Normal basic 2D echocardiographic values to screen and follow up the athlete's heart from juniors to adults: What is known and what is missing. A critical review.
In the last few years, multiple echocardiographic nomograms have been published. However, normal values calculated in the general population are not applicable to athletes, whose hearts may be enlarged and hypercontractile. Accordingly, athletes require specific nomograms. Our aim is to provide a critical review of echocardiographic nomograms on two-dimensional (2D) measures for athletes. We performed a systematic search in the National Library of Medicine for Medical Subject Headings and free text terms including echocardiography, athletes, normal values and nomograms. The search was refined by adding the keywords heart, sport, elite, master, children and young. Twenty-eight studies were selected for the final analysis. Our research revealed that currently available ranges of normality for athletes reported by different authors are quite consistent, with limited exceptions (e.g. atria, aorta). Numerical and methodological limitations, however, emerged. Numerical limitations included a limited sample size (e.g. < 450 subjects) of the population assessed and the paucity of data in women, non-Caucasian athletes, and junior and master athletes. Some data on M-mode measurements are available, while those for some specific structures (e.g. left atrial (LA) area and volumes, right ventricular diameters and aorta) are limited or rare (e.g. LA area). There was heterogeneity in data normalization (by gender, sport type and ethnicity) and their expression was limited to mean values (Z-scores have rarely been employed), while variability analysis was often lacking or incomplete. We conclude that comprehensive nomograms using an appropriate sample size, evaluating a complete dataset of 2D (and three-dimensional) measures and built using a rigorous statistical approach are warranted.


Search for genes positively selected during primate evolution by 5'-end-sequence screening of cynomolgus monkey cDNAs.
It is possible to assess positive selection by using the ratio of K(a) (nonsynonymous substitutions per plausible nonsynonymous sites) to K(s) (synonymous substitutions per plausible synonymous sites). We have searched candidate genes positively selected during primate evolution by using 5'-end sequences of 21,302 clones derived from cynomolgus monkey (Macaca fascicularis) brain cDNA libraries. Among these candidates, 10 genes that had not been shown by previous studies to undergo positive selection exhibited a K(a)/K(s) ratio > 1. Of the 10 candidate genes we found, 5 were included in the mitochondrial respiratory enzyme complexes, suggesting that these nuclear-encoded genes coevolved with mitochondrial-encoded genes, which have high mutation rates. The products of other candidate genes consisted of a cell-surface protein, a member of the lipocalin family, a nuclear transcription factor, and hypothetical proteins.


Effect of microtextured substrates on the molecular orientation of a nematic liquid-crystal sample.
The in-plane orientation of a nematic liquid-crystal sample, confined by two periodic microtextured substrates, is theoretically analyzed by means of the Frank-Oseen continuum elastic theory and a suitable surface term. In addition, an easy optical method to produce such textures using photopolymeric films is presented. It is shown that, in the limit of large pattern period, the orientation depends only on the ratio of the splay and bend elastic constants K1/K3 and on the easy axis direction of the individual stripes. In the particular case for which K1 = K3, the stability depends only on the easy axis direction for a general pattern period.


A Retrospective Analysis of Bloodstream Infections in Pediatric Allogeneic Stem Cell Transplant Recipients: The Role of Central Venous Catheters and Mucosal Barrier Injury.
Bloodstream infections (BSIs) are a leading cause of morbidity and mortality in children undergoing hematopoietic stem cell transplant (HSCT). Indwelling central venous catheters (CVCs) increase risk for BSIs, yet mucosal barrier injury-associated laboratory-confirmed bloodstream infection (MBI-LCBI) may also occur due to translocation of pathogenic organisms from the gastrointestinal tract into the bloodstream. The purpose of this study was to determine the association between stool organisms and BSIs in children with CVCs who underwent HSCT. We performed a retrospective analysis of 78 children who received allogeneic HSCT over 3 years (2012-2014). Surveillance stool cultures were analyzed pre- and post-HSCT to assess correlations between organisms isolated from stool and CVC cultures. Twenty-four of 78 children experienced 31 BSIs. Fifteen (48%) of these isolates were identified in stool within 30 days of the positive blood culture, and 11 (36%) isolates met criteria for MBI-LCBI. Mucosal barrier injury leads to translocation of pathogenic organisms into the bloodstream and accounts for a significant number of BSIs in children undergoing HSCT. Nursing assessment of mucosal changes during HSCT and interventions to preserve intact mucosa are essential to prevent MBI-LCBI.


Severe cyclophosphamide-related hyponatremia in a patient with acute glomerulonephritis.
Cyclophosphamide is frequently used to treat cancer, autoimmune and renal diseases, such as rapidly progressive glomerulonephritis. Its side effects are well-known, including bone marrow depression, infections, alopecia, sterility, bladder malignancy and hemorrhagic cystitis. Moreover, in some cases cyclophosphamide use has been related to the onset of hyponatremia, by development of a syndrome of inappropriate antidiuresis. Indeed, severe hyponatremia has been previously reported in patients treated with high-dose or moderate-dose of intravenous cyclophosphamide, while only few cases have been reported in patients treated with low dose. Here, we discuss a case of a syndrome of inappropriate antidiuresis followed to a single low-dose of intravenous cyclophosphamide in a patient with a histological diagnosis of acute glomerulonephritis, presenting as acute kidney injury. After cyclophosphamide administration (500 mg IV), while renal function gradually improved, the patient developed confusion and headache. Laboratory examinations showed serum sodium concentration dropped to 122 mmol per liter associated with an elevated urinary osmolality of 199 mOsm/kg, while common causes of acute hyponatremia were excluded. He was successfully treated with water restriction and hypertonic saline solution infusion with the resolution of the electrolyte disorder. This case, together with the previous ones already reported, highlights that electrolyte profile should be strictly monitored in patients undergoing cyclophosphamide therapy in order to early recognize the potentially life-threatening complications of acute water retention.


Cervical spinal epidural abscess following acupuncture: successful treatment with antibiotics.
A 67-year-old man with poorly controlled diabetes mellitus (DM) had acupuncture several times a month for chronic shoulder muscle stiffness. A few days after acupuncture in the posterior nuchal region, a low-grade fever and backache developed, and subacutely progressed. Finally he complained of gait disturbance, and then respiratory distress appeared. Magnetic resonance imaging (MRI) demonstrated high cervical epidural abscess with massive soft tissue inflammation and vertebral osteomyelitis. Conservative treatment with antibiotics was effective and it was well documented by following serial MRIs. This case suggested that needle acupuncture should be avoided for immunocompromised subjects such as patients with poorly controlled DM.


Partner violence and psychological well-being: buffer or indirect effect of social support.
To determine the effect of two kinds of intimate partner violence (IPV) (physical and psychological) in the previous 12 months (current) and before the previous 12 months (past) on psychological well-being among women aged 18 to 70 years who attend primary healthcare centers in Spain; and to analyze the effect of the duration of lifetime IPV and social support on psychological well-being. A cross-sectional survey was carried out among 10,322 women randomly recruited in primary healthcare centers in Spain. Outcome variables were three indicators of psychological well-being (psychological distress, psychotropic drug use, and self-perceived health). Predictor variables were the different types of IPV, IPV timing (current and past), duration of lifetime IPV, and social support. Logistic regression models were fitted. Both types of IPV increased the probability of worse psychological well-being in both IPV timings (current and past). Longer duration of lifetime IPV, friends network size, and tangible support were independently associated with worse psychological well-being. However, an interaction between current IPV and family network size was found. The probability of poor self-perceived health status was reduced by 29% among women exposed to current IPV who had a large family network (odds ratio, 0.71; 95% confidence interval, 0.54-0.94). Psychological well-being was independently affected by IPV (types and duration) and social support (friends network size, tangible support). Only family network size mitigates the negative consequences of IPV on self-perceived health status.


Sacha inchi (Plukenetia volubilis): a seed source of polyunsaturated fatty acids, tocopherols, phytosterols, phenolic compounds and antioxidant capacity.
Fatty acids (FA), phytosterols, tocopherols, phenolic compounds, total carotenoids and hydrophilic and lipophilic ORAC antioxidant capacities were evaluated in 16 cultivars of Sacha inchi (SI) seeds with the aim to valorise them and offer more information on the functional properties of SI seeds. A high α linolenic (α-Ln) fatty acid content was found in all cultivars (ω3, 12.8-16.0 g/100 g seed), followed by linoleic (L) fatty acid (ω6, 12.4-14.1g/100g seed). The ratio ω6/ω3 was within the 0.83-1.09 range. γ- and δ-tocopherols were the most important tocopherols, whereas the most representative phytosterols were β-sitosterol and stigmasterol. Contents of total phenolics, total carotenoids and hydrophilic and lipophilic antioxidant capacities ranged from 64.6 to 80 mg of gallic acid equivalent/100g seed; from 0.07 to 0.09 mg of β-carotene equivalent/100g of seed; from 4.3 to 7.3 and, from 1.0 to 2.8 μmol of Trolox equivalent/g of seed, respectively, among the evaluated SI cultivars. Results showed significant differences (p<0.05) among the evaluated SI cultivars in the contents of ω3, ω6, antioxidant capacities and other evaluated phytochemicals. SI seeds should be considered as an important dietary source of health promoting phytochemicals.


Influencing Early Stages of Neuromuscular Junction Formation through Glycocalyx Engineering.
Achieving molecular control over the formation of synaptic contacts in the nervous system can provide important insights into their regulation and can offer means for creating well-defined in vitro systems to evaluate modes of therapeutic intervention. Agrin-induced clustering of acetylcholine receptors (AChRs) at postsynaptic sites is a hallmark of the formation of the neuromuscular junction, a synapse between motoneurons and muscle cells. In addition to the cognate agrin receptor LRP4 (low-density lipoprotein receptor related protein-4), muscle cell heparan sulfate (HS) glycosaminoglycans (GAGs) have also been proposed to contribute to AChR clustering by acting as agrin co-receptors. Here, we provide direct evidence for the role of HS GAGs in agrin recruitment to the surface of myotubes, as well as their functional contributions toward AChR clustering. We also demonstrate that engineering of the myotube glycocalyx using synthetic HS GAG polymers can replace native HS structures to gain control over agrin-mediated AChR clustering.


[HDL, or non-HDL: that is the question. Possibilities of pharmacological treatment in residual dyslipidaemia].
Instead of LDL-cholesterol, non-HDL-cholesterol is proposed as a secondary lipid target when triglyceride level is above 2.3 mmol/L. Non-HDL-cholesterol target values are 0.8 mmol/L higher than those for LDL-cholesterol in the same cardiovascular risk category. Currently, the main issue of lipidology is the degree by which the cardiovascular risk can be reduced with the treatment of residual dyslipidemia that exists under statin therapy. In such a role the examined agents have essentially failed despite their more or less profound effect on HDL-cholesterol and/or non-HDL-cholesterol. The largest loser has been the nicotinic acid. The results of cardiovascular, otherwise controversial fish oil studies cannot be considered convincing because of the administered low doses. In a combination with statin (i) ezetimibe may have role if the LDL-cholesterol target cannot be reached with statin monotherapy, or (ii) fibrates, in case of large increase of triglyceride level, or in less severe hypertriglyceridemia if it is associated with considerable decrease in HDL-cholesterol level. Potential further possibilities are: (i) cholesterol ester transfer protein inhibitors that dramatically raise HDL-cholesterol, while reduce LDL-cholesterol, or (ii) proprotein convertase subtilisin/kexin 9 inhibitors that markedly decrease LDL-cholesterol even on the top of statin.


Combining NMR Spectroscopy and Chemometrics to Monitor Structural Features of Crude Hep-arin.
Because of the complexity and global nature of the heparin supply chain, the control of heparin quality during manufacturing steps is essential to ensure the safety of the final active pharmaceutical ingredient (API). For this reason, there is a need to develop consistent analytical methods able to assess the quality of heparin early in production (i.e., as the crude heparin before it is purified to API under cGMP conditions). Although a number of analytical techniques have been applied to characterize heparin APIs, few of them have been applied for crude heparin structure and composition analyses. Here, to address this issue, NMR spectroscopy and chemometrics were applied to characterize 88 crude heparin samples. The samples were also analyzed by strong anion exchange HPLC (SAX-HPLC) as an orthogonal check of the purity levels of the crudes analyzed by NMR. The HPLC data showed that the chemometric analysis of the NMR data differentiated the samples based on their purity. These orthogonal approaches differentiated samples according their glycosaminoglycan (GAG) composition and their mono and disaccharide composition and structure for each GAG family (e.g., heparin/heparan, dermatan sulfate, and chondroitin sulfate A). Moreover, quantitative HSQC and multivariate analysis (PCA) were used to distinguish between crude heparin of different animal and tissue sources.


Urinary Phytoestrogens Are Associated with Subtle Indicators of Semen Quality among Male Partners of Couples Desiring Pregnancy.
Phytoestrogens have been associated with subtle hormonal changes, although effects on male fecundity are largely unknown. We evaluated associations between male urinary phytoestrogen (isoflavone and lignan) concentrations and semen quality. This study was a prospective cohort study of 501 male partners of couples desiring pregnancy and discontinuing contraception. Each participant provided up to 2 semen samples that were analyzed for 35 semen quality endpoints the following day. Linear mixed-effects models were used to estimate associations between baseline urinary phytoestrogen concentrations and semen quality parameters, adjusted for age, body mass index (BMI), research site, and serum lipid and cotinine concentrations. Most associations between urinary phytoestrogens and semen quality parameters were null. However, select individual phytoestrogens were associated with semen quality parameters, with associations dependent on the class of phytoestrogens and modified by BMI. Specifically, genistein and daidzein were associated with a lower percentage of normal sperm and increased abnormalities in semen morphology, with reduced associations observed as BMI increased (P < 0.05) [percentages (95% CIs) of normal morphology by WHO traditional criteria: genistein, main effect: -5.61% (-9.42%, -1.79%); interaction: 0.19% (0.06%, 0.31%) per log unit increase; daidzein, main effect: -5.35% (-9.36%, -1.34%); interaction: 0.18% (0.05%, 0.32%) per log unit increase]. Enterolactone was associated with fewer abnormalities in semen morphometry and morphology and decreased DNA fragmentation, with reduced associations observed as BMI increased (P < 0.05) [percentages (95% CIs) of abnormalities in the neck and midpiece: enterolactone, main effect: -3.35% (-6.51%, -0.19%); interaction: 0.11% (0.01%, 0.21%) per log unit increase]. These results suggest that male urinary phytoestrogen concentrations characteristic of the US population may be associated with subtle indicators of male fecundity and semen quality but were not associated with couple fecundity.


[Central nervous system tumours in children. An evaluation of the completeness and validity of the Cancer Registry].
The aim of this study was to evaluate the registration of childhood CNS tumours in the Danish Cancer Registry (CR) from 1980 to 1996, based on completeness and validity. The completeness of the CR was estimated by examination of the Danish National Hospital Register and an independent hospital registry. To determine the validity of the CR, 640 cases of childhood CNS tumours identified in the CR were compared with the corresponding medical record, with regard to cancer morphology and date of diagnosis. The completeness of the CR was 98-99%. For 82% of all cases, the morphology registered in the CR was identical with that in the medical record. The validity of the morphological diagnosis was 84% for astrocytomas, 88% for ependymomas, 95% for medulloblastomas, 47% for other gliomas and 76% for miscellaneous intracranial and intraspinal neoplasms. In a further 7% of all cases, the morphological diagnosis in the CR was incorrect with respect to details but correct within these main diagnostic groups, 6% were tumours of another main diagnostic group than that registered in the CR and 5% were not tumours, were tumours outside the study criteria or were registered in the hospital journal as suspected tumours. The date of diagnosis in the CR and that in the medical records were concordant in 88% of the evaluated cases. Registration of childhood CNS tumours in the CR was highly complete, while the validity of the morphological diagnosis differed among the main diagnostic groups. The relatively low validity might be explained by the anatomic location of CNS tumours, which makes tissue sampling for histological verification and therefore diagnosis difficult.


Cytoplasmic water and hydration layer dynamics in human red blood cells.
The dynamics of water in human red blood cells was measured with quasielastic incoherent neutron scattering in the temperature range between 290 and 320 K. Neutron spectrometers with time resolutions of 40, 13, and 7 ps were combined to cover time scales of bulk water dynamics to reduced mobility interfacial water motions. A major fraction of approximately 90% of cell water is characterized by a translational diffusion coefficient similar to bulk water. A minor fraction of approximately 10% of cellular water exhibits reduced dynamics. This slow water fraction was attributed to dynamically bound water on the surface of hemoglobin which accounts for approximately half of the hydration layer.


Flexed femoral component improves kinematics and biomechanical effect in posterior stabilized total knee arthroplasty.
The kinematics and biomechanics of the knee joint are important in ensuring patient satisfaction and functional ability after total knee arthroplasty (TKA). There has been no study on knee joint mechanics with regard to the sagittal alignment of the femoral component. The objective of this study is to determine the extent of the impact of the femoral component's sagittal alignment on kinematics and biomechanics. A validated computational TKA model was used. The femoral component was simulated at - 3°, 0°, 5°, and 7° of flexion in the sagittal plane. This study evaluated the tibiofemoral (TF) joint kinematics, contact point, quadriceps force, and contact stress on the patellofemoral (PF) joint under a deep-knee-bend condition. The kinematics of the TF joint in the posterior direction increased with the flexion of the femoral component position. For all tasks, the overall posterior locations of the TF contact points were observed in the medial and lateral compartments as the femoral component flexion angle increased. The quadriceps force and contact stress on the PF joint decreased with the femoral component flexion. This study found that the femoral component sagittal position is an important factor in knee joint mechanics. In this study, the flexion of femoral component showed a stable reconstruction of the knee extensors' mechanism. Surgeons may consider neutral-to-mild flexed femoral component position, without concerns of anterior notching of the femoral cortex.


Life lessons after classes: investigating the influence of an afterschool sport program on adolescents' life skills development.
The purpose of this study was to investigate the influence of an afterschool sport program on adolescents' life skills development and to identify which characteristics of the program would have an influence on their life skills acquisition. The participants were six children (4 boys, 2 girls) who participated in a 12-week afterschool program implemented in two elementary schools, as well as the two program instructors who implemented the afterschool sport program. Data were collected from individual interviews with program participants and instructors. The inductive analysis of data revealed four categories of life skills developed through program participation: (1) playing well and being more active, (2) connecting well and having better social skills, (3) coping well and becoming a better problem solver, and (4) dreaming well and having a better sense of purpose. Regarding the characteristics of the program that influenced life skills development, three themes emerged: (1) having a clear goal and building consensus with stakeholders, (2) establishing a firm yet flexible structure, and (3) instructors' use of effective strategies for teaching life skills.


Does childhood personality predict longevity?
Key models relating personality and health predict that personality in childhood is indicative of later health and longevity. Longevity predictions are tested using data derived from the 7-decade longitudinal study initiated by L. M. Terman 1921 (L. M. Terman & M. H. Oden, 1947). Variables representing major dimensions of personality are used in statistical survival analyses of longevity in 1,178 males and females. Conscientiousness in childhood was clearly related to survival in middle to old age. This finding (a) establishes that childhood personality is related to survival decades into the future, (b) confirms the validity of the conscientiousness dimension in conceptualizing personality, and (c) points to likely and unlikely pathways linking personality to health. Contrary to expectation, cheerfulness (optimism and sense of humor) was inversely related to longevity, suggesting a possible need for reconceptualization of its health relevance.


Increased gene expression of selected vesicular and glial glutamate transporters in the frontal cortex in rats exposed to voluntary wheel running.
Though positive effects of exercise on mood and well being are well recognised, the central regulatory mechanisms are still not fully understood. The present study was aimed to testing the hypothesis that voluntary wheel running activates the gene expression of glutamate transporters in the brain cortex of rats. The animals were assigned to the control and voluntary wheel running groups. Voluntary wheel running rats had free access to a stainless steel activity wheel for 3 weeks. The daily running distance gradually increased to 6.21 ± 1.05 km by day 21. Vesicular glutamate transporter 3 (VGLUT3) mRNA levels in the frontal cortex were significantly elevated in the group of running animals compared to the values in sedentary controls, while the expression of other vesicular transporters were unchanged. The concentrations of mRNA coding for glial glutamate transporter 1 (GLT-1), but not glutamate aspartate transporter (GLAST) were increased by running. Voluntary wheel running resulted in an elevation of plasma corticosterone and increased expression of brain derived neurotrophic factor (BDNF) in the frontal cortex. In conclusion, chronic voluntary wheel running results in increased gene expression of VGLUT3 and GLT-1 in the brain cortex without changes in other glutamate transporter subtypes.


Normative values of visual evoked potential in adults.
Visual evoked potentials (VEP) are used to determine the function of visual pathway from the optic nerve to visual cortex. Various factors may affect VEP response, viz., technical and environmental. The aim of this study is to obtain the normative value of VEP latency and amplitude parameters in adulthood in Indonesia, as well as the relationship of height, weight, body mass index (BMI), head circumference, and visual acuity with the variety of latency and amplitude values of VEP parameters. It is a cross-sectional study on 120 healthy subjects consisting of 60 males and 60 females between 18 and 65 years old. Height, weight, BMI, head circumference, and visual acuity were measured and continued with VEP examination using a 26' checkerboard pattern on the left and right eyes alternately. All data were collected and analyzed with the Shapiro-Wilk test using statistical software R version 3.5.2. Mean value of P100 latency (interocular latency) of left and right eye were 104.6 ± 3.4 ms and 104.1 ± 3.4 ms, respectively, as well as 9.8 ± 4.7 μV and 10.3 ± 5.4 μV for the amplitude. There was no significant difference between the male and female group, as well as on the age group. Female significantly exhibited a higher P100 amplitude than male. The greater the age, the lower amplitude of P100 significantly. Gender and age do not affect the P100 latency value but only affect P100 amplitude. Height, weight, BMI, head circumference, and visual acuity also do not affect the P100 latency and amplitude.


Field-induced structural aging in glasses at ultralow temperatures.
In nonequilibrium experiments on the glasses Mylar and BK7, we measured the excess dielectric response after the temporary application of a strong electric bias field at millikelvin temperatures. A model recently developed describes the observed long time decays qualitatively for Mylar [Phys. Rev. Lett. 90, 105501(2003)]], but fails for BK7. In contrast, our results on both samples can be described by including an additional mechanism to the mentioned model with temperature independent decay times of the excess dielectric response. As the origin of this novel process beyond the "tunneling model" we suggest bias field induced structural rearrangements of "tunneling states" that decay by quantum mechanical tunneling.


Tuning the phase transition temperature of thermal-responsive OEGylated poly-L-glutamate via random copolymerization with L-alanine.
Two series of copolymers were prepared by ring-opening polymerization (ROP) of γ-(2-methoxyethoxy)esteryl-L-glutamate (L-EG2Glu) N-carboxyanhydride (NCA) and L-alanine (L-Ala) using HMDS and PEG-NH2 as initiator, respectively. Poly-(L-EG2Glu-co-L-Ala) displayed lower critical solution temperature (LCST) behavior but had a lower phase transition temperature than poly-L-EG2Glu at similar molecular weight (MW). The clouding point (CP) of random copolypeptides can be tuned by altering the alanine content and overall MW. Circular dichroism (CD) and Fourier transform infrared spectroscopy (FTIR) indicated that the thermal-responsive properties depended on the content of ordered conformations. PEG-b-poly-(L-EG2Glu-co-L-Ala) can spontaneously form hydrogels in water at room temperature. Transmission electron microscopy (TEM) and atomic force microscopy (AFM) revealed that these hydrogels were formed by nanoribbons. The intermolecular hydrogen bonding among copolypeptide blocks accounted for the nanoribbon assemblies and hydrogel network formation.


Biological deodorization of hydrogen sulfide using porous lava as a carrier of Thiobacillus thiooxidans.
Biological deodorization of hydrogen sulfide (H2S) was studied using porous lava as a carrier of Thiobacillus thiooxidans in a laboratory-scale biofilter. Three different samples of porous lava, A, B, and C, which were obtained from Cheju Island in Korea, were used. The water-holding capacities of samples A, B and C were 0.38, 0.25, and 0.47 g-H2O/g-lava, respectively. The pHs and densities of the lava samples ranged from 8.25-9.24 and 920-1190 kg/m3, respectively. The buffering capacities, expressed as the amount of sulfate added to lower the pH to 4, were 60 g-SO4(2-)/kg-lava for sample A, 50 g-SO4(2-)/kg-lava for B, and 90 g-SO4(2-)/kg-lava for C. To investigate the removal characteristics of H2S by the lava biofilters, T. thiooxidans was immobilized on the lava samples. Biofilters A and C showed a removal capacity of 428 g-S.m(-3).h(-1) when H2S was supplied with 428 g-S.m(-3).h(-1) of inlet load at a space velocity (SV) of 300 h(-1). At the same inlet load and SV, the removal capacity of biofilter B was 396 g-S.m(-3).h(-1). The H2S critical loads of biofilters A, B and C at a SV of 400 h(-1) were 396, 157 and 342 g-S.m(-3).h(-1), respectively. It is suggested that natural, porous lava is a promising candidate as a carrier of microorganisms in biofiltration.


Efficacy of a "Rescue" Ciprofloxacin-Based Regimen for Eradication of Helicobacter pylori Infection after Treatment Failures.
The aim of our study was to evaluate the efficacy and tolerability of a ciprofloxacin-based regimen for H. pylori eradication failures as an alternative to bismuth based quadruple therapy. Methods. prospective single-center study. Patients in whom a first eradication trial with omeprazole/esomeprazole, clarithromycin plus amoxicillin or tinidazole/metronidazole had failed were included. H. pylori status: established by histology, rapide urease test and polymerase chain reaction. esomeprazole 20 mg, ciprofloxacin 500 mg, and metronidazole 500 mg, administered together before breakfast and dinner for 10 days. Susceptibility testing was performed by the Epsilometer test. Ciprofloxacin resistance was defined as a MIC of ≥1 μg/mL. Eradication was established by a negative 13C-UBT and 4-6 weeks post-therapy. Efficacy and side effects were determined. Results. 34 patients were enrolled, 32 completed the study. Compliance was excellent (100%). Side effects were mild. Ciprofloxacin-based therapy cured 65% (22/34) of patients by intention to treat and 69% (22/32) per protocol analysis. The prevalence of ciprofloxacin resistance was 8%. Conclusions. The effectiveness of ciprofloxacin-based therapy was greatly reduced despite the high prevalence of ciprofloxacin sensitive H. pylori strains. Bismuth based quadruple therapy still remain the best choice as a "rescue" regimen in our region.


Longitudinal analysis of data with multiple binary category choices.
In many experiments, subjects mark all categories that apply when responding to a cafeteria or multiple-response question. One exact and two approximate permutation methods are described to analyze binary answers to multiple-response questions in longitudinal experimental designs, wherein the same or matched subjects respond to the same multiple-response question over two or more trials. The described methods provide probabilities, under the null hypothesis, that the multiple binary responses do not differ over trials.


Levoatrial cardinal vein with normal left ventricle: A forgotten cause of pulmonary arterial hypertension.
Levoatrial cardinal vein (LACV) is anomalous connection between left atrium or pulmonary veins and systemic veins such as innominate vein or superior vena cava. This persistence of splanchnic circulation occurs when there is left-sided obstructive cardiac lesions such as hypoplastic left heart or mitral atresia. In this report we present three cases of LACV with well-developed left heart, without any obstructive lesions. All our cases presented with pulmonary arterial hypertension (PAH) and had associated intracardiac shunt such as ventricular/atrial septal defect and supracardiac partial anomalous pulmonary venous connection. Apart from the above shunts, LACV contributed to PAH in these cases. It is important to detect and report LACV as this may require surgical correction along with other defects. If LACV goes undetected during imaging workup, it may cause persistent PAH postoperatively.


[Use of endoscopic surgery and combined radiotherapy for inoperable cancer of the esophagus].
A comparative evaluation of the efficacy of combined radiotherapy (112 - group 1) carried out in conjunction with a battery of procedures of endoscopic surgery plus combined radiotherapy (76 - group 2) for inoperable cancer of the esophagus was conducted in 118 patients. Maximum local regression was reported in group 2 (77.6%) as compared with only 33.9% in group 1. Relatively longer relapse-free period (133 days) and lower residual growth incidence (44.6%) were in group 2, too, as compared with 107 days and 63.5% in group 1. Mean survival duration was nearly identical in both groups - ca.15 months. Similarly, survival rates in groups 2 and 1 were: 69.2 and 58.8% (year 1), 22.2 and 22.3% (year 2), and 11.3 and 12.9% (year 3), respectively. It was concluded that combinations of endoscopic surgery and combined radiotherapy for inoperable cancer of the esophagus improved immediate results and reduced the rates of residual tumor incidence. However, no significant differences in mean duration or rates of survival were observed.


[Peripheral arteriography at an advanced age using a new contrast agent].
A new non-ionic contrast agent containing 300 mg iodine/ml ( Jopamidol ) was used in angiographic examination of over 200 patients with a median age of about 70 years. A total of 492 arterial injections was performed. There were no serious side-effects, especially, there were no cardio-vascular disturbances nor any renal dysfunctions. It was remarkable though to note, the lack of subjective discomfort in most patients.


Fractures of the mandible.
An overview of the various methods available for treatment of mandibular fractures is presented; these range from the application of arch bars and intermaxillary fixation alone to open reduction with compression plating. Whenever possible, particularly in young patients, mandibular fractures requiring open reduction are approached transorally.


Nanowire photodetectors.
The use of nanowires and nanowire structures as photodetectors is an emerging research topic. Despite the large amount of reports on nanowire photoresponse that appeared in the literature over the last decade, the mechanism leading to high photosensitivity and photoconductive gain in high aspect ratio nanostructures has been elucidated only recently. Novel device architectures integrated in single nanowire devices are also being actively studied and developed. In this article, the general nanowire photodetector concepts are reviewed, together with a detailed description of the physical phenomena occurring in nanowire photoconductors and phototransistors, with some examples from recent experimental results obtained in our groups. An outlook on future directions toward the use of semiconductor nanowire photoconductors as intrachip interconnects, single-photon detectors, and image sensors, is also given.


Increased apoptotic neutrophils and macrophages and impaired macrophage phagocytic clearance of apoptotic neutrophils in systemic lupus erythematosus.
To evaluate whether patients with systemic lupus erythematosus (SLE) have a higher rate of apoptosis in and secondary necrosis of polymorphonuclear neutrophils (PMNs) and macrophages compared with controls; to compare the rate of macrophage phagocytic clearance of apoptotic PMNs in patients with SLE and healthy controls; to evaluate whether in vitro PMN and macrophage apoptosis and secondary necrosis, and the ability of macrophages to phagocytose apoptotic bodies, are correlated with lupus disease activity; and to determine whether macrophage clearance of apoptotic bodies in patients with SLE and normal controls is related to certain serum factors. Thirty-six patients with SLE and 18 healthy, nonsmoking volunteers were studied. PMNs and monocytes were isolated from fresh blood and cultured in the presence of different sources of serum. Apoptotic PMNs and macrophages were examined by annexin V binding and morphology on May-Giemsa-stained cytopreparations, at different time points. The presence of secondary necrotic PMNs and macrophages was verified by staining with trypan blue. Macrophage phagocytosis of apoptotic PMNs was measured using a coded, observer-blinded, microscopically quantified phagocytosis assay. Cells were cultured in the presence of serum obtained from healthy subjects or from patients with SLE. At 5 and 24 hours, the percentage of apoptotic PMNs from patients with SLE was significantly higher than that of PMNs from healthy subjects. At 24 and 48 hours, the percentage of secondary necrotic PMNs from patients with SLE was also significantly higher than the percentage of necrotic PMNs from controls. Serum from patients with SLE accelerated the rate of apoptosis in and secondary necrosis of PMNs from healthy subjects. Macrophages from SLE patients were less capable of phagocytosing apoptotic PMNs compared with macrophages obtained from controls. Macrophages from patients with active SLE were less capable of phagocytosing apoptotic PMNs than were macrophages from patients with inactive SLE, but the difference was not statistically significant. The percentage of phagocytosis of apoptotic PMNs by macrophages from SLE patients correlated negatively with the SLE Disease Activity Index, serum levels of anti-double-stranded DNA, and the erythrocyte sedimentation rate, and correlated positively with serum levels of C3, C4, and albumin, the hemoglobin level, and the leukocyte count. Serum from SLE patients not only significantly increased macrophage apoptosis in cells from healthy subjects but also remarkably down-regulated the clearance of apoptotic PMNs by macrophages from healthy subjects. In contrast, serum from healthy subjects significantly increased phagocytosis of apoptotic PMNs by macrophages from SLE patients. The observed increase of apoptotic PMNs and macrophages and the poor ability of macrophages from patients with SLE to phagocytose apoptotic bodies may indicate an impaired clearance mechanism, which may be mediated by factors in a patient's serum.


Escitalopram-associated rhabdomyolysis.
This case history describes a case of rhabdomyolysis resulting from treatment with escitalopram as monotherapy at the recommended dose. This is a rare and little-known side effect of selective serotonin reuptake inhibitors.


Detection of SARS-CoV-2 Proteins in Wastewater Samples by Mass Spectrometry.
The recent COVID-19 pandemic overwhelmed the health system worldwide, and there was a need to track outbreaks and try to use this information as an early warning system. Wastewater-based epidemiology (WBE) enabled detection of the SARS-CoV-2 virus in wastewater treatment plant influents. Until now, the most used technique for this detection has been the quantitative polymerase chain reaction (qPCR)-based quantification of SARS-CoV-2 RNA. This study proposes a mass spectrometry (MS)-based method that detected specific SARS-CoV-2 proteins in wastewater, 5 and 6 days ahead of the case data for two municipalities. We identified unique peptides of eight proteins related to the SARS-CoV-2 virus and COVID-19 infection. We detected the nonstructural protein (NSP) pp1ab (transcribed after host cell infection) most frequently in all of the samples. As a result, we suspect that in the active cases of COVID-19, the pp1ab protein is present in high abundance in the urine and feces and that this protein could be used as an alternative biomarker. These data were collected before mass vaccination occurred in the population.


A modified method to culture human osteoblasts from bone tissue specimens using fibrin glue.
To establish primary osteoblast cultures is a challenge. The methods for isolation mostly comprise digestion with extracellular matrix degrading enzymes after mincing the bone samples. These methods are labour intensive and lead to an inefficient recovery of cells. Therefore, the aim of this study was to develop a more reliable method for culturing human osteoblasts. Bone tissue specimens were obtained from 20 patients undergoing reconstructive operations. Bone specimens were dissected and put into petri dishes with the bottom covered with fibrin glue. To identify the nature of the outgrowing cells, cytological staining was performed, i.e. Von Kossa, Azan, Dahl's, alkaline phosphatase, and collagen type I. Mean time interval of cellular outgrowth was 12 days after preparing the bone tissue specimens. Confluence of the cell cultures was reached after four to five weeks on average. All cells were positively stained using Von Kossa, alkaline Phosphatase and collagen type I. The matrix consisted of lime, calcium and collagens. A simplified method to culture osteoblasts from all kinds of bone tissue specimens is presented. The fibrin glue allows firm adhesion of the specimens to the petri dish. This allows the cells to grow out without disturbance. Normally, due to movements during medium exchange the adhesive bonds are disrupted. The fibrin glue retains the adhesive bonds. This method allows studying human osteoblasts in different clinical settings.


Large deletions in the CBF gene cluster at the Fr-B2 locus are associated with reduced frost tolerance in wheat.
Wheat plants which are exposed to periods of low temperatures (cold acclimation) exhibit increased survival rates when they are subsequently exposed to freezing temperatures. This process is associated with large-scale changes in the transcriptome which are modulated by a set of tandemly duplicated C-repeat Binding Factor (CBF) transcription factors located at the Frost Resistance-2 (Fr-2) locus. While Arabidopsis has three tandemly duplicated CBF genes, the CBF family in wheat has undergone an expansion and at least 15 CBF genes have been identified, 11 of which are present at the Fr-2 loci on homeologous group 5 chromosomes. We report here the discovery of three large deletions which eliminate 6, 9, and all 11 CBF genes from the Fr-B2 locus in tetraploid and hexaploid wheat. In wild emmer wheat, the Fr-B2 deletions were found only among the accessions from the southern sub-populations. Among cultivated wheats, the Fr-B2 deletions were more common among varieties with a spring growth habit than among those with a winter growth habit. Replicated freezing tolerance experiments showed that both the deletion of nine CBF genes in tetraploid wheat and the complete Fr-B2 deletion in hexaploid wheat were associated with significant reductions in survival after exposure to freezing temperatures. Our results suggest that selection for the wild-type Fr-B2 allele may be beneficial for breeders selecting for varieties with improved frost tolerance.


[Expression and effects of microRNA-155 in the livers of septic mice].
To evaluate the effects of microRNA-155 (miR-155) on liver injury in mice with sepsis. One hundred and twenty BALB/c mice were randomly divided into two groups of equal number according to random number table. Sepsis was induced by intraperitoneal injection of lipopolysaccharide (LPS,20 mg/kg). The mice were sacrificed at the time-points of 0, 2, 6, 12, 24, 48 hours. Blood and liver tissue were collected, and the levels of tumor necrosis factor- α (TNF- α ), interleukin (IL-6, IL-10) in serum and liver homogenate and alanine transaminase (ALT) in serum were determined by enzyme linked immunosorbent assay(ELISA). The injury of liver tissue was evaluated by histopathology. The expression of miR-155 in liver tissue was assessed by fluorescent quantitation reverse transcription-polymerase chain reaction (RT-PCR). The levels of TNF- α , IL-6 and IL-10 in serum and liver homogenate of septic mice increased with passage of time, and then the levels of TNF-α and IL-6 lowered after reaching the peak value, but remained higher than that of control group.TNF-α (ng/L) reached the peak value at 2 hours post-LPS-injection (serum: 1538.46 ± 102.12 vs. 64.52 ± 18.44,liver homogenate: 255.26 ± 41.23 vs. 60.21 + 13.55, both P<0.05). The level of IL-6 (μg/L) reached the peak value at 6 hours post-LPS-injection (serum: 875.33 ± 102.37 vs. 153.72 ± 20.67, liver homogenate: 9.22 + 0.82 vs. 3.35 ±0.36, both P<0.05), and that of IL-10 (ng/L) reached the peak value at 48 hours post-LPS-injection (serum: 520.13 ± 88.52 vs. 23.43 3.01, liver homogenate: 260.12 + 50.38 vs. 16.37 ± 3.71, both P<0.05). There were significant differences in above indexes between septic and control group (all P<0.05). The serum level of ALT (U/L) rose with passage of time, reaching the peak value at 48 hours post-LPS-injection (603.26 + 70.21 vs. 45.84 + 5.64, P<0.05). The values showed significant differences between septic and control group (P<0.05). A large number of leucocytic infiltration was found in liver. Hepatic tissue showed architectural distortion. Hepatocyte vacuolation and nodular necrosis were obvious at 12 hours post-LPS-injection. Relative expression of miR-155 was found to be increased at 2 hours post-LPS-injection, reaching its peak value at 12 hours post-LPS-injection [(72.96 ± 9.34)-fold of control group, P<0.05]. The increase in miR-155 expression might play an important role in the mechanism of liver injury during sepsis.


[Study on patients with benign prostate hyperplasia treated by the therapeutic regimen of watchful waiting during a twenty-four-month follow-up period].
To analyze the changes of the main clinic parameters in patients with benign prostate hyperplasia (BPH) treated by watchful waiting and to find out the risk factors contributing the progress of BPH. According to the inclusion and exclusion criteria,61 patients diagnosed as BPH were recruited in the group of watchful waiting. Data on IPSS, prostate volume, prostate specific antigen (PSA), maximum flow rate, average flow rate and residual urine volume during follow-up period of 24 months, were recorded. At 0, 12, 24 months, the IPSS, prostate volume (ml), PSA(ng/ml), maximum flow rate (ml/s) were 7 +/- 4, 4 +/- 3, 4 +/- 3; 33.0 +/- 9.0, 33.8 +/- 7.6, 30.9 +/- 6.8; 1.53 +/- 1.35, 1.43 +/- 0.95, 1.22 +/- 0.99; 17.1 +/- 5.0, 17.2 +/- 6.1, 19.2 +/- 8.0, respectively. At the end of the 24-months follow-up, all observed parameters had a little improvement except the average prostate volume in this group. Of the 61 patients, 42 (62%) progressed slowly or became better when comparing with baseline data of the study. Moreover, the difference between at 24-month and at baseline period, IPSS showed statistical significance (P < 0.0001) in t test. In the study of BPH progression risk factors by logistic regression analysis, prostate volume (P = 0.0910) and residual urine volume (P = 0.0780) showed a trend of becoming the risk factors. Our study showed that patients treated with watchful waiting had slow progression and majority of these patients did not need to alter their treatment options. Through data analysis, we noticed that the changes of data watchful waiting patients could help us to choose more precise and reasonable treatment option in clinical practice.


Molecular subtypes based on Wnt-signaling gene expression predict prognosis and tumor microenvironment in hepatocellular carcinoma.
Based on increasing research evidence, hepatocellular carcinoma (HCC) is heterogeneous, and genetic profiling has led to the identification of multiple subtypes of this disease. To advance our knowledge and the ability to use individualized medicine in the treatment of HCC, it is essential to perform a complete and methodical characterization of various molecular subtypes. The canonical Wnt/β-catenin pathway is an evolutionarily conserved complicated signaling mechanism that plays a role in carcinogenesis and progression of HCC. In this study, we acquired RNA sequencing, somatic mutation, and clinical data from 701 patients from The Cancer Genome Atlas and Gene Expression Omnibus databases and stratified patients into two subgroups: WNT-high and WNT-low. In general, the WNT-high subtype is associated with an immunosuppressive microenvironment, poor prognosis, cancer-related pathways, and a low response to immune checkpoint therapy. We also found that WNT3 is negatively linked to CD8+ T-cell infiltration using multiple immunofluorescence assays. Finally, we developed a WNT-related prognostic model to predict the survival time of patients with HCC. In summary, we developed a new classification scheme for HCC based on Wnt signaling signatures. This classification produced substantial clinical effects, both in terms of assessing patient prognosis and immunotherapy administered to patients with HCC.


Static and time-resolved mid-infrared spectroscopy of Hg0.95Cd0.05Cr2Se4 spinel.
Static and time-resolved mid-infrared spectroscopy of ferromagnetic single crystal Hg0.95Cd0.05Cr2Se4 was performed below the absorption edge, in order to reveal the origin of the electronic transitions contributing to the magneto-optical properties of this material. The mid-infrared spectroscopy reveals a strong absorption peak around 0.236 eV which formerly was assigned to a transition within the selenide-chromium complexes ([Formula: see text] Se-Cr2+). To reveal the sensitivity of the transition to the magnetic order, we performed the studies in a temperature range across the Curie temperature and magnetic fields across the value at which the saturation of ferromagnetic magnetization occurs. Despite the fact that the Curie temperature of this ferromagnetic semiconductor is around 107 K, the intensity of the mid-infrared transition reduces substantially increasing the temperature, so that already at 70 K the absorption peak is hardly visible. Such a dramatic decrease of the oscillator strength is observed simultaneously with the strong red-shift of the absorption edge in the magnetic semiconductor. Employing a time-resolved pump-and-probe technique enabled us to determine the lifetime of the electrons in the excited state of this optical transition. In the temperature range from 7 K to 80 K, the lifetime changes from 3 ps to 6 ps. This behavior agrees with the phenomenon of giant oscillator strength described earlier for weakly bound excitons in nonmagnetic semiconductors.


In Situ Rapid Analysis of Squalene, Tocopherols, and Sterols in Walnut Oils Based on Supercritical Fluid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry.
Quantification of liposoluble micronutrients in large-scale vegetable oil samples is urgently needed, because their health benefits are increasingly emphasized. However, current analytical methods are limited to either labor-intensive preparation processes or time-consuming chromatography separation. In this work, an online oil matrix separation strategy for direct, rapid, and simultaneous determination of squalene, tocopherols, and phytosterols in walnut oil (WO) was developed on the basis of the lipid class separation mode of supercritical fluid chromatography. A single run was completed in 13 min containing 6 min of column cleaning and balancing. Satisfactory limit of detections (0.05-0.20 ng/mL), limit of quantifications (0.15-0.45 ng/mL), recoveries (70.61-101.44%), and matrix effects (78.43-91.62%) were achieved, indicating the reliability of this method. In addition, eight sterol esters were identified in WO, which have not previously been reported. The proposed method was applied to characterize the liposoluble micronutrient profile of WO samples obtained from different walnut cultivars, geographical origins, and processes.


[Russia-Halle reciprocity in medicine of the 18th century. V. Halle graduates employed in Russia and their medical fields].
In the 18th century about 40 medical men of non-Russian descent graduated in Halle temporarily or permanently entered the Tsarist services. Their activities are to be proved in nearly all fields of medicine. They occupied positions as court-physicians and military surgeons, worked in hospitals or as free practitioners. Some of them occupied important positions in research and education at the Academy of Petersburg and the University of Moscow.


Neoplastic transformation of 3T3 mouse embryo cells with c-myc- and c-Ha-ras-1 oncogenes.
1. Peptide growth factors and products of some oncogenes are likely to be active in common regulatory pathways that control the cell cycle. 2. Cell transformation by DNA-mediated transfections with cloned oncogenes is an approach that can provide insight into the mechanisms of both growth factor action and cell cycle regulation. 3. This paper deals with this approach, summarizing and discussing transfection experiments of mouse c-myc and human c-Ha-ras-1 cloned oncogenes into mouse embryo Balb-3T3 cells.


Oligo(ethylene glycol) Length Effect of Water-Soluble Ru-Based Olefin Metathesis Catalysts on Reactivity and Removability.
A study of reaction kinetics and removal efficiency of a family of ruthenium (Ru)-based olefin metathesis catalysts containing ethylene-glycol-oligomer-tethered N-heterocyclic carbene (NHC) ligands has been carried out, with a focus on variation of ethylene glycol oligomer length. The length of ethylene glycol oligomer was precisely defined by sequential addition of repeating units. Due to the dual solubility of ethylene glycol oligomer, the produced catalyst was highly soluble in both aqueous and organic solvents (dichloromethane). In aqueous solution, the polarity increase with longer ethylene glycol oligomers enhanced the reactivity in homogeneous solution. The length of ethylene glycol oligomer did not significantly affect olefin metathesis rate in organic solution. Yet the removal efficiency of catalyst strongly relies on the length of ethylene glycol oligomer. A longer ethylene glycol oligomer demonstrated better catalyst removal efficiency. The tested catalyst removal method was aqueous extraction from organic solution using its higher water solubility property compared to its lower organic solvent (dichloromethane) solubility property. The results obtained from the aqueous extraction catalyst removal method demonstrated similar and/or better removal rates compared to previously reported host-guest catalyst removal methods.


[Antibiotic activity of P. aeruginosa against MRSA and Candida albicans].
The antibiotic activity demonstrated by P. aeruginosa (Bacillus pyocyaneus) has been reported more than one hundred years ago by Emmerich et al (1899). Studies on such bacterial interference between P. aeruginosa and other pathogenic bacteria or fungi have not been extensively reported in recent years. In this paper, we report on the anti MRSA activity and anti Candida activity demonstrated by clinical isolates of P. aeruginosa (34 strains). The antibiotic activity was tested by reversed agar plate method, as previously reported, and the degree of the activity was expressed as the diameter of the zone of growth inhibition. The stability of both anti MRSA activity and anti Candida activity was evaluated at the time after 24 and 48-hr incubation. Also the effect of agar plate with or without 5% sheep blood on antibiotic activity was evaluated. Strong anti MRSA activity and anti Candida activity was shown at the time after 24-hr incubation. At the time after 48-hr incubation, anti MRSA activities were significantly suppressed but anti Candida activities were persisted. The inhibitory activity was correlated with dye production of P. aeruginosa. Some strains having non or weak dye production, showed the inhibitory activity by 48-hr incubation. Result from these strains without suppression of anti Candida activity by additional blood may suggest that the existence of a new factor produced by P. aeruginosa. Because of frequent isolation of MRSA or Candida from clinical materials, we must consider bacterial flora and bacterial interference against pathogenic bacteria at the time of the antibiotic choice for the patients infected or colonized with P. aeruginosa.


Reappraisal on pharmacological and mechanical treatments of heart failure.
Heart failure (HF) is a highly frequent disorder with considerable morbidity, hospitalization, and mortality; thus, it invariably places pressure on clinical and public health systems in the modern world. There have been notable advances in the definition, diagnosis, and treatment of HF, and newly developed agents and devices have been widely adopted in clinical practice. Here, this review first summarizes the current emerging therapeutic agents, including pharmacotherapy, device-based therapy, and the treatment of some common comorbidities, to improve the prognosis of HF patients. Then, we discuss and point out the commonalities and areas for improvement in current clinical studies of HF. Finally, we highlight the gaps in HF research. We are looking forward to a bright future with reduced morbidity and mortality from HF.


Red cell distribution width in coronary heart disease: prediction of restenosis and its relationship with inflammatory markers and lipids.
Red cell distribution width (RDW) is associated with a poor prognosis and adverse events in cardiovascular diseases. The aims of this study were to investigate the relationship between serum RDW levels and outcomes after percutaneous coronary intervention and to identify potential novel laboratory markers for evaluating the risk of in-stent restenosis (ISR) with stable angina pectoris. A total of 261 patients with coronary heart disease from Dongfeng General Hospital implanted with a coronary drug-eluting stent (DES) were enrolled in the study. We retrospectively analysed the role and prognosis values of serum parameters that were measured before angiography at the first admission. According to the results of the second angiogram, the patients were divided into two groups as follows: the non-ISR group (n=143) and the ISR group (n=118). The clinical characteristics and all laboratory data were considered for univariate and multivariate logistic regression analyses. The white cell count, RDW, neutrophil count, C-reactive protein (CRP), total cholesterol, low-density lipoprotein cholesterol (LDL-C), blood urea nitrogen and uric acid levels were higher in the ISR group than in the non-ISR group. There were no differences in the rates of hypertension, fasting plasma glucose, red cell count, neutrophil to lymphocyte ratio, platelet count, triglyceride, high-density lipoprotein cholesterol and creatinine levels. In the univariate regression analysis, age, diabetes, white cell count, neutrophil count, RDW, CRP, total cholesterol, LDL-C, blood urea nitrogen, Gensini score and number of stents were predictors of ISR. According to the multiple logistic regression analysis, age, RDW and number of stents were independent predictors of ISR. Preprocedural blood parameters can independently predict ISR. Our study results demonstrated that a high preprocedural RDW is an independent predictor of DES restenosis.


Sustained attention and aging: overcoming the decrement?
A literature review found equivocal evidence of a performance decline at senescence on sustained attention (vigilance) tasks. The strongest evidence for such age effects was from Parasuraman and Giambra (PG; 1991). It was hypothesized that reduced perceptual and information-processing abilities of older adults (i.e., non-sustained attentional components of the task) were responsible for the age effects reported by PG and that such outcomes could be eliminated or reduced by minimizing the influence of those components. In Tasks 1 (n = 457) and 2 (n = 427), which used PG's procedure and stimulus conditions, age effects on detection accuracy and on the detection time decrement were not found. False alarms were significantly greater in the old group than in the young group. In Task 3 (n = 417), which minimized non-sustained attention components, some marginal evidence of age effects emerged. Potential explanations of these outcomes, such as an extremely small age effect, sampling bias, power differences, and undetected visual difficulties are considered, and further manipulations and controls are proposed.


Trends in postneonatal mortality in the United States. 1962 through 1978.
Trends in postneonatal mortality (PNM) rates in the United States were analyzed for the period 1962 through 1978 using National Center for Health Statistics birth and death certificate data. The PNM rates declined from 5.5 to 3.6 per 1,000 live births for whites and from 15.6 to 7.6 per 1,000 live births for blacks. Most of the decline in PNM rates could be accounted for by a drop in mortality from infectious diseases. A dramatic increase occurred in the reported rates of unexplained sudden infant death (SID), which emerged as the leading reported cause of PNM. The second leading cause of PNM was birth defects among whites and infectious diseases among blacks. Gaps in PNM continued to exist between whites and blacks, and between metropolitan and nonmetropolitan areas. These gaps suggest that further improvement in PNM may be possible by improving access to health care. The massive increase in the rates of SID, although partially explained by coding or reporting phenomena, warrants active pursuit for a better pathophysiologic and etiologic delineation of the entity.


Specific requirement for ATP at an early step of in vitro transcription of human mitochondrial DNA.
The ATP concentrations allowing transcription of both heavy- and light-strand of human mtDNA in a HeLa cell mitochondrial lysate were found to cover a broad range, with a maximum around 2.5 mM, and with reproducible differences in the ATP response curves for the two transcription events. Direct measurements showed that nonspecific ATP degradation during the assay did not account for the high ATP requirement. 5'-Adenylyl imidodiphosphate (p[NH]ppA), an ATP analog with a nonhydrolyzable beta-gamma bond, was unable to substitute for ATP in supporting mtDNA transcription but greatly stimulated this transcription in the presence of a low concentration of exogenous ATP. Evidence was obtained indicating that p[NH]ppA did not support an early event in mtDNA transcription (formation of preinitiation complex or initiation), whereas this analog could substitute effectively for ATP in the subsequent elongation steps. These results pointed to a specific requirement for ATP at an early step of the transcription process.


A review on 5-aminosalicylic acid colon-targeted oral drug delivery systems.
Site-specific colon drug delivery is a practical approach for the treatment of local diseases of the colon with several advantages such as rapid onset of action and reduction of the dosage of the drug as well as minimization of harmful side effects. 5-aminosalicylic acid (5-ASA) is a drug of choice in the treatment of inflammatory bowel disease and colitis. For the efficient delivery of this drug, it is vital to prevent 5-ASA release in the upper part of the gastrointestinal tract and to promote its release in the proximal colon. Different approaches including chemical manipulation of drug molecule for production of prodrugs or modification of drug delivery systems using pH-dependent, time-dependent and/or bacterially biodegradable materials have been tried to optimize 5-ASA delivery to the colon. In the current review, the different strategies utilized in the design and development of an oral colonic delivery dosage form of 5-ASA are presented and discussed.


[Recent results of carotid stenting for treatment of extracranial carotid occlusive disease].
To analyze the recent results of CAS performed by vascular surgeons to treat extracranial carotid occlusive disease (ECOD) retrospectively in a single medical center. Forty-eight carotid arteries underwent CAS. Procedures were transfemoral. The postoperative follow-up was separated to 2 periods (<or=30 d and >30 d). The mortality and all kinds of complications were analyzed. 91.7% of them were men; 8.3% were women; mean age was (70.6 +/- 5.9) years. Preoperative asymptomatic cases were 37.5%; symptomatic cases were 62.5%. Mean internal carotid artery diameter stenosis was (71.2 +/- 14.8)%. 43.8% patients had single preoperative risk factors; two or more of these risk factors were present in 47.9%. In 33.3% cases the contralateral carotid artery had 50% or greater stenosis or was completely occluded. Technical success was achieved in 100%. There were no death, no major or minor stroke but 4.2% TIA. Carotid sinus compression syndrome occurred in 18.8% of patients. At follow-up > 30 days, there had been 4.2% instances of in-stent recurrent stenosis great than 50%, noted by color doppler ultrasound scanning. No stent deformity happened. CAS can be preformed safely enough in patients with ECOD at high CEA risk, with lower perioperative morbidity and mortality.


Enthalpy of oxygen addition to anthraquinone derivatives determines their ability to mediate NADH oxidation.
Anthraquinone derivatives are important anti-cancer drugs possessing undesirable cardiotoxic properties related to their peroxidating activity. Previous studies have suggested that this activity can be caused by the binding of a singlet oxygen molecule to an anthraquinone, followed by the one-electron reduction of the complex formed, and its further dissociation into anthraquinone and the superoxide anion radical. In this study, we have carried out semi-empirical PM3 calculations of the energetics of the formation of peroxides and hydroperoxides from hydroxy, amino and imino derivatives of 9,10-anthracenedione. These calculations were supplemented with ab initio calculations, using STO-3G, 4-31G and 6-31G basis sets, on the energetics of oxygen binding to 1,4-dihydroxy and 1,4-diaminobenzene. It was found that for anthraquinones possessing hydroxyl groups, the formation of hydroperoxides is significantly favored energetically compared with the formation of peroxides. In the case of anthraquinones containing only amino groups, the formation of hydroperoxides is less favorable, owing to a greater enthalpy of amino group deprotonation compared with that of hydroxyl group. The effect of electrostatic solvation on the energetics of oxygen addition was also investigated using the Conductor-like Screening Model (COSMO) approach. The effect of solvation on peroxide formation was found to be small, while in the case of hydroperoxides solvation was found to lower the enthalpy of this reaction by approximately 10 kcal/mol for epsilon = 78 (simulating an aqueous environment). Significant stabilization of hydroperoxides was estimated in weakly polar media (epsilon = 4) which can simulate the quinone-reducing center of the mitochondrial NADH dehydrogenase. The enthalpies obtained for oxygen addition to anthraquinones involving the formation of the most stable of the peroxide and hydroperoxide species are in good correlation with the rates of NADPH oxidation stimulated by these compounds and, in turn, with their peroxidating properties. This correlation can be directly implemented in the design of non-peroxidating anthraquinone-derived anti-cancer drugs.


Epidemiology of parturient paresis: predisposing factors with emphasis on dry cow feeding and management.
Dry cow feeding and management were examined for predisposing factors for parturient paresis in 1,983 Holstein cows from New York Dairy Herd Improvement Cooperative records, monthly technician visits to 31 farms, and questionnaires. Variables were estimated transmitting ability, season of calving, lactation number, parturient paresis, estimated potential hours per day of exercise, and estimated nutrient intakes (protein, calcium, phosphorus, and energy) during the preceding dry period. Nutrient intakes were estimated by farmers for the average dry cow (season dependent) in their herd for the early (greater than or equal to 3 wk prepartum) and late portions of the dry period. Intakes were percentages of National Research Council requirements for a 550 kg dry cow in the last 2 mo of gestation. Nutrient intakes were coded by ranking the herds by percentage of each requirement. Codes represented the approximate lower third, middle third, and top third of the herds. Individual cows were assigned their herd nutrition codes by their season of calving. For stepwise discriminant analysis, the group variable was parturient paresis (94 cases, 1,889 controls). As lactation number (most important) and estimated transmitting ability (second most important) increased, incidence of parturient paresis increased. Parturient paresis was reduced with high dietary protein fed during the early stage of the dry period, with low phosphorus and high energy (lead feeding) closer to calving, and with decreased opportunity for exercise. Most cows were overfed calcium, especially in the late stage of the dry period, but calcium intake was not important when phosphorus was low.


A Metabolomics Approach Uncovers Differences between Traditional and Commercial Dairy Products in Buryatia (Russian Federation).
Commercially available and traditional dairy products differ in terms of their manufacturing processes. In this study, commercially available and traditionally fermented cheese, yogurt, and milk beverages were analyzed and compared. The metabolomic technique of ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-Q-TOF) in the MSE mode was used in combination with statistical methods, including univariate analysis and chemometric analysis, to determine the differences in metabolite profiles between commercially and traditionally fermented dairy products. The experimental results were analyzed statistically and showed that traditional and commercial dairy products were well differentiated in both positive and negative ion modes, with significant differences observed between the samples. After screening for metabolite differences, we detected differences between traditional milk beverages and yogurt and their commercial counterparts in terms of the levels of compounds such as l-lysine, l-methionine, l-citrulline, l-proline, l-serine, l-valine and l-homocysteine, and of short peptides such as Asp-Arg, Gly-Arg, His-Pro, Pro-Asn. The greatest difference between commercially available and traditional cheese was in the short peptide composition, as commercially available and traditional cheese is rich in short peptides.


The economic burden of child maltreatment in the United States, 2015.
Child maltreatment incurs a high lifetime cost per victim and creates a substantial US population economic burden. This study aimed to use the most recent data and recommended methods to update previous (2008) estimates of 1) the per-victim lifetime cost, and 2) the annual US population economic burden of child maltreatment. Three ways to update the previous estimates were identified: 1) apply value per statistical life methodology to value child maltreatment mortality, 2) apply monetized quality-adjusted life years methodology to value child maltreatment morbidity, and 3) apply updated estimates of the exposed population. As with the previous estimates, the updated estimates used the societal cost perspective and lifetime horizon, but also accounted for victim and community intangible costs. Updated methods increased the estimated nonfatal child maltreatment per-victim lifetime cost from $210,012 (2010 USD) to $830,928 (2015 USD) and increased the fatal per-victim cost from $1.3 to $16.6 million. The estimated US population economic burden of child maltreatment based on 2015 substantiated incident cases (482,000 nonfatal and 1670 fatal victims) was $428 billion, representing lifetime costs incurred annually. Using estimated incidence of investigated annual incident cases (2,368,000 nonfatal and 1670 fatal victims), the estimated economic burden was $2 trillion. Accounting for victim and community intangible costs increased the estimated cost of child maltreatment considerably compared to previous estimates. The economic burden of child maltreatment is substantial and might off-set the cost of evidence-based interventions that reduce child maltreatment incidence.


The effect of fucoidan on tyrosinase: computational molecular dynamics integrating inhibition kinetics.
Fucoidan is a complex sulfated polysaccharide extracted from brown seaweed and has a wide variety of biological activities. In this study, we investigated the inhibitory effect of fucoidan on tyrosinase via a combination of inhibition kinetics and computational simulations. Fucoidan reversibly inhibited tyrosinase in a mixed-type manner. Time-interval kinetics showed that the inhibition was processed as first order with biphasic processes. For further insight, we simulated dockings with various sizes of molecular models (monomer to decamer) of fucoidan and showed that the best binding energy change results were obtained from the pentamer (-1.89 kcal/mol) and the hexamer (-1.97 kcal/mol) models of AutoDock Vina. The molecular dynamics simulation confirmed the binding mechanisms between tyrosinase and fucoidan and suggested that fucoidan mostly interacts with several residues including copper ions located in the active site. Our study suggests that fucoidan might be a potential natural antipigment agent.


[Contraceptive efficacy of bioadhesive benzalkonium chloride gel in comparison with nonoxynol-9 gel].
To compare the contraceptive efficacy of a new spermicide, bioadhesive benzalkonium chloride (BZK) gel, with the traditional nonoxynol (NP-9) gel. A total of 240 child-bearing age women volunteers were randomly divided into two groups: 120 using the BZK gel for contraception, and the other 120 using the NP-9 gel. Using life table method and log-rank test, we compared the pregnancy rates and discontinuation rates after follow-up for 6 months in two groups. No abnormal findings of cervical smears were detected before and after this clinical trial in all 240 women. The follow-up rates at 6 months were 100.0% and 99.2% in the BZK group and the NP-9 group, respectively. The 6-month gross cumulative pregnancy rates of typical use were 1.72 and 0.91 per 100 women (P > 0.05), respectively. If we excluded the 2 pregnant women (1 in each group), who did not correctly or consistently use the spermicides for every intercourse, the cumulative pregnancy rates at 6 months in perfect use would be 0.87 and 0 per 100 women (P > 0.05). And the gross cumulative discontinuation rates due to allergy or other adverse reactions at 6 months in typical use were 0 and 2.68 per 100 women (P > 0.05), respectively. The contraceptive efficacy of bioadhesive BZK gel is the same as that of the NP-9 gel, and it is more acceptable in clinical use.


Underuse of Oral Anticoagulants and Inappropriate Prescription of Antiplatelet Therapy in Older Inpatients with Atrial Fibrillation.
Several studies have shown that the prescription of antiplatelet therapy (APT) is associated with an increased risk of oral anticoagulant (OAC) underuse in patients aged 75 years and over with atrial fibrillation (AF). An associated atheromatous disease may be the underlying reason for APT prescription. The objective of the study was to determine whether the association between underuse of OAC and APT prescription was explained by the presence of an atheromatous disease. We performed a retrospective, observational, single-centre study between 2009 and 2013 based on administrative data. Patients aged 75 years and over with non-valvular AF were identified in a database of 72,090 hospital stays. Prescriptions of anti-thrombotic medications and their association with the presence of atheromatous disease were evaluated by the mean of a logistic regression. A total of 2034 hospital stays were included (mean age 84.3 ± 5.2 years). The overall prevalence of known atheromatous disease was 25.9%. OAC underuse was observed in 58.5% of the stays. In multivariable analysis, the prescription of an APT was associated with an increased risk of OAC underuse [odds ratio (OR) 6.85; 95% confidence interval (CI) 5.50-8.58], independently of the presence of a concomitant known atheromatous disease (OR 0.78; 95% CI 0.60-1.01). Among the 692 stays with APT monotherapy (34.0%), 232 (33.5%) displayed an atheromatous disease. The underuse of OAC is associated with the prescription of APT in older patients with AF, regardless of the presence or absence of known atheromatous disease. Our results suggest that APT is often inappropriately prescribed instead of OAC.


Attentional bias for smoking and affective stimuli: a Stroop task study.
Prior research has demonstrated attentional biases to smoking-related cues among smokers, and several lines of research suggest strong ties between smoking and negative affect. The authors tested attentional biases to both smoking and affective cues in 27 smokers using an emotional Stroop paradigm, and examined the relationship between these forms of attentional bias. Findings indicated significant attentional biases to smoking-related and negative-affect words, but not positive-affect words. In addition, there was a significant correlation between the degree of attentional bias to smoking and negative-affect words. These data provide evidence of a close association between smoking-related and affective cue processing from a cognitive perspective. Potential theoretical and clinical implications for these findings are discussed.


Data-Efficient Computational Pathology Platform for Faster and Cheaper Breast Cancer Subtype Identifications: Development of a Deep Learning Model.
Breast cancer subtyping is a crucial step in determining therapeutic options, but the molecular examination based on immunohistochemical staining is expensive and time-consuming. Deep learning opens up the possibility to predict the subtypes based on the morphological information from hematoxylin and eosin staining, a much cheaper and faster alternative. However, training the predictive model conventionally requires a large number of histology images, which is challenging to collect by a single institute. We aimed to develop a data-efficient computational pathology platform, 3DHistoNet, which is capable of learning from z-stacked histology images to accurately predict breast cancer subtypes with a small sample size. We retrospectively examined 401 cases of patients with primary breast carcinoma diagnosed between 2018 and 2020 at the Department of Pathology, National Cancer Center, South Korea. Pathology slides of the patients with breast carcinoma were prepared according to the standard protocols. Age, gender, histologic grade, hormone receptor (estrogen receptor [ER], progesterone receptor [PR], and androgen receptor [AR]) status, erb-B2 receptor tyrosine kinase 2 (HER2) status, and Ki-67 index were evaluated by reviewing medical charts and pathological records. The area under the receiver operating characteristic curve and decision curve were analyzed to evaluate the performance of our 3DHistoNet platform for predicting the ER, PR, AR, HER2, and Ki67 subtype biomarkers with 5-fold cross-validation. We demonstrated that 3DHistoNet can predict all clinically important biomarkers (ER, PR, AR, HER2, and Ki67) with performance exceeding the conventional multiple instance learning models by a considerable margin (area under the receiver operating characteristic curve: 0.75-0.91 vs 0.67-0.8). We further showed that our z-stack histology scanning method can make up for insufficient training data sets without any additional cost incurred. Finally, 3DHistoNet offered an additional capability to generate attention maps that reveal correlations between Ki67 and histomorphological features, which renders the hematoxylin and eosin image in higher fidelity to the pathologist. Our stand-alone, data-efficient pathology platform that can both generate z-stacked images and predict key biomarkers is an appealing tool for breast cancer diagnosis. Its development would encourage morphology-based diagnosis, which is faster, cheaper, and less error-prone compared to the protein quantification method based on immunohistochemical staining.


Epidermal growth factor and its influencing variables in healthy children and adults.
Epidermal growth factor (EGF) stimulates cell proliferation and differentiation after binding to its receptor. Next to its role in magnesium homeostasis, EGF disturbances have been described in oncology, diabetes and autism spectrum disorders. The aim of this study was to determine EGF serum and urine values for both healthy children and adults. Next, we investigated the relation between several variables and urinary and serum EGF concentrations. Both healthy adults (n = 50) and children (n = 78) were included. Serum and urinary EGF concentrations were measured with ELISA technology. Serum EGF was inversely correlated with age (r = -0.873; p<0.001) and positively correlated with serum magnesium (r = 0.597; p<0.001). The urinary EGF was also inversely correlated with age (r = -0.855; p<0.001). In adults and children older than 13 years of age, the urinary EGF significantly differed between sexes (p = 0.001). Urinary EGF was positively correlated with serum magnesium (r = 0.583; p<0.001) and creatinine clearance (r = 0.524; p<0.001) and negatively correlated with the fractional excretion of magnesium (r = 0.248; p = 0.014). In a multivariate model, age and serum magnesium remained independently related to serum EGF while age, serum EGF and serum magnesium remained independently related to urinary EGF. This study provides valuable insights in urinary and serum EGF patterns in healthy subjects. By systematically correcting EGF for body surface, significant correlations with age, gender and magnesium were observed.


Application of Statistical Methods for Central Statistical Monitoring and Implementations on the German Multiple Sclerosis Registry.
Monitoring of clinical trials is a fundamental process required by regulatory agencies. It assures the compliance of a center to the required regulations and the trial protocol. Traditionally, monitoring teams relied on extensive on-site visits and source data verification. However, this is costly, and the outcome is limited. Thus, central statistical monitoring (CSM) is an additional approach recently embraced by the International Council for Harmonisation (ICH) to detect problematic or erroneous data by using visualizations and statistical control measures. Existing implementations have been primarily focused on detecting inlier and outlier data. Other approaches include principal component analysis and distribution of the data. Here we focus on the utilization of comparisons of centers to the Grand mean for different model types and assumptions for common data types, such as binomial, ordinal, and continuous response variables. We implement the usage of multiple comparisons of single centers to the Grand mean of all centers. This approach is also available for various non-normal data types that are abundant in clinical trials. Further, using confidence intervals, an assessment of equivalence to the Grand mean can be applied. In a Monte Carlo simulation study, the applied statistical approaches have been investigated for their ability to control type I error and the assessment of their respective power for balanced and unbalanced designs which are common in registry data and clinical trials. Data from the German Multiple Sclerosis Registry (GMSR) including proportions of missing data, adverse events and disease severity scores were used to verify the results on Real-World-Data (RWD).


Why consumers misattribute sponsorships to non-sponsor brands: Differential roles of item and relational communications.
Brands engaged in sponsorship of events commonly have objectives that depend on consumer memory for the sponsor-event relationship (e.g., sponsorship awareness). Consumers however, often misattribute sponsorships to nonsponsor competitor brands, indicating erroneous memory for these relationships. The current research uses an item and relational memory framework to reveal sponsor brands may inadvertently foster this misattribution when they communicate relational linkages to events. Effects can be explained via differential roles of communicating item information (information that supports processing item distinctiveness) versus relational information (information that supports processing relationships among items) in contributing to memory outcomes. Experiment 1 uses event-cued brand recall to show that correct memory retrieval is best supported by communicating relational information when sponsorship relationships are not obvious (low congruence). In contrast, correct retrieval is best supported by communicating item information when relationships are obvious (high congruence). Experiment 2 uses brand-cued event recall to show that, against conventional marketing recommendations, relational information increases misattribution, whereas item information guards against misattribution. Results suggest sponsor brands must distinguish between item and relational communications to enhance correct retrieval and limit misattribution. Methodologically, the work shows that choice of cueing direction is critical in differentially revealing patterns of correct and incorrect retrieval with pair relationships. (PsycINFO Database Record


Geographic biotype and host-associated local adaptation in a polyphagous species, Lambdina fiscellaria (Lepidoptera: Geometridae) feeding on balsam fir on Anticosti Island, Canada.
The debate about mechanisms underlying the evolution of host specialization by herbivorous insects remains open. Natural selection may act locally and lead to different patterns of geographic variation in life history traits of polyphagous herbivores. The hypothesis of genetically-based trade-offs in offspring performance on different hosts has been proposed but this has rarely been demonstrated. Under laboratory conditions, the biological performance of two populations of the hemlock looper Lambdina fiscellaria (Guenée), a highly polyphagous lepidopteran, was compared when reared on three different tree host species: balsam fir, eastern hemlock and sugar maple. One population originated from Anticosti Island, Québec, Canada, where the insect has evolved without having access to two of the three tree species tested, the other being from the mainland where all tree species are present. When reared on balsam fir foliage, which was naturally available to each population, larvae from Anticosti Island underwent four instars compared with five for the mainland population, indicating the existence of geographic biotypes in L. fiscellaria. When reared on the foliage of non-naturally available host trees, larvae from Anticosti Island had a higher incidence of supernumerary instars. This is a unique example where local adaptation to environmental conditions of an insect herbivore is expressed through a differential number of larval instars. Moreover, the Anticosti Island population showed a higher growth related index on the host available to both populations indicating that a fitness trade-off was the evolutionary process underlying the local adaptation of this population on balsam fir.


Identifying systematic errors in a power spectral analysis of simulated lipid membranes.
The elastic properties of lipid membranes can be measured by monitoring their thermal fluctuations. For instance, comparing the power spectra of membrane shape or lipid director fluctuations with predictions based on suitable continuum theories gives access to bending-, tilt-, and twist-moduli. However, to do so in a computer simulation, we must first define a continuum surface shape and lipid director field from the discrete configurations of lipid molecules in a typically fairly small box. Here, we show that the required mapping choices, as well as the details of the subsequent data analysis, can shift the measured values of these moduli by far more than their statistical uncertainties. We investigate the resulting systematic errors on the basis of atomistic simulation trajectories for 13 different lipids, previously published by Venable et al. [Chem. Phys. Lipids 192, 60-74 (2015)]. Specifically, we examine mapping choices for surface- and tilt-field definitions, normalizing and averaging lipid directors, accounting for wave vector dependent time autocorrelations, error propagation, and finding the right fitting range. We propose a set of criteria that may help to decide upon a particular combination of choices underlying the fluctuation analysis, and we make several recommendations based on these. While systematic shifts in observables that are extracted from large-wavelength limits vanish, in principle, for sufficiently large system size, no such exact limit exists for intrinsically local parameters, such as the twist modulus or the splay-tilt coupling, and so not all potential choices can be trivially verified.


Suppression of TRIF-dependent signaling pathway of toll-like receptors by allyl isothiocyanate in RAW 264.7 macrophages.
Toll-like receptors (TLR) play a significant role in the induction of innate immune responses that are essential for host defense against invading microbial pathogens. In general, TLRs have two major downstream signaling pathways: myeloid differential factor 88 (MyD88)-dependent and toll-interleukin-1 receptor domain-containing adapter inducing interferon-β (TRIF)-dependent pathways. Allyl isothiocyanate (AITC) found in cruciferous vegetables has an effect on treatment of many chronic diseases. However, the exact molecular targets of AITC are still unidentified. Here, it was investigated whether AITC can modulate TLR signaling pathways and what is the molecular target of AITC in TLRs signaling pathways. AITC suppressed the activation of nuclear factor-κB by lipopolysaccharide (LPS) or polyinosinic-polycytidylic acid (poly[I:C]), but not by macrophage-activating lipopeptide of 2kDa (MALP-2) or cytosine-phosphate-guanine dinucleotide (CpG DNA). AITC also suppressed the activation of interferon regulatory factor 3 (IRF3) and the expression of interferon inducible protein-10 (IP-10) induced by LPS or poly[I:C]. These results suggest that AITC can modulate TRIF-dependent signaling pathways of TLRs leading to decreased inflammatory gene expression.


Plasmacytoid monocytes (so-called plasmacytoid T cells) in Hodgkin's disease.
The occurrence and distribution of plasmacytoid monocytes (so-called plasmacytoid T cells) were investigated immunohistochemically in 40 cases of Hodgkin's disease. Large numbers of plasmacytoid monocytes were found in all cases of lymphocyte predominance, nodular sclerosing, and mixed cellularity Hodgkin's disease, characterized by a minor degree of architectural effacement. They occurred at the periphery of lymphoid aggregates which mimic the composite nodule of the reactive lymph node and which contained Reed-Sternberg cells and their variants. Despite some immunophenotypic similarities, no further arguments were found to support a relationship between plasmacytoid monocytes and Reed-Sternberg cells. We conclude that plasmacytoid monocytes represent one of the monocyte-derived cells that contribute to the cellular reaction in Hodgkin's disease.


The use of monoamine oxidase inhibitors in the treatment of elderly, depressed patients.
Depression is an extremely common illness in the elderly, and is, at times, refractory to the usual therapies. The elderly are also particularly prone to develop toxic side effects from standard antidepressive agents. Monoamine oxidase inhibitors are rarely used in this population, although much evidence and clinical experience would indicate that they can be extremely effective and non-toxic. This paper outlines the indications and precautions for use and side effects of monoamine oxidase inhibitors in the treatment of depression in elderly patients.


Lung function in Pakistani welding workers.
Our objective was to study the effects of welding fumes and their duration of exposure on lung function. This was a matched case-control cross-sectional study of spirometry in 50 nonsmoking manual metal arc welders who work without the benefit of welding fume control ventilation or respiratory protective devices. Welding workers, with exposures longer than 9 years, showed a significant reduction in spirometry (forced expiratory volume in one second [FEV1], FEV1/forced vital capacity [FVC%], and peak expiratory flow [PEF]) relative to controls. Lung function in nonsmoking welding workers is impaired and stratification of results shows a dose-effect of years of welding on lung function. This effect primarily shows an obstructive pattern of airways disease. Preventive measures in developing countries have to be adopted to avert long-term lung damage in welders.


Has dopamine a physiological role in the control of sexual behavior? A critical review of the evidence.
The role of dopaminergic systems in the control of sexual behavior has been a subject of study for at least 40 years. Not surprisingly, reviews of the area have been published at variable intervals. However, the earlier reviews have been summaries of published research rather than a critical analysis of it. They have focused upon the conclusions presented in the original research papers rather than on evaluating the reliability and functional significance of the data reported to support these conclusions. During the last few years, important new knowledge concerning dopaminergic systems and their behavioral functions as well as the possible role of these systems in sexual behavior has been obtained. For the first time, it is now possible to integrate the data obtained in studies of sexual behavior into the wider context of general dopaminergic functions. To make this possible, we first present an analysis of the nature and organization of sexual behavior followed by a summary of current knowledge about the brain structures of crucial importance for this behavior. We then proceed with a description of the dopaminergic systems within or projecting to these structures. Whenever possible, we also try to include data on the electrophysiological actions of dopamine. Thereafter, we proceed with analyses of pharmacological data and release studies, both in males and in females. Consistently throughout this discussion, we make an effort to distinguish pharmacological effects on sexual behavior from a possible physiological role of dopamine. By pharmacological effects, we mean here drug-induced alterations in behavior that are not the result of the normal actions of synaptically released dopamine in the untreated animal. The conclusion of this endeavor is that pharmacological effects of dopaminergic drugs are variable in both males and females, independently of whether the drugs are administered systemically or intracerebrally. We conclude that the pharmacological data basically reinforce the notion that dopamine is important for motor functions and general arousal. These actions could, in fact, explain most of the effects seen on sexual behavior. Studies of dopamine release, in both males and females, have focused on the nucleus accumbens, a structure with at most a marginal importance for sexual behavior. Since accumbens dopamine release is associated with all kinds of events, aversive as well as appetitive, it can have no specific effect on sexual behavior but promotes arousal and activation of non-specific motor patterns. Preoptic and paraventricular nucleus release of dopamine may have some relationship to mechanisms of ejaculation or to the neuroendocrine consequences of sexual activity or they can be related to other autonomic processes associated with copulation. There is no compelling indication in existing experimental data that dopamine is of any particular importance for sexual motivation. There is experimental evidence showing that it is of no importance for sexual reward.


Ablation of ceramide synthase 2 exacerbates dextran sodium sulphate-induced colitis in mice due to increased intestinal permeability.
Ceramides mediate crucial cellular processes including cell death and inflammation and have recently been implicated in inflammatory bowel disease. Ceramides consist of a sphingoid long-chain base to which fatty acids of various length can be attached. We now investigate the effect of alerting the ceramide acyl chain length on a mouse model of colitis. Ceramide synthase (CerS) 2 null mice, which lack very-long acyl chain ceramides with concomitant increase of long chain bases and C16-ceramides, were more susceptible to dextran sodium sulphate-induced colitis, and their survival rate was markedly decreased compared with that of wild-type littermates. Using mixed bone-marrow chimeric mice, we showed that the host environment is primarily responsible for intestinal barrier dysfunction and increased intestinal permeability. In the colon of CerS2 null mice, the expression of junctional adhesion molecule-A was markedly decreased and the phosphorylation of myosin light chain 2 was increased. In vitro experiments using Caco-2 cells also confirmed an important role of CerS2 in maintaining epithelial barrier function; CerS2-knockdown via CRISPR-Cas9 technology impaired barrier function. In vivo myriocin administration, which normalized long-chain bases and C16-ceramides of the colon of CerS2 null mice, increased intestinal permeability as measured by serum FITC-dextran levels, indicating that altered SLs including deficiency of very-long-chain ceramides are critical for epithelial barrier function. In conclusion, deficiency of CerS2 influences intestinal barrier function and the severity of experimental colitis and may represent a potential mechanism for inflammatory bowel disease pathogenesis.