Tracking the affective state of unseen persons.
Emotion recognition is an essential human ability critical for social functioning. It is widely assumed that identifying facial expression is the key to this, and models of emotion recognition have mainly focused on facial and bodily features in static, unnatural conditions. We developed a method called affective tracking to reveal and quantify the enormous contribution of visual context to affect (valence and arousal) perception. When characters' faces and bodies were masked in silent videos, viewers inferred the affect of the invisible characters successfully and in high agreement based solely on visual context. We further show that the context is not only sufficient but also necessary to accurately perceive human affect over time, as it provides a substantial and unique contribution beyond the information available from face and body. Our method (which we have made publicly available) reveals that emotion recognition is, at its heart, an issue of context as much as it is about faces.


Use of a dual monoclonal solid phase and a polyclonal detector to create an immunoassay for the detection of human cardiac troponin I.
We report the development of a fully automated, random access, chemiluminescent immunoassay, for the detection of human cardiac Troponin I (cTnI) in serum and plasma for use on the ACS:180(R) System. This assay format uses a combination of two monoclonal antibodies covalently coupled to paramagnetic (PMP) particles as a solid phase and an affinity purified polyclonal antibody, specific to the N-terminal domain of cTnI (peptide-3 region) labeled with a chemiluminescent compound as the detector antibody. The assay offers excellent low-end sensitivity and precision. No interferences are observed from by blood components such as HAMA and drugs used in cardiac therapy. Patient samples tested on the ACS:180 cTnI assay showed good correlation with the Stratus cTnI assay (ACS: cTnI = 1. 02*Stratus + 0.05 g/L, r = 0.96, n = 1170). Paired with the other ACS:180 cardiac assays, myoglobin and CKMBII, the ACS:180 system now offers an excellent panel of cardiac assay for use in rapid and accurate diagnosis of a myocardial event.


Determinants of coronary events in patients with stable angina: results from the impact of nicorandil in angina study.
IONA was a randomized trial of nicorandil (20 mg twice daily) versus placebo in 5126 patients with stable angina of effort. We present the characteristics as measured at baseline that were found to be associated with increased risk of major outcomes. The primary end point of the study was coronary heart disease death, nonfatal myocardial infarction (MI), or unplanned hospitalization for cardiac chest pain. The secondary outcome excluded the softer outcome of unplanned hospitalization for chest pain. Potential prognostic factors included nicorandil treatment, sex, smoking, severity of angina (Canadian Cardiovascular Society [CCS] grading), previous MI, coronary artery bypass graft/percutaneous transluminal coronary angioplasty (CABG/PTCA), left ventricular dysfunction, left ventricular hypertrophy (LVH) on electrocardiography (ECG), histories of diabetes or hypertension, baseline cardiovascular drugs, age, blood pressures, heart rate, height, weight, and body mass index. A total of 5047 patients had complete baseline information. There were 724 primary outcomes and 240 secondary outcomes. The strongest determinants of the hard secondary end point were CCS score (hazards ratio [HR] 2.25, 95% confidence intervals [CI] 1.50-3.38) for grades III and IV versus grade I, age (HR 1.23, 95% CI 1.13-1.33) for 5-year risk, and previous MI (HR 2.05, 95% CI 1.48-2.85). The results for the primary outcome were similar, with stronger associations with LVH on ECG and smoking, and a weaker association with age. We present models of risk factors for coronary outcomes in a population with angina of effort. The strongest risk factors were the CCS score and previous MI.


Maternal nest building by pseudopregnant mice.
Pseudopregnant mice displayed maternal nest-building behaviour. Their nests were smaller but qualitatively identical to those constructed by pregnant animals.


Identification of Canadian durum wheat varieties using a single PCR.
Accurate and reliable means of variety identification are necessary to assess purity of seed supplies, to support claims relating to plant breeders' rights and, in Canada, to provide quality assurances in the grain handling system. A single, multiplexed set of seven simple-sequence-repeat (SSR) markers was found to uniquely identify all 18 durum wheat varieties that have been developed in Canada and are currently, or were formerly, registered for commercial production. Significant features of this multiplexed set include an allele that is specific, within Canadian durum varieties, to those having high gluten strength, and redundancy that was included in an effort to increase the capacity to accommodate future varieties. In combination with a reasonably rapid individual-kernel DNA extraction protocol and automated allele calling, this marker system offers a higher resolution alternative to complement established protein-based variety identification methods.


Engineering CpG island DNA methylation in pluripotent cells through synthetic CpG-free ssDNA insertion.
Cellular differentiation requires global changes to DNA methylation (DNAme), where it functions to regulate transcription factor, chromatin remodeling activity, and genome interpretation. Here, we describe a simple DNAme engineering approach in pluripotent stem cells (PSCs) that stably extends DNAme across target CpG islands (CGIs). Integration of synthetic CpG-free single-stranded DNA (ssDNA) induces a target CpG island methylation response (CIMR) in multiple PSC lines, Nt2d1 embryonal carcinoma cells, and mouse PSCs but not in highly methylated CpG island hypermethylator phenotype (CIMP)+ cancer lines. MLH1 CIMR DNAme spanned the CGI, was precisely maintained through cellular differentiation, suppressed MLH1 expression, and sensitized derived cardiomyocytes and thymic epithelial cells to cisplatin. Guidelines for CIMR editing are provided, and initial CIMR DNAme is characterized at TP53 and ONECUT1 CGIs. Collectively, this resource facilitates CpG island DNAme engineering in pluripotency and the genesis of novel epigenetic models of development and disease.


Monotherapy with the calcium channel antagonist nisoldipine for systemic hypertension and comparison with diuretic drugs.
A comparative, double-blind, placebo-controlled, double-dummy, randomized, crossover trial was performed in 32 hypertensive patients (initial blood pressure [BP] 165/105 +/- 3/2 mm Hg), most of them obese women, to evaluate the antihypertensive efficacy and tolerability of the new calcium channel blocking drug nisoldipine, 10 mg once or twice daily, over 6 weeks compared with the diuretic hydrochlorothiazide-amiloride (hydrochlorothiazide, 25 mg, in combination with amiloride, 2.5 mg once or twice daily). Adequate 24-hour control of BP (supine diastolic BP less than 90 mm Hg) was achieved in 15 of 32 patients (47%) with monotherapy by 1 agent and in 23 of 32 patients (72%) when including those who responded to either agent. Both nisoldipine and the diuretic had a flat dose-response curve. The larger dose of diuretic yielded lower systolic and exercise BP values (erect and supine) than high-dose nisoldipine (p less than 0.05), with less headache (p less than 0.05). In the other 9 patients who did not respond, the combination of nisoldipine 10 mg plus hydrochlorothiazide (25 mg)-amiloride (2.5 mg) was administered and yielded a response in 8 patients (overall response including monotherapy 96%). Ten patients were given nisoldipine for an additional period of 6 months, and they required an average dose of 33 mg/day for BP control. In both the 6-week and 6-month studies, nisoldipine monotherapy caused frequent subjective adverse effects. In contrast, in the 6-week study the combination of low-dose nisoldipine and low-dose diuretic gave good BP control with no adverse effects.


CREATE Childhood Cancer Rehabilitation Program development: Increase access through interprofessional collaboration.
Cancer and its treatment can lead to functional limitations affecting ongoing development in children and adolescents. We developed a pediatric cancer rehabilitation program that integrates evidence-based rehabilitative care into cancer treatment. The program utilizes the CREATE (collaboration, rehabilitation/research, education, assessment, treatment, evaluation) Childhood Cancer Rehabilitation model. We aim to describe the structural and process components of our rehabilitation program and provide an access and utilization analysis. To evaluate the rehabilitation program, we identified new patients with oncologic diagnoses from 2002 to 2019 using our database. To evaluate rehabilitative care, descriptive data, including the timing and type of rehabilitation services utilized within 5 years of a child's diagnosis, were collected and reviewed. Statistical analysis focused on change over time. Among 1974 children assessed, 1580 (80.0%) received care from at least one rehabilitation service. Between 2002 and 2018, the percentage of children receiving rehabilitation services grew significantly throughout all disciplines, except for outpatient speech-language pathology. Utilization differed by age and diagnosis. Integrating therapists in the clinic improved patient access, reduced the time to access outpatient services, and increased the number of attended visits. Additional factors supporting program growth included: identifying leaders, using a prospective surveillance model, education, and program evaluation. A multimodal interprofessional approach, such as the CREATE model, improves access to and the efficiency of evidence-based rehabilitation services promoting recovery, ongoing development, and quality of life.


Resource level affects relative performance of the two motility systems of Myxococcus xanthus.
The adventurous (A) and social (S) motility systems of the microbial predator Myxococcus xanthus show differential swarming performance on distinct surface types. Under standard laboratory conditions, A-motility performs well on hard agar but poorly on soft agar, whereas the inverse pattern is shown by S-motility. These properties may allow M. xanthus to swarm effectively across a greater diversity of natural surfaces than would be possible with one motility system alone. Nonetheless, the range of ecological conditions under which dual motility enhances effective swarming across distinct surfaces and how ecological parameters affect the complementarity of A-motility and S-motility remain unclear. Here we have examined the role of nutrient concentration in determining swarming patterns driven by dual motility on distinct agar surfaces, as well as the relative contributions of A-motility and S-motility to these patterns. Swarm expansion rates of dually motile (A+S+), solely A-motile (A+S-), and solely S-motile (A-S+) strains were compared on hard and soft agar across a wide range of casitone concentrations. At low casitone concentrations (0-0.1%), swarming on soft agar driven by S-motility is very poor, and is significantly slower than swarming on hard agar driven by A-motility. This reverses at high casitone concentration (1-3.2%) such that swarming on soft agar is much faster than swarming on hard agar. This pattern greatly constrained the ability of M. xanthus to encounter patches of prey bacteria on a soft agar surface when nutrient levels between the patches were low. The swarming patterns of a strain that is unable to produce extracellular fibrils indicate that these appendages are responsible for the elevated swarming of S-motility at high resource levels. Together, these data suggest that large contributions by S-motility to predatory swarming in natural soils may be limited to soft, wet, high-nutrient conditions that may be uncommon. Several likely benefits of S-motility to the M. xanthus life cycle are discussed, including synergistic interactions with A-motility across a wide variety of conditions.


Subcutaneous fibrosis after whole neck irradiation.
To identify the risk factors for moderate to severe subcutaneous fibrosis after whole neck irradiation. We analyzed 233 cases of patients who had undergone whole neck irradiation with 4-MV X-ray or 8-10-MeV electrons, or both, and had been followed with regard to their skin condition for at least 1 year. The prescribed dose to the whole neck ranged from 19.2 to 72.4 Gy (median 50). The skin-absorbed dose was specified as that at a depth of 4.1 mm (d4.1-mm(depth)), and a biologically equivalent dose (BED) of d4.1-mm(depth) was also estimated (BED(1.8) 4.1-mm(depth)). Univariate analysis revealed that previous neck dissection, concurrent chemotherapy, corticosteroid administration as a part of chemotherapy, fractionation, and BED(1.8) 4.1-mm(depth) were significant prognostic variables. Multivariate analysis showed that BED(1.8) 4.1-mm(depth) and previous neck dissection were the only prognostic variables for moderate to severe subcutaneous fibrosis. A high dose to a 4.1-mm depth of the skin and a history of neck dissection were identified as the predominant risk factors for moderate to severe subcutaneous fibrosis after whole neck irradiation. A subcutaneous dose should be considered in radiotherapy treatment planning involving the whole neck, especially in cases in which patients have undergone previous neck dissection.


Density-dependent regulation of ramet recruitment by the red:far-red ratio of solar radiation: a field evaluation with the bunchgrass Schizachyrium scoparium.
Depressions in the red to far-red ratio (R:FR) of solar radiation arising from the selective absorption of R (600-700 nm) and scattering of FR (700-800 nm) by chlorophyll within plant canopies may function as an environmental signal directly regulating axillary bud growth and subsequent ramet recruitment in clonal plants. We tested this hypothesis in the field within a single cohort of parental ramets in established clones of the perennial bunchgrass, Schizachyrium scoparium. The R:FR was modified near leaf sheaths and axillary buds at the bases of individual ramets throughout the photoperiod without increasing photosynthetic photon flux density (PPFD) by either (1) supplementing R beneath canopies to raise the naturally low R:FR or (2) supplementing FR beneath partially defoliated canopies to suppress the natural R:FR increase following defoliation. Treatment responses were assessed by simultaneously monitoring ramet recruitment, PPFD and the R:FR beneath individual clone canopies at biweekly intervals over a 12-week period. Neither supplemental R nor FR influenced the rate or magnitude of ramet recruitment despite the occurrence of ramet recruitment in all experimental clones. In contrast, defoliation with or without supplemental FR beneath clone canopies reduced ramet recruitment 88% by the end of the experiment. The hypothesis stating that the R:FR signal directly regulates ramet recruitment is further weakened by evidence demonstrating that (1) the low R:FR-induced suppression of ramet recruitment is only one component of several architectural modifications exhibited by ramets in response to the R:FR signal (2) immature leaf blades, rather than leaf sheaths or buds, function as sites of R:FR perception on individual ramets, and (3) increases in the R:FR at clone bases following partial canopy removal are relatively transient and do not override the associated constraints on ramet recruitment resulting from defoliation. A depressed R:FR is probably of greater ecological significance as a signal of competition for light in vegetation canopies than as a density-dependent signal which directly regulates bud growth and ramet recruitment.


Antimicrobial activity of syringic acid against Cronobacter sakazakii and its effect on cell membrane.
Syringic acid (SA) has been reported to exhibit antibacterial ability against various microorganisms, but little work has been done on its effect on Cronobacter sakazakii. In this study, minimum inhibitory concentrations (MICs) of SA against various C. sakazakii strains were determined. Moreover, changes in intracellular ATP concentration, intracellular pH (pHin), membrane potential and membrane integrity were measured to evaluate the influence of SA on cell membrane. Finally, field emission scanning electron microscope (FESEM) was used to assess the morphological changes of bacterial cells caused by SA. It was shown that the MICs of SA against all tested C. sakazakii strains were 5mg/mL. SA retarded bacterial growth, and caused cell membrane dysfunction, which was evidenced by intracellular ATP concentration decrease, pHin reduction, cell membrane hyperpolarization and changes in cellular morphology. These findings indicated that SA has potential to be developed as a natural preservative to control C. sakazakii in foods associated with this pathogen and prevent related infections.


Cloning and expression of medaka Dachshund.
The nuclear factor dachshund (dac) is a regulator of retinal cell fate determination in Drosophila. We have cloned a Dachshund homologue of a lower vertebrate, the teleost medaka (Oryzias latipes). Sequence comparison reveals high similarity of medaka Dachshund (OlDach) to the known homologues in higher vertebrates and Drosophila. OlDach is first expressed at early somitogenesis stages in the otic placode territory and forming somites. Subsequently, expression is detected in the retina, specific regions of the central nervous system, pancreas and the finbuds.


Measurements of the acidification kinetics of single SynaptopHluorin vesicles.
Uptake of neurotransmitters into synaptic vesicles is driven by the proton gradient established across the vesicle membrane. The acidification of synaptic vesicles, therefore, is a crucial component of vesicle function. Here we present measurements of acidification rate constants from isolated, single synaptic vesicles. Vesicles were purified from mice expressing a fusion protein termed SynaptopHluorin created by the fusion of VAMP/synaptobrevin to the pH-sensitive super-ecliptic green fluorescent protein. We calibrated SynaptopHluorin fluorescence to determine the relationship between fluorescence intensity and internal vesicle pH, and used these values to measure the rate constant of vesicle acidification. We also measured the effects of ATP, glutamate, and chloride on acidification. We report acidification time constants of 500 ms to 1 s. The rate of acidification increased with increasing extravesicular concentrations of ATP and glutamate. These data provide an upper and a lower bound for vesicle acidification and indicate that vesicle readiness can be regulated by changes in energy and transmitter availability.


Further studies on the colorimetric determination of ronidazole in feeds.
A previously published colorimetric method for determining ronidazole, (1-methyl-5-nitro-imidazol-2-yl)methyl carbamate, can be used as an analytical technique for measuring the stability of this drug in medicated feeds. Although the color reaction per se is not selective, elution profiles of ronidazole and its demonstrated hydrolytic degradation product, 1-methyl-2-hydroxymethyl-5-nitroimidazole, show that the chromatographic separation used in the sample preparation efficiently isolates the drug from the degradation product. No interference was found in feeds containing 0.010% ronidazole and up to 0.010% degradation product.


The role of sphingosine-1-phosphate in bone remodeling and osteoporosis.
Osteoporosis is a systemic bone disease that affects more than 200 million people worldwide and is caused by the disruption of the equilibrium between osteoclastic bone resorption and osteoblastic bone formation. Sphingosine-1-phosphate (S1P) is a natural, bioactive sphingolipid that has been shown to play a major role in cardiovascular and immunological pathologies by regulating biological and cellular processes, including migration, differentiation, proliferation and survival. Recent studies also suggest a central role for S1P in bone diseases, including osteoporosis; however, the effects of S1P, particularly in bone metabolism, remain to be further elucidated. In this review, we summarize the available literature on the role of S1P in bone metabolism with a focus on osteoporosis. On the cellular level, S1P acts as an osteoclast-osteoblast coupling factor to promote osteoblast proliferation and bone formation. Moreover, the recruitment of osteoclast precursors to resorption sites is regulated by the interplay of S1P gradients and S1P receptor expression. From a clinical perspective, increasing evidence suggests that systemically elevated S1P blood levels may serve as an independent risk factor for osteoporosis-related fractures. Taken together, S1P signaling is a potential therapeutic target and may serve as a novel biomarker in patients with systemic bone disease.


Metabolism of prostate cancer by magnetic resonance spectroscopy (MRS).
Understanding the metabolism of prostate cancer (PCa) is important for developing better diagnostic approaches and also for exploring new therapeutic targets. Magnetic resonance spectroscopy (MRS) techniques have been shown to be useful in the detection and quantification of metabolites. PCa illustrates metabolic phenotype, showing lower levels of citrate (Cit), a key metabolite of oxidative phosphorylation and alteration in several metabolic pathways to sustain tumor growth. Recently, dynamic nuclear polarization (DNP) studies have documented high rates of glycolysis (Warburg phenomenon) in PCa. High-throughput metabolic profiling strategies using MRS on variety of samples including intact tissues, biofluids like prostatic fluid, seminal fluid, blood plasma/sera, and urine have also played a vital role in understanding the abnormal metabolic activity of PCa patients. The enhanced analytical potential of these techniques in the detection and quantification of a large number of metabolites provides an in-depth understanding of metabolic rewiring associated with the tumorigenesis. Metabolomics analysis offers dual advantages of identification of diagnostic and predictive biomarkers as well as in understanding the altered metabolic pathways which can be targeted for inhibiting the cancer progression. This review briefly describes the potential applications of in vivo 1H MRS, high-resolution magic angle spinning spectroscopy (HRMAS) and in vitro MRS methods in understanding the metabolic changes of PCa and its usefulness in the management of PCa patients.


A high yielding IFNAR1 ECD mammalian expression process for use in autoimmune disease drug development.
Interferon-alpha receptor 1 (IFNAR1) is a target of interest for recombinant biotherapeutics that block the JAK/STAT pathway. This pathway is believed to play a role in many diseases including Hepatitis B and C, Herpes Simplex, Multiple Sclerosis, and other autoimmune disorders. By using IFNAR1 as a target to block Type I IFN from binding to the JAK/STAT pathway and prevent activation of this target, autoimmune disease progression can be modulated. Current IFNAR1 extracellular domain (ECD) expression and purification protocols are labor intensive with low product yield and limited scalability. In this work, we evaluate three different expression systems (baculovirus, human embryonic kidney 293 (HEK293×), and Chinese hamster ovary (CHO)) to improve expression of IFNAR1 ECD. We demonstrate the benefits of utilizing mammalian CHO cell transient transfection to increase expression titer, as well as an improved two-step purification process performed using immobilized metal affinity chromatography (IMAC) as the capture step and Ceramic Hydroxyapatite (CHT) Type II for HMW impurity removal in flow through mode. This process showed an 20-fold increase in productivity compared to the baseline process as measured by grams purified per liter of cell culture fluid. Lastly, the improved process showed good scalability, enabling efficient purification of 3.6 g of product from a 30 L scale bioreactor.


Successful percutaneous coronary intervention of a chronic totally occluded left anterior descending artery via an ipsilateral intraseptal channel using intravascular ultrasound-guided retrograde wire-crossing technique.
We herein report a 59-year-old man with a chronic totally occluded left anterior descending artery treated by percutaneous coronary intervention via an ipsilateral intraseptal channel using an intravascular ultrasound-guided retrograde wire-crossing technique. When an antegrade approach is not feasible or fails, a retrograde approach to a chronic totally occluded lesion is reasonable. However, a retrograde approach from the contralateral coronary artery is not always feasible. We herein report that an ipsilateral intraseptal channel can serve as one route by which to perform a retrograde approach to chronic totally occluded lesions of the left anterior descending artery.


Frequency of Medication Administration Timing Error in Hospitals: A Systematic Review.
Medication administration timing error (MATE) leads to poor medication efficacy, harm, and death. Frequency of MATE is understudied. To determine MATE frequency, and characteristics and quality of reporting studies. A systematic review of articles between 1999 and 2021 was conducted using the Cumulative Index of Nursing and Allied Health Literature, ProQuest, and PubMed databases. Articles were scored for quality using the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist. Initially, 494 articles were screened; 23 were included in this review. MATE was defined as administration beyond 60 minutes before or after the scheduled time in 13 (57%) of the included studies. Measurement procedures included data abstraction, self-report, and observation. Frequency of MATE was 1% to 72.6%. Moderate study quality was found in 78% of articles. Research on MATE is characterized by inconsistent definitions, measurements procedures, and calculation techniques. High-quality studies are lacking. Many research improvement opportunities exist.


Network simulation modeling of equine infectious anemia in the non-racehorse population in Japan.
An equine infectious anemia (EIA) transmission model was developed by constructing a network structure of horse movement patterns in a non-racehorse population. This model was then used to evaluate the effectiveness and efficiency of several EIA surveillance strategies. Because EIA had not been detected in Japan since 1993, it was appropriate to review the current surveillance strategy, which aims to eradicate EIA by intensive testing, and to consider alternative strategies suitable for the current EIA status in Japan. The non-racehorse population was divided into four sectors based on horse usage: the equestrian sector, private owner sector, exhibition sector, and fattening sector. To evaluate the risk of disease spread within and between sectors accompanied by horse movements, a stochastic individual-based network model was developed based on a previous survey of horse movement patterns. Surveillance parameters such as targeting sectors and frequency of testing were added into the model to compare surveillance strategies. The disease spread heterogeneously among sectors. Infection occurred mainly in the equestrian sector; the infection was less disseminated in other sectors. Therefore, we considered that the equestrian sector posed a higher risk of disease dissemination within and between sectors through horse movements. However, surveillance strategies targeting only the equestrian sector were not effective enough for early detection of the disease. Alternatively, targeting horses that moved permanently and those in the private owner sector in addition to the equestrian sector is recommended to achieve effectiveness equivalent to that of the current surveillance. In terms of surveillance efficacy, by increasing the testing interval (once yearly to once every 3 years), this testing scheme could reduce the number of tested horses to 44% of the current surveillance, while maintaining almost equivalent effectiveness. Intensive strategies targeting high-risk populations are considered to enhance effectiveness and efficiency of surveillance. The approach in this study may be helpful in the decision-making process that is involved in setting up strategies for risk-based surveillance.


Degradation of dibutyl phthalate by ozonation in the ultrasonic cavitation-rotational flow interaction coupled-field: performance and mechanism.
Dibutyl phthalate (DBP) is present in hydraulic fracturing flowback and produced water. Degradation of DBP in aqueous by means of ozonation in ultrasonic cavitation-rotational flow interaction coupled-field (UC-RF coupled-field) was studied. The effect of ozone dosage, ozone intake flow, operating temperature, initial pH, DBP initial concentration, liquid flow rate, and ultrasonic power on the DBP removal was investigated. Results indicated that the DBP degradation rate was strongly influenced by the liquid flow rate and the ultrasonic power over the range investigated. HCO3- and Cl- revealed an inhibitory effect on the DBP removal. SO42- seemed to have no effect on DBP removal. The ozone utilization efficiencies in the UC-RF coupled-field were 2.77 and 1.13 times higher than those in the conventional microporous aeration (CMA) and rotating-flow microbubble aeration (RFMA), respectively. The DBP degradation rate was diminished in the presence of tert-butyl alcohol. Cavitation bubbles are considered as innumerable microreactors. Degradation of DBP by direct ozonation, hydroxyl radical (·OH) oxidation, high pressure, and high-temperature pyrolysis was demonstrated. Finally, a possible degradation pathway of DBP is obtained on the basis of the main reaction intermediates.


Dawn of a New Dawn: Advances in Sleep Health to Optimize Performance.
Optimal sleep health is a critical component to high-level performance. In populations such as the military, public service (eg, firefighters), and health care, achieving optimal sleep health is difficult and subsequently deficiencies in sleep health may lead to performance decrements. However, advances in sleep monitoring technologies and mitigation strategies for poor sleep health show promise for further ecological scientific investigation within these populations. The current review briefly outlines the relationship between sleep health and performance as well as current advances in behavioral and technological approaches to improving sleep health for performance.


Binding of OTULIN to the PUB domain of HOIP controls NF-κB signaling.
Linear ubiquitin chains are implicated in the regulation of the NF-κB pathway, immunity, and inflammation. They are synthesized by the LUBAC complex containing the catalytic subunit HOIL-1-interacting protein (HOIP) and are disassembled by the linear ubiquitin-specific deubiquitinase OTULIN. Little is known about the regulation of these opposing activities. Here we demonstrate that HOIP and OTULIN interact and act as a bimolecular editing pair for linear ubiquitin signals in vivo. The HOIP PUB domain binds to the PUB interacting motif (PIM) of OTULIN and the chaperone VCP/p97. Structural studies revealed the basis of high-affinity interaction with the OTULIN PIM. The conserved Tyr56 of OTULIN makes critical contacts with the HOIP PUB domain, and its phosphorylation negatively regulates this interaction. Functionally, HOIP binding to OTULIN is required for the recruitment of OTULIN to the TNF receptor complex and to counteract HOIP-dependent activation of the NF-κB pathway.


Association between urethral funneling in stress urinary incontinence and the biological properties of the urethral rhabdosphincter muscle based on shear wave elastography.
To apply shear wave elastography (SWE) combined with transperineal ultrasonography (TPUS) to study the association between urethral funneling in stress urinary incontinence (SUI) and the biological properties of the urethral rhabdosphincter muscle in women. This single-center retrospective study included 166 women with SUI (SUI group) and 185 women who underwent a routine physical examination (control group). The control group and SUI group were divided into nonfunneling and funneling groups according to the presence or absence of urethral funneling, respectively, and their ultrasound findings were compared to analyze the association between funneling and ultrasound measurements. The SUI group had a lower mean E than the control group (15.54 vs. 20.82 kPa, p < 0.001). The SUI-funneling group had a lower mean E than the SUI-nonfunneling group (15.50 vs. 17.21 kPa, p < 0.001). The area under the (AUC) receiver operating characteristic (ROC) curve of the mean E for predicting SUI was 0.864, with a cutoff value of 19.19 kPa. The AUC of the mean E for predicting urethral funneling was 0.832, with a cutoff value of 17.15 kPa. The stiffness of the urethral rhabdosphincter was an independent factor related to SUI and urethral funneling in SUI. SWE can be used to assess the biological properties of the urethral rhabdosphincter, and reduced stiffness of the rhabdosphincter was significantly correlated with SUI and funneling in SUI. Thus, women with urethral funneling in SUI may have a weak urethral rhabdosphincter.


Season of birth as a risk factor for multiple sclerosis in Brazil.
Risk factors for development of multiple sclerosis (MS) are still a matter of debate. Latitude gradient, vitamin D deficiency and season of birth are among the most investigated environmental factors associated with the disease. Several international studies suggest that birth in spring is a substantial risk factor for MS. We investigated the season of birth as a potential risk for MS in different geographical regions of Brazil. We conducted a cross-sectional retrospective study with 2257 clinically definite MS patients enrolled in 13 Brazilian MS clinics in the south, southeast, and northeast regions of Brazil. Demographic and clinical data relating to date of birth and clinical features of the disease were collected and analysed, and subsequently compared with birth date among the general Brazilian population. The distribution of date of birth of MS patients showed an increase in spring and a decrease in autumn, with no difference being observed in the other seasons. In conclusion, season of birth is a probable risk factor for MS in most parts of Brazil. These findings may be related to the role that vitamin D plays in MS pathogenesis.


[Evaluation of highly damaged renal function following extracorporeal circulation--usefulness of alpha 1-microglobulin index].
The patients with highly damaged renal functions following extracorporeal circulation (ECC) were reviewed. Markers such as serum and urine creatinine (SCr, UCr), blood urea nitrogen (BUN), alpha 1-microglobulin in urine (as a marker of renal tubular function, abbreviated as U alpha 1-m), microalbumin in urine (as a marker of renal glomerular function, abbreviated as UA1b) were measured in each cases. Twenty patients were selected with the maximum value of U alpha 1-mover 60 micrograms/dl during or after ECC. The patients were classified into three groups according to preoperative value of alpha 1-m index (alpha 1-m index (I) = U alpha 1-m/UCr x 100 mg/g Cr), and Albumin index (Albumin index (I) = UA1b/UCr x 100 mg/g Cr). Group I (n = 13); alpha 1-m I > 10 and, Alb I > or = 50 (abnormal value of tubular and glomerular function), Group II (n = 3); alpha 1-m I < or = 10, Alb I > or = 50 (abnormal value of glomerular function), Group III (n = 4); alpha 1-m I < or = 10, Alb I < 50 (normal value of tubular and glomerular function). Six patients in Group I required postoperative hemodialysis (HD) and one patient in Group II. No one required HD in Group III. These facts suggest that preoperative damage of tubular and glomerular functions may become prolonged or irreversible damages may occur after operation. HD is required frequently in patients with alpha 1-m I level over 500 mg/g Cr, especially continuous HD may be needed in patient with alpha 1-m I level over 1000 mg/g Cr.


Linear IgA dermatosis of the childhood-Report of an amoxicillin-induced case.
Linear IgA dermatosis (LAD) is a rare autoimmune disorder in children. A 9-year-old boy was presented with blisters on the intact skin (face, body, arms, hands, soles, perigenital and perianal area) after amoxicillin treatment. Systemic corticosteroids and dapsone treatment for 6 weeks was successful. Clinical and immunofluorescence examinations are most important for differentiation of LAD and other drug-induced bullous dermatoses. They enable an early introduction of proper therapy.


Targeting apoptosis in MCF-7 and Ehrlich ascites carcinoma cells by saponifiable fractions from green and black Vitis vinifera seed oil.
Grape seed (GS) oil is one of the potential functional foods. For the first time, we evaluated the therapeutic effects of GS oil saponifiable (Sap)-fraction from black (BSap) and green (GSap) grapes on MCF-7 cells and Ehrlich ascites carcinoma (EAC) in mice. The fatty acid composition of BSap and GSap was determined using gas chromatography-mass spectrometry analysis. Approximately twelve distinct fatty acids were detected in BSap and eleven in GSap. BSap showed a greater cytotoxic effect on MCF-7 cells than GSap did by inducing apoptosis and reducing inflammation, while both grape fractions had superior potency to 5-FU. Furthermore, BSap massively boosted apoptosis and lowered redox potential (Eh) and CD44+ cells in EAC cells of EAC-bearing mice more than GSap, and both fractions were more efficient than 5-FU. Blood tests and liver histopathology revealed significant improvement in EAC-induced pathological alterations with these fractions. The in silico analysis implied the competitive inhibitory impacts of the most abundant fatty acid composites in BSap and GSap on cancer-metastasis-associated proteases (cathepsin B and MMP9). Also, this analysis predicted that the apoptotic action of these Sap fractions is independent of the 5'AMP-activated protein kinase. Therefore, grape Sap-fraction, especially BSap, may be a useful agent for cancer prevention.


Improved design of peptides exhibiting angiogenic activities for clinical applications.
Vascularization is one of the key steps for engraftment in regenerative medicine. Previously one of the authors had discovered peptides exhibiting significant angiogenic activities designated AGP and elucidated the active core. For neovascularization basic fibroblast growth factor is used although permeation can be envisaged. The original AGPs did not suffer from this although their half-life times are short because of decomposition by endogenous enzymes. Several new AGP-libraries have been constructed and their enzymatic resistance has been investigated by the use of human umbilical vein endothelial cells to find candidates for clinical applications.


Expanding the Substrate Scope of Acyltransferase LovD9 for the Biosynthesis of Statin Analogues.
This study identifies new acyl donors for manufacturing statin analogues through the acylation of monacolin J acid by the laboratory evolved acyltransferase LovD9. Vinyl and p-nitrophenyl esters have emerged as alternate substrates for LovD9-catalyzed acylation. While vinyl esters can reach product yields as high as the ones obtained by α-dimethyl butyryl-S-methyl-3-mercaptopropionate (DMB-SMMP), the thioester for which LovD9 was evolved, p-nitrophenyl esters display a reactivity even higher than DMB-SMMP for the first acylation step yet the acylation product yield is lower. The reaction mechanisms were elucidated through quantum mechanics (QM) calculations.


Distribution of rabies antigen in infected brain material: determining the reliability of different regions of the brain for the rabies fluorescent antibody test.
To assist in making recommendations for sampling of brains for the fluorescent antibody test (FAT), a study was conducted to determine the regions of the brain where rabies antigen is found most reliably. Each identifiable part of 252 rabies-positive brains of various species was re-tested using routine FA tests. It was found that there was frequent variation in the quantity of antigen between regions of the brain. The thalamus, pons and medulla were the most reliable parts of the brain as they were positive in all specimens tested. The cerebellum, hippocampus and different parts of the cerebrum were negative in, respectively, 4.5, 4.9 and 3.9-11.1% of positive brains. It is recommended that specimens for rabies diagnosis must include the brain stem. The structure of choice would be the thalamus as it was positive in all specimens and had the most frequent prevalence (97.8%) of abundant antigen. These findings contradict many old studies that state that the hippocampus should be the structure of choice for rabies diagnosis. The current data demonstrate that the reason for the old recommendations is that the hippocampus has the highest frequency of large inclusion bodies, as the reliability of the histological tests used previously depended on inclusion body size.


Mild hypothermia inhibits IL-10 production in peripheral blood mononuclear cells.
Hypothermia is often associated with compromised host defenses and infections. Deterioration of immune functions related to hypothermia have been investigated, but the involvement of cytokines in host defense mechanisms and in infection remains unclear. Therefore, we determined whether mild hypothermia affects the production of several types of cytokines in peripheral blood mononuclear cells (PBMCs), and the balance between pro-inflammatory and anti-inflammatory states. PBMCs obtained from 12 healthy humans were cultured with phytohemagglutinin (PHA) in normothermic (37 degrees C: control) or hypothermic (33 degrees C) conditions for 24 h. The production levels of tumor necrosis factor (TNF)-alpha, the interleukins (ILs) IL-6, IL-8 and IL-10, and interferon (IFN)-gamma in the culture supernatants were measured by means of enzyme-linked immunosorbent assay (ELISA). Under hypothermic conditions (33 degrees C), PHA-induced production of IL-10 and IFN-gamma in PBMCs was significantly lower, by 34% and 84%, respectively, when compared with controls, while production of TNF-alpha, IL-6 and IL-8 did not change. The magnitude of reduction of IL-10 in hypothermic conditions resulted in IL-10/pro-inflammatory cytokine ratios decreasing to approximately 30-45% of those of controls. The present study clearly demonstrates that mild hypothermia (33 degrees C) inhibits IL-10 and IFN-gamma production in cultured PBMCs. The profound inhibition of IL-10 and the pro-inflammatory reaction-dominated state induced suggests that the host defense mechanism against secondary infection may be maintained rather than inhibited in hypothermia. Thus, the reduction of IL-10 could be an important characteristic of immune responses in mild hypothermia.


Insight into aerobic phosphorus removal from wastewater in algal-bacterial aerobic granular sludge system.
This study aimed to figure out the main contributors to aerobic phosphorus (P) removal in the algal-bacterial aerobic granular sludge (AGS)-based wastewater treatment system. Kinetics study showed that aerobic P removal was controlled by macropore (contributing to 64-75% P removal) and micropore diffusion, and the different light intensity (0, 4.0, 12.3, and 24.4 klux) didn't exert significant (p > 0.05) influence on P removal. On the other hand, the increasing light intensity did promote microalgae metabolism, leading to the elevated wastewater pH (8.0-9.8). The resultant pH increase had a strongly negative relationship (R2 = 0.9723) with P uptake by polyphosphate-accumulating organisms, while promoted chemical Ca-P precipitation at a molar Ca/P ratio of 1.05. Results from this work could provide an in-depth understanding of microalgae-bacteria symbiotic interaction, which is helpful to better design and operate the algal-bacterial AGS systems.


Chemical upcycling of polyethylene, polypropylene, and mixtures to high-value surfactants.
Conversion of plastic wastes to fatty acids is an attractive means to supplement the sourcing of these high-value, high-volume chemicals. We report a method for transforming polyethylene (PE) and polypropylene (PP) at ~80% conversion to fatty acids with number-average molar masses of up to ~700 and 670 daltons, respectively. The process is applicable to municipal PE and PP wastes and their mixtures. Temperature-gradient thermolysis is the key to controllably degrading PE and PP into waxes and inhibiting the production of small molecules. The waxes are upcycled to fatty acids by oxidation over manganese stearate and subsequent processing. PP ꞵ-scission produces more olefin wax and yields higher acid-number fatty acids than does PE ꞵ-scission. We further convert the fatty acids to high-value, large-market-volume surfactants. Industrial-scale technoeconomic analysis suggests economic viability without the need for subsidies.


SNHG3 correlates with malignant status and poor prognosis in hepatocellular carcinoma.
Long noncoding RNAs (lncRNAs) have been found dysregulated in human disease, especially in cancer. Small nucleolar RNA host gene 3 (SNHG3) is an lncRNA whose potential function and mechanism in hepatocellular carcinoma (HCC) remain largely unknown. In the present study, we aimed to determine SNHG3 expression and its clinical significance in HCC. Our results showed that the expression level of SNHG3 was significantly upregulated in HCC tissues compared with paired noncancerous tissues from 51 HCC patients, as determined by quantitative real-time polymerase chain reaction (qRT-PCR; P < 0.001), which was consistent with the results of two independent HCC cohorts from The Cancer Genome Atlas (TCGA) and Oncomine databases (P < 0.0001 and P = 0.0325, respectively). These results were further confirmed in 144 paired paraffin-embedded HCC specimens by in situ hybridization assay (ISH). Furthermore, SNHG3 expression was significantly correlated with tumor size (P = 0.003), portal vein tumor thrombus (PVTT; P = 0.014), and relapse (P = 0.038). The high expression level of SNHG3 was markedly correlated with overall survival (OS; P < 0.0001), recurrence-free survival (RFS; P = 0.006), and disease-free survival (DFS; P < 0.0001). More importantly, multivariate analysis indicated that SNHG3 expression was an independent prognostic factor for HCC patients (P < 0.001). In conclusion, increased SNHG3 expression is associated with malignant status and poor prognosis in HCC patients.


FoxO1 is a negative regulator of neointimal hyperplasia in a rat model of patch angioplasty.
Neointimal hyperplasia persists as a barrier following vascular interventions. Forkhead Box O1 (FoxO1) is a transcription factor that possesses a distinctive fork head domain and indirectly contributes to various physiological processes. FoxO1 expression and signaling also impact the energy metabolism of vascular smooth muscle cells, potentially influencing neointimal hyperplasia. Our hypothesis is that FoxO1 inhibits neointimal hyperplasia in a rat patch angioplasty model. Four groups were compared in a rat aorta patch angioplasty model: the control group without treatment, patches coated with AS184286 (a FoxO1 inhibitor) in a PLGA matrix, patches coated with FoxO1 in a PLGA matrix, and patches coated with MLN0905 (a PLK1 inhibitor) in a PLGA matrix. The patches were harvested on Day 14 and subjected to analysis. FoxO1-positive and p-FoxO1 cells were observed after patch angioplasty. The addition of FoxO1 through patches coated with exogenous FoxO1 protein in a PLGA matrix significantly inhibited neointimal thickness (p = 0.0012). The treated groups exhibited significantly lower numbers of CD3 (p = 0.0003), CD45 (p < 0.0001), and PCNA (p < 0.0001)-positive cells. PLK1 is an upstream transcriptional regulator of FoxO1, governing the expression and function of FoxO1. MLN0905 PLGA-coated patches exhibited comparable reductions in neointimal thickness and inflammatory cell accumulation. FoxO1 represents a promising therapeutic strategy for inhibiting neointimal hyperplasia.


[Management of the perineal wound in the postoperative treatment of patients with cancer of the rectum].
The material showing causes of the appearance of purulent complications of the perineum would after extirpation of the rectum for cancer is presented. The pathogenes of the purulent infection were found to be polyresistant staphylococcus and gram-negative intestinal flora in most cases. The authors recommend using antibiotic therapy directly at the time of performing the operation, good drainage of the postoperative wound, irradiation of the postoperative wound by a laser radiation of a harmless intensity.


Politics or Economics? International Migration during the Nicaraguan Contra War.
The issue of whether Central Americans in the United States are 'political' or 'economic' migrants has been widely debated, yet little empirical research has informed the controversy. Earlier studies have relied primarily on cross-sectional aggregate data. In order to overcome these limitations we draw on recent surveys conducted in five Nicaraguan communities by the Latin American Migration Project. Using retrospective data, we reconstruct a history of a family's migration to the United States and Costa Rica from the date of household formation to the survey date and link these data to national-level data on GDP and Contra War violence. While out migration to both Costa Rica and the United States is predicted by economic trends, US-bound migration was more strongly linked to the level of Contra War violence independent of economic motivations, especially in an interactive model that allows for a higher wartime effect of social networks. We conclude that elevated rates of Nicaraguan migration to the United States during the late 1980s and early 1990s were a direct result of the US-Contra intervention. The approach deployed here - which relates to the timing of migration decisions to macro-level country trends - enables us to address the issue of political versus economic motivations for migration with more precision than prior work.


In vitro expression of cytotoxicity by macrophages is independent of the actual serum concentration.
In utilizing the same effector and target cells, similar arrangement and population density of cells but varying the actual serum concentration in the range between 1 and 50% fetal calf serum, it was attempted to accurately assess the dependence of in vitro cytolysis expressed by adherent, predominantly phagocytic mononuclear cells ('macrophages') on the actual serum concentration. The results show that the extent to which cytotoxicity by activated macrophages against a given target cell type was expressed, was within a comparable range independent of the actual serum concentration. This holds true for each of the 9 target cell lines examined although with some of the cell lines there was a certain tendency towards high cytotoxicity in the range between 5 and 20% serum.


Multifocal osseous tuberculosis involving hand and feet.
A rare case of multifocal cystic tuberculosis of hands and feet is presented in an adolescent female. The presence of multiple lytic areas mimicked secondary metastases and biopsy remained the mainstay for final diagnosis.


DNA damage-mediated cellular senescence promotes hand-foot syndrome that can be relieved by thymidine prodrug.
Hand-foot syndrome (HFS) is a widely recognized dose-limiting cutaneous toxicity effect of fluoropyrimidine chemotherapy agents that impairs clinical benefits and treatment outcomes. Even though the cause and pathophysiology of HFS are relatively widely reported, how the toxicity of fluoropyrimidine translates into persistent inflammation has not been studied. Additionally, prevention and treatment strategies for HFS based on its mechanistic occurrence and development are scarce. In our study, we demonstrated that cGAS-STING signaling pathway-mediated cellular senescence played a critical role in the inflammatory reaction and provided a therapeutic solution for HFS. Mechanistically, DNA damage, as the primary cytotoxic cause, in keratinocytes induces cell cycle arrest, activates the cGAS-STING signaling pathway, and subsequently mediates cellular senescence, ultimately fueling a robust secondary inflammatory response that results in HFS. More importantly, the thymidine prodrug thymidine diacetate was proven to be effective in preventing HFS by compensating for thymidylate deficiency to facilitate the replication and repair of DNA and thus causing the escape from cellular senescence. These data highlight the importance of DNA damage-mediated cellular senescence in the etiology of HFS and provide a potential therapeutic anchor point for fluoropyrimidine-induced HFS.


Oral treatment of transmissible gastroenteritis with natural human interferon alpha: a field study.
During a natural outbreak of transmissible gastroenteritis (TGE), groups of piglets were treated orally for 4 consecutive days with placebo or 1.0, 10.0 or 20.0 international units (IU) natural human interferon alpha (nHuIFN alpha). Piglets that were 1-12 days of age and given 1.0, 10.0 or 20.0 IU nHuIFN alpha had significantly (P < 0.01) greater survival rates than placebo-treated piglets; survival rates were the greater for the highest level of nHuIFN alpha treatment. In contrast, beneficial effects of nHuIFN alpha were not observed in piglets farrowed during the disease outbreak and given nHuIFN alpha within hours of birth. Oral nHuIFN alpha therapy modulates the natural course of high morbidity and mortality commonly seen with TGE.


Pharmaceutical approval update.
Cabozantinib (Cometriq) for metastatic medullary thyroid cancer; ponatinib (Iclusig) for two forms of leukemia; and raxibacumab for inhalational anthrax.


New nordihydroguaiaretic acid derivatives as anti-HIV agents.
Reaction of nordihydroguaiaretic acid with various alkyl chloride, 1-piperidinecarbonyl chloride, methyl chloroformate, or 1,1'-carbonyldiimidazole under alkaline conditions produced the corresponding phenol ethers, carbamates and carbonates, respectively, in 67-83% yields. Among these derivatives, the nitrogen-containing compounds were converted to the corresponding hydrochloride salts. Having good solubility, these NDGA derivatives were found stable in aqueous solution. These new compounds exerted appealing activity against HIV Tat-regulated transactivation in human epithelial cells. The most potent compound meso-2,3-dimethyl-1,4-bis(3,4-[2-(piperdino)ethoxyphenyl])butane tetrakishydrochloride salt (5b) showed IC(50) value of 0.88 microM.


Level of protein kinase C activity correlates directly with resistance to adriamycin in murine fibrosarcoma cells.
In this report, we demonstrate a direct correlation between protein kinase C (PKC) activity and adriamycin (ADR) resistance in mouse fibrosarcoma cells. PKC activity was measured in four murine UV-2237M fibrosarcoma cell lines that differed in the degrees to which they expressed resistance to ADR, which is an inhibitor of PKC. A comparison of the four cell lines revealed a positive correlation between the level of PKC activity and resistance to ADR. Incubation of the cells with the PKC inhibitor H-7 produced a partial reversal of ADR resistance. Taken together, these results suggest a role for PKC in the mechanism of ADR resistance.


Emerging Insights into the Impact of Air Pollution on Immune-Mediated Asthma Pathogenesis.
Increases in ambient levels of air pollutants have been linked to lung inflammation and remodeling, processes that lead to the development and exacerbation of allergic asthma. Conventional research has focused on the role of CD4+ T helper 2 (TH2) cells in the pathogenesis of air pollution-induced asthma. However, much work in the past decade has uncovered an array of air pollution-induced non-TH2 immune mechanisms that contribute to allergic airway inflammation and disease. In this article, we review current research demonstrating the connection between common air pollutants and their downstream effects on non-TH2 immune responses emerging as key players in asthma, including PRRs, ILCs, and non-TH2 T cell subsets. We also discuss the proposed mechanisms by which air pollution increases immune-mediated asthma risk, including pre-existing genetic risk, epigenetic alterations in immune cells, and perturbation of the composition and function of the lung and gut microbiomes. Together, these studies reveal the multifaceted impacts of various air pollutants on innate and adaptive immune functions via genetic, epigenetic, and microbiome-based mechanisms that facilitate the induction and worsening of asthma.


Phytochemical investigation of Bidens biternata (Lour.) Merr. and Sheriff.--a nutrient-rich leafy vegetable from Western Ghats of India.
Bidens biternata, belonging to the family Asteraceae, is an erect annual herb, up to 1 cm in height, and a widespread weed of cultivated areas. This plant is common, particularly in the Western Ghats regions of Kerala state in India. It is used as a leafy vegetable by the Paniya and Kattunaayika tribes of Waynadu Districts in Kerala and also to cure hepatitis, cold, cough, dysentery, etc. The multiplication and utilization of this leafy vegetable will help to overcome the nutritional deficiency problem and also to maintain the biodiversity. For effective biochemical analysis, plant extract was taken using different solvents. Various phytochemicals like reducing sugar, glycosides, flavonoids, alkaloids, tannins, steroids, terpenoids, coumarins, saponins, anthraquinones, phlobatannins and iridoids were estimated. Different nutritional factors like total carbohydrates, total proteins, total reducing sugar, different amino acids, free fatty acids, crude fibre, lipids, total moisture content, vitamins, etc. were tested by standard estimation methods. Anti-nutritional factors like phytic acid, total phenol, tannic acid, etc., were also estimated. Micronutrients and different pigments were quantified. The present studies revealed that this wild leafy plant has numerous nutritional factors with a low level of anti-nutritional factors. Therefore, this nutritive herb with diverse health-promoting compounds can be effectively utilized to overcome the nutritional deficiency problem around the globe.


[Histochemical reaction to biogenic amines of the nervous system of the larval and mature cestode Microsomacanthus microskrjabini].
Histochemical reaction with glyoxylic acid has revealed a specific fluorescence caused by the presence of indolamine (apparently serotonin) in the nervous system of larva and mature cestode. Fluorescence manifests itself in neurons and nerve fibres of the central ganglion and its commissure, in nerve cells of the proboscis, in longitudinal trunks and transverse commissures, and in the nerve elements connected with genital system.


Maximal amniotic fluid index as a prognostic factor in pregnancies complicated by polyhydramnios.
Polyhydramnios is present in approximately 2% of pregnancies and has been associated with a variety of adverse pregnancy outcomes. Our aim was to evaluate the association between the maximal amniotic fluid index (AFI) and the frequency of specific adverse outcomes. This was a retrospective chart review of 524 singleton pregnancies diagnosed with polyhydramnios and delivered in a single tertiary referral center between 2003 and 2008. Polyhydramnios was defined as either AFI ≥ 25 cm or a maximum vertical pocket (MVP) ≥ 8 cm even in the presence of AFI < 25 cm. The cohort was stratified into four groups based on the maximal AFI noted during the pregnancy: < 25 cm but with MVP ≥ 8 cm; 25-29.9 cm; 30-34.9 cm; and ≥ 35 cm. Data were collected to determine the frequency of the following adverse pregnancy outcomes: prenatally diagnosed congenital anomalies, fetal aneuploidy, preterm delivery, Cesarean delivery, low birth weight, 5-min Apgar score < 7 and perinatal mortality. Higher AFI was associated with a statistically significant increase in the frequency of adverse pregnancy outcomes. The most severe form of polyhydramnios, as based on the maximal AFI (≥ 35 cm; n = 67), was associated with the highest rates of prenatally diagnosed congenital anomalies (79%), preterm delivery (46%), small-for-gestational-age neonate (16%), aneuploidy (13%) and perinatal mortality (27%). No significant association between degree of polyhydramnios and adverse outcome was demonstrated in cases of idiopathic polyhydramnios (n = 253). There is an association between the frequencies of a variety of adverse pregnancy outcomes and the severity of polyhydramnios as reflected by the maximal AFI.


Effects of the internal contact surfaces of dental implants on screw loosening: A 3-dimensional finite element analysis.
The effects of the internal contact surfaces of dental implants on screw loosening have yet to be investigated. The purpose of this 3-dimensional finite element analysis (FEA) study was to evaluate and compare the mechanical effects of the abutment implant angle (θ), the abutment screw head diameter (D), and the abutment screw length (L) on screw loosening. A total of 27 models presenting various mechanical scenarios were built by using combinations of 3 different θ (30 degrees, 45 degrees, and 60 degrees), D (2.65 mm, 2.75 mm, and 2.85 mm), and L (4 mm, 5 mm, and 6 mm). In FEA, a static test with a 200-N force inclined 30 degrees in the implant axial direction was applied to the upper surface of the abutment to evaluate and compare the maximum von Mises stresses of the implant components and the maximum total deformation in all models. In addition, modal analysis was applied to identify the natural frequencies in all models under free (unforced) vibration, and a Kruskal-Wallis statistical test (α=.05) was performed, followed by multiple pairwise comparisons by using the Dunn test. The Kruskal-Wallis test found a significant influence of the θ on implant stress, total deformation, and natural frequency (P<.001). For example, increasing the θ from 30 degrees to 45 degrees and 60 degrees can considerably reduce the model's natural frequencies to 18% and 26%, respectively. Similarly, the test underscored the significant impact of the D on both abutment screw stress and abutment stress (P=.010 and P=.002, respectively). However, the L appeared to have no significant effect on any of the dependent variables (P>.05). The θ and the D significantly influenced the stresses of dental implant components, total deformation, and natural frequency of the model, which may impact the mechanical stability of the screw joint. However, the L does not appear to affect these values significantly.


Robotic vs. minimally invasive mitral valve repair: A 5-year comparison of surgical outcomes.
Minimally invasive mitral valve repair (MVr) is commonly performed. Data on the outcomes of robotic MVr versus nonrobotic minimally invasive MVr are lacking. We sought to compare the short-term and mid-term outcomes of robotic and nonrobotic MVr. We reviewed all patients who underwent robotic MVr (n = 424) or nonrobotic MVr via right mini-thoracotomy (n = 86) at Mayo Clinic, Rochester, MN, from January 2015 to February 2020. Data on baseline and operative characteristics, operative and long-term outcomes were analyzed. Patients were matched 1:1 using propensity scores. Sixty-nine matched pairs were included in the study. The median age was 59 years (interquartile range [IQR]: 54-69) and 75% (n = 103) were male. Baseline characteristics were similar after matching. Robotic and nonrobotic MVr had similar operative characteristics, except that robotic had longer cross-clamp times (57 [48-67] vs. 47 [37-58] min, p < .001) and more P2 resections (83% vs. 68%, p = .05) compared to nonrobotic MVr. There was no difference in operative outcomes between groups. Hospital stay was shorter after robotic MVr (4 [3-4] vs. 4 [4-6] days, p = .003). After a median follow-up of 3.3 years (IQR, 2.1-4.5), there was no mortality in either group, and there was no difference in freedom from mitral valve reoperations between robotic and nonrobotic MVr (5 years: 97.1% vs. 95.7%, p = .63). Follow-up echocardiogram analysis predicted excellent freedom from recurrent moderate-or-severe mitral regurgitation at 3 years after robotic and nonrobotic MVr (90% vs. 92%, p = .18, respectively). Both short-term and mid-term outcomes of robotic and nonrobotic minimally invasive mitral repair surgery are comparable.


A prediction model for overall survival after transarterial chemoembolization for hepatocellular carcinoma invading the hepatic vein or inferior vena cava.
An effective therapeutic option has not yet been established for hepatocellular carcinoma (HCC) invading the hepatic vein (HV) or inferior vena cava (IVC). This study aimed to determine the therapeutic effect of transarterial chemoembolization (TACE) in HCC patients with HV or IVC invasion, and to build a risk prediction model. Data from patients who underwent TACE as a first-line treatment for HCC invading the HV or IVC between 1997 and 2019 were retrospectively evaluated. Data from 296 patients were included (1997-2006 comprised the training cohort, n = 174; 2007-2019 comprised the validation cohort, n = 122). The median post-TACE survival was 7.3 months and an objective tumor response was achieved in 34.1% of patients. Multivariable Cox analysis of the training cohort identified five pretreatment factors (maximal tumor size > 10 cm, infiltrative HCC, combined portal vein invasion, extrahepatic metastasis, and ECOG performance status 1), which were used to create predictive models for overall survival. Median overall survival times in the validation cohort were 14 and 4.2 months for the low (sum of risk score: 0-3)- and high-risk (sum of risk score: 4-7) groups, respectively (p < 0.001). Time-dependent ROC curves for the predictive models for overall survival applied to the validation cohort showed acceptable AUC values (0.723 and 0.667 at 6 months and 1 year). TACE seems effective for selected patients with HCC invading the HV or IVC. The predictive model may help to identify candidates most likely to benefit from TACE. • To develop a risk prediction model for patients with HCC with HV or IVC invasion treated with TACE, five factors were selected from a multivariate Cox regression model for overall survival. • The combination of these factors helped to identify two prognostic categories: low- and high-risk. • The predictive model can help to select candidates who will benefit most from TACE in this patient group.


Rule shift under long-term PCP challenge in rats.
Performance of Long-Evans rats repeatedly treated with a high dose of phencyclidine (PCP) was compared with that of controls on two tasks involving rule shifts. Fifteen hours after receiving 12 daily doses of PCP (10mg/kg) or saline, rats were tested in the first task where a fixed or variable goal had to be recognized among four maze-arm locations. After receiving the last of 33 injections, rats were subjected to a second task: they had to discriminate the relevant perceptual dimension in a pair of stimuli and choose the appropriate stimulus in each problem. Results from both tasks revealed no difference between controls and rats injected with PCP either during acquisition using a constant rule or during testing with rule shifts. Consequently, PCP appears to lack consistency in disturbing frontal cognitive functions in animal models of schizophrenia.


Testicular torsion: a complication of laparoscopic orchidopexy.
A 19-month-old boy presented with an impalpable right testis. At second-stage Fowler-Stephens laparoscopic orchidopexy, the testicle was found to be torted, a complication that has not been described previously. The procedure, known complications, possible reasons for torsion and possible techniques to avoid torsion occurring are reviewed.


Highly Selective Olefin Production from CO2 Hydrogenation on Iron Catalysts: A Subtle Synergy between Manganese and Sodium Additives.
Mn and Na additives have been widely studied to improve the efficiency of CO2 hydrogenation to valuable olefins on Fe catalysts, but their effects on the catalytic properties and mechanism are still under vigorous debate. This study shows that Fe-based catalysts with moderate Mn and Na contents are highly selective for CO2 hydrogenation to olefins, together with low selectivities for both CO and CH4 and much improved space-time olefin yields compared to state-of-the-art catalysts. Combined kinetic assessment and quasi in situ characterizations further unveil that the sole presence of Mn suppresses the activity of Fe catalysts because of the close contact between Fe and Mn, whereas the introduction of Na mediates the Fe-Mn interaction and provides strong basic sites. This subtle synergy between Na and Mn sheds light on the importance of the interplay of multiple additives that could bring an enabling strategy to improve catalytic activity and selectivity.


Effect of rising intragastric pH induced by several antacids on serum gastrin concentrations in duodenal ulcer patients and in a control group.
The interrelationship of the effects of antacids and of rising intragastric pH on serum gastrin levels was examined by comparing the effect of three antacids (Mg(OH)2Al(OH)3, and CaCO3), and their nonbuffering chloride compounds (MgCl2, AlCl3, and CaCl2), on serum gastrin and intragastric pH in duodenal ulcer patients. In the case of calcium, the effect of CaCl2 with a pH of 10, and in another group, CaCl2 with a pH of 2, was studied. In the case of magnesium, a control group was also investigated. In another group, the effect of a nonionized suspension (BaSO4) was studied in order to assess the contribution of intragastric volume. Serum gastrin was determined radioimmunologically, and pH measurements were performed in vitro using a glass electrode. Serum gastrin concentrations rose significantly whenever intragastric pH was raised. Serum gastrin also rose after MgCl2, AlCl3, and CaCl2 with a pH of 2, when intragastric pH was not significantly altered. This rise, however, was significantly smaller than after administration of the antacids, except in the MgCl2-Mg(OH)2 and in the CaCl2 pH 10-CaCO3 groups. No significant rise of serum gastrin levels was observed after BaSO4. In nonulcer subjects, gastrin response was smaller than in the duodenal ulcer patients. The results suggest that administration of nonbuffering Mg-, Al-, and Ca-chlorides leads to elevated serum gastrin levels in duodenal ulcer patients; rising intragastric pH, however, exerts an additional serum gastrin response.


Keloid formation in a simple syndactyly release: a case report.
Keloid formation on the palms of the hands and soles of the feet is rare. A keloid developed 2 months after release of simple syndactyly in a young black child. The process of keloid formation is not completely understood, and surgical correction is not effective.


Relationship between disease activity and hearing impairment in patients with rheumatoid arthritis compared with controls.
The characteristics of hearing impairment (HI) in rheumatoid arthritis (RA) are still poorly understood, and their association with disease activity is based on conflicting information. This study compared HI between RA patients and controls and between active and remission RA groups using multi-frequency audiometry. This study enrolled 88 RA patients and 50 controls. The pure-tone hearing thresholds at 500 to 4000 Hz for air (AC) and bone (BC) conduction were compared between RA and controls as well as between active and remission RA patients using DAS28-CRP scores. The pure-tone hearing thresholds for AC and BC were significantly higher at high frequencies (2000 and 4000 Hz) in the RA group for both ears compared with controls. In addition, the BC threshold at 1000 Hz for the right ear was higher in the RA group than controls. When active and remission RA patients were compared, the thresholds were higher only at 4000 Hz for both ears for AC and BC in patients with active RA. The air-bone gap differed significantly at 2000 and 4000 Hz in both ears. This study demonstrated that patients with RA have a heightened risk of HI, and disease activity increases this risk, particularly at high frequencies. Clinicians who manage RA should be aware of HI and consider performing audiological evaluations in RA patients with active disease in particular.


The medial and lateral cell groups of the sexually dimorphic area of the gerbil hypothalamus are essential for male sex behavior and act via separate pathways.
Male reptiles, birds and mammals do not copulate if the medial preoptic area (MPOA) is destroyed but the MPOA cell groups necessary for male sexual behavior were not known. Here, two cell groups essential for copulation are identified in the sexually dimorphic area (SDA) of the gerbil (Meriones unguiculatus) MPOA. Bilateral cell-body lesions of either the medial or lateral SDA eliminated mating in sexually experienced male gerbils given testosterone. Nearby MPOA lesions did not. The medial and lateral SDA affect sex behavior via separate pathways since lesioning the medial SDA on one side of the brain and the lateral SDA on the other did not stop sexual behavior.


Quantitative recovery of expired nitrogen and nitrous oxide from venous gas emboli.
It has not been previously established whether venous gas emboli dissolve from pulmonary blood vessels into adjacent airways, or pass as microbubbles directly into the systemic circulation. We reported here the quantitative recovery of embolized gases from the airways, in amounts which substantiate the complete elimination of such gases by dissolution. A computer controlled quadrupole mass spectrometer was used to measure the net expired volumes of N2 or N2O following the injection of 40 ml boluses of these gases into the airways (AW) or right ventricles (RV) of 5 mongrel dogs. Every 20 ms, linearized flow signals were multiplied by gas concentrations, and the products summed for inspired and expired volumes of each breath. Intubated dogs were ventilated with 100% oxygen under Na-pentobarbital and either succinylcholine chloride or pancuronium bromide anesthesia; Swan-Ganz catheters were used for RV injections and for monotoring cardiovascular parameters. The overall mean % volume recoveries were 70.4 for AW-N2O, 68.2 for RV-N2O, 83.7 for AW-N2, and 46.7 for RV-N2. As expected, the AW percent volume recoveries increased with decreasing aqueous solubilities, and represented maximal values obtainable for RV emboli, due to alveolar reabsorption of gases excreted from the pulmonary circulation. Although all RV-N2O could thus be accounted for, RV-N2 recoveries were significantly less than AW-N2. The remaining RV-N2 did not pass as bubbles into the pulmonary veins, but continued to obstruct the pulmonary arterioles, as demonstrated with the use of nitrous oxide challenges in the inspired gas mixture.


Mutation screening and association study of the beta-adrenergic receptor kinase 2 gene in schizophrenia families.
Chromosome 22q12 is one of the most promising regions for harboring a risk gene for schizophrenia. We have reported significant linkage of intermediate phenotypes for schizophrenia with markers within or near the beta-adrenergic receptor kinase 2 (ADRBK2, or GRK3) gene, which is highly expressed in dopaminergic pathways in the central nervous system, and mediates homologous desensitization for a variety of neurotransmitters and hormones through phosphorylation of G protein-coupled receptors (GPCRs). A polymorphism in the promoter region of the ADRBK2 was reported to be associated with bipolar disorder. We screened the putative promoter region, and all 21 exonic and flanking intronic regions of the ADRBK2 gene for mutations in 48 schizophrenia probands (including 16 Japanese and 32 Chinese patients), and evaluated the detected polymorphisms and those reported in the JSNP database for associations with schizophrenia in 113 family trios of schizophrenia probands. Four single nucleotide variants in the 5'-UTR/promoter region, and 16 rare variants in exonic and flanking regions, were identified. Among them, the Cys208Ser variant was the only non-synonymous mutation. Cys208Ser was found in one family without cosegregation between the variant and schizophrenia. Moreover, allelic, genotypic and haplotypic analyses provided no evidence for association between alleles at these polymorphisms and schizophrenia. The present study indicates that the ADRBK2 gene is unlikely to contribute strongly to schizophrenia susceptibility in this set of families.


An ameliorated anti-hTNF-α therapy for arthritis via carrier-free macromolecular nanoparticles consisted of infliximab.
Infliximab (INF) is intravenously used for the clinical treatment of rheumatoid arthritis. However, it can cause serious side effects, which are mainly associated with systemic exposure and high doses. Here, we developed a modified hydrophobic ion-pairing complexes (INF HIPC) through the sequential introduction of bovine lactoferrin (BLF) and hyaluronic acid (HA) with opposite charges into the INF solution. INF and BLF were found to be not only integrally responsible for the structural integrity of HIPC but also were determined to have respective biological activities by binding human tumor necrosis factor-alpha (hTNF-α) or promoting the proliferation of osteoblasts. The INF HIPC had good stability, high drug-loading efficiency, and long-term retention effects. Whether via knee joint injection or intravenous injection, INF HIPC resulted in lower hTNF-α levels and less cartilage destruction than INFs in the transgenic mouse model. At the same time, INF HIPC could reduce toxicity based on body weight changes in transgenic mice. Our findings provide a simple and promising avenue to develop advanced delivery systems for other antibodies and macromolecules.


Single and multiple exposure tolerance study of cellulose sulfate gel: a Phase I safety and colposcopy study.
Vaginally applied gels offer a promising approach for preventing unwanted pregnancies and sexually transmitted infections. Cellulose sulfate (CS) is a non-cytotoxic antifertility agent that also exhibits in vitro antimicrobial activity against sexually transmitted pathogens, including HIV. This was a randomized, double-blinded, Phase I study of 2.5 mL and 5.0 mL doses of 6% CS gel. A single vaginal application of the gel followed by five consecutive daily doses was assessed for genital irritation, safety, vaginal leakage, and product acceptability compared to two controls, Conceptrol, which is a marketed contraceptive gel containing nonoxynol-9, and K-Y jelly. The results suggest that the safety of 6% CS was comparable to that of Conceptrol and K-Y jelly, and it may be associated with less genital irritation. The 2.5 mL dose of CS may be preferable according to the participants' reports of leakage. All the products had similar acceptability profiles.


Sex determination of early medieval individuals through nested PCR using a new primer set in the SRY gene.
One of the first questions asked about excavated human skeletal remains is the sex. As the morphological sex determination is complicated in cases involving fragmentary bones and in skeletons from infants and children, the development of DNA-based techniques has led to improvements in sex determination. This study is focused on sex determination from ancient DNA obtained from 25 skeletons found in Middle Aged burials in western Slovakia. We performed separate amplifications of DXZ4 repetitive satellite sequences on the X chromosome, and SRY gene - testis determined factor on the Y chromosome, using nested PCR. Our results showed that DXZ4 was amplified in the case of 23 individuals. With newly designed internal and external primer sets for SRY detection with internal PCR products in lengths of 102 bp and 85 bp we succeeded in detecting the SRY locus in 9 samples. Finally, the gender was determined in 23 individuals (14 females and 9 males). In 20 samples, the gender was determined by morphological and molecular methods. Sex determination of 17 samples using nested PCR matched the morphological one, providing evidence of the authenticity and ancient origin of the PCR amplifications. The DXZ4/SRY nested PCR method represents a useful technique in sex determination of medieval human remains and it is a critical addition to anthropological studies.


A potent and selective inhibition of parainfluenza 1 (Sendai) virus by new 6-oxiranyl-, 6-methyloxiranyluracils, and 4(3H)-pyrimidinone derivatives.
Several new 6-oxiranyl-, 6-methyloxiranyluracils, and pyrimidinone derivatives, synthesized by the lithiation-alkylation sequence of 1,3,6-trimethyluracil, 1,3-dimethyl-6-chloromethyluracil, and 2-alkoxy-6-methyl-4(3H)-pyrimidinones, showed a potent and selective antiviral activity against the parainfluenza 1(Sendai) virus replication.


Ipriflavone suppresses NLRP3 inflammasome activation in host response to biomaterials and promotes early bone healing.
Emerging studies have shown that immune response to biomaterial implants plays a central role in bone healing. Ipriflavone is clinically used for osteoporosis. However, the mechanism of ipriflavone in immune response to implants in early stages of osseointegration remains unclear. In this study, we aimed to investigate the potential role of ipriflavone in early bone healing process and uncover the underlying mechanism. We carried out histological examination as well as analysis of proinflammatory cytokines and NLRP3 inflammasome activation in a tibial implantation mouse model with intra-peritoneal injection of ipriflavone. In addition, we explored the mechanism of ipriflavone in the regulation of NLRP3 inflammasome activation in macrophages. In vivo, ipriflavone ameliorated host inflammatory response related to NLRP3 inflammasome activation at implantation sites, characterized by reductions of inflammatory cell infiltration and proinflammatory cytokine interleukin-1β levels. Ipriflavone treatment also showed beneficial effects on early osseointegration. Further investigations of the molecular mechanism showed that the suppression of NLRP3 inflammasome acts upstream of NLRP3 oligomerization through abrogating the production of reactive oxygen species. These results revealed an anti-inflammatory role of ipriflavone in NLRP3 inflammasome activation through improving mitochondrial function. This study provides a new strategy for the development of immune-regulated biomaterials and treatment options for NLRP3-related diseases.


Escherichia coli prereplication complex assembly is regulated by dynamic interplay among Fis, IHF and DnaA.
Initiator DnaA and DNA bending proteins, Fis and IHF, comprise prereplication complexes (pre-RC) that unwind the Escherichia coli chromosome's origin of replication, oriC. Loss of either Fis or IHF perturbs synchronous initiation from oriC copies in rapidly growing E. coli. Based on dimethylsulphate (DMS) footprinting of purified proteins, we observed a dynamic interplay among Fis, IHF and DnaA on supercoiled oriC templates. Low levels of Fis inhibited oriC unwinding by blocking both IHF and DnaA binding to low affinity sites. As the concentration of DnaA was increased, Fis repression was relieved and IHF rapidly redistributed DnaA to all unfilled binding sites on oriC. This behaviour in vitro is analogous to observed assembly of pre-RC in synchronized E. coli. We propose that as new DnaA is synthesized in E. coli, opposing activities of Fis and IHF ensure an abrupt transition from a repressed complex with unfilled weak affinity DnaA binding sites to a completely loaded unwound complex, increasing both the precision of DNA replication timing and initiation synchrony.


Spontaneous Pan-Carpal Metacarpal Fusion After a Case of Pediatric Septic Arthritis of the Wrist: A Case Report.
A 46-year-old female patient with a history of Streptococcus pyogenes septic arthritis 32 years earlier presented to an outpatient clinic with complaints of chronic wrist pain and stiffness. Imaging revealed complete pan-carpal metacarpal fusion with advanced radiocarpal arthritis. The patient's pain improved with 3 months of nonoperative management, and she was able to return to previous levels of activity. Pediatric septic arthritis of the wrist is an exceedingly rare diagnosis but may result in spontaneous complete pan-carpal metacarpal fusion.


Guidelines for successful motor cortex ultrasonic neurostimulation in mice.
Ultrasound neurostimulation (USNS) is a non-invasive neuromodulation technique that might hold promise for treating neuropsychiatric disorders with regards to its noninvasiveness, penetration depth, and high resolution. We sought in this experimental study to provide detailed and optimized protocol and methodology for a successful ultrasonic neurostimulation of the Primary Motor Cortex (M1) in mice addressed to young researchers/students beginning their research in the field of ultrasonic neurostimulation and encountering practical challenges. A 500 kHz single-element transducer was used for stimulating the primary motor cortex at different acoustic pressures in C57BL/6 mice at various anesthesia levels. To further illustrate the effect of anesthesia, real time visual observations of motor responses validated with video recordings as well as electromyography were employed for evaluating the success and reliability of the stimulations. Detailed experimental procedure for a successful stimulations including targeting and anesthesia is presented. Our study demonstrates that we can achieve high stimulation success rates (91 % to 100 %) at acoustic pressures ranging from 330 kPa to 550 kPa at anesthesia washout period. This study shows a reliable and detailed methodology for successful USNS in mice addressed to beginners in ultrasonic brain stimulation topic. We showed an effective USNS protocol. We offered a simple and consistent non-invasive technique for locating and targeting brain zones. Moreover, we illustrated the acoustic pressure and stimulation success relationship and focused on the effect of anesthesia level for successful stimulation.


Concepts and classification of neurodegenerative diseases.
Neurodegenerative diseases are disorders characterized by progressive loss of neurons associated with deposition of proteins showing altered physicochemical properties in the brain and in peripheral organs. Molecular classification of neurodegenerative disease is protein-based. This emphasizes the role of protein-processing systems in the pathogenesis. The most frequent proteins involved in the pathogenesis of neurodegenerative diseases are amyloid-β, prion protein, tau, α-synuclein, TAR-DNA-binding protein 43kDa, and fused-in sarcoma protein. There are further proteins associated mostly with hereditary disorders such as proteins encoded by genes linked to trinucleotide repeat disorders, neuroserpin, ferritin, and familial cerebral amyloidoses. The clinical presentations are defined by the distinct involvement of functional systems and do not necessarily indicate the molecular pathologic background. Seeding of pathologic proteins and hierarchic involvement of anatomic regions is commonly seen in neurodegenerative diseases. Overlap of neurodegenerative diseases and combinations of different disorders is frequent. Translation of neuropathologic categories of neurodegenerative diseases into in vivo detectable biomarkers is only partly achieved but intensive research is performed to reach this goal.


The feasibility of using Saffron to reduce the photosensitivity reaction of selected photosensitizers using red blood cells and staphylococcusAureus bacteria as targets.
The photosensitivity reaction which appears after a Photodynamic therapy treatment session is a challenge that needs further investigation. The goal of this research is to evaluate the possibility of using saffron to reduce or control this photosensitivity reaction and to present mathematical modeling of the cell survival curves and their dependency on saffron concentration. Red blood cells (RBC) and Staphylococcus aureus Bacteria (STB) were used as targets in this study. The Photosensitivity of Rose Bengali, Methylene Blue, and Photofrin independently and incorporated with saffron was investigated for continued irradiation at different Saffron concentrations. Gompertz's function was used to fit the survival curve parameters. The 50% cell survival rate was fit to an empirical formula based on Saffron concentrations. Saffron inhibits the photosensitivity reaction of the three photosensitizers and causes a significant increase in the 50% survival rate time (t50) for RBC`s and STB. Saffron didn't show phototoxicity when incubated alone with RBC`s and STB. The survival curve parameters of the RBCs and STB showed a good fit to the Gompertz function. Saffron concentration is related to the RBC`s t50 based on power dependency of 0.56, 0.38 and 0.31 for Photofrin, Methylene Blue and Rose Bengali respectively and 0.1 on STB for Rose Bengali. Saffron can efficiently be used to reduce the photosensitivity reaction of Photosensitizers after a PDT treatment session. Gompertz function was found to be an appropriate mathematical model for survival rate curves. The t50 and the saffron concentration are well related through a power dependence empirical formula.


Perspectives on Mycophenolate Mofetil in the Management of Autoimmunity.
Before becoming a cornerstone in the treatment of numerous immune-mediated diseases, mycophenolate mofetil (MMF) was first introduced as an immunosuppressive agent in transplant immunology and later received the attention of rheumatologists and clinicians involved in the management of autoimmune diseases. MMF is now a widespread immunosuppressive drug for the treatment of several conditions, including lupus nephritis, interstitial lung disease associated with systemic sclerosis, and anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis while being efficacious also as rescue therapy in various orphan diseases, including dermatomyositis and IgA-associated nephropathy. Similarly, case reports or series support a possible use of MMF in other rare autoimmune diseases. Beyond modulating lymphocyte activation, MMF acts on other immune and non-immune cells and these effects may explain the therapeutic profile of this medication. The effects of MMF are broadly characterized by the impact on the immune system and the antiproliferative and antifibrotic changes induced. In this latter case, mechanistic data on fibroblasts may in the future allow to reevaluate the use of MMF in selected patients with inflammatory arthritis or systemic sclerosis. Attention must be paid towards the possible occurrence of adverse events, such as gastrointestinal complaints and teratogenicity, while the risk of infections and cancer related to MMF needs to be further investigated.


Frontal EEG asymmetry in borderline personality disorder is associated with alexithymia.
Frontal EEG asymmetry is a widely studied correlate of emotion processing and psychopathology. Recent research suggests that frontal EEG asymmetry during resting state is related to approach/withdrawal motivation and is also found in affective disorders such as major depressive disorder. Patients with borderline personality disorder (BPD) show aberrant behavior in relation to both approach and withdrawal motivation, which may arguably be associated with their difficulties in emotion processing. The occurrence and significance of frontal EEG asymmetry in BPD, however, has received little attention. Thirty-seven BPD patients and 39 controls underwent resting EEG and completed several psychometric questionnaires. While there were no between-group differences in frontal EEG asymmetry, in BPD frontal EEG asymmetry scores correlated significantly with alexithymia. That is, higher alexithymia scores were associated with relatively lower right-frontal activity. A subsequent analysis corroborated the significant interaction between frontal EEG asymmetry and alexithymia, which was moderated by group. Our findings reveal that lower right frontal EEG asymmetry is associated with alexithymia in patients with BPD. This finding is in accordance with neurophysiological models of alexithymia that implicate a right hemisphere impairment in emotion processing, and could suggest frontal EEG asymmetry as a potential biomarker of relevant psychopathology in these patients.


[Dichotic listening performance in children--development of a reliable test (author's transl)].
With a new developed and reliable dichotic test (one part monosyllable words, other part monosyllable digits) we could show a significant Right-Ear-Advantage (REA) in children from age six to eight. The determination of an auditory-dominance-index (DI)--in analogy to the DI of handedness by Schilling (1977)--made it possible to determine the different degrees of REA/LEA in individuals or groups. Within the near future the auditory-dominance-index could be an important measure in diagnosis and therapy of child development (i.e. discrimination of language features like phonematics, syntax, semantic, and their lateralisation within ages) as far as standard-scales for all-over-accuity and lateralisation will exist. Our test is the first step to do this.


Experimental and numerical investigations on reliability of air barrier on oil containment in flowing water.
Air barriers have been recently developed and employed as a new type of oil containment boom. This paper presents systematic investigations on the reliability of air barriers on oil containments with the involvement of flowing water, which represents the commonly-seen shearing current in reality, by using both laboratory experiments and numerical simulations. Both the numerical and experimental investigations are carried out in a model scale. In the investigations, a submerged pipe with apertures is installed near the bottom of a tank to generate the air bubbles forming the air curtain; and, the shearing water flow is introduced by a narrow inlet near the mean free surface. The effects of the aperture configurations (including the size and the spacing of the aperture) and the location of the pipe on the effectiveness of the air barrier on preventing oil spreading are discussed in details with consideration of different air discharges and velocities of the flowing water. The research outcome provides a foundation for evaluating and/or improve the reliability of a air barrier on preventing spilled oil from further spreading.


WITHDRAWN: Comparative evaluation of two vaginal self-sampling devices for the detection of human papillomavirus infections.
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Genetic resistance to fowl cholera is linked to the major histocompatibility complex.
Chickens of the Iowa State S1 line have been selected for ability to regress Rous sarcoma virus-induced (RSV) tumors, humoral immune response to GAT (Ir-GAT), and erythrocyte antigen B. Sublines homozygous at the major histocompatibility complex (MHC), as well as F1 heterozygotes and F2 segregants, were tested for resistance to fowl cholera by challenge with Pasteurella multocida strain X73. Control of the response at high doses was associated in a preliminary study with Ir-GAT and response to RSV tumors. Genetic control of resistance to low doses of P. multocida was demonstrated via sublines and F2 segregants to be linked with genes of the B-G region. Thus, genetic control of resistance to fowl cholera in chickens after exposure to Pasteurella multocida was shown to be linked to the major histocompatibility B complex, in this first demonstration of MHC-linked resistance to bacterial disease challenge.


H2.0-like homeobox 1 acts as a tumor suppressor in hepatocellular carcinoma.
H2.0-like homeobox 1 (HLX1) is a homeobox transcription factor gene expressed primarily in cytotrophoblast cell types in the early pregnancy human placenta and involved in the development of enteric nervous system. However, the biological function of HLX1 in hepatocellular carcinoma (HCC) remains unclear. In the present study, semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), quantitative real-time RT-PCR, western blot, and immunohistochemical staining were used to examine the expression level of HLX1 in a total of 125 cases of HCC tissues and their matched adjacent nontumorous tissues (ANLTs), and its correlation with clinical features of HCC patients was analyzed. Our findings showed that the expression level of HLX1 was significantly reduced in HCCs compared to ANLTs. Besides, it was also remarkably downregulated in HCC cell lines compared to normal liver cell line. We further found that the HLX1 level was significantly associated with the tumor size (p = 0.016), tumor number (p = 0.004), vascular invasion (p = 0.031), Edmondson-Steiner grade (p = 0.041), tumor-node-metastasis (TNM) stage (p < 0.001), and Barcelona clinic liver cancer (BCLC) stage (p = 0.008). Moreover, HLX1 was an independent risk factor for overall survival (OS, p = 0.020) and disease-free survival (DFS, p = 0.024) of HCC patients. In vitro experiments showed that overexpression of HLX1 markedly suppressed the invasion, migration, proliferation, and colony formation of HCC cells; in contrast, downregulation of HLX1 significantly promoted the invasion, migration, proliferation, and colony formation of HCC cells. In vivo study indicated that overexpression of HLX1 significantly inhibited the tumorigenic capacity of HCC cells in nude mice. Based on these findings, we suggest that HLX1 acts as a tumor suppressor in HCC.