who are fortunate enough to have only stage I disease. Stage IV disease has only a 3 per cent survival rate. Surgical removal of the tumor is still the primary therapy; irradiation is of significant benefit in patients with stage III disease. Immunotherapy offers an optimistic modality for future improvement in survival rates.


Methods of Monitoring Internal and External Loads and Their Relationships with Physical Qualities, Injury, or Illness in Adolescent Athletes: A Systematic Review and Best-Evidence Synthesis.
With the increasing professionalisation of youth sports, training load monitoring is increasingly common in adolescent athletes. However, the research examining the relationship between training load and changes in physical qualities, injury, or illness in adolescent athletes is yet to be synthesised in a systematic review. The aim of this review was to systematically examine the research assessing internal and external methods of monitoring training load and physical qualities, injury, or illness in adolescent athletes. Systematic searches of SPORTDiscus, Web of Science, CINAHL and SCOPUS were undertaken from the earliest possible records to March 2022. Search terms included synonyms relevant to adolescents, athletes, physical qualities, injury, or illness. To be eligible for inclusion, articles were required to (1) be original research articles; (2) be published in a peer-reviewed journal; (3) include participants aged between 10 and 19 years and participating in competitive sport; (4) report a statistical relationship between a measure of internal and/or external load and physical qualities, injury or illness. Articles were screened and assessed for methodological quality. A best-evidence synthesis was conducted to identify trends in the relationships reported. The electronic search yielded 4125 articles. Following screening and a review of references, 59 articles were included. The most commonly reported load monitoring tools were session ratings of perceived exertion (n = 29) and training duration (n = 22). Results of the best-evidence synthesis identified moderate evidence of positive relationships between resistance training volume load and improvement in strength, and between throw count and injury. However, evidence for other relationships between training load and change in physical qualities, injury, or illness were limited or inconsistent. Practitioners should consider monitoring resistance training volume load for strength training. Additionally, where appropriate, monitoring throw counts may be useful in identifying injury risk. However, given the lack of clear relationships between singular measures of training load with physical qualities, injury, or illness, researchers should consider multivariate methods of analysing training load, as well as factors that may mediate the load-response relationship, such as maturation.


Utility of a modified vascular corrosion casting technique in the diagnosis of fetal total anomalous pulmonary venous connection.
Total anomalous pulmonary venous connection (TAPVC) is a rare congenital cardiac malformation, and prenatal detection of TAPVC malformation remains a challenging. TAPVC can be easily missed or misdiagnosed in prenatal examinations. This study was aimed to use the modified vascular corrosion casting technique to prepare fetal cardiovascular casts with TAPVC and investigate the utility of cardiovascular casting for the demonstration of fetal TAPVC. The retrospective study enrolled twenty fetuses (22 to 29 + 4 gestational weeks) with TAPVC diagnosed by prenatal echocardiography and casting technique from May 2015 to May 2020. Pre- and postnatal medical records, including results obtained by prenatal ultrasound, postpartum computed tomography angiography, as well as anatomic and cardiovascular casting findings were carefully reviewed and analyzed. In twenty cases, 80% (16/20) had intra- or extracardiac malformations. The TAPVC types were supracardiac (n = 8), cardiac (n = 6), infracardiac (n = 4), and mixed (n = 2). The diagnosis of 1 case each of supracardiac and cardiac TAPVC was modified to partial anomalous pulmonary venous connection; additionally, 4 malformations were missed and 2 were misdiagnosed, including an anomalous left brachiocephalic vein in supracardiac TAPVC, abnormal inflow of the hepatic vein and a double inferior vena cava in infracardiac TAPVC; and bilateral ductus arteriosus in infracardiac TAPVC; a tetralogy of Fallot in cardiac TAPVC that was corrected to right ventricular double outlet; and an absence of ductus arteriosus that was misdiagnosed as slim ductus arteriosus. Comparing with ultrasound, casting technique has its own superiority in exhibiting TAPVC abnormalities, especially in certain types such as course, origin and absence abnormalities of ductus. Postpartum cardiovascular casts can accurately depict the branch structure of the heart's larger vessels, and may be used as a clinical assessment and teaching method in complex cardiac malformations.


Abdominal muscle activity during abdominal hollowing in four starting positions.
The aim of this study was to investigate the activity of the rectus abdominis (RA), external abdominal oblique (EO), and transversus abdominis/internal abdominal oblique (TrA/IO) muscles during abdominal hollowing (AH) in four positions: crook lying, prone lying, four-point kneeling, and wall support standing. Thirty-two healthy participants, aged 21.3+/-0.8 years were recruited. They were instructed to perform maximal voluntary contraction (MVC) and AH. The electromyography (EMG) data of each muscle during AH were normalized as a percentage of MVC. During AH in all four starting positions, significant differences were found in the EMG activity of RA, EO, and TrA/IO (p<0.001). The TrA/IO exhibited the highest while the RA exhibited the lowest EMG activity. Among the four different starting positions, only the TrA/IO showed significant difference in mean EMG activity (p<0.001). The results suggest that all four starting positions can facilitate TrA/IO activity with minimal activity from RA and EO.


Synthesis in Vibrio cholerae and secretion of hepatitis B virus antigens fused to Escherichia coli heat-labile enterotoxin subunit B.
A simple and effective electroporation method for the transformation of Vibrio cholerae with nonmobilizable plasmids is described. Expression plasmids directing the synthesis of fusion proteins with the subunit B of Escherichia coli heat-labile enterotoxin B (LT-B) were transformed into nontoxinogenic V. cholerae vaccine strains. A protein consisting of two overlapping immunodominant antibody-binding sites of the hepatitis B virus (HBV) middle surface antigen fused to the C terminus of full-length LT-B was secreted into the supernatant of V. cholerae cultures, whereas two other LT-B/HBV fusion proteins were mostly retained within the cells or rapidly degraded in the culture supernatant. While the secretion of fusion proteins with cholera toxin subunit B (CT-B) from V. cholerae has been described, this is to our knowledge the first report describing extracellular secretion of defined foreign epitopes fused to LT-B in V. cholerae. The fusion of guest epitopes to LT-B or CT-B and secretion in V. cholerae could be an interesting system to rapidly produce pure fusion proteins for immunisation, functional studies or diagnostic procedures. An LT-B/pre-S2 fusion protein purified from the supernatant of recombinant V. cholerae induced serum IgG antibodies against LT-B and against the HBV middle surface antigen in mice after parenteral and oral immunisation.


Selenium levels in human blood, urine, and hair in response to exposure via drinking water.
Blood, hair, urine, and tap water samples were obtained from participants in a population exposed to varying amounts of selenium via water from home wells. Concentrations of selenium in urine and hair produced significant positive correlations with well-water selenium levels. Blood selenium with well-water selenium did not produce a significant correlation. Urine selenium correlation with hair selenium and urine selenium correlation with blood selenium were found to be significant. No significant correlation for hair selenium with blood selenium was found. We conclude that blood selenium alone is not an adequate monitor of selenium exposure or body burden at levels below chronic toxicity.


Improvement of the Mass-Rearing Protocols for the South American Fruit Fly for Application of the Sterile Insect Technique.
The existing rearing protocols for Anastrepha fraterculus must be reviewed to make economically viable the production of sterile flies for their area-wide application. Additionally, evidence of sexual incompatibility between a long-term mass-reared Brazilian strain and wild populations has been found. To address these issues, this study aimed to refine rearing protocols and to assess the suitability of an A. fraterculus strain for the mass production of sterile flies. A series of bioassays were carried out to evaluate incubation times for eggs in a bubbling bath and to assess the temporal variation of egg production from ovipositing cages at different adult densities. A novel larval diet containing carrageenan was also evaluated. Egg incubation times higher than 48 h in water at 25 °C showed reduced larval and pupal yields. Based on egg production and hatchability, the density of 0.3 flies/cm2 can be recommended for adult cages. The diet with carrageenan was suitable for mass production at egg-seeding densities between 1.0 and 1.5 mL of eggs/kg of diet, providing higher insect yields than a corn-based diet from Embrapa. Even after two years of being reared under the new rearing protocols, no sexual isolation was found between the bisexual strain and wild flies.


Conformations of individual quadruplex units studied in the context of extended human telomeric DNA.
G-quadruplex conformations within a sequence of three quadruplex units of human telomeric DNA were studied by two-frequency pulsed electron paramagnetic resonance (EPR) spectroscopy. In contrast to some individual G-quadruplexes, within the higher-order human telomeric sequence a (3+1) hybrid structure is formed.


Increased circulating levels of angiotensin-(1-7) in severely ill COVID-19 patients.
This letter reports an unexpected increase of the ACE2 product angiotensin-(1-7) and a parallel decrease of its substrate angiotensin II, suggesting a dysregulation of the renin-angiotensin system towards angiotensin-(1-7) formation in #COVID19 patients https://bit.ly/3xFXuTU.


At-line coupling of UPLC to chip-electrospray-FTICR-MS.
Since highly sensitive on-line coupling of UPLC with FTICR-MS is technically infeasible due to their different scan rates, at-line coupling of these techniques was developed for rapid analysis. To enable cutting of one peak of the chromatogram into one fraction, several conditions and relationships were investigated, e.g. the optimum volume of the inserted delay loop, the relationship between retention time, loop outlet drop speed, individual drop volume versus mobile phase composition under constant speed, and linear solvent strength gradient elution modes. Good and reproducible results were achieved applying UPLC as an efficient separation and fast fractionation tool before the FTICR-MS measurements. A chip-based nanoelectrospray ionization system was employed which was perfectly suited to handling the small-volume fractions and was thus chosen for the at-line coupling. The method was initially applied to spiked extracts of cell-free bacterial culture supernatants in which bacterial signalling compounds, namely N-acyl homoserine lactones (AHL), were detected. Good reproducibility and high recovery was observed. Afterwards, a culture supernatant of Erwinia sp. JX3.2, a putative AHL producer, was investigated and N-hexanoyl-homoserine lactone was determined as a possible signalling molecule. More reliable assignments were achieved by use of at-line coupling of UPLC and FTICR-MS compared with off-line measurements.


A sequential explanatory study of the employment experiences of population-based breast, colorectal, and prostate cancer survivors.
Cancer treatment often leads to work disruptions including loss of income, resulting in long-term financial instability for cancer survivors and their informal caregivers. In this sequential explanatory study, we conducted a cross-sectional survey of employment experiences among ethnically diverse, working-age individuals diagnosed with breast, colorectal, or prostate cancer. Following the survey, we conducted semi-structured interviews with cancer survivors and informal caregivers to explore changes in employment status and coping techniques to manage these changes. Among employed survivors (n = 333), cancer caused numerous work disruptions including issues with physical tasks (53.8%), mental tasks (46.5%) and productivity (76.0%) in the workplace. Prostate cancer survivors reported fewer work disruptions than female breast and male and female colorectal cancer survivors. Paid time off and flexible work schedules were work accommodations reported by 52.6% and 36.3% of survivors, respectively. In an adjusted regression analysis, household income was positively associated with having received a work accommodation. From the qualitative component of the study (survivors n = 17; caregivers n = 11), three key themes emerged: work disruptions, work accommodations, and coping mechanisms to address the disruptions. Survivors and caregivers shared concerns about lack of support at work and resources to navigate issues caused by changes in employment. This study characterized employment changes among a diverse group of cancer survivors. Work accommodations were identified as a specific unmet need, particularly among low-income cancer survivors. Addressing changes in employment among specific groups of cancer survivors and caregivers is critical to mitigate potential long-term consequences of cancer.


Baroreflex function in hypertension: consequences for antihypertensive therapy.
Studies performed in experimental animal models of hypertension as well as in human hypertension have unequivocally shown that reflex cardiovascular control undergoes profound changes with high blood pressure and participates throughout direct and indirect mechanisms at the development and progression of hypertension-related target organ damage. This explains why investigation of the effects of antihypertensive drugs on neural cardiovascular control has a significant impact on hypertension treatment. This review will examine the main features of cardiovascular reflex control in hypertension and the effects of the different classes of antihypertensive drugs in uncomplicated and complicated hypertension.


Inhibition of current perception thresholds in A-delta and C fibers through somatosensory stimulation of the body surface.
Somatosensory stimulation of the body surface, such as through tactile and noxious stimulation, is widely known to inhibit pain. However, no studies have measured the threshold changes due to somatosensory stimulation of each nerve fiber (Aβ, Aδ, and C) separately. We examined the changes in the current perception thresholds of Aδ, C, and Aβ fibers induced by non-noxious and noxious somatosensory stimulation of the body surface. The current stimuli were sinusoidal waves at frequencies of 2000 Hz, 250 Hz, and 5 Hz, which selectively stimulated the Aβ, Aδ, and C fibers, respectively. In the case of non-noxious stimulation, lightly rubbing the dorsal side of the forearm with a brush showed no significant physiological or clinical changes in the current perception thresholds of the Aδ, and C fibers; a significant increase was observed only in the Aβ fibers. However, applying noxious stimulation to the body surface through hand immersion in cold water increased pain thresholds in both the Aδ and C fibers, and sensory threshold of the Aβ fibers; changes in tactile thresholds were not significant. Inhibition of sensory information by nociceptive inputs may selectively suppress nociceptive stimuli.


Controlled extracellular proteolysis of thrombospondins.
Limited proteolysis of thrombospondins is a powerful mechanism to ensure dynamic tuning of their activities in the extracellular space. Thrombospondins are multifunctional matricellular proteins composed of multiple domains, each with a specific pattern of interactions with cell receptors, matrix components and soluble factors (growth factors, cytokines and proteases), thus with different effects on cell behavior and responses to changes in the microenvironment. Therefore, the proteolytic degradation of thrombospondins has multiple functional consequences, reflecting the local release of active fragments and isolated domains, exposure or disruption of active sequences, altered protein location, and changes in the composition and function of TSP-based pericellular interaction networks. In this review current data from the literature and databases is employed to provide an overview of cleavage of mammalian thrombospondins by different proteases. The roles of the fragments generated in specific pathological settings, with particular focus on cancer and the tumor microenvironment, are discussed.


Primary endodermal sinus tumor of the liver detected by CT.
We report a case of primary endodermal sinus tumor of the liver. Endodermal sinus tumors are rare neoplasms which usually arise in the testis or ovary. Extragonadal endodermal sinus tumors are uncommon and primary tumors of the liver are very rare. The tumor was detected using CT and the diagnosis was made by percutaneous biopsy.


Improving background suppression in diffusion-weighted imaging of the abdomen and pelvis using STIR with single-axis diffusion encoding.
Bowel contents and peripheral nerves often show high signal intensity at diffusion-weighted imaging (DWI) of the abdomen and pelvis, obscuring or mimicking pathology. This study introduced and compared short tau inversion recovery (STIR) with single-axis DWI to the usual combination of spectral fat suppression (SFS) with trace DWI in the suppression of bowel contents and peripheral nerves. Five volunteers underwent both STIR with single-axis DWI and SFS with trace DWI of the abdomen and pelvis. Images were evaluated by two observers with respect to the suppression of signal of bowel contents and peripheral nerves using four-point grading scales (4=poor suppression; 3=moderate suppression; 2=good suppression; 1=excellent suppression). Mean scores (±S.D.) regarding the suppression of bowel contents were 1.60±0.55 and 1.40±0.89 for STIR with single-axis DWI and 3.40±0.55 and 3.00±1.00 for SFS with trace DWI for observers 1 and 2, respectively. Mean scores regarding the suppression of peripheral nerves were 1.20±0.45 and 1.20±0.45 for STIR with single-axis DWI and 2.40±0.89 and 2.80±0.84 for SFS with trace DWI for observers 1 and 2, respectively. In conclusion, STIR with single-axis DWI is superior to SFS with trace DWI in the suppression of bowel signal and peripheral nerves.


Trunk stiffness and dynamics during active extension exertions.
Spinal stability is related to the recruitment and control of active muscle stiffness. Stochastic system identification techniques were used to calculate the effective stiffness and dynamics of the trunk during active trunk extension exertions. Twenty-one healthy adult subjects (10 males, 11 females) wore a harness with a cable attached to a servomotor such that isotonic flexion preloads of 100, 135, and 170 N were applied at the T10 level of the trunk. A pseudorandom stochastic force sequence (bandwidth 0-10 Hz, amplitude +/-30 N) was superimposed on the preload causing small amplitude trunk movements. Nonparametric impulse response functions of trunk dynamics were computed and revealed that the system exhibited underdamped second-order behavior. Second-order trunk dynamics were determined by calculating the best least-squares fit to the IRF. The quality of the model was quantified by comparing estimated and observed displacement variance accounted for (VAF), and quality of the second-order fits was calculated as a percentage and referred to as fit accuracy. Mean VAF and fit accuracy were 87.8 +/- 4.0% and 96.0 +/- 4.3%, respectively, indicating that the model accurately represented active trunk kinematic response. The accuracy of the kinematic representation was not influenced by preload or gender. Mean effective stiffness was 2.78 +/- 0.96 N/mm and increased significantly with preload (p < 0.001), but did not vary with gender (p = 0.425). Mean effective damping was 314 +/- 72 Ns/m and effective trunk mass was 37.0 +/- 9.3 kg. We conclude that stochastic system identification techniques should be used to calculate effective trunk stiffness and dynamics.


Comparison of the antitussive effect of remifentanil during recovery from propofol and sevoflurane anaesthesia.
This prospective randomised study compared the antitussive effect of remifentanil during recovery from either propofol or sevoflurane anaesthesia. Seventy-four female patients undergoing thyroidectomy were anaesthetised with either propofol and remifentanil or sevoflurane and remifentanil. During recovery, remifentanil was maintained at an effect-site concentration of 2 ng.ml(-1) until extubation and the occurrence of coughing, haemodynamic parameters and recovery profiles were compared between the two groups. During recovery, neither the incidence nor the severity of cough (incidence 20% with propofol; 24% with sevoflurane, p = 0.77), nor the haemodynamic parameters were different between the two groups. Time to awakening and time to extubation were significantly shorter in the propofol group (4.7 min, 6.1 min min, respectively) compared with the sevoflurane group (7.9 min and 8.9 min respectively) (p < 0.001 and p = 0.002, respectively). An effect-site concentration of 2 ng.ml(-1) of remifentanil was associated with smooth emergence from both propofol and sevoflurane anaesthesia.


Early Diagnosis and Treatment of Purine Nucleoside Phosphorylase (PNP) Deficiency through TREC-Based Newborn Screening.
Purine nucleoside phosphorylase (PNP) deficiency is a rare inherited disorder, resulting in severe combined immunodeficiency. To date, PNP deficiency has been detected in newborn screening only through the use of liquid chromatography tandem mass spectrometry. We report the first case in which PNP deficiency was detected by TREC analysis.


Extraordinary experiences in its cultural and theoretical context.
The growing complexity, opaqueness and specialization of many areas of life and - above all - a booming psychological and esoteric market create the necessity for counselling and advice for individuals who encounter so-called 'paranormal' experiences. These experiences are often interpreted as 'transpersonal' or 'spiritual', depending on the cultural background and religious traditions. The term 'spiritual crisis' has become a fashionable diagnosis with some transpersonal psychotherapists. Paranormal experiences, regardless of their acceptance of academic psychology and psychiatry, are still a taboo subject in society. The Parapsychological Counselling Office in Freiburg is a professional unit with governmental support, which helps individuals to cope with such experiences adequately. The work and responsibilities of the counselling centre are presented. A large collection of cases in the form of letters, which were sent in by individuals wanting to communicate their unusual or extraordinary experiences have been analysed. Some of the results are reported here. Finally, we discuss a special form of 'inexplicable experiences' based on a theoretical model. Its recommendations seem counter-intuitive but are ultimately successful. The model starts from a system-theoretical viewpoint and uses concepts such as complementarity and entanglement of generalized quantum theory (GQT) and the model of pragmatic information (MPI). Since it turned out that individuals who contact the counselling centre also offer their own interpretations and 'explanation', the question arises, how these resources can be used to help clients.


Concerns about transmission, changed services and place of birth in the early COVID-19 pandemic: a national survey among Danish pregnant women. The COVIDPregDK study.
The outbreak of the COVID-19 pandemic caused great uncertainty about causes, treatment and mortality of the new virus. Constant updates of recommendations and restrictions from national authorities may have caused great concern for pregnant women. Reports suggested an increased number of pregnant women choosing to give birth at home, some even unassisted ('freebirth') due to concerns of transmission in hospital or reduction in birthplace options. During April and May 2020, we aimed to investigate i) the level of concern about coronavirus transmission in Danish pregnant women, ii) the level of concern related to changes in maternity services due to the pandemic, and iii) implications for choice of place of birth. We conducted a nationwide cross-sectional online survey study, inviting all registered pregnant women in Denmark (n = 30,009) in April and May 2020. The response rate was 60% (n = 17,995). Concerns of transmission during pregnancy and birth were considerable; 63% worried about getting severely ill whilst pregnant, and 55% worried that virus would be transmitted to their child. Thirtyeight percent worried about contracting the virus at the hospital. The most predominant concern related to changes in maternity services during the pandemic was restrictions on partners' attendance at birth (81%). Especially nulliparous women were concerned about whether cancelled antenatal classes or fewer physical midwifery consultations would affect their ability to give birth or care for their child postpartum.. The proportion of women who considered a home birth was equivalent to pre-pandemic home birth rates in Denmark (3%). During the temporary discontinue of public home birth services, 18% of this group considered a home birth assisted by a private midwife (n = 125), and 6% considered a home birth with no midwifery assistance at all (n = 41). Danish pregnant womens' concerns about virus transmission to the unborn child and worries about contracting the virus during hospital appointments were considerable during the early pandemic. Home birth rates may not be affected by the pandemic, but restrictions in home birth services may impose decisions to freebirth for a small proportion of the population.


Infiltrating spinal angiolipoma with paraplegia and hydrocephalus: A rare case report.
Angiolipoma is a rare subtype of lipoma that contains both mature adipocytes and a rich vascular component. Infiltrating spinal angiolipomas causes surgical challenges with potential on-table injuries to adjacent structures. We present a rare case of infiltrating spinal angiolipoma in a 76-year-old woman who presented with paraplegia and hydrocephalus. At the time of presentation, the patient was bedridden for 3 months due to a complete loss of motor power. Imaging examination revealed a lesion involving the T6 vertebra with compressive myelopathy. The patient underwent spinal decompression and resection of the lesion, which turned out to be an infiltrating angiolipoma by histological examination. This is a unique case because spinal angiolipoma is extremely uncommon and such lesions generally manifest without infiltration. This case report highlights the existence and importance of spinal angiolipoma as a differential diagnosis of chronic backache resulting in neurological deficits and hydrocephalus.


Mass Spectrometry-Based Profiling of Plant Sphingolipids from Typical and Aberrant Metabolism.
Mass spectrometry has increasingly been used as a tool to complement studies of sphingolipid metabolism and biological functions in plants and other eukaryotes. Mass spectrometry is now essential for comprehensive sphingolipid analytical profiling because of the huge diversity of sphingolipid classes and molecular species in eukaryotes, particularly in plants. This structural diversity arises from large differences in polar head group glycosylation as well as carbon-chain lengths of fatty acids and desaturation and hydroxylation patterns of fatty acids and long-chain bases that together comprise the ceramide hydrophobic backbone of glycosphingolipids. The standard methods for liquid chromatography-mass spectrometry (LC-MS)-based analyses of Arabidopsis thaliana leaf sphingolipids profile >200 molecular species of four sphingolipid classes and free long-chain bases and their phosphorylated forms. While these methods have proven valuable for A. thaliana based sphingolipid research, we have recently adapted them for use with ultraperformance liquid chromatography separations of molecular species and to profile aberrant sphingolipid forms in pollen, transgenic lines, and mutants. This chapter provides updates to standard methods for LC-MS profiling of A. thaliana sphingolipids to expand the utility of mass spectrometry for plant sphingolipid research.


Comparison of sexual function changes in recipients of kidney transplant in females receiving kidney from the living donor and deceased donor.
Chronic renal failure can result in different sexual and reproductive problems for women. Due to lack of information about sexual dysfunction of women with transplanted kidney and superiority of either living or deceased donor, we designed this retrospective cohort study to compare sexual function changes in recipients of kidney transplant in two groups receiving kidney from the living donor and deceased donor using Female Sexual Function Index score. We included 55 female patients who underwent kidney transplant from 22 May 2015 to 22 May 2016 in Sina Hospital (Tehran, Iran). Laboratory factors, including creatinine, blood urea nitrogen, hemoglobin, fasting blood glucose, triglyceride, cholesterol, low-density lipoprotein, and high-density lipoprotein, were evaluated before and after the transplantation. Female Sexual Function Index questionnaire was used to evaluate sexual function of the patients before the transplant, 3 months after the transplant, and 9 months after the transplant. Our results revealed that there is significant improvement in the Female Sexual Function Index score of the patients after the transplant (p-value < .001). However, we found no significant difference between the scores of the patients with living donor and deceased donor (p-value > .05). Patients' age, creatinine level, low-density lipoprotein, and diastolic blood pressure are negative predictors of Female Sexual Function Index scores.


COVIDrugNet: a network-based web tool to investigate the drugs currently in clinical trial to contrast COVID-19.
The COVID-19 pandemic poses a huge problem of public health that requires the implementation of all available means to contrast it, and drugs are one of them. In this context, we observed an unmet need of depicting the continuously evolving scenario of the ongoing drug clinical trials through an easy-to-use, freely accessible online tool. Starting from this consideration, we developed COVIDrugNet ( http://compmedchem.unibo.it/covidrugnet ), a web application that allows users to capture a holistic view and keep up to date on how the clinical drug research is responding to the SARS-CoV-2 infection. Here, we describe the web app and show through some examples how one can explore the whole landscape of medicines in clinical trial for the treatment of COVID-19 and try to probe the consistency of the current approaches with the available biological and pharmacological evidence. We conclude that careful analyses of the COVID-19 drug-target system based on COVIDrugNet can help to understand the biological implications of the proposed drug options, and eventually improve the search for more effective therapies.


Influenza virus surveillance, vaccine strain selection, and manufacture.
As outlined in other chapters, the influenza virus, existing laboratory diagnostic abilities, and disease epidemiology have several peculiarities that impact on the timing and processes for the annual production of influenza vaccines. The chapter provides an overview on the key biological and other factors that influence vaccine production. They are the reason for an "annual circle race" beginning with global influenza surveillance during the influenza season in a given year to the eventual supply of vaccines 12 months later in time before the next seasonal outbreak and so on. As influenza vaccines are needed for the Northern and Southern Hemisphere outbreaks in fall and spring, respectively, global surveillance and vaccine production has become a year round business. Its highlights are the WHO recommendations on vaccine strains in February and September and the eventual delivery of vaccine doses in time before the coming influenza season. In between continues vaccine strain and epidemiological surveillance, preparation of new high growth reassortments, vaccine seed strain preparation and development of standardizing reagents, vaccine bulk production, fill-finishing and vaccine release, and in some regions, clinical trials for regulatory approval.


Intrapartum group B Streptococcus screening in the labor ward by Xpert® GBS real-time PCR.
Group B Streptococcus (GBS) is the leading cause of neonatal infections in industrialized countries. Intrapartum antibiotic prophylaxis (IAP) given to colonized parturients is a key step for the prevention of neonatal early-onset infection. We compared the performances of Xpert® GBS polymerase chain reaction (PCR) (Cepheid, Sunnyvale, CA, USA) as a point-of-care system in labor wards to standard culture for intrapartum GBS detection. Pregnant women with a GBS-positive antenatal screening were prospectively included. A vaginal double swab was collected at the time of delivery for point-of-care Xpert® GBS PCR and GBS culture. A total of 565 pregnant women were included. Valid Xpert® GBS results were obtained for 488 (86.4%) women on the first attempt. Repeat testing improved the PCR success to 516 (91.3%) women. Among the 305 women positive for GBS by culture at delivery, only 238 (78.0%) were positive by Xpert® GBS PCR, cycle thresholds being correlated to culture quantification. Among 260 women negative for GBS culture, 56 (21.5%) were positive by Xpert® GBS PCR, including 50 where IAP was initiated before vaginal sampling. Overall, among the 565 women with GBS antenatal positive culture, only 335 (59.3%) were still positive at delivery whatever the technique used, resulting in unnecessary IAP for 40% of them. This large cohort study comparing intrapartum to antepartum GBS detection provides evidence that (i) Xpert® GBS PCR might be a valuable solution for intrapartum GBS detection compared to culture-based strategies and (ii) laboratory training of non-specialized staff is mandatory to reach the performances required for point-of-care tests.


Brief assessment of readiness to change tobacco use in treated youth.
This study examined the concurrent and predictive validity of four brief measures of readiness to change tobacco use for use with adolescents in clinical practice (Readiness Ruler, Thoughts About Abstinence, motivation to abstain, and confidence to abstain) and a single-item measure of difficulty to abstain. Participants were 154 adolescent smokers recruited from outpatient addictions treatment, who completed assessments shortly after admission and at 6- and 12-month follow-up. Concurrent validity analyses indicated that the four readiness measures were moderately correlated at each time point. Predictive validity analyses indicated that the Ruler and the motivation to abstain ratings predicted number of cigarettes smoked at 6 and 12 months. Perceived difficulty to abstain predicted cigarette use over and above the readiness to change measures. Results support the clinical utility of the Ruler and motivation to abstain as brief measures of readiness to change, and perceived difficulty to abstain as a tool to aid adolescent tobacco cessation.


Intermittent mild cold stimulation improves the immunity and cold resistance of spleens in broilers.
In order to investigate the effect of intermittent mild cold stimulation (IMCS) on immune function of spleens and adaptability to cold stress in broilers, 400 healthy 1-day-old Ross-308 chickens were divided into 5 groups: CC (control) reared in normal thermal environment from 1 to 49 d; CS3, CS4, CS5, and CS6 (treatments) raised at 3°C below the temperature of CC for 3, 4, 5, or 6 h at 1-d intervals from 15 to 35 d, respectively. Subsequently, CS3-6 was raised at 20°C from 36 to 49 d. At 50 d, all groups were exposed to acute cold stress (ACS) for 12 h. The spleen immunity index at 22, 29, 36, 43, and 49 d, expression levels of toll-like receptors (TLRs), cytokines and immunoglobulins at 22, 43, and 49 d and heat shock proteins (HSPs) before and after ACS at 50 d were examined. The spleen index of broilers aged 22 to 49 d did not differ between CS and CC (P > 0.05), and the spleen index of CS5 was higher than that of CS3 at 49 d (P < 0.05). The mRNA levels of TLR5, TLR15, TLR21, and IL-2 in CS3, TLR3, TLR4, TLR15, TLR21, IL-2, IL-6, and IFN-ϒ in CS4, TLR1, TLR3, TLR4, TLR21, IL-2, IFN-a, IFN-ϒ, IgA, and IgG in CS6, but all TLRs, immunoglobulins and cytokines except IFN-ϒ in CS5 differential expressed stably compared with CC at 43 and 49 d (P < 0.05). Compared with Pre-ACS, the mRNA levels of HSP60, HSP70, and HSP90 were upregulated in CS after ACS (P < 0.05). Except for HSP90 mRNA and HSP70 protein in CS6, and HSP90 protein in CS3, the levels of HSPs after ACS in all treatment groups were higher than those in CC (P < 0.05), and the highest HSPs levels after ACS were found in CS5. We concluded that IMCS could enhance immunity of spleens and adaptability to ACS in broilers, besides CS5 was the optimal program.


EDTA stabilizes the concentration of platelet-derived extracellular vesicles during blood collection and handling.
Citrate is the recommended anticoagulant for studies on plasma extracellular vesicles (EVs). Because citrate incompletely blocks platelet activation and the release of platelet-derived EVs, we compared EDTA and citrate in that regard. Blood from healthy individuals (n = 7) was collected and incubated with thrombin receptor-activating peptide-6 (TRAP-6) to activate platelets, subjected to pneumatic tube transportation (n = 6), a freeze-thaw cycle (n = 10), and stored before plasma preparation (n = 6). Concentrations of EVs from platelets (CD61+), activated platelets (P-selectin+), erythrocytes (CD235a+), and leukocytes (CD45+) were measured by flow cytometry. Concentrations of EVs from platelets and activated platelets increased 1.4-fold and 1.9-fold in EDTA blood upon platelet activation, and 4.2-fold and 9.6-fold in citrate blood. Platelet EV concentrations were unaffected by pneumatic tube transport in EDTA blood but increased in citrate blood, and EV concentrations of erythrocytes and leukocytes were comparable. The stability of EVs during a freeze-thaw cycle was comparable for both anticoagulants. Finally, the concentration of platelet EVs was stable during storage of EDTA blood for six hours, whereas this concentration increased 1.5-fold for citrate blood. Thus, EDTA improves the robustness of studies on plasma EVs.


Transtibial Ertl amputation for children and adolescents: a case series and literature review.
Despite advances in limb reconstruction, there are still a number of young patients who require trans-tibial amputation. Amputation osteoplasty is a technique first described by Ertl to enhance rehabilitation after trans-tibial amputation. The purpose of the study reported here was to evaluate the results of the original Ertl procedure in skeletally immature patients and to assess whether use of this procedure would result in a diminished incidence of bony overgrowth. The cases of four consecutive patients (five amputations) treated between January 2005 and June 2008 were reviewed. Clinical evaluation consisted of the completion of the prosthesis evaluation questionnaire (PEQ) and physical examination. Radiographic analysis was performed to evaluate bone-bridge healing, bone overgrowth, and the development of genu varum as measured by the medial proximal tibial angle (MPTA). The best mean PEQ score in the question section was 91.8 (range 74-100) for 'well being' and the worst mean score was 66.6 (range 50-78) for 'residual limb health'. Examination of the residual limbs revealed no bursae, and all knees were stable with full range of movement. All bony bridges united at an average age of 1.7 (range 1-2) months. One case required stump revision for bony overgrowth, and one case developed asymptomatic mild genu varum. The original Ertl osteomyoplasty may serve as one of the options for treatment of trans-tibial amputation in older children. Our results suggest that the Ertl osteomyoplasty is a feasible option in this challenging patient population.


Hyperandrogenism in carriers of CYP21 mutations: the role of genotype.
It has been hypothesized that carriers of CYP21 mutations are at increased risk of developing clinically evident hyperandrogenism. In the present study, we assessed the risk for symptoms of androgen excess in carriers of CYP21 gene mutations and the effect of different mutations on phenotype. All subjects underwent clinical evaluation, ACTH stimulation testing, and molecular analysis of the CYP21 gene. One hundred and eighty-seven subjects were included in the study. Five groups were defined according to genotype: A, 38 patients with classical-congenital adrenal hyperplasia (CAH); B, 16 patients with non classical CAH; C, 66 family member carriers; D, 24 children and adolescents with symptoms suggestive of hyperandrogenism who were found to be heterozygous and E, 43 subjects with androgen excess symptoms who had normal genotype. Cortisol and 17-hydroxyprogesterone (17OHP) were measured basally and 60 min after ACTH stimulation. Analysis of seven common mutations of the CYP21 gene, which collectively cover 95% of the mutations in the Israeli population, was performed. The hormonal results were correlated with the genotype. The symptomatic carriers had a significantly higher rate of the mild mutation V281L compared with the family members (58% vs. 22%) and significantly higher levels of ACTH-stimulated 17OHP (mean 37.2 and 21 nmol/l, respectively; P = 0.025). Higher values of peak 17OHP levels were found in the carriers of the V281L mutation compared with carriers of other mutations (P = 0.025). Stimulated 17OHP levels were significantly higher in carriers compared with normal genotype subjects (P < 0.0001). Our findings are the first to show that there is increased risk of androgen excess in carriers of CYP21 mutations and that the risk is related to genotype. Carriers for the mild, V281L mutation, are at higher risk of symptoms of androgen excess than carriers of the severe mutations. It appears that the variable phenotypes can be at least partially attributed to the degree of impairment of enzyme activity in different mutations. The severe consequences of hyperandrogenism in some of the carrier subjects indicate the need for long-term follow-up in these patients.


Spontaneous resolution of a spontaneous steinstrasse: a case report.
A 63-year-old man presented with a 4-day history of right sided loin-to-groin pain. Computed tomography imaging revealed a 22 mm by 7 mm volume of contiguous ureteric calculi at the right vesicoureteric junction. Spontaneous steinstrasse was diagnosed with no recent history of extracorporeal shock wave lithotripsy (ESWL) or other urological intervention to the right kidney. Metabolic testing was negative. An initial plan was made for urgent primary ureteroscopy and lithotripsy, however, the patient spontaneously passed 20-25 calculi at home whilst awaiting his operation date. He was reviewed in clinic and his symptoms had resolved. His ureteroscopy was cancelled. This case represents an example of spontaneous steinstrasse with no identified causative factors, a rare occurrence on which little literature is available presenting a management dilemma to the treating clinician. The case described resolved prior to intervention prompting us to suggest that spontaneous steinstrasse can be initially managed conservatively, as in ESWL-associated steinstrasse.


A Scoping Review of Risk and Protective Factors for Negative Cannabis Use Consequences.
Numerous reviews have examined risk and protective factors for alcohol-related negative consequences, but no equivalent review of risk and protective factors exists for cannabis-related negative consequences (CRNCs)-a gap filled by the present study. This scoping review examined survey-based research of risk and protective factors for CRNCs such as neglecting responsibilities, blacking out, or needing more cannabis. Three databases (PubMed, PsycINFO, and Google Scholar) were searched for peer-reviewed manuscripts published between January 1, 1990, and December 31, 2021. A qualitative synthesis was performed using the matrix method and the results were organized using the socioecological model as a framework. Eighty-three studies were included in the review. There was considerable variation in measures and operationalizations of CRNCs across studies. Risk factors were identified in the intrapersonal (depression, social anxiety, PTSD, impulsivity, sensation seeking, motives, expectancies), interpersonal/community (trauma, victimization, family and peer substance use, social norms), and social/policy (education, employment, community attachment, legalization, availability of substances) domains of influence. Protective behavioral strategies were a robust protective factor for CRNCs. Males consistently reported more CRNCs than females, but there were no differences observed across race. Future research should identify person- and product-specific patterns of CRNCs to refine theoretical models of cannabis misuse and addiction. Public health interventions to reduce the risk of negative consequences from cannabis should consider utilizing multilevel interventions to attenuate the cumulative risk from a combination of psychological, contextual, and social influences.


Acute viral infections of upper respiratory tract in elderly people living in the community: comparative, prospective, population based study of disease burden.
To evaluate the disease burden of upper respiratory infections in elderly people living at home. Prospective surveillance of elderly people. None. Leicestershire, England 533 subjects 60 to 90 years of age. Pathogens, symptoms, restriction of activity, duration of illness, medical consultations, interval between onset of illness and medical consultation, antibiotic use, admission to hospital, and death. 231 pathogens were identified for 211 (43%) of 497 episodes for which diagnostic specimens were available: 121 (52%) were rhinoviruses, 59 (26%) were coronaviruses, 22 (9.5%) were influenza A or B, 17 (7%) were respiratory syncytial virus, 7 (3%) were parainfluenza viruses, and 3 (1%) were Chlamydia species; an adenovirus and Mycoplasma pneumoniae caused one infection each. Infections occurred at a rate of 1.2 episodes per person per annum (95% confidence interval 1.0 to 1.7; range 0-10) and were clinically indistinguishable. Lower respiratory tract symptoms complicated 65% of upper respiratory infections and increased the medical consultation rate 2.4-fold (chi 2 test P < 0.001). The median interval between onset of illness and medical consultation was 3 days for influenza and 5 days for other infections. Rhinoviruses caused the greatest disease burden overall followed by episodes of unknown aetiology, coronaviruses, influenza A and B, and respiratory syncytial virus. Respiratory viruses cause substantial morbidity in elderly people. Although respiratory syncytial virus and influenza cause considerable individual morbidity, the burden of disease from rhinovirus infections and infections of unknown aetiology seems greater overall. The interval between onset of illness and consultation together with diagnostic difficulties raises concern regarding the role of antiviral drugs in treating influenza.


Outcomes of Warfarin Home INR Monitoring vs Office-Based Monitoring: a Retrospective Claims-Based Analysis.
Home INR testing (patient self-testing) is feasible and effective for warfarin patients but little is known about real-world differences in outcomes for patients using PST versus laboratory-based INR monitoring. To compare the safety/efficacy of patient self-testing of real-world warfarin therapy versus office/lab-based monitoring of therapy. A retrospective claims-based analysis of warfarin patients enrolled in the MarketScan® Commercial Claims and Encounters and Medicare databases between January 1, 2013, and March 30, 2020. Stratification was based on INR testing method: patient self-testing versus testing at physicians' offices/local laboratory. The probability of adverse events in each cohort was determined after adjusting for demographic and baseline clinical characteristics using a repeated measures analysis. Rates of all adverse events: deep venous thrombosis, pulmonary embolism, bleeding, and stroke. A secondary outcome of interest was emergency department visits. A total of 37,837 patients were included in the analysis: 1592 patients in the patient self-testing group and 36,245 in the office-based therapy group. After adjusting for demographic and baseline clinical characteristics, patients in the office-based group had statistically significantly higher rates of all adverse events (incidence rate ratio [IRR]=2.07, 95% CI [1.82, 2.36]), and specific adverse events including thromboembolism (IRR=4.38, 95% CI [3.29, 5.84]), major bleed (IRR=1.45, 95% CI [1.28, 1.64]), and stroke (IRR=1.30, 95% CI [1.05, 1.61]) than patients in the patient self-testing group. Office-based patients also had a statistically significant higher rate of emergency department visits than patient self-testing patients (IRR = 1.65, 95% CI [1.47, 1.84]). This analysis of real-world claims data shows lower rates of stroke, thromboembolism, and major bleeding, as well as fewer emergency department visits, with patient self-testing compared to office-based/lab INR monitoring. Our finding that PST is safe and effective among current users suggests that more patients may benefit from its use.


The exposure of gadolinium at environmental relevant levels induced genotoxic effects in Arabidopsis thaliana (L.).
Rare Earth Elements (REEs) are increasingly being used in agriculture and are also used to produce high end technological devices, thereby increasing their anthropogenic presence in the environment. However, the ecotoxicological mechanism of REEs on organisms is not fully understood. In this study, the effects of gadolinium (Gd) addition on Arabidopsis thaliana (L.) were investigated at both physiological and molecular levels. Four treatments (0, 10, 50 and 200 μmol·L-1 Gd) were used in the exposure tests. Biomass, root length and chlorophyll content in shoots/roots were measured to investigate the plant's physiological response to Gd stress. Random amplified polymorphic (RAPD)-Polymerase Chain Reaction (PCR) and methylation sensitive arbitrarily primed (MSAP)-PCR were used to investigate changes in genetic variation and DNA methylation of A. thaliana when exposed to Gd. At the physiological level, it was found that low concentration of Gd (10 μmol·L-1) could significantly increase the plant biomass and root length, while the growth of A. thaliana was significantly inhibited when exposed to 200 μmol·L-1 of Gd, yet the total soluble protein content in aerial plant parts increased significantly by 24.2% when compared to the control group. Among the 12 primers considered in the RAPD assessment, at the molecular level, only four primers revealed different patterns in their genomic DNA. Compared to the control group, the treatment with 50 μmol·L-1 of Gd was associated with lower polymorphism, while the treatment with 200 μmol·L-1 of Gd was associated with higher polymorphism. The polymorphism frequencies for the 50 μmol·L-1 of Gd and the 200 μmol·L-1 of Gd were 4.67% and 20.33%, respectively. The MSAP analysis revealed that the demethylation (D) type of Arabidopsis genomic DNA increased significantly under 10 and 50 μmol·L-1 of Gd, while the methylation (M) type was also significantly increased under 200 μmol·L-1 of Gd. Generally, the total methylation polymorphism (D+M) increased with an increase of Gd concentration. It was found that high concentrations of Gd appeared to cause DNA damage, but low concentrations of Gd (as low as 10 μmol·L-1) were associated with DNA methylation change. Further, it was verified by Real time Reverse Transcription PCR (RT-PCR) on the bands detected by the MSAP analysis, that the genes relative to processes including cell cycle, oxidative stress and apoptosis, appeared to be regulated by methylation under Gd stress. These findings reveal new insight regarding ecotoxicity mechanisms of REEs on plants.


Development of the "POP" scoring system for predicting obstetric and gynecological diseases in the emergency department: a retrospective cohort study.
Obstetric and gynecological (OBGY) diseases are among the most important differential diagnoses for young women with acute abdominal pain. However, there are few established clinical prediction rules for screening OBGY diseases in emergency departments (EDs). This study aimed to develop a prediction model for diagnosing OBGY diseases in the ED. This single-center retrospective cohort study included female patients with acute abdominal pain who presented to our ED. We developed a logistic regression model for predicting OBGY diseases and assessed its diagnostic ability. This study included young female patients aged between 16 and 49 years who had abdominal pain and were examined at the ED between April 2017 and March 2018. Trauma patients and patients who were referred from other hospitals or from the OBGY department of our hospital were excluded. Out of 27,991 patients, 740 were included. Sixty-five patients were diagnosed with OBGY diseases (8.8%). The "POP" scoring system (past history of OBGY diseases + 1, no other symptoms + 1, and peritoneal irritation signs + 1) was developed. Cut-off values set between 0 and 1 points, sensitivity at 0.97, specificity at 0.39, and negative likelihood ratio (LR-) of 0.1 (95% CI: 0.02-0.31) were considered to rule-out, while cut-off values set between 2 and 3 points, sensitivity at 0.23 (95% CI 0.13-0.33), specificity at 0.99 (95% CI 0.98-1.00), and positive likelihood ratio (LR+) of 17.30 (95% CI: 7.88-37.99) were considered to rule-in. Our "POP" scoring system may be useful for screening OBGY diseases in the ED. Further research is necessary to assess the predictive performance and external validity of different data sets.


Endovascular treatment for acute ischemic stroke in patients with versus without atrial fibrillation: a matched-control study.
The effect of atrial fibrillation (AF) on outcomes of endovascular treatment (EVT) for acute ischemic stroke (AIS) is controversial. This study aimed to investigate the association of AF with outcomes after EVT in AIS patients. Subjects were selected from ANGEL-ACT registry (Endovascular Treatment Key Technique and Emergency Work Flow Improvement of Acute Ischemic Stroke) - a prospective consecutive cohort of AIS patients undergoing EVT at 111 hospitals in China between November 2017 and March 2019, and then grouped according to having a history of AF or not. After 1:1 propensity score matching, the outcome measures including the 90-day modified Rankin Scale (mRS) score, successful recanalization after final attempt, symptomatic intracranial hemorrhage (ICH) within 24 h, and death within 90 days were compared. A total of 1755 patients, 550 with AF and 1205 without AF, were included. Among 407 pairs of patients identified after matching, no significant differences were found in the mRS score (median: 3 vs. 3 points; P = 0.29), successful recanalization (87.2 vs. 85.3%; P = 0.42), symptomatic ICH (9. 4 vs. 9.1%; P = 0.86) and death (16.3 vs. 18.4%; P = 0.44) between patients with and without AF. The findings of this matched-control study show comparable outcomes of EVT in Chinese AIS patients with and without AF, which do not support withholding EVT in patients with both AIS and AF. NCT03370939 First registration date: 28/09/2017 First posted date: 13/12/2017.


Developing partnerships for health and social science research: the International Clinical Epidemiology Network (INCLEN) social science component.
A decade after its inception, the International Clinical Epidemiology Network (INCLEN) adopted a social science component. Health social science concepts were added to a physician training curriculum encompassing epidemiology, biostatistics and clinical economics, and a position was created for qualified social scientists at 26 clinical epidemiology units in developing country medical schools. This paper describes the INCLEN model for strengthening partnerships among clinical epidemiologists and social scientists. The rationale for interdisciplinary training is presented along with the difficulties inherent in attracting social scientists to a new career path. These include problems of recruitment, training curricula, re-entry, and career sustainability. The need is identified for collaborative international efforts to promote an infrastructure for professional growth and sustainable careers in health social science.


Free Online Decision Tools to Support Parents Making Decisions About Their Children's Chronic Health Condition: An Environmental Scan.
Medical decisions parents make on their children's behalf can be challenging. Free online decision support tools are created to help parents faced with these decisions. We used an environmental scan to identify free, online tools that support parents in making decisions about their children's chronic health condition. We described the tools and assessed their potential to harm, content, development process, readability, and whether their use changed decision makers' knowledge and alignment of their preferences with their final decision. Decision aid repositories, Google searches, and key informants identified decision support tools. Eligible tools were freely available online and for parents of children with chronic health conditions. Two reviewers independently assessed the tools' quality based on the International Patient Decision Aid Standards (IPDAS). Tool readability was assessed using the Flesch Reading Ease test. From 21 free, online decision support tools, 14 (67%) provided sufficient detail for making a specific decision (IPDAS qualifying criteria). None sufficiently met IPDAS certification criteria necessary to reduce the possibility of patient harms when using the tool. Three (14%) were fairly easy or easy to read. Of those evaluated by developers (n = 6), 2 improved knowledge and 4 improved alignment of preferences with the available options. Google searches and key informant sources are not replicable. Free, online decision support tools for parents of children with chronic health conditions are of variable quality, most are difficult to read, and there is limited evidence their use achieves intended outcomes. Registered with Open Science Framework 20 July 2021(AEST) osf.io/b94yj.


[Insufficient participation in prevention programs for infants by Turkish, Moroccan, Chinese and Vietnamese parents in large cities].
To establish the participation in a number of effective prevention programmes for infants of Turkish, Maroccan, Chinese and Vietnamese inhabitants of the four major cities in the Netherlands. Enquiry. Health centres in Amsterdam, Rotterdam, The Hague and Utrecht. Health centre staff members in 1994 asked 194 Turkish and 158 Maroccan parents to participate in the study: the responses were 142 (73%) and 104 (66%), respectively. With the aid of Chinese and Vietnamese female interpreters, 44 parents of Chinese and 75 of Vietnamese infants were persuaded to participate. Previously instructed interviewers presented the parents of all children with a number of structured questions in their own languages regarding use of vitamins (A)D and K and about vaccination against diphtheria, pertussis, tetanus and poliomyelitis (DKTP) and with BCG vaccine. Bottle feeding alone was given to 18% of the Turkish, 43% of the Maroccan, 71% of the Chinese and 51% of the Vietnamese children. 82% Of the children were given vitamin A(D), the Maroccan children the most and the Vietnamese children the least often. Of the breast-fed children, 65% were given vitamin K, the Turkish children the most often. The DKTP vaccination degrees (1st, 2nd and 3rd vaccination) of the Turkish, Vietnamese and Chinese children was in accordance with those of Dutch children, but of the Maroccan children, one in five had not been vaccinated according to the parents. The BCG vaccination degrees were too low among the Turkish (55%) and the Maroccan (42%) children. Of the mothers, 27% reported having been vaccinated against rubella; 2% had vaccination certificates. Participation of the four groups of allochtonous children in the effective prevention programmes investigated was insufficient. At contacts of health workers with these groups, participation in prevention programmes should always be established. Support by means of educative material to be developed specifically should be made a subject of research.


The effects of electroacupuncture treatment on the postoperative cognitive function in aged rats with acute myocardial ischemia-reperfusion.
Many literatures have proven that postoperative cognitive dysfunction (POCD) was very common in old patients after the injury of acute myocardial ischemia-reperfusion (AMIR) clinically such as the off-pump coronary artery bypass surgery (OPCAB) without definite mechanism; however, reports on the animal experiments were rarely seen. We hypothesized that AMIR could contribute to cognitive dysfunction, and this severe injury might be impeded by EA via hindering neuroinflammation and oxidative stress response as well as modulating the balance of the autonomic nervous system. The aged male Sprague Dawley rats were randomly assigned into three experimental groups: sham (sham operation), AMIR, and EA (electroacupunture treatment, acupoints GV20 and ST36+AMIR) groups. The survival rate, heart rate variability analysis, examination of pathology within the hippocampal CA1, oxidative stress, systemic inflammation and the behavior testing were evaluated by their corresponding methods. The results showed that the rats subjected to AMIR had lower survival rates, higher malondialdehyde (MDA), decreased superoxide dismutase (SOD) activity, more microglial activation, and presented evidence of severe brain injury and cognitive dysfunction on the 1st, 3rd, 7th days after reperfusion compared to sham-operated controls. Most important of all, the above damages induced by the AMIR were significantly improved by the EA treatment. Our findings indicated that EA treatment could be a neuroprotective therapy for the cognitive dysfunction induced by the AMIR event, which might be attributablefor balancing the autonomic nervous system, inhibiting the neuronic apoptosis, hindering microglial activation, attenuating oxidative stress and restraining the central and peripheral inflammation reactions.


Systematic review of the role of biomarkers in diagnosing anastomotic leakage following colorectal surgery.
Anastomotic leakage (AL) following colorectal surgery can be difficult to diagnose owing to varying clinical presentations. This systematic review aimed to assess biomarkers as potential diagnostic tests for preclinical detection of AL. A comprehensive literature review was conducted according to PRISMA guidelines. All published studies evaluating biomarkers, both systemic and peritoneal, in the context of AL following colorectal surgery were included. Studies were sought in three electronic databases (MEDLINE, PubMed and Embase) from January 1990 to June 2016. Thirty-six studies evaluated 51 different biomarkers in the context of AL after colorectal surgery. Biomarkers included markers of ischaemia and inflammation, and microbiological markers, and were measured in both peritoneal drain fluid and the systemic circulation. The most commonly evaluated peritoneal drain fluid biomarkers were interleukin (IL) 6, IL-10 and tumour necrosis factor. Significantly raised drain levels in the early postoperative period were reported to be associated with the development of AL. C-reactive protein, procalcitonin and leucocytes were the most commonly evaluated systemic biomarkers with significant negative and positive predictive values. Associated area under the curve values ranged from 0·508 to 0·960. Peritoneal drain fluid and systemic biomarkers are poor predictors of AL after colorectal surgery. Combinations of these biomarkers showed improvement in predictive accuracy.


Identification of the prion-related protein gene (PRNT) sequences in various species of the Cervidae family.
Chronic wasting disease (CWD) is caused by abnormal deleterious prion protein (PrPSc), and transmissible spongiform encephalopathy occurs in the Cervidae family. In recent studies, the susceptibility of prion disease has been affected by polymorphisms of the prion gene family. However, the study of the prion-related protein gene (PRNT) is rare, and the DNA sequence of this gene was not fully reported in all Cervidae families. In the present study, we amplified and first identified PRNT DNA sequences in the Cervidae family, including red deer, elk, sika deer and Korean water deer, using polymerase chain reaction (PCR). We aligned nucleotide sequences of the PRNT gene and the amino acid sequences of prion-related protein (Prt) protein among several species. In addition, we performed phylogenetic analysis to measure the evolutionary relationships of the PRNT gene in the Cervidae family. Furthermore, we performed homology modeling of the Prt protein using SWISS-MODEL and compared the structure of Prt protein between sheep and the Cervidae family using the Swiss-PdbViewer program. We obtained much longer PRNT sequences of red deer compared to the PRNT gene sequence registered in GenBank. Korean water deer denoted more close evolutionary distances with goats and cattle than the Cervidae family. We found 6 Cervidae family-specific amino acids by the alignment of Prt amino acid sequences. There are significantly different distributions of hydrogen bonds and the atomic distance of the N-terminal tail and C-terminal tail between sheep and the Cervidae family. We also detected the mRNA expression of PRNT gene in 3 tissues investigated. To our knowledge, this report is the first genetic study of the PRNT gene in the Cervidae family.


A patient-centered model to improve metrics without cost increase: viewing all care through the eyes of patients and families.
The need for patient-centeredness in care delivery has been articulated for decades, yet meaningful progress toward patient-centered healthcare has been hobbled by the lack of a replicable patient-centered care model and method. The authors describe the patient- and family-centered care method, built around viewing every care experience through the eyes of the patient and family, and its outcomes proving the approach is replicable and sustainable while improving outcomes without additional cost. A follow-up article on patient and family shadowing will be published in the January 2011 issue.


Psychomotor Slowing in Schizophrenia: Implications for Endophenotype and Biomarker Development.
Motor abnormalities (e.g., dyskinesia, psychomotor slowing, neurological soft signs) are core features of schizophrenia that occur independent of drug treatment and are associated with the genetic vulnerability and pathophysiology for the illness. Among this list, psychomotor slowing in particular is one of the most consistently observed and robust findings in the field. Critically, psychomotor slowing may serve as a uniquely promising endophenotype and/or biomarker for schizophrenia considering it is frequently observed in those with genetic vulnerability for the illness, predicts transition in subjects at high-risk for the disorder, and is associated with symptoms and recovery in patients. The purpose of the present review is to provide an overview of the history of psychomotor slowing in psychosis, discuss its possible neural underpinnings, and review the current literature supporting slowing as a putative endophenotype and/or biomarker for the illness. This review summarizes substantial evidence from a diverse array of methodologies and research designs that supports the notion that psychomotor slowing not only reflects genetic vulnerability, but is also sensitive to disease processes and the pathophysiology of the illness. Furthermore, there are unique deficits across the cognitive (prefix "psycho") and motor execution (root word "motor") aspects of slowing, with cognitive processes such as planning and response selection being particularly affected. These findings suggest that psychomotor slowing may serve as a promising endophenotype and biomarker for schizophrenia that may prove useful for identifying individuals at greatest risk and tracking the course of the illness and recovery.


Analogues of Dehydroacetic Acid as Selective and Potent Agonists of an Ectopic Odorant Receptor through a Combination of Hydrophilic and Hydrophobic Interactions.
Identification of potent agonists of odorant receptors (ORs), a major class of G protein-coupled receptors, remains challenging due to complex receptor-ligand interactions. ORs are present in both olfactory and non-chemosensory tissues, indicating roles beyond odor detection that may include modulating physiological functions in non-olfactory tissues. Selective and potent agonists specific for particular ORs can be used to investigate physiological functions of ORs in non-chemosensory tissues. In this study, we designed and synthesized novel synthetic dehydroacetic acid analogues as agonists of odorant receptor 895 (Olfr895) expressed in bladder. Among the synthesized analogues, (E)-3-((E)-1-hydroxy-3-(piperidin-1-yl)allylidene)-6-methyl-2H-pyran-2,4(3H)-dione (10) exhibited extremely high agonistic activity for Olfr895 in Dual-Glo luciferase reporter (EC50 =9 nm), Ca2+ imaging, and chemotactic migration assays. Molecular docking and site-directed mutagenesis studies suggested that a combination of hydrophilic and hydrophobic interactions is central to the selective and specific binding of 10 to Olfr895. The design of agonists armed with both hydrophilic and hydrophobic portions could therefore lead to highly potent and selective ligands for ectopic ORs.


Exploiting the antiproliferative potential of spiropyrazoline oxindoles in a human ovarian cancer cell line.
Cancer is still one of the deadliest diseases worldwide despite the efforts in its early detection and treatment strategies. However, most chemotherapeutic agents still present side effects in normal tissues and acquired resistance that limit their efficacy. Spiropyrazoline oxindoles might be good alternatives as they have shown antiproliferative activity in human breast and colon cancer cell lines, without eliciting cytotoxicity in healthy cells. However, their potential for ovarian cancer was never tested. In this work, the antiproliferative activity of five spiropyrazoline oxindoles was assessed in ovarian cancer cells A2780 and the biological targets and mechanism of action of the most promising compound evaluated. Compound 1a showed the highest antiproliferative effect, as well as the highest selectivity for A2780 cells compared to healthy fibroblasts. This antiproliferative effect results from the induction of cell death by mitochondria-mediated apoptosis and autophagy. In vitro DNA interaction studies demonstrated that 1a interacts with DNA by groove-binding, without triggering genotoxicity. In addition, 1a showed a strong affinity to bovine serum albumin that might be important for further inclusion in drug delivery platforms. Proteomic studies reinforced 1a role in promoting A2780 endoplasmatic reticulum (ER) stress by destabilizing the correct protein folding which triggers cell death via apoptosis and autophagy.


Multi-disciplinary supportive end of life care in long-term care: an integrative approach to improving end of life.
Optimal supportive end of life care for frail, older adults in long term care (LTC) homes involves symptom management, family participation, advance care plans, and organizational support. This 2-phase study aimed to combine multi-disciplinary opinions, build group consensus, and identify the top interventions needed to develop a supportive end of life care strategy for LTC. A consensus-building approach was undertaken in 2 Phases. The first phase deployed modified Delphi questionnaires to address and transform diverse opinions into group consensus. The second phase explored and prioritized the interventions needed to develop a supportive end of life care strategy for LTC. Development of the Delphi questionnaire was based on findings from published results of physician perspectives of barriers and facilitators to optimal supportive end of life care in LTC, a literature search of palliative care models in LTC, and published results of patient, family and nursing perspectives of supportive end of life care in long term care. The second phase involved World Café Style workshop discussions. A multi-disciplinary purposive sample of individuals inclusive of physicians; staff, administrators, residents, family members, and content experts in palliative care, and researchers in geriatrics and gerontology participated in round one of the modified Delphi questionnaire. A second purposive sample derived from round one participants completed the second round of the modified Delphi questionnaire. A third purposive sample (including participants from the Delphi panel) then convened to identify the top priorities needed to develop a supportive end-of-life care strategy for LTC. 19 participants rated 75 statements on a 9-point Likert scale during the first round of the modified Delphi questionnaire. 11 participants (participation rate 58 %) completed the second round of the modified Delphi questionnaire and reached consensus on the inclusion of 71candidate statements. 35 multidisciplinary participants discussed the 71 statements remaining and prioritized the top clinical practice, communication, and policy interventions needed to develop a supportive end of life strategy for LTC. Multi-disciplinary stakeholders identified and prioritized the top interventions needed to develop a 5-point supportive end of life care strategy for LTC.


Dermoid cyst of the scalp: intracranial extension.
Intracranial dermoids are rare and are usually associated with cutaneous scalp lesions. Five hundred forty-two scalp lesions were treated in a 22-year period, and were associated with intracranial lesions in three cases. High-risk cases can be identified by clinical and radiological features, confirmed by a computed tomography scan, and then referred for neurosurgical treatment.


A 48 kilodalton enterotoxin-related protein from Clostridium perfringens vegetative and sporulating cells.
Sporulating and vegetative cell extracts of enterotoxin-positive and enterotoxin-negative strains of Clostridium perfringens were examined by Western blotting using enterotoxin antiserum. A 48-kDa enterotoxin-related protein was found in vegetative and sporulating cell extracts of both toxin types. The results question previous reports about the ability of vegetative cells and presumptive enterotoxin-negative strains of this organism to produce enterotoxin, a protein with a molecular weight of 34 kDa.


Occupational Safety Climate in the Swedish Equine Sector.
The Swedish equine sector is considered a high-risk work environment, with relatively high injury rates and high severity of injuries. General safety research has identified a correlation between the safety performance and safety culture, but little is known about the intricacies of the safety culture in the Swedish equine sector, especially concerning managers' and employees' perceptions of their work environment. The safety climate assessment is recognised as an effective tool for identifying potential problems in the workplace, thus enhancing safety behaviour and decreasing the frequency and severity of injuries. The aim was to evaluate the safety climate at riding schools and trotting stables through the Nordic Safety Climate Questionnaire (NOSACQ-50) diagnostic tool, and to get a better understanding of the workers' perceptions regarding safety and safety management at their workplace through complementary interviews. The results showed that the safety climate was generally positive and that employees were aware of the risks relating to their work. Riding schools commonly had routines in place for risk assessment and work environment management, but such routines were often lacking at trotting stables, indicating inadequate prioritisation of safety by the management. The main area that should be targeted to improve safety in the sector is employees' prioritisation and non-acceptance of risks. Proactive instead of reactive safety management should be promoted, where safety is an integral part of daily work and all employees are encouraged to identify factors contributing to occupational injuries and develop strategies for injury prevention.


[A Case of Internal Hernia Incarceration of a Mesenteric Defect following Laparoscopic Ileocecal Resection].
A 75-year-old man underwent laparoscopic ileocecal and partial small bowel resections for the management of appendiceal cancer. The pathological diagnosis was cecal cancer(T4b[ileum, abdominal wall],N0[0/13], M0, pStage Ⅱc). After 4 months of surgery, he suddenly experienced abdominal pain and vomiting and was presented to our emergency room. He was diagnosed with bowel obstruction following which, conservative treatment was initiated through a nasogastric ileus tube implantation; however, he did not show any improvement. Subsequently, he underwent experimental laparotomy on the 18th day of the disease. Intraabdominal examination revealed herniated small intestine through a mesenteric defect, which was closed following repositioning of the herniated small intestine. The postoperative course was good, and the patient was discharged on the 10th day after surgery. No recurrence of intestinal obstruction has been observed after 1 year and 6 months. Closure of the mesenteric defect, although not commonly performed in laparoscopic colorectal surgery, is worth considering because of the risk of developing an internal hernia requiring surgical treatment, as in our case.


Indeno[1,2-c]pyrazolone acetic acids as semirigid analogues of the nonsteroidal anti-inflammatory drugs.
A series of 3-substituted indeno[1,2-c]pyrazol-4(1H)-one-2-acetic acids (3a-e) and 3-substituted indeno[1,2-c]pyrazol-4(1H)-one-1-acetic acids (4a-e) were synthesized as semirigid analogues of tolmetin (1). These compounds were evaluated for their anti-inflammatory action by investigating their ability to block arachidonic acid metabolism in vitro as well as the ability to block carrageenan-induced rat foot edema in vivo. No consistent pattern of biological activity was noted.