Single-world intervention graphs for defining, identifying, and communicating estimands in clinical trials.
Confusion often arises when attempting to articulate target estimand(s) of a clinical trial in plain language. We aim to rectify this confusion by using a type of causal graph called the Single-World Intervention Graph (SWIG) to provide a visual representation of the estimand that can be effectively communicated to interdisciplinary stakeholders. These graphs not only display estimands, but also illustrate the assumptions under which a causal estimand is identifiable by presenting the graphical relationships between the treatment, intercurrent events, and clinical outcomes. To demonstrate its usefulness in pharmaceutical research, we present examples of SWIGs for various intercurrent event strategies specified in the ICH E9(R1) addendum, as well as an example from a real-world clinical trial for chronic pain. code to generate all the SWIGs shown is this paper is made available. We advocate clinical trialists adopt the use of SWIGs in their estimand discussions during the planning stages of their studies.


Noninvasive methods to study drug distribution.
Positron emission tomography (PET) and nuclear magnetic resonance spectroscopy (MRS) are two techniques that allow the noninvasive monitoring of drug distribution in living systems (humans, animals), and dynamic contrast-enhanced magnetic resonance imaging (dMRI) provides noninvasive physiological information relevant for drug distribution. PET yields series of cross-sectional images that can be used to monitor the absolute radioactivity concentrations in tissues pixel-by-pixel, but does not allow direct identification of each of the products present. MRS produces spectra showing changes in the concentration of both the parent drug and of the metabolites separately for a sensitive volume, but does not provide a simple means for measuring absolute concentrations. dMRI, which measures the changes in the rates of relaxation of water, proportional to the concentrations of the contrast agent (usually Gd-DTPA), readily allows the determination of functional changes in cross-sectional images down to a pixel-by-pixel level. All of these methods are of special interest to evaluate the amounts of drug that can reach the target tissue, penetrate it, remain present at such targets for a sufficient length of time, and how they are metabolized at the target site. Such information may be of particular interest in the study of solid malignant tumors and may become very relevant for determining better treatment strategies. This article presents examples of successful studies of tissue pharmacokinetics with MRS and dMRI. The following article is devoted to PET.


Risk of Bacteremia in Febrile Children and Young Adults With Sickle Cell Disease in a Multicenter Emergency Department Cohort.
Bacteremia is a major cause of morbidity and mortality in children and young adults with sickle cell disease (SCD), but among those presenting to the emergency department (ED) with fever, the absolute risk of, risk factors associated with, and outcomes of bacteremia are poorly defined. To obtain contemporary data on the absolute risk of, risk factors associated with, and outcomes associated with bacteremia in children and young adults with SCD presenting to the ED with fever. A multicenter retrospective cohort study was conducted of individuals with SCD younger than 22 years (young adults) presenting to EDs within the Pediatric Health Information Systems database from January 1, 2016, to December 31, 2021, with fever (identified by diagnostic codes for fever or the collection of blood samples for cultures and intravenous antibiotic administration). Data analysis was performed from May 17 to December 15, 2022. The risk of bacteremia (defined by diagnostic coding) was identified in these children and young adults, and univariate analyses and multivariable regression were used to examine patient-level factors and bacteremia. A total of 35 548 encounters representing 11 181 individual patients from 36 hospitals were evaluated. The median age of the cohort was 6.17 (IQR, 2.36-12.11) years and 52.9% were male. Bacteremia was present in 405 encounters (1.1%, 95% CI, 1.05%-1.26%). A history of bacteremia, osteomyelitis, stroke, central line-associated bloodstream infection (CLABSI), central venous catheter, or apheresis was associated with the diagnosis of bacteremia, while age, sex, hemoglobin SC genotype, and race and ethnicity were not. In the multivariable analysis, individuals with a history of bacteremia (odds ratio [OR], 1.36; 95% CI, 1.01-1.83), CLABSI (OR, 6.39; 95% CI, 3.02-13.52), and apheresis (OR, 1.77; 95% CI, 1.22-2.55) had higher odds of bacteremia. The findings of this large cohort study suggest that bacteremia in children and young adults with SCD presenting with fever is rare. A history of invasive bacterial infection, CLABSI, or a central line appears to be associated with bacteremia, while age and SCD genotype are not.


[Evaluation of airway resistance determined by whole-body plethysmography].
Methods of estimation of the airway resistance by flow-pressure curve obtained in whole-body plethysmography are investigated. The analysis of the physical processes controlling the flow-limitation during expiration shows that these methods are useful only for healthy subjects for the estimation of the airway resistance. The way for estimation of the airway resistance by flow-pressure curve is proposed.


Failure to tolerate continuous subcutaneous treprostinil in pediatric pulmonary hypertension patients.
Continuous subcutaneous (SubQ) treprostinil is an effective therapy for pediatric patients diagnosed with pulmonary hypertension (PH). To date, the clinical characteristics and factors associated with failure to tolerate this therapy have not been described. The purpose was to describe patient-reported factors contributing to SubQ treprostinil intolerance in pediatric patients with PH. A retrospective descriptive study was performed at 11 participating sites in the United States and Canada for patients younger than 21 years of age diagnosed with PH who failed treatment to tolerate SubQ treprostinil between January 1, 2009, and December 31, 2019. All data were summarized using descriptive statistics. Forty-one patients met the inclusion criteria. The average age at SQ treprostinil initiation, and length of treatment, was 8.6 years and 22.6 months, respectively. The average maximum dose, concentration, and rate were 95.8 ng/kg/min, 6.06 mg/mL, and 0.040 mL/h, respectively. The reasons for failure to tolerate SubQ treprostinil included intractable site pain (73.2%), frequent site changes (56.1%), severe site reactions (53.7%), infections (26.8%), and noncompliance/depression/anxiety (17.1%). Thirty-nine (95.1%) patients transitioned to a prostacyclin therapy with 23 patients transitioning to intravenous prostacyclin, 5 to inhaled prostacyclin, 5 to oral prostacyclin, and 7 to a prostacyclin receptor agonist. A subset of pediatric PH patients failed to tolerate SubQ treprostinil infusions despite advances in SubQ site maintenance and pain management strategies. Intractable site pain, frequent SubQ site changes, and severe localized skin reactions were the most common reasons for failure.


Pulmonary embolism during pregnancy: a 17-year single-center retrospective MDCT pulmonary angiography study.
To determine the prevalence of pulmonary embolism (PE) and alternative diagnoses detected by computed tomography pulmonary angiography (CTPA) in pregnant women; and to assess changes over time regarding radiation dose, technical quality, and examination frequency. This retrospective study included all pregnant women referred for CTPA due to clinically suspected PE over 17 years. Two blinded radiologists reviewed the CTPAs in consensus with regard to PE, alternative diagnoses, and technical quality. We retrieved patient data regarding radiation dose metrics and associated clinical and laboratory parameters. Subgroup comparisons were performed (Wilcoxon and Kruskal-Wallis tests). Of the 237 identified patients, 8 (3.3%) were excluded due to inadequate technical CTPA quality, and 229 patients were analyzed (mean age, 31.7 years; mean gestational age, 28 ± 7 weeks). The four different CT systems used over the study period had similar technical quality (p = 0.28). Of 229 patients 16 (7%) patients had PE, 144 (62.9%) had no abnormal findings, and 69 (30.1%) had an alternative diagnosis (consolidation, other pulmonary opacities, pleural effusion, and basal atelectasis). Gestational age, symptoms, and D-dimer levels were not significantly different between patients with or without PE (p > 0.05). Over time, radiation dose exposure decreased by 30% (p < 0.001), while the number of annual examinations increased by > 4-folds. In pregnant women, CTPA rarely indicates PE and more often shows alternative diagnoses. Over 17 years, the use of CTPA in pregnancy has notably increased, while the radiation dose exposure has decreased by one third. • The use of CTPA in pregnancy has steadily risen over the last 17 years • In pregnant women, CTPA rarely reveals PE and more often shows alternative diagnoses • Recent technical improvements have substantially decreased the radiation dose exposure inherent in CTPA without reducing diagnostic image quality.


The Multidisciplinary Approach to The Study of Chronic Pelvic Pain (MAPP) Research Network*: Design and implementation of the Symptom Patterns Study (SPS).
The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network initiated a second observational cohort study-the Symptom Patterns Study (SPS)-to further investigate the underlying pathophysiology of Urologic Chronic Pelvic Pain Syndrome (UCPPS) and to discover factors associated with longitudinal symptom changes and responses to treatments. This multisite cohort study of males and females with UCPPS features a run-in period of four weekly web-based symptom assessments before a baseline visit, followed by quarterly assessments up to 36 months. Controls were also recruited and assessed at baseline and 6 months. Extensive clinical data assessing urological symptoms, nonurological pain, chronic overlapping pain syndromes, and psychosocial factors were collected. Diverse biospecimens for biomarker and microbiome studies, quantitative sensory testing (QST) data under multiple stimuli, and structural and functional neuroimaging scans were obtained under a standardized protocol. Recruitment was initiated (July 2015) and completed (February 2019) at six discovery sites. A total of 620 males and females with UCPPS and 73 Controls were enrolled, including 83 UCPPS participants who re-enrolled from the first MAPP Network cohort study (2009-2012). Baseline neuroimaging scans, QST measures, and biospecimens were obtained on 578 UCPPS participants. The longitudinal follow-up of the cohort is ongoing. This comprehensive characterization of a large UCPPS cohort with extended follow-up greatly expands upon earlier MAPP Network studies and provides unprecedented opportunities to increase our understanding of UCPPS pathophysiology, factors associated with symptom change, clinically relevant patient phenotypes, and novel targets for future interventions.


Prevalence, risk factors and treatment practices in diarrhoeal diseases in south India.
This study was done to determine the risk factors, management practices and awareness about diarrhoea. It was a cross sectional study done in a semi urban and rural areas of South Canara district of India in February 2013. A total of 167 households (575 study population) chosen systematic randomly were visited and one adult member in each house was interviewed. The houses were also inspected to assess the living conditions. Mean age of study population was 31.1 ± 20.2 years. The period prevalence of diarrhoea was 69 (12 %). Commonest associated symptoms in cases of diarrhoea were fever 30 (43.4 %) followed by abdominal cramps 29 (42 %). Nearly half of the cases with diarrhoea 34 (49.3 %) did not take any medications. Commonest treatment taken was allopathic medicines 26 (37.8 %) followed by home remedies 8 (22.9 %). Age ≤10 years (p < 0.001) was associated with risk of developing diarrhoea using binary logistic regression analysis. Among the 167 participants, awareness level about the disease was poor among 16 (9.6 %) and moderate among 149 (89.2 % participants). Awareness level was more among females (p = 0.001) and literate participants (p = 0.013). One hundred and sixteen (69.5 %) participants were not aware of any sign or symptom of dehydration other than loose stools. Majority of the participants 138 (82.6 %) preferred home remedies as the initial management of diarrhoea. Misconception about fluid restriction in diarrhoea was stated by 12(7.2 %) participants. Public education program on proper feeding and management practices is required to address the various issues identified and for containment of diarrhoea cases in future.


transFold: a web server for predicting the structure and residue contacts of transmembrane beta-barrels.
Transmembrane beta-barrel (TMB) proteins are embedded in the outer membrane of Gram-negative bacteria, mitochondria and chloroplasts. The cellular location and functional diversity of beta-barrel outer membrane proteins makes them an important protein class. At the present time, very few non-homologous TMB structures have been determined by X-ray diffraction because of the experimental difficulty encountered in crystallizing transmembrane (TM) proteins. The transFold web server uses pairwise inter-strand residue statistical potentials derived from globular (non-outer-membrane) proteins to predict the supersecondary structure of TMB. Unlike all previous approaches, transFold does not use machine learning methods such as hidden Markov models or neural networks; instead, transFold employs multi-tape S-attribute grammars to describe all potential conformations, and then applies dynamic programming to determine the global minimum energy supersecondary structure. The transFold web server not only predicts secondary structure and TMB topology, but is the only method which additionally predicts the side-chain orientation of transmembrane beta-strand residues, inter-strand residue contacts and TM beta-strand inclination with respect to the membrane. The program transFold currently outperforms all other methods for accuracy of beta-barrel structure prediction. Available at http://bioinformatics.bc.edu/clotelab/transFold.


Cerebral palsy - beyond hip deformities.
Cerebral palsy is a neurologic condition with myriad musculoskeletal and articular manifestations. While every patient is unique with innumerable variations in presentation, symptoms and treatments, there are broad themes and recognizable patterns of development. Many of these findings spill over to other neurodevelopmental disorders, and lessons learned from children with cerebral palsy translate well to multiple neurologic conditions. This review focuses on the more common manifestations involving the spine, knee, foot and ankle, with an emphasis on collecting and describing imaging features, along with clinical and radiologic pearls and pitfalls.


[Anomalies of human gonadal function in periodic hemodialysis: role of the etiology of kidney failure and the role of iron overload].
Levels of testosterone, free testosterone, oestrogen, LH, FSH, prolactin were measured in 39 dialysed men. A LHRH stimulation test was performed. This study was analysed in function of the underlying renal disease, the duration of hemodialysis, and serum ferritin levels. In chronic glomerulonephritis serum gonadotrophins concentrations were significantly higher than in chronic interstitial nephritis or polycystic disease. A correlation between prolactin and ferritin was found, which may reflect the pituitary iron overload. Free testosterone levels were significantly lower in patients with gynecomastia (23-29 patients). In fact, the most direct relationship that we found with gynecomastia in dialysed men was with the free testosterone/oestrogen ratio.


Prevalence of Toxoplasma gondii antibodies in stray cats in Sari, northern Iran.
Cats are important in the epidemiology of Toxoplasma gondii because they are the only hosts that can excrete environmentally resistant oocysts. T.gondii is a major zoonotic agent which infects up to one-third of the world population. Toxoplasmosis in neonates and immunocompromised patients can lead to severe disease and death. A cross- sectional parasitological and serological survey with latex agglutination test (LAT) to detect anti-T. gondii antibodies was conducted on 100 serum samples collected from stray cats in five urban areas of Sari, Northern Iran, from April to November 2004. Classification by age, sex, weight, season and region was made. Results analyzed according to specific variables. The overall prevalence of T. gondii IgG antibodies (LAT titre > or = 1:1) were found in 40 of 100(40%) of stray cats, with regional variations. Overall 16 of 100(16%) of stray cats had diagnostically significant antibody titres (LAT > or = 1:64). Prevalence was significantly higher in adult cats (1.5-3.0 kg, 54.5% of 66) than in juvenile cats and kittens (< or = 1.4 kg, 11.8% of 34) and higher in female stray cats (44.4% of 72) than in male stray cats (28.6% of 28). Toxoplasma seroprevalence was highest in the season of spring (22.4%). There was a significant difference in the prevalence of infection relative to host age and weight (P < 0.05). No significant difference was found between the prevalence of infection relative to host gender, urban sites and season (P > 0.05). Prevalence of T. gondii oocyst was also analyzed by a routine coprological method in 100 cats. T. gondii oocysts were not found in any faecal samples analyzed. Only 2 out of 100 smear preparations of intestinal mucosa showed trophozoites of T. gondii.


Increased serum placenta growth factor level is significantly associated with progression, recurrence and poor prognosis of oral squamous cell carcinoma.
We recently found that the expression of placenta growth factor (PlGF) in oral squamous cell carcinoma (OSCC) specimens is correlated with the progression and prognosis of OSCC. In this study, serum samples were obtained from 72 OSCC patients before and 3 months after surgical cancer excision and from 30 normal controls. Serum PlGF levels were determined by enzyme-linked immunosorbent assay (ELISA). The mean serum PlGF levels were significantly higher in pre-surgery OSCC patients than in normal controls (19.1±10.7 vs. 10.1±4.5, P<0.001). Serum PlGF levels dropped to near the normal control levels after surgical cancer removal. Higher pre-surgery serum PlGF levels were significantly associated with larger tumor size (P=0.015), positive lymph node metastasis (P=0.001), more advanced clinical stages (P=0.002), and loco-regional recurrence (P=0.037). The serum PlGF level was identified as an independent unfavorable prognosis factor by multivariate Cox regression analyses (P=0.014). Kaplan-Meier curve showed that OSCC patients with a higher serum PlGF level had a significantly poorer cumulative recurrence-free survival than those with a lower serum PlGF level (log-rank test, P=0.009). When we used the serum PlGF level of 19.1 pg/ml (mean normal control value plus 2 standard deviations) as a cutoff point, the sensitivity, specificity, and positive predictive value for tumor recurrence was 80%, 56% and 78%, respectively. We conclude that the serum PlGF level may be a valuable biomarker for prediction of therapeutic effect, progression, recurrence and prognosis of OSCC.


Comprehensive Genomic Profiling Identifies Frequent Drug-Sensitive EGFR Exon 19 Deletions in NSCLC not Identified by Prior Molecular Testing.
Reliable detection of drug-sensitive activating EGFR mutations is critical in the care of advanced non-small cell lung cancer (NSCLC), but such testing is commonly performed using a wide variety of platforms, many of which lack rigorous analytic validation. A large pool of NSCLC cases was assayed with well-validated, hybrid capture-based comprehensive genomic profiling (CGP) at the request of the individual treating physicians in the course of clinical care for the purpose of making therapy decisions. From these, 400 cases harboring EGFR exon 19 deletions (Δex19) were identified, and available clinical history was reviewed. Pathology reports were available for 250 consecutive cases with classical EGFR Δex19 (amino acids 743-754) and were reviewed to assess previous non-hybrid capture-based EGFR testing. Twelve of 71 (17%) cases with EGFR testing results available were negative by previous testing, including 8 of 46 (17%) cases for which the same biopsy was analyzed. Independently, five of six (83%) cases harboring C-helical EGFR Δex19 were previously negative. In a subset of these patients with available clinical outcome information, robust benefit from treatment with EGFR inhibitors was observed. CGP identifies drug-sensitive EGFR Δex19 in NSCLC cases that have undergone prior EGFR testing and returned negative results. Given the proven benefit in progression-free survival conferred by EGFR tyrosine kinase inhibitors in patients with these alterations, CGP should be considered in the initial presentation of advanced NSCLC and when previous testing for EGFR mutations or other driver alterations is negative. Clin Cancer Res; 22(13); 3281-5. ©2016 AACR.


[Diagnostic significance of tests with toxoplasmin in clinical practice].
Intracutaneous test (ICT) with toxoplasmin is a technically simple and inexpensive method of laboratory diagnosis of toxoplasmosis. Of the 5472 examined sick persons, 54.28 percent displayed a positive ICT. With a positive ICT, any titer of any serological reaction of toxoplasmosis is regarded as a diagnostic titer.


Regional analgesia on pediatric medical and surgical wards.
Regional anesthetic approaches to pain management were examined in 72 children and young adults (ages 3 weeks to 31 years) who were observed on the surgical or medical wards of a children's hospital separate from intensive care areas. A protocol was devised to permit safe conduct of these techniques on the ward. Full resuscitation supplies were kept at each bedside. All patients receiving epidural narcotics had an apnea monitor, hourly counting of respiratory rates, and restriction of systemic analgesics. All bolus re-injections into the catheters were performed by an anesthesiologist who monitored the patient for 20 min. Minor side-effects, including pruritus, nausea, and urinary retention were common, but manageable. Significant complications included: one case of decubitus ulcers requiring skin-grafting, one episode of mild hypotension in a patient with terminal malignancy, requiring ephedrine and phenylephrine, and one mild toxic reaction on test dosing due to presumed intravascular migration of a lumber sympathetic catheter. Regional analgesic techniques can provide excellent analgesia on the wards for selected children and young adults, provided precautions are taken. Further study is required to define specific indications, risks and benefits relative to simpler techniques.


The mutational profiles and corresponding therapeutic implications of PI3K mutations in cancer.
Genetic alterations of the PIK3CA gene, encoding the p110α catalytic subunit of PI3Kα enzyme, are found in a broad spectrum of human cancers. Many cancer-associated PIK3CA mutations occur at 3 hotspot locations and are termed canonical mutations. Canonical mutations result in hyperactivation of PI3K and promote oncogenesis via the PI3K/AKT/mTOR and PI3K/COX-2/PGE2 signaling pathways. These mutations also may serve as predictive biomarkers of response to PI3K inhibitors, as well as NSAID therapy. A large number of non-canonical PIK3CA mutations have also been identified in human tumors, but their functional properties are poorly understood. Here we review the landscape of PIK3CA mutations in different cancers and efforts underway to define the functional properties of non-canonical PIK3CA mutations. In addition, we summarize what has been learned from clinical trials of PI3K inhibitors as well as current trials incorporating these molecular targeting agents.


Evaluating the evidence for sex differences: a scoping review of human neuroimaging in psychopharmacology research.
Although sex differences in psychiatric disorders abound, few neuropsychopharmacology (NPP) studies consider sex as a biological variable (SABV). We conducted a scoping review of this literature in humans by systematically searching PubMed to identify peer-reviewed journal articles published before March 2020 that (1) studied FDA-approved medications used to treat psychiatric disorders (or related symptoms) and (2) adequately evaluated sex differences using in vivo neuroimaging methodologies. Of the 251 NPP studies that included both sexes and considered SABV in analyses, 80% used methodologies that eliminated the effect of sex (e.g., by including sex as a covariate to control for its effect). Only 20% (50 studies) adequately evaluated sex differences either by testing for an interaction involving sex or by stratifying analyses by sex. Of these 50 studies, 72% found statistically significant sex differences in at least one outcome. Sex differences in neural and behavioral outcomes were studied more often in drugs indicated for conditions with known sex differences. Likewise, the majority of studies conducted in those drug classes noted sex differences: antidepressants (13 of 16), antipsychotics (10 of 12), sedative-hypnotics (6 of 10), and stimulants (6 of 10). In contrast, only two studies of mood stabilizers evaluated SABV, with one noting a sex difference. By mapping this literature, we bring into sharp relief how few studies adequately evaluate sex differences in NPP studies. Currently, all NIH-funded studies are required to consider SABV. We urge scientific journals, peer reviewers, and regulatory agencies to require researchers to consider SABV in their research. Continuing to ignore SABV in NPP research has ramifications both in terms of rigor and reproducibility of research, potentially leading to costly consequences and unrealized benefits.


Effect of nitro groups on the photo physical properties of benzimidazolone: a solvatochromic study.
Electronic absorption and fluorescence spectra of mono, di, and tri-nitro benzimidazolones are measured at room temperature (298 K) in nine solvents with different polarities and the observed shifts are compared with benzimidazolone. Ground and excited state electric dipole moments are determined using the solvatochromic method based on the bulk solvent properties, F(1)(ε, n) and F(2)(ε, n). A reasonable agreement is observed between the experimental and ab initio dipole moments. Change in dipole moment is also determined using the solvatochromic method based on the microscopic solvent polarity parameter, (E(T)(N)), which considers the polarization changes due to hydrogen bonding in different solvents. It has been observed that the correlation of the solvatochromic Stokes shifts with the parameter (E(T)(N)), is superior to that derived using bulk solvent polarity functions for all the benzimidazolones reported in the present study. Calculated difference between excited state and ground state dipole moments seems to be a good measure of the effect of nitro group when correlated with (E(T)(N)).


Therapeutic effects of cell-permeant peptides that activate G proteins downstream of growth factors.
In eukaryotes, receptor tyrosine kinases (RTKs) and trimeric G proteins are two major signaling hubs. Signal transduction via trimeric G proteins has long been believed to be triggered exclusively by G protein-coupled receptors (GPCRs). This paradigm has recently been challenged by several studies on a multimodular signal transducer, Gα-Interacting Vesicle associated protein (GIV/Girdin). We recently demonstrated that GIV's C terminus (CT) serves as a platform for dynamic association of ligand-activated RTKs with Gαi, and for noncanonical transactivation of G proteins. However, exogenous manipulation of this platform has remained beyond reach. Here we developed cell-permeable GIV-CT peptides by fusing a TAT-peptide transduction domain (TAT-PTD) to the minimal modular elements of GIV that are necessary and sufficient for activation of Gi downstream of RTKs, and used them to engineer signaling networks and alter cell behavior. In the presence of an intact GEF motif, TAT-GIV-CT peptides enhanced diverse processes in which GIV's GEF function has previously been implicated, e.g., 2D cell migration after scratch-wounding, invasion of cancer cells, and finally, myofibroblast activation and collagen production. Furthermore, topical application of TAT-GIV-CT peptides enhanced the complex, multireceptor-driven process of wound repair in mice in a GEF-dependent manner. Thus, TAT-GIV peptides provide a novel and versatile tool to manipulate Gαi activation downstream of growth factors in a diverse array of pathophysiologic conditions.


Pharmacologic effects of lactones isolated from Pulsatilla alpina subsp. apiifolia.
Two lactone compounds, protoanemonin and anemonin, were determined in the flowering aerial parts of P. alpina subsp. apiifolia. Anemonin is the primary compound responsible for the antipyretic activity and both anemonin and protoanemonin participate in the sedating effect.


[Remote results of surgical treatment of chronic nonspecific suppurative lung diseases under conditions of Extreme North].
137 patients, who underwent various lung operations under the conditions of the Extreme North, were examined within the period from 1.5 to 9 years after operation. Good results were found in 87 patients (63.5%), satisfactory ones in 30 patients (20.9%) and poor results - in 20 patients (14.6%).


Therapeutic effectiveness of acetazolamide in hindbrain hernia headache.
A 43-year-old man had been suffering from exertional headache for 10 years. Sagittal sections on magnetic resonance imaging showed a Chiari type 1 malformation and a cerebellar arachnoid cyst. This syndrome, named hindbrain hernia headache, disappeared with oral acetazolamide. This treatment should be tried in patients with hindbrain hernia headache prior to considering surgical decompression of the foramen magnum.


Performance limitations from delay in human and mechanical motor control.
We discuss natural limitations on motor performance caused by the time delay required for feedback signals to propagate within the human body or mechanical control systems. By considering a very simple delayed linear servomechanism model, we show there exists a best possible speed-accuracy trade-off similar to Fitts' law that cannot be exceeded when delay is present. This is strictly a delay effect and does not occur for the ideal case of instantaneous feedback. We then examine the performance of the vector integration to endpoint (VITE) circuit as a model of human movement and show that when this circuit is generalized to include delayed feedback the performance may not exceed that of the servomechanism with an equal delay. We suggest the existence of such a limitation may be a ubiquitous consequence of delay in motor control with the implication that the index of performance in Fitts' law cannot arbitrarily large.


Day-to-day variability of myocardial ischemic episodes in coronary artery disease.
Twenty patients with chronic stable angina pectoris, proved coronary artery disease, positive treadmill stress test response, and at least 2 episodes of ischemia per day underwent 72 hours of Holter monitoring during daily activities. During this period they had 389 ischemic episodes: 104 (27%) symptomatic and 285 (73%) silent. Marked variability was observed between patients in the number of ischemic episodes (range 2 to 15 per day, mean 6.5), duration of ischemia (range 6 to 419 minutes/day, mean 76.5), maximal ST depression (range 1 to 6 mm, mean 3.4) and heart rate at the beginning of ST depression (range 75 to 105 beat/min, mean 91). The day-to-day variability in individual patients between the different days in the number of ischemic episodes was 36%, in duration 51%, and in maximal degree of ST depression 31%. Only 9% variability was noted in heart rate at the beginning of ST depression. Similar day-to-day variability in individual patients was noted in the symptomatic and silent episodes. For clinical purposes of evaluation of ischemia during daily activities, 1 day of monitoring appears to be sufficient because within the first day, 78% of the maximal number of ischemic episodes, 64% of their duration, and 84% of the maximal degree of ST depression were detected. However, for evaluation of anti-ischemic drugs at least 2 monitoring days are required.


The effect of synthetic peptides corresponding to Fc sequences in human IgG1 on various steps in the B cell activation pathway.
The influence of synthetic peptides comprising sequences in the exposed positions of the Fc region of human IgG 1 was tested on B lymphocyte activation. CH 2 domain peptides having an inhibitory effect on antibody-dependent cellular cytotoxicity, as well as the whole Fc fragment, induced the appearance of the early signs of activation on resting B lymphocytes such as increase in cell volume and HLA-DR antigen expression or leukocyte migration inhibitory factor production. The peptides did not induce proliferation of resting B cells even when B cell growth factor (BCGF)-containing supernatants were added. Exposure to Fc fragment, however, induced a weak proliferation which was significantly enhanced by BCGF. On the other hand, both the Fc fragment and the CH 2 or CH 3 domain peptides enhanced the IgM synthesis of human blood mononuclear cells when a suboptimal dose of pokeweed mitogen was present. This effect was lost when Fc fragment or the peptides were added on the third day of culture. These results suggest that the early steps of B cell activation can be induced by Fc fragment and by small molecular weight Fc peptides, which are potential ligands of Fc receptors. The Fc fragment activates B cells to the state where they respond to BCGF, but the peptides do not possess this activity. Furthermore, both Fc fragment and Fc peptides are able to enhance the IgM synthesis, when accessory cells and the appropriate differentiating factors are present.


Rate of pathologic complete response with increased interval between preoperative combined modality therapy and rectal cancer resection.
Recent data suggest a favorable prognosis for rectal cancer patients with a pathologic complete response to preoperative combined modality therapy. Prolongation of the interval between preoperative combined modality therapy and surgery (RT-surgery interval) as a means of increasing pathologic complete response rate has not been fully examined. One hundred and fifty-five rectal cancer patients undergoing preoperative pelvic external beam radiation therapy and 5-fluorouracil-based chemotherapy followed by rectal resection were identified. All patients had endorectal ultrasound prior to combined modality therapy. Final pathology reports were reviewed for ypT and ypN stage and margin status. Medical records were reviewed for sphincter preservation, operative time, estimated blood loss, hospital stay, and morbidity (overall, anastomotic, and perineal). A pathologic complete response (ypT0N0) occurred in 24 patients (15 percent). Median RT-surgery interval was 44 (range, 15-206) days. A pathologic complete response occurred in 19 percent of patients with an interval >44 days, vs. 12 percent in those with an interval < or =44 days ( P = 0.27). Downstaging by three stages occurred more frequently in the long-interval group (15 percent vs. 6 percent, P = 0.11). The rates of sphincter preservation, positive margins, estimated blood loss, and operative time were not significantly different. Overall morbidity was similar between groups. Our results demonstrate a trend toward increased pathologic complete response rate and downstaging with increased RT-surgery interval. However, sphincter preservation is not increased. Until prospective analyses are conducted assessing the impact of prolonged RT-surgery interval on long-term outcome, the benefit of a prolonged interval between the completion of preoperative combined modality therapy and surgery remains unclear.


Comparison of direct and indirect measurements of the central motor conduction time in the monkey.
The goal of the present study was to compare the indirect estimate of the central motor conduction time (CMCT) with direct measurement of the corticospinal conduction time between the motor cortex and cervical enlargement in macaque monkeys. Responses to transcranial magnetic stimulation of the motor cortex were recorded from intrinsic hand muscles in adult macaque monkeys. The CMCT was calculated by subtracting the peripheral conduction time, measured with the F-wave method, from the latency of the motor evoked potentials (MEPs). In two monkeys, the actual conduction time between the motor cortex and cervical enlargement was measured directly by different invasive techniques. We found that the indirect calculation of CMCT overestimates the corticospinal conduction time to a significant extent. One possible source of error is an underestimate of the MEP peripheral conduction time. A collision test confirmed this hypothesis and showed that only a marginal proportion of the motoneurones that respond to a weak corticospinal input also participate in the F-wave. A more accurate estimate of the CMCT could be obtained by using the longest F-wave latency, rather than the shortest, to calculate the peripheral conduction time.


Fatal right-sided nonbacterial endocarditis associated with pulmonary artery catheterization.
Pulmonary artery (PA) catheterization is now a routine procedure in the care of critically ill patients. We report a case in which a pulmonary artery catheter was a major factor in the demise of a patient who developed adult respiratory distress syndrome following a septic abortion.


Lycopene attenuates chlorpyrifos-induced hepatotoxicity in rats via activation of Nrf2/HO-1 axis.
Chlorpyrifos (CPF), is an organophosphate pesticide that is widely used for agricultural purposes. However, it has well-documented hepatotoxicity. Lycopene (LCP) is a plant-derived carotenoid with antioxidant and anti-inflammatory activities. The present work was designed to evaluate the potential hepatoprotective actions of LCP against CPF-induced hepatotoxicity in rats. Animals were assigned into five groups namely: Group I (Control), Group II (LCP), Group III (CPF), Group IV (CPF + LCP 5 mg/kg), and Group V (CPF + LCP 10 mg/kg). LCP offered protection as evidenced by inhibiting the rise in serum activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) induced by CPF. This was confirmed histologically as LCP-treated animals showed liver tissues with less proliferation of bile ducts and periductal fibrosis. LCP significantly prevented the rise in hepatic content of malondialdehyde (MDA), depletion of reduced glutathione (GSH), and exhaustion of glutathione-s-transferase (GST) and superoxide dismutase (SOD). Further, LCP significantly prevented hepatocyte death as it ameliorated the increase in Bax and the decrease in Bcl-2 expression induced by CPF in liver tissues as determined immunohistochemically. The observed protective effects of LCP were further confirmed by a significant enhancement in heme oxygenase-1 (HO-1) and NF-E2-related factor 2 (Nrf2) expression. In conclusion, LCP possesses protective effects against CPF-induced hepatotoxicity. These include antioxidation and activation of the Nrf2/HO-1 axis.


The role of adenosine triphosphate in migraine.
Classical migraine is associated with two distinct phases; an initial vasoconstriction followed by vasodilatation. The "purinergic" hypothesis for migraine was originally put forward in 1981 as a basis for the reactive hyperaemia and pain during the headache phase. It was suggested that adenosine 5'-triphosphate (ATP) and its breakdown products adenosine 5'-monophosphate and adenosine were strong contenders for mediating the vasodilatation following the initial vasospasm and subsequent hypoxia. ATP was also implicated in the pathogenesis of pain during migraine via stimulation of primary afferent nerve terminals located in the cerebral vasculature. Recent studies have shown that the ATP-induced cerebral vasodilation is endothelium-dependent via activation of P2Y-purinoceptors on the endothelial cell surface and subsequent release of endothelium-derived relaxing factor (EDRF); and that the endothelial cells are the main local source of the ATP involved, although adenosine 5'-diphosphate and ATP released from aggregating platelets may also contribute to this vasodilatation. These findings have extended the "purinergic" hypothesis for migraine in two ways. Firstly, they have clarified the mechanism of purinergic vasodilatation during the headache phase of migraine. Secondly, they suggest that a purinergic mechanism may also be involved in the initial local vasospasm, via P2X-purinoceptors on smooth muscle cells occupied by ATP released either as a cotransmitter with noradrenaline from perivascular sympathetic nerves or from damaged endothelial cells.


Use of Praise and Reprimands as Critical Ingredients of Teacher Behavior Management: Effects on Children's Development in the Context of a Teacher-Mediated Classroom Intervention.
This intervention study examined teachers' use of verbal praise and reprimands as specific components of teacher behavior management that can promote children's development in schools. The impact of teacher praise and reprimands on children's development was examined in the context of a teacher-mediated, classroom intervention. The sample involved 570 children and 30 teachers from second grade classrooms in 15 primary schools. The Good Behavior Game was implemented in half of the classrooms based on random assignment within schools. Teacher behavior management (praise for appropriate behavior and reprimands for inappropriate behavior) was observed during regular classroom lessons. Hyperactive, disruptive, and withdrawn child behavior were assessed using teacher and peer reports, global self-concept and emotional engagement were assessed using child self-reports. All variables were assessed at the beginning (pre-test) and at the end (post-test) of the school year. Multilevel regression models accounted for the nested structure of the data. The results suggested positive effects of fewer reprimands and more praise on child outcomes (except emotional school engagement), although the results differed by informant. We also found indirect effects of the Good Behavior Game (GBG) on child outcomes via teacher praise and reprimands. Overall, the study suggests that teachers' use of praise and reprimands is a malleable classroom factor that influences children's behavioral and socio-emotional development.


Fluctuations of extreme eigenvalues of sparse Erdős-Rényi graphs.
We consider a class of sparse random matrices which includes the adjacency matrix of the Erdős-Rényi graph G ( N , p ) . We show that if N ε ⩽ N p ⩽ N 1 / 3 - ε then all nontrivial eigenvalues away from 0 have asymptotically Gaussian fluctuations. These fluctuations are governed by a single random variable, which has the interpretation of the total degree of the graph. This extends the result (Huang et al. in Ann Prob 48:916-962, 2020) on the fluctuations of the extreme eigenvalues from N p ⩾ N 2 / 9 + ε down to the optimal scale N p ⩾ N ε . The main technical achievement of our proof is a rigidity bound of accuracy N - 1 / 2 - ε ( N p ) - 1 / 2 for the extreme eigenvalues, which avoids the ( N p ) - 1 -expansions from Erdős et al. (Ann Prob 41:2279-2375, 2013), Huang et al. (2020) and Lee and Schnelli (Prob Theor Rel Fields 171:543-616, 2018). Our result is the last missing piece, added to Erdős et al. (Commun Math Phys 314:587-640, 2012), He (Bulk eigenvalue fluctuations of sparse random matrices. arXiv:1904.07140), Huang et al. (2020) and Lee and Schnelli (2018), of a complete description of the eigenvalue fluctuations of sparse random matrices for N p ⩾ N ε .


Education in the management of juvenile chronic arthritis. Changes in self-reported competencies among adolescents and parents of young children.
The purpose was to evaluate changes in self-reported competencies following an education program among parents of children with juvenile chronic arthritis (JCA) and among adolescents with JCA. The self-reported, 24-item MEPS questionnaire was used for evaluating the program. Fifty-five parents and 11 adolescents completed the questionnaire before, directly after, and four months after the eight-hour program. Parents in the education program improved significantly concerning their self-reported competencies on medical, exercise, pain and social support issues, while the adolescents showed only minor improvement. The parents' positive development in some comparisons was also significant in relation to that of a non-educated group, whose responses remained mainly unchanged over the four months. Given the advantages of the education program indicated in the study, parent education should be a self-evident part of the treatment in JCA.


The relationship among cognitive schemas, job-related traumatic exposure, and posttraumatic stress disorder in journalists.
American newspaper journalists (N = 906) participated in a study examining a cognitive mediational model for explaining the relationship between exposure to work-related traumatic events and work-related posttraumatic stress disorder (PTSD). Results indicated (a) greater exposure to work-related traumatic events was associated with work-related PTSD symptoms, as well as negative cognitive schemas; (b) cognitive beliefs partially accounted for PTSD symptoms, but the full cognitive mediational model was not supported. Implications include targeting interventions for journalists who experience traumatic stress and modifying theories about PTSD symptoms in journalists.


Helminths revive to survive.
Helminth parasites are well known to have co-evolved a diverse arsenal of immunomodulatory factors to aid their persistence following infection. In this issue, Karo-Atar et al. (2022. J. Exp. Med.https://doi.org/10.1084/jem.20212311) demonstrate that products released by the gut-dwelling helminth Heligmosomoides polygyrus barkeri modify intestinal stem cells into a "revival" state, which is associated with a loss of helminth-expelling secretory cell types from the epithelium.


IMPARO: inferring microbial interactions through parameter optimisation.
Microbial Interaction Networks (MINs) provide important information for understanding bacterial communities. MINs can be inferred by examining microbial abundance profiles. Abundance profiles are often interpreted with the Lotka Volterra model in research. However existing research fails to consider a biologically meaningful underlying mathematical model for MINs or to address the possibility of multiple solutions. In this paper we present IMPARO, a method for inferring microbial interactions through parameter optimisation. We use biologically meaningful models for both the abundance profile, as well as the MIN. We show how multiple MINs could be inferred with similar reconstructed abundance profile accuracy, and argue that a unique solution is not always satisfactory. Using our method, we successfully inferred clear interactions in the gut microbiome which have been previously observed in in-vitro experiments. IMPARO was used to successfully infer microbial interactions in human microbiome samples as well as in a varied set of simulated data. The work also highlights the importance of considering multiple solutions for MINs.


Ontogeny of the rabbit's circadian rhythms without an external zeitgeber.
We have monitored parturition and different behavioral rhythms of does, the activity of suckling pups and behavioral rhythms of rabbits after weaning until adulthood. All animals were living in continuous light conditions (LL). As a consequence of the free-run of the does parturition, which takes place during the resting period of the animal, occurred at almost any time of the day. The once/day nursing was advanced during the first 7-10 days until it was in synchrony with the time of main activity. The pups significantly anticipated nursing by day 5: the 60 min bin prior to nursing exceeded the 24-h mean by 63 +/- 30%. The anticipatory activity (AA) was entrained by an artificial nursing schedule of T = 24 h, the 60 min bin prior to nursing exceeding the 24-h mean by 123 +/- 50%. Since AA persisted during a 48 h fast, its phase is controlled endogenously. At weaning behavioral rhythms of rabbits free-ran with a main tau < 24 h (average 23:35 +/- 17'), period length extending with increasing age. 7/10 animals had an additional component > 24 h (average: 24:24 +/- 16') which became increasingly dominant, the components < 24 h fading out within 30 days after weaning. Between days 340-350 a stable period length of 24:35 +/- 8' and a consolidation of the circadian rhythms was attained. These results confirm that during the first days of the rabbit's life the circadian system is controlled by a feeding entrainable oscillator, the light entrainable oscillators taking over control later.


Health Economic Impact of a Multicenter Quality-of-Care Initiative for Reducing Unplanned Healthcare Utilization Among Patients With Inflammatory Bowel Disease.
A multicenter adult inflammatory bowel disease learning health system (IBD Qorus) implemented clinical care process changes for reducing unplanned emergency department visits and hospitalizations using a Breakthrough Series Collaborative approach. Using Markov decision models, we determined the health economic impact of participating in the Collaborative from the third-party payer perspective. Across all 23 sites, participation in the Collaborative was associated with lower annual costs by an average of $2,528 ± $233 per patient when compared with the baseline period. Implementing clinical care process changes using a Collaborative approach was associated with overall cost savings. Future work should examine which specific interventions are most effective and whether such cost savings are sustainable.


Plasma lipidomic profiles after a low and high glycemic load dietary pattern in a randomized controlled crossover feeding study.
Dietary patterns low in glycemic load are associated with reduced risk of cardiometabolic diseases. Improvements in serum lipid concentrations may play a role in these observed associations. We investigated how dietary patterns differing in glycemic load affect clinical lipid panel measures and plasma lipidomics profiles. In a crossover, controlled feeding study, 80 healthy participants (n = 40 men, n = 40 women), 18-45 y were randomized to receive low-glycemic load (LGL) or high glycemic load (HGL) diets for 28 days each with at least a 28-day washout period between controlled diets. Fasting plasma samples were collected at baseline and end of each diet period. Lipids on a clinical panel including total-, VLDL-, LDL-, and HDL-cholesterol and triglycerides were measured using an auto-analyzer. Lipidomics analysis using mass-spectrometry provided the concentrations of 863 species. Linear mixed models and lipid ontology enrichment analysis were implemented. Lipids from the clinical panel were not significantly different between diets. Univariate analysis showed that 67 species on the lipidomics panel, predominantly in the triacylglycerol class, were higher after the LGL diet compared to the HGL (FDR < 0.05). Three species with FA 17:0 were lower after LGL diet with enrichment analysis (FDR < 0.05). In the context of controlled eucaloric diets with similar macronutrient distribution, these results suggest that there are relative shifts in lipid species, but the overall pool does not change. Further studies are needed to better understand in which compartment the different lipid species are transported in blood, and how these shifts are related to health outcomes. This trial was registered at clinicaltrials.gov as NCT00622661.


Effect of caerulein in patients with biliary colic pain.
A randomized placebo-controlled double-blind trial was carried out in 24 patients with biliary colic pain in order to evaluate the analgesic effect of caerulein (CRL). Caerulein (1 ng/kg . min infused intravenously over 15 min) showed an analgesic effect that was significantly higher than placebo (p less than 0.001). The analgesic action of CRL was not inhibited by naloxone (0.4 mg intravenously, administered two times). Further, the effect of i.v. CRL or saline on artificially induced biliary tree hypertension was studied in 7 patients with a T-tube common bile duct drainage. During saline intravenous administration, increasing biliary tree pressure resulted in pain in 5 patients, with the threshold for pain being 40 cmH2O. During CRL intravenous infusion, significantly higher perfusion pressures were required to achieve a given common bile duct pressure and the pressure threshold for pain was not reached. Consequently, pain was prevented in all patients. These data suggest that CRL relieves biliary colic pain by reducing biliary tract pressure.


Assessing the impact of green consumption behavior and green purchase intention among millennials toward sustainable environment.
Social media is playing a vital role in the promotion of green products by reshaping the millennial green purchasing intention and green consumption behaviors, resulting in progressive growth toward sustainable environment and lower carbon emission. Non-organic consumption among humans has increased the carbon emission in contrary risked environment; therefore, consumption behavior and purchasing intention are required to change for better sustainable environment. This study's goal is to determine the effects of social media in molding the consumption behaviors while considering eco-labeling, eco-branding, social norms, and purchase intensions among millennials to promote green consumption and lower carbon emission. It was decided to use a cross-sectional questionnaire survey to get information from the students of different faculties including social sciences, engineering, and bio-sciences. SPSS.V.22 and Smart-PLS were used to analyzed the data. Results indicated that social media has a profoundly good impact on molding and impacting youth behaviors regarding the green consumption, resulting in increasing intention toward sustainable environment which results in lower carbon emission. The results are in line with the predictions and contextual analysis, as the whole world is coming back toward natural life and is working for environmental protection and sustainability specially to lower the carbon emission. Therefore, students are molding themselves toward green consumption. The study recommends that future research may be conducted to study more contextual variables, who has influence on the green consumption among the general public regarding green consumptions and lowering carbon emission and stepping toward the sustainable environment.


Exploring the efficacy and safety of topical Jaungo application in patients with atopic dermatitis: A pilot randomized, double-blind, placebo-controlled study.
Atopic dermatitis (AD) is a chronic relapsing eczematous skin disease with an increasing prevalence. In Korea, Jaungo is a traditional medicinal ointment, which is commonly used for treating skin wounds. Thus, we aim to explore the basic clinical efficacy and safety data for Jaungo in patients with AD. This study was a pilot randomized, double-blind, placebo-controlled, single-center trial with three groups. The participants in treatment group 1 applied Jaungo to the lesion twice a day for 3 weeks. Those in treatment group 2 applied Jaungo and placebo ointments to the lesion once a day for 3 weeks. Those in the placebo group applied placebo ointments to the lesion twice a day for 3 weeks. The Eczema Area and Severity Index and SCORing Atopic Dermatitis scores, transepidermal water loss value, and Dermatology Life Quality Index score were assessed. The outcomes used to evaluate safety were the Draize score, blood test results, and expert opinion. In total, 28 patients (82.4%) completed the study. During the study, significant decline of EASI scores in treatment group 2 and placebo group was observed (p < 0.05). And there was significant decline of SCORAD scores in treatment group1 and placebo group (p < 0.05). Patients in all groups showed decreased TEWL and DLQI scores with no significant difference. There was significant decline of IL-17 in all groups (p < 0.05). No serious adverse event was observed. This is the first study that has explored the potential therapeutic effect of Jaungo as a complementary therapy for AD. However, further large study with adjusting placebo ingredients is needed to confirm the effectiveness of Jaungo in patients with chronic-phase AD.


Characterization of the thromboxane receptor mediating prostacyclin release from cultured endothelial cells.
The thromboxane A2 (TXA2) mimetic, 9,11-dideoxy-11,9-epoxymethano-prostaglandin F 2 alpha (U46619), mobilized calcium in the bovine aortic endothelial cell line AG4762 and stimulated release of prostacyclin from these cells. The U46619-stimulated release of prostacyclin could be inhibited by TXA2 antagonists with the order of potency [Is-[1 less than a, 2 less than b(5z), 3 less than b, 4 less than a]]-7-[3-[[2-[(phenylamino)carbonyl]hydrazino]methyl]-7-oxabicyclo- [2.2.1]hept-2-yl]-5- heptenoic acid (SQ29548) greater than 4-[2-(4-chlorobenzene-sulphonamido) ethyl]phenylacetic acid (BM13505) greater than 4-[2-(phenylsulphonamido)-ethyl]phenoxyacetic acid (BM13177), which was consistent with release being mediated by a TXA2 (TP) receptor. The TP receptor ligands, [3H]SQ29548 and 9,11-dimethylmethano-16(3-[125I]iodo-4-hydroxyphenyl)-13,14-dih ydr o-13-aza- 15-omega-o-tetranor-thromboxane ([125I]-PTA-OH), both appeared to bind to a homogenous population of sites in AG4762 cell membranes. The affinities of [3H]SQ29548 and [125I]PTA-OH were approximately 10 nM and approximately 0.3 nM, respectively, and the density of sites labelled by either ligand was approximately 25 fmol/mg protein. Under conditions where equilibrium was approached, the specific binding of [3H] SQ29548 or [125I]PTA-OH was displaced by SQ29548, BM13505 and BM13177 with the same order of potency and similar apparent affinities as in the functional assay, suggesting that these binding sites represent bona fide TP receptors.


Associations between health literacy, cognitive function and general literacy in people with schizophrenia attending community mental health clinics in Australia.
Health literacy (HL) has been defined as the ability of individuals to access, understand, and utilise basic health information. HL is crucial to patient engagement in treatment through supporting patient autonomy, informed consent and collaborative care. In people with physical disorders, poor HL is associated with poor health outcomes, but less is known about HL in people with severe mental illness. This study aimed to assess HL and investigate the associations between education, cognitive function, general literacy, and HL in participants with schizophrenia attending community mental health clinics. Fifty-two outpatients with schizophrenia attending a public community mental health clinic in Adelaide, Australia completed the Test of Functional Health Literacy in Adults-Short Form (S-TOFHLA) along with tests of cognition, aural and reading literacy and numeracy including Digit Symbol Coding (DSC), verbal fluency, the Wechsler Adult Intelligence Scale (WAIS-IV), Woodcock-Johnson III (Part 4 and 9) and the Lipkus numeracy scale. Sixty-one percent of participants were male. Participants had a mean age of 41.2 (SD 9.9) years and a mean of 11.02 (SD 1.5) years of education. The majority of participants had very poor aural and verbal literacy and poorer literacy correlated with fewer years of education. On the S-TOFHLA, 81% of participants had adequate HL; 6% were marginal and 13% were inadequate. There was a positive correlation between education and HL, with those with more years of education scoring higher for HL. There was also a significant association between better HL and better working memory and attention. Consistent with previous research in schizophrenia, our participants had reduced educational attainment, aural and reading literacy and cognitive function compared to population norms. However, HL was better than expected given that previous research has found that people with psychiatric disorders tend to have lower HL, compared to the general population. This may reflect effective case management of our participants whilst attending the community clinics and supports ongoing research and intervention regarding HL in people living with mental illness.


Investigation on the effectiveness of ventilation dilution on mitigating COVID-19 patients' secondary airway damage due to exposure to disinfectants.
Chlorine-containing disinfectants are widely used in hospitals to prevent hospital-acquired severe acute respiratory syndrome coronavirus 2 infection. Meanwhile, ventilation is a simple but effective means to maintain clean air. It is essential to explore the exposure level and health effects of coronavirus disease 2019 patients' inhalation exposure to by-products of chloride-containing disinfectants under frequent surface disinfection and understand the role of ventilation in mitigating subsequent airway damage. We determined ventilation dilution performance and indoor air quality of two intensive care unit wards of the largest temporary hospital constructed in China, Leishenshan Hospital. The chloride inhalation exposure levels, and health risks indicated by interleukin-6 and D-dimer test results of 32 patients were analysed. The mean ± standard deviation values of the outdoor air change rate in the two intensive care unit wards were 8.8 ± 1.5 h-1 (Intensive care unit 1) and 4.1 ± 1.4 h-1 (Intensive care unit 2). The median carbon dioxide and fine particulate matter concentrations were 480 ppm and 19 μg/m3 for intensive care unit 1, and 567 ppm and 21 μg/m3 for intensive care unit 2, all of which were around the average levels of those in permanent hospitals (579 ppm and 21 μg/m3). Of these patients, the median (lower quartile, upper quartile) chloride exposure time and calculated dose were 26.66 (2.89, 57.21) h and 0.357 (0.008, 1.317) mg, respectively. A statistically significant positive correlation was observed between interleukin-6 and D-dimer concentrations. To conclude, ventilation helped maintain ward air cleanliness and health risks were not observed.


Social Media Videos on Contraceptive Implants: An Assessment of Video Quality and Reliability.
There are many videos on contraception on YouTube and TikTok, and women around the world use video platforms extensively to seek health information from videos of uncertain reliability and quality. The main objective of this research was to evaluate the scientific reliability and quality of the most popular social media videos about contraceptive subdermal implants. TikTok and YouTube videos were assessed separately by two gynecologists. The video quality was evaluated according to the DISCERN score, modified DISCERN score, and Global Quality Scale (GQS) score. The study included the 100 most popular videos, 44 of which were uploaded by health care professionals. The median DISCERN score for videos shared by health care professionals was 50 (range 15-75), whereas it was 22 (range 15-56) for videos shared by independent users (P < .001). The median modified DISCERN score was 4 (min-max 0-5), and the median GQS score was 4 (min-max 1-5) for the videos uploaded by health care professionals. The modified DISCERN and GQS scores of TikTok videos were lower than those of YouTube videos (both P < .001). Social media videos about contraceptive subdermal implants are popular and have been viewed tens of thousands of times, but the overall medical validity, which we evaluated according to the scoring systems, was poor. Despite the large number of videos, the content's quality and reliability are quite limited. There is a need to prioritize the education provided to patients by gynecologists, as well as to create high-quality content for YouTube and other similar platforms.


High Variation in Single Nucleotide Polymorphisms (SNPs) and Insertions/Deletions (Indels) in the Highly Invasive Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) Middle East-Asia Minor 1 (MEAM1).
Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) Middle East-Asia Minor 1 (MEAM1) is invasive and adaptive to varied environments throughout the world. The adaptability is closely related to genomic variation such as single nucleotide polymorphisms (SNPs) and insertions/deletions (indels). In order to elucidate the feature of SNPs and indels in MEAM1, and reveal the association between SNPs/indels and adaptive capacity to various environments, a computational approach with QualitySNP was used to identify reliable SNPs and indels on the basis of 9110-expressed sequence tags of MEAM1 present in the NCBI database. There were 575 SNPs detected with a density of 10.1 SNPs/kb and 6.4 SNPs/contig. Also, 237 transitions (39.3%) and 366 transversions (60.7%) were obtained, where the ratio of transitions to transversions was 0.65:1. In addition, 581 indels with a density of 14.1 indels/kb and 9.2 indels/contig were detected. Collectively, it showed that invasive MEAM1 has high SNPs density, and higher SNPs percentage than non-invasive B. tabaci species. A high SNPs density/percentage in MEAM1 yielded a high genomic variation that might have allowed it to adapt to varied environments, which provides some support to understand the invasive nature of MEAM1 at the genomic level. High levels of genomic variation are implicated in the level of adaptive capacity and invasive species are thought to exhibit higher levels of adaptive capacity than non-invasive species.


Approaches to analysis of length of hospital stay related to antibiotic therapy in a randomized clinical trial: linezolid versus vancomycin for treatment of known or suspected methicillin-resistant Staphylococcus species infections.
As length of hospital stay (LOS) represents about 70-90% of the total cost of treating serious infections, it represents a key variable in analyzing the health economic differences between treatments for hospitalized patients. In a retrospective analysis using LOS data from a multinational, randomized, phase III clinical trial, we examined two methods (the log-logistic model and Kaplan-Meier survival function) and three approaches (unadjusted total LOS, total LOS adjusted for nontreatment factors, and adjusted LOS based on antibiotic treatment [the antibiotic treatment LOS]) for estimating antibiotic treatment effect on LOS and determined if these approaches could reduce the variation in LOS and control for the imbalance between treatment groups. The trial enrolled patients who were hospitalized with known or suspected Staphylococcus species infections who received at least one dose of linezolid or vancomycin (intent-to-treat sample) and who continued taking the study drug for at least 7 days (clinically evaluable sample). In the intent-to-treat sample, the linezolid group had a 2- (unadjusted) or 4-day (adjusted for nontreatment factors) shorter LOS at the 25th percentile; a 1- or 2-day advantage, respectively, at the 50th percentile (median); and a 0.6- or 1.6-day mean LOS advantage, compared with the vancomycin group. With the antibiotic treatment LOS approach, the linezolid group had mean and median LOS reductions comparable to or greater than those seen in the nontreatment-factor-adjusted results. Results for the clinically evaluable sample were similar to those of the intent-to-treat sample, but the differences between the treatment groups were greater. Linezolid-treated patients had significant LOS reductions that otherwise would be masked without the use of more appropriate, but less commonly used, methods.


Peptidyl human heart chymase inhibitors. 2. Discovery of highly selective difluoromethylene ketone derivatives with Glu at P3 site.
Appropriate structural modification of the difluoromethylene ketone derivatives at both P3 and P' positions led us to the discovery of peptidyl human heart chymase inhibitor 12h which shows potent activity with Ki = 6 nM and high selectivity against closely related serine protease bovine alpha-chymotrypsin (chymotrypsin Ki = > 100 microM). Using the compound 12b, a docking study with human heart chymase was carried out to presume probable interactions.


Expression of cadherins and CD44 isoforms in human endometrium and peritoneal endometriosis.
To evaluate (a) cadherins and CD44 expression in normal endometrium and in peritoneal endometriosis, and (b) to correlate, their expressions with clinicopathological parameters. E- and N-cadherin, CD44 isoforms, CD44v3 and CD44v6 expressions were evaluated: (a) by immunoblotting in endometrium (n = 6) and in peritoneal endometriotic samples (n = 7) and, (b) by immunohistochemistry in endometrium (n = 15) and in peritoneal endometriotic samples (n = 23). By immunoblotting, endometrium expressed E- and N-cadherin, CD44 isoforms, CD44v3 and CD44v6. Similar results were observed in peritoneal endometriosis. By immunohistochemistry, in endometrium, E-cadherin was restricted to epithelial cells. Its expression remained constant throughout the menstrual cycle. N-cadherin was detected in both epithelial and stromal cells in the proliferative phase but was restricted to epithelial cells in the secretory phase. CD44 immunostaining was detected in the secretory but not in the proliferative phase. Decreased expression of E-cadherin (p < 0.01) and CD44 (p < 0.01) in epithelial cells was found in peritoneal endometriosis as compared with normal endometrium. In endometriotic stromal cells, decreased CD44 expression was found. In peritoneal endometriosis, we observed a decreased expression of E-cadherin in advanced stages of the disease (p < 0.01). Our results suggest that E-cadherin and CD44 proteins could be involved in the development of endometriotic lesions. Investigation of the mechanisms of altered adhesion molecule expression may contribute to the understanding of the behavior of endometriotic cells.


Binding of ovalbumin to mouse spleen cells with and without carbodiimide.
We studied the binding of ovalbumin (OVA) to mouse spleen cells. In the presence or absence of carbodiimide (ECDI), uptake increased with greater cell numbers, increasing OVA concentration and increasing time up to 60 min. Between 60 and 210 microgram OVA could be coupled with ECDI to 2 X 10(8) cells. In the absence of ECDI, however, OVA uptake was still appreciable, but appeared to be of low avidity as it did not occur in the presence of competing fetal calf serum. These experiments provide a basis for the use of protein coupled to autologous cells in the induction of immunologic tolerance.


Acute post-streptococcal glomerulonephritis followed shortly by acute rheumatic fever.
A 16 year old girl with post-streptococcal glomerulonephritis developed acute rheumatic fever 19 days afterwards. Previous publications on concurrent post-streptococcal glomerulonephritis and acute rheumatic fever are reviewed.


Inhibiting Radiative Transition-Mediated Multifunctional Polymeric Nanoplatforms for Highly Efficient Tumor Phototherapeutics.
It is highly desired to explore ideal phototherapeutic nanoplatforms, especially containing satisfactory phototherapeutic agents (PTAs), for potential cancer therapies. Herein, we proposed an effective strategy for designing a highly efficient PTA through inhibiting radiative transition (IRT). Specifically, we developed an ultralow radiative BODIPY derivative (TPA-IBDP) by simply conjugating two triphenylamine units to iodine-substituted BODIPY, which could simultaneously facilitate the nonradiative decay channels of singlet-to-triplet intersystem crossing and intramolecular charge transfer. In comparison to the normal BODIPY compound, TPA-IBDP exhibited an outstanding singlet oxygen yield (31.8-fold) and a higher photothermal conversion efficiency (PCE; over 3-fold), respectively, benefiting from the extended π-conjugated donor-to-accepter (D-A) structure and the heavy atom effect. For tumor phototherapy using TPA-IBDP, TPA-IBDP was conjugated with a H2O2-responsive amphiphilic copolymer POEGMA10-b-[PBMA5-co-(PS-N3)2] to construct a multifunctional phototherapeutic BODIPY-based nanoplatform (PB). PB produced abundant singlet oxygen (1O2) and heat along with negligible fluorescence emission under near-infrared laser irradiation. Additionally, PB could generate a GSH-depletion scavenger (quinone methide, QM) after reacting with the abundant intracellular H2O2 in tumor for the cooperative enhancement of IRT-mediated phototherapy. We envision that this highly efficient multifunctional phototherapeutic nanoplatform cooperated by GSH-depletion could be a valuable paradigm for tumor treatments.


Treatment of alcoholics with logotherapy.
This study evaluates the results of group logoanalysis with selected hospitalized alcoholics using the Purpose in Life (PIL) Test as a before-and-after measure of therapeutic outcome in comparison with controls. Results suggest that closed-end logoanalysis groups are superior to open-end groups, and that both are superior to controls in improving the patient's sense of meaning and purpose in life as measured by the PIL.


Effect of Two Soybean Varieties Treated with Different Heat Intensities on Ileal and Caecal Microbiota in Broiler Chickens.
Soybean products are of high importance for the protein supply of poultry. Heat treatment of soybeans is essential to ensure optimal digestibility because of intrinsic antinutritive factors typical for this feed category. However, excessive treatment promotes the Maillard reaction and reduces protein digestibility. Furthermore, Europe's efforts are to decrease dependence on imports of soybean products and enlarge local production. This process will include an increase in the variability of soybean batches, posing great challenges to adequate processing conditions. Intrinsic soybean properties plus heat treatment intensity might be able to modulate the gut microbiota, which is of crucial importance for an animal's health and performance. To assess the influence of heat treatment and soybean variety on gut microbiota, 2 soybean cakes from 2 varieties were processed at 110 °C or 120 °C and subsequently fed to 336 one-day-old broiler chickens. After 36 days, the animals were slaughtered, and the digesta of the ileum and caecum was collected. Next, 16S rRNA amplicon sequencing of the extracted DNA revealed a high discrepancy between gut sections, but there were no differences between male and female birds. Significant differences attributed to the different soybean varieties and heat intensity were detected for certain bacterial taxa. However, no effect on specific families or genera appeared. In conclusion, the results indicated the potential of processing conditions and soybean variety as microbiota-modulating factors.


Comprehensive analysis of lncRNA expression profiles in postmenopausal osteoporosis.
To explore the key lncRNAs affecting postmenopausal osteoporosis (PMOP) progression, the transcriptome sequencing of peripheral blood mononuclear cells from fifteen early postmenopausal women, according to bone mineral density, were divided into groups of osteoporosis, osteopenia and normality, in each of which the expression profiles of lncRNAs was investigated. From the results we observed nine candidates of lncRNAs, which were to be compared with miRBase, and found that MIR22HG as one candidate of lncRNA was most likely to be directly used as miRNA precursor. Based on the KEGG annotation and lncRNA-miRNA-mRNA-KEGG network, we analyzed the potential role of candidate lncRNAs. The results showed that the expression profiles of lncRNAs could help identify the novel ones involved in the progression of PMOP, and that MIR22HG could serve as a miRNA precursor to regulate FoxO signaling pathway in bone metabolism. Our findings can be of great help in predicting and diagnosing early PMOP.


Molecular analysis of an EL4 cell line that expresses H-2Db but not H-2Kb or beta 2-microglobulin.
EL4/Mar is a variant cell line that expresses H-2Db but neither H-2Kb nor beta 2-microglobulin (beta 2m). Southern and RNA blot analysis and immunoprecipitation of metabolically labeled proteins established that the B2m gene(s), beta 2m mRNA, and beta 2m protein are normal in this cell line. Somatic cell hybridization showed that the defect in this cell line was in the synthesis of H-2Kb, and RNA blot analysis with an H-2Kb specific oligonucleotide established that the H-2Kb gene(s) in this cell line was not transcribed into a stable mRNA species. The apparent absence of beta 2m on the surface of this cell line suggests that there may be some feature of the H-2Db molecule that allows it to be expressed in the absence of detectable beta 2m.


Enhanced CO2 fixation and lipid production of Chlorella vulgaris through the carbonic anhydrase complex.
Photosynthesis of C. vulgaris shows slow growth and low lipid production due to the low solubility of CO2, and it is thus necessary to increase the dissolved inorganic carbon source to solve this problem. In this study, carbonic anhydrase (CA) was fused with dockerin to form a CA complex by cohesion-dockerin interaction. The CA complex was displayed on the surface of C. vulgaris by a cellulose binding module. The CA complex increased activity and stability compared to those of a single enzyme. Additionally, C. vulgaris showed an average of 1.6-fold rapid growth during log phase through the influence of the CA complex. The bicarbonate produced by the CA complex increased the lipid production about 1.7-fold (23.3%), compared to 13.6% for the control group. The present results suggest that the CA complex successfully enhances the CO2 fixation, which should be an essential study for 4th generation biofuels.


In vitro growth and phenotypic characterization of mesodermal-derived and epithelial components of normal and abnormal human thymus.
Long-term in vitro cultures of human thymic tissue were established and phenotypically characterized using monoclonal reagents that define distinct components of the human thymic microenvironment. The epithelial component of the thymus, defined by monoclonal antibodies TE-3, TE-4, BBTECS, and AE1 (anti-keratin) was isolated from the mesodermal component, defined by antibody TE-7, and maintained separately in long-term culture. The epithelial cells were subcultured repeatedly and recovered from storage in liquid nitrogen. The in vitro phenotype of the cultured cells was compared to that of cultured human epidermal cells. A subpopulation of cultured thymic epithelial cells along with a subpopulation of cultured epidermal cells expressed antigens (TE-8, TE-15) characteristic of late stages of keratinized epithelial cell differentiation. Thus, we have established a system whereby components of the human thymic microenvironment can be cultivated in vitro while maintaining the capacity to differentiate. This approach can be used to evaluate the role of components of the thymic microenvironment at various stages of differentiation on developing T lymphocytes. In addition, keratin-containing thymic epithelial cells were successfully cultured from thymuses obtained from patients with myasthenia gravis and thymoma. Cultivation of abnormal thymic epithelium will provide insight into aberrant T lymphocyte-thymic epithelial interaction.


Investigation on primary stability of dental implants through considering peri-implant bone damage, caused by small and large deformations: A validated non-linear micro finite element study.
Primary stability of a dental implant is defined as its ability to resist the applied load without showing excessive damage in peri-implant bone, which is a prerequisite for secondary stability, and consequently for implantation success. The main goal of this study was to develop a validated micro-finite element (μFE) approach to assess the primary stability of dental implants in terms of stiffness, stiffness reduction, and irreversible displacement of the bone-implant system, subjected to an increasing step-wise quasi-static compressive loading-unloading test. The μFE models were generated based on the μCT images of bone, taken from extracted bovine tibia trabecular bone samples after drilling and implantation. A tissue constitutive model was considered for trabecular bone by describing elasto-plasticity with a modified von Mises yield criterion and element deletion technique to account for trabecular bone damage behavior. Then, the obtained force-displacement curves from the simulation were compared with the in-vitro mechanical test curves to evaluate the validity of the model. The results showed that the proposed μFE model could be properly predict the bone-implant system mechanical response in terms of irreversible displacement (R2 = 0.99), stiffness (R2 = 0.77), and stiffness reduction (R2 = 0.72) of the bone-implant construct for all the applied displacements without a significant difference from the unit slope and zero intercept of the QQ-plot (p-value<0.05). Moreover, a qualitative agreement was seen between the peri-implant bone damage predicted by the μFE model and the observed from μCT images. The adopted methodology used in this study can predict the mechanical failure response of the bone-implant system, which can be employed as a representative tool to study the effects of various dental implant design parameters on the primary stability with the ultimate goal of optimizing dental implants design.


[Leg length changes after upper tibial osteotomy: analysis of different preoperative planning methods].
The amount of change in the length of the lower limb resulting from upper tibial osteotomy depends on the type of osteotomy performed, the preoperative length of the limb, the degree of preoperative deformity and the amount of correction obtained. Wedge resection, for example, removes bone tissue and can lead to shortening. Inversely, a lengthening effect may result from correction of deformity. The purpose of this article was to present an analysis of the differences between different types of osteotomies and compare their effect on leg length. Change in length of the lower limb was studied with a mathematical analysis in opening wedge osteotomy, closing wedge osteotomy, and dome osteotomy. Leg length was calculated for several preoperative deformity angles of the entire limb (hip-knee-ankle angle) and several values of planned correction. The theoretical mathematical model demonstrated that the greatest changes in leg length are obtained with opening wedge osteotomy, followed by dome, then closing wedge osteotomy. Tables were established showing calculated change in leg length. Tracings on radiographs or CT scans used to measure these changes are explained. Methods applicable in case of flexion contracture of the knee are presented. Once the initial question regarding length changes is posed, many of the points become evident on image tracings. This work points out how quickly tables can be used to recognize significant differences in leg length changes produced by different osteotomies.


Sweet/Fat Preference Taste in Subjects Who are Lean, Obese and Very Obese.
This study assessed the perception of sweetness, creaminess, and pleasantness from a sweet/fat preference test in subjects who are lean (BMI: 19-25), obese (BMI: 30-33) or very obese (BMI: 34-40) using categorical modeling. Subjects tasted 16 dairy solutions consisting of 0%, 3.5%, 11.3% and 37.5% fat and each containing 0%, 5%, 10%, or 20% sugar and rated them for sweetness, creaminess and pleasantness. A proportional odds model described the perception of sweetness using an Emax for the effect of sugar and a linear effect for fat. Perception of creaminess was dependent on the fat and sugar content and was described with proportional odds model with linear effects of sugar and fat. Perception of pleasantness increased with sugar and fat but decreased in solutions containing 37.5% fat. A differential odds model using an Emax model for fat and sugar with a negative interaction between them allowed the sugar content to be less than proportional and the fat content to be greater than proportional for pleasantness. Application of modeling provided understanding of these complex interactions of sugar and fat on the perception of sweetness, creaminess, and pleasantness and provides a tool to investigate obesity and pharmacological intervention.


Enhanced selective separation of vanadium(V) and chromium(VI) using the CeO2 nanorod containing oxygen vacancies.
Adsorption of vanadium from wastewater defends the environment from toxic ions and contributes to recover the valuable metal. However, it is still challenging for the separation of vanadium (V5+) and chromium (Cr6+) because of their similar properties. Herein, a kind of CeO2 nanorod containing oxygen vacancies is facilely synthesized which displays ultra-high selectivity of V5+ against various competitive ions (i.e., Fe, Mn, Cr, Ni, Cu, Zn, Ga, Cd, Ba, Pb, Mg, Be, and Co). Moreover, a large separation factor (SFV/Cr) of 114,169.14 for the selectivity of V5+ is achieved at the Cr6+/V5+ ratio of 80 with the trace amount of V5+ (~ 1 mg/L). The results show that the process of V5+ uptake is the monolayer homogeneous adsorption and is controlled by external and intraparticle diffusions. In addition, it also shows that V5+ is reduced to V3+ and V4+ and then formation of V-O complexation. This work offers a novel CeO2 nanorod material for efficient separation of V5+ and Cr6+ and also clarifies the mechanism of the V5+ adsorption on the CeO2 surface.


Application of the simple and efficient Mpeak modeling in binding peak identification in ChIP-chip studies.
Chromatin immunoprecipitation and hybridization of high-density promoter microarray (ChIP-chip) is a powerful strategy to identify target genes for specific transcription factors and other DNA-binding nuclear proteins in a genome-wide manner. Services of core facilities have greatly enhanced the accessibility of these technologies to new investigators to the field. The Mpeak modeling is a simple and efficient computer program, capable of identifying chromatin-binding peaks in ChIP-chip datasets. It utilizes advanced statistical computation, but yet offers a simple procedure with user inputs on parameters in its operation. The Mpeak-fitted signals are tabulation in convenient formats and can be visualized in various genome-display graphic programs, including SignalMap and Genome Browser, and analyzed together with other datasets, such as microarray expression patterns. Several research groups have used the Mpeak program in their respective ChIP-chip studies. The various features of Mpeak will be illustrated with ChIP-chip datasets from a study designed to identify the target genes for the sex-determining factor, SRY, in mouse embryonic gonads at the time of sex determination.


[Reconstructive surgery of sequelae of compartment syndrome of the lower leg and/or foot. Presentation of a new classification].
The sequelae of an undiagnosed insufficiently treated or unpreventable (by crush injury) compartment or postischemic syndrome, most often after lower leg fracture or popliteal artery injury, are caused by necrosis and contracture of the extrinsic foot muscles. Therefore claw toes, pes equinus or other forms, such as a severe pes equino varus related to the compartment involved will decide the kind of foot deformity. In cases of a combined compartment syndrome of the lower leg and foot, not only the extrinsic but also the intrinsic muscles especially the short flexors are involved, leading to extensive claw toeing of the hallux and the lesser toes as well. In the case of an isolated compartment syndrome of the foot one will see contracted hammer toes most often after open or third degree closed calcaneal fractures. A new classification of all the different deformities of the foot and ankle as sequelae of a compartment and/or postischemic syndrome, is introduced distinguishing 5 degrees of deformity. Between 1994 and 2006, a total of 66 patients with sequelae of a compartment and/or postischemic syndrome were treated at the Department of Trauma and Reconstructive Surgery of the University Hospital"Carl Gustav Carus" of the Technical University of Dresden. Patients with contract hammer toes after calcaneal fractures were seen most often (n=26). Another large group of 24 patients suffered from the sequelae of a compartment and/or postischemic syndrome of the extrinsic muscles of the superficial and deeper compartment of the flexor tendons, producing a severe pes equino varus. Less common (n=16) were the deformities caused by an isolated compartment syndrome, such as necrosis of the anterior tibialis, long extensor muscles, peroneal muscles or a combined compartment syndrome of the lower leg and foot.


Who needs to be screened for primary aldosteronism?
The prevalence of patients with primary aldosteronism (PA) is about 5%-15% in hypertensive patients, and it is common cause of secondary hypertension in clinical practice. Two major causes of PA are noted, namely bilateral adrenal hyperplasia and aldosterone-producing adenoma, and the general diagnosis is based on three steps: (1) screening, (2) confirmatory testing, and (3) subtype differentiation (Figure 1). The recommendation for screening patients is at an increased risk of PA, here we focus on which patients should be screened for PA, not only according to well-established guidelines but for potential patients with PA. We recommend screening for 1) patients with resistant or persistent hypertension, 2) hypertensive patients with hypokalemia (spontaneous or drug-induced), 3) young hypertensive patients (age <40 years), and 4) all hypertensive patients with a history of PA in first-degree relatives. Moreover, we suggest screening for 1) hypertensive patients themselves or first-degree relatives with early target organ damage, such as stroke and other diseases, 2) all hypertensive patients with a concurrent adrenal incidentaloma, 3) hypertensive patients with obstructive sleep apnea, 4) hypertensive patients with atrial fibrillation unexplained by structural heart defects and/or other conditions resulting in the arrhythmia, 5) hypertensive patients with anxiety and other psychosomatic symptoms, and 6) hypertensive patients without other comorbidities to maintain cost-effectiveness.


Fluid shift across the placenta: I. The effect of dextran T 40 in the isolated guinea-pig placenta.
In an effort to understand better the transplacental water flux induced by osmotic forces, 17 near-term guinea-pig placentae were perfused on both sides with an artificial cell-free fluid containing dextran. Maternal and fetal arterial inflow rates were kept constant by syringe pumps and inflow and outflow pressures were recorded continuously. Precise measurements of outflow rates were made by weight determination and transplacental fluid shifts calculated by weight changes during placental passage. The content of dextran T 40 in the perfusion fluid was altered in stepwise manner from 0 to 60 to 120 g/l, and the effects of all possible combinations of fetal--maternal concentration differences on the transplacental fluid shift were observed. On the average, about 1 X 10(-3) ml/min/g placenta was moved per 1 g/l concentration difference. In two experiments venous colloid osmotic pressures were recorded continuously. In ten experiments the oncotic fluid shift was counterbalanced by an additional hydrostatic pressure difference; an average 1 mmHg hydrostatic pressure counterbalancing 15 g/l of dextran concentration osmotic force. The calculated hydraulic conductance, Lp, was approximately 0.017 ml/min/mmHg/g and the reflection coefficient, s, for dextran T 40 was 0.1. Both parameters characterize the isolated guinea-pig placenta as leaky.


Impedimetric determination of Staphylococcal enterotoxin B using electrochemical switching with DNA triangular pyramid frustum nanostructure.
An electrochemical switching strategy is presented for the sensitive determination of Staphylococcus enterotoxin B (SEB). It is based on the use of DNA triangular pyramid frustum nanostructure (TPFDNA) consisting of (a) three thiolated probes, (b) one auxiliary probe, and (c) an aptamer against SEB. The TPFDNA was assembled on the gold electrode, with the SEB aptamer designed on top of the TPFDNA. The electron transfer to hexacyanoferrate acting as an electrochemical probe is strongly inhibited in the TPFDNA-modified electrode. This is assumed to be due to the formation of a 3D TPFDNA structure that limits access of hexacyanoferrate to the electrode. Therefore, the Faradaic impedance is large. However, in the presence of SEB, it will bind to the aptamer and dehybridize the hybrid formed between aptamer and its complementary sequence. As a result, the TPFDNA nanostructure changes to an equilateral triangle DNA nanostructure. This results in a more efficient electron transfer and a smaller Faradaic impedance. The method has a detection limit of 0.17 ng mL-1 of SEB (at an S/N of 3) and a dynamic range that covers the 0.2-1000 ng mL-1 concentration range. The applicability and reliability of the method was demonstrated by anayzing (spiked) milk samples, and the results were compared to those obtained with an ELISA kit. The relative standard deviations between the two methods range between -6.59 and 9.33%. Graphical abstract An electrochemical switching strategy is presented for the sensitive detection of Staphylococcus enterotoxin B based on 3D DNA structure conversion of nanostructure from triangular pyramid frustum to equilateral triangle.


The role of diacylglycerol-carrying lipoprotein I in lipid transport during insect vitellogenesis.
A diacylglycerol-carrying lipoprotein was isolated from mature eggs of the silkworm, Philosamia cynthia and compared, for physiochemical properties, with the major diacylglycerol-carrying lipoprotein I (LP-I) of hemolymph. The two molecules are identical an electrophoretic mobility, structural configuration as revealed by electron microscopy, and amino acid composition. In addition mannose was detected in the lipid-free protein moiety, thus enabling classification of the molecules as glycoproteins. The molecules differ in lipid content with egg-LP-I containing only 3.6% of the diacylglycerol content of hemolymph LP-I and the phospholipid and cholesterol components also showing a marked reduction. Analysis of the LP-I and vitellogenin (another diacylglycerol-carrying lipoprotein; LP-II) concentrations of mature eggs indicates that the amounts of the two glycolipoproteins in eggs are insufficient to account for the total acylglycerol content of the eggs. The results suggest that LP-I functions as a true carrier-protein serving to transport diacylglycerol from the fat body to the ovary. This proposal is supported by the observation that LP-I isolated from the egg retains the physiological capacity of hemolymph-LPi to take up diacylglycerol from fat body. Thus it is suggested that LP-I is the major source of lipid for vitellogenesis, whereas vitellogenin is the primary source of protein.


Excitation function for 63Cu(n,p)63Ni reaction in neutron energy range up to 15 MeV.
The excitation function for the (63)Cu(n,p)(63)Ni reaction has been measured by activation method using the 4.5 MV Dynamitron accelerator of the Fast Neutron Laboratory of Tohoku University. Copper plates and hollow spherical copper shells were irradiated by neutrons of various energy up to 14.9 MeV produced by the T(p,n), D(d,n), and T(d,n) reactions. The (63)Ni produced in the irradiated copper target was chemically separated. The beta-rays emitted from the extracted (63)Ni were measured by a liquid scintillation method. The cross sections obtained were compared with the evaluated data files of JENDL-3.3, ENDF/B-VI and FENDL/A-2.0. Consequently, it is found that FENDL/A-2.0 is consistent with our experimental data in the energy range studied in this work. The effect of proton shell appeared in the excitation function obtained is also discussed.


Usefulness of virtual reassembly of the skull and spine in cases of fragmentation due to high-energy trauma: A feasibility study.
With the widespread use of postmortem computed tomography (PMCT) beside forensic autopsies for investigation of causes of death, three-dimensional (3D) reconstruction and fusion imaging using PMCT data are now becoming common. In the present study, the applicability of virtual reassembly from PMCT data was investigated in three cases involving fragmentation of the skull or spine due to high-energy trauma, as in such cases it is sometimes difficult to obtain detailed information on fractures using macroscopic observation alone. In the first case, virtual reassembly of the skull provided more information about the fractures than conventional reconstruction with adhesive. In the second case, although the skull was severely fractured and could not be examined macroscopically, virtual reassembly allowed detailed visualization of the fractures. In the last case, virtual reassembly of the spine helped to clarify that the 6th-8th thoracic vertebrae had been run over by a vehicle at the scene. Thus, virtual reassembly was shown to be useful for assessment of injury patterns, and event reconstruction.