Neuroprotective agents for neonatal hypoxic-ischemic brain injury.
Hypoxic-ischemic (H-I) brain injury in newborns is a major cause of morbidity and mortality that claims thousands of lives each year. In this review, we summarize the promising neuroprotective agents tested on animal models and pilot clinical studies of neonatal H-I brain injury according to the different phases of the disease. These agents target various phases of injury including the early phase of excitotoxicity, oxidative stress and apoptosis as well as late-phase inflammatory reaction and neural repair. We analyze the cell survival and cell death pathways modified by these agents in neonatal H-I brain injury. We aim to 'build a bridge' between animal trials of neuroprotective agents and potential candidate treatments for future clinical applications against H-I encephalopathy.


Atrial kinetics and left ventricular diastolic filling in the healthy elderly.
A delay of left ventricular isovolumic relaxation and decrease in myocardial compliance may result in a decline of measured early filling rates in elderly subjects. Previous studies of diastolic function, however, have not excluded coronary artery disease or addressed the contribution of atrial contraction to diastole. The present study evaluated radionuclide-derived diastolic variables in 13 healthy elderly volunteers aged 75 +/- 6 years without symptoms or risk factors for coronary disease who had normal findings on the stress electrocardiogram, stress gated blood pool imaging and two-dimensional echocardiogram. Results were compared with those of a group of 10 healthy young volunteers aged 26 +/- 5 years. High count, 32 frame, double-buffered gated blood pool acquisitions were obtained at rest in the left anterior oblique view with an RR interval variation less than 5%. Left ventricular time-activity curves were analyzed and flow-volume loops for each group were constructed. In the healthy elderly: peak early diastolic filling rate is decreased, time of peak early filling and time to first third of diastolic filling are delayed, and peak late left ventricular filling rate and percent of atrial filling volume are augmented, suggesting an adaptive response of the atria to diminished left ventricular compliance.


Relationship of Mitochondrial-Related Protein Expression with the Differentiation, Metastasis, and Poor Prognosis of Oral Squamous Cell Carcinoma.
Mitochondrial dysfunction and respiratory function changes have been consistently associated with the initiation and progression of cancer. The purpose of this study was to retrospectively investigate the expression of mitochondrial tumor-suppressor and DNA-repair proteins in patients with oral squamous cell carcinoma (OSCC) and to evaluate the relationship between their expression and prognosis. We enrolled 197 patients with OSCC who underwent surgical resection between August 2013 and October 2018. Clinical, pathological, and epidemiological data were retrospectively collected from hospital records. The expression of peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), mitochondrial transcription factor A, mitochondrial tumor suppressor gene 1, silent information regulator 3, and 8-hydroxyguanine DNA glycosylase was investigated using immunochemistry. The 3-year disease-specific survival (DSS) rates of patients showing positive expression of all selected proteins were significantly higher than those of patients showing a lack of expression. Multivariate analysis revealed that the expression of PGC-1α (hazard ratio, 4.684) and vascular invasion (hazard ratio, 5.690) can predict the DSS rate (p < 0.001). Low PGC-1α expression and vascular invasion are potential clinically effective predictors of the prognosis of OSCC.


Molecular basis of the PED/PEA15 interaction with the C-terminal fragment of phospholipase D1 revealed by NMR spectroscopy.
PED/PEA15 is a small protein involved in many protein-protein interactions that modulates the function of a number of key cellular effectors involved in major cell functions, including apoptosis, proliferation and glucose metabolism. In particular, PED/PEA15 interacts with the phospholipase D (PLD) isoforms 1 and 2 increasing protein kinase C-α isoform activity and affects both insulin-stimulated glucose transport and glucose-stimulated insulin secretion. The C-terminal portion (residues 712-1074) of PLD1, named D4, is still able to interact with PED/PEA15. In this study we characterized, by means of NMR spectroscopy, the molecular interaction of PED/PEA15 with D4α, a smaller region of D4, encompassing residues 712-818, shown to have the same affinity for PED/PEA15 and to induce the same effects as D4 in PED/PEA15-overexpressing cells. Chemical shift perturbation (CSP) studies allowed to define D4α binding site of PED/PEA15 and to identify a smaller region likely affected by an allosteric effect. Moreover, ELISA-like experiments showed that three 20-mer overlapping synthetic peptides, covering the 762-801 region of D4α, strongly inhibit PED/PEA15-D4α interaction through their binding to PED/PEA15 with KDs in low micromolar range. Finally, molecular details of the interaction of PED/PEA15 with one of the three peptides have been revealed by CSP and saturation transfer difference (STD) analyses.


Bedding Material Affects Mechanical Thresholds, Heat Thresholds, and Texture Preference.
It has long been known that the bedding type on which animals are housed can affect breeding behavior and cage environment, yet little is known about its effects on evoked behavior responses or nonreflexive behaviors. C57BL/6 mice were housed for 2 weeks on 1 of 5 bedding types: aspen Sani-Chips (standard bedding for our institute), ALPHA-Dri, Cellu-Dri, Pure-o'Cel, or TEK-Fresh. Mice housed on aspen exhibited the lowest (most sensitive) mechanical thresholds and those on TEK-Fresh exhibited 3-fold higher thresholds. Although bedding type had no effect on responses to punctate or dynamic light touch stimuli, TEK-Fresh-housed animals exhibited greater responsiveness in a noxious needle assay than did those housed on the other bedding types. Heat sensitivity was also affected by bedding because animals housed on aspen exhibited the shortest (most sensitive) latencies to withdrawal, whereas those housed on TEK-Fresh had the longest (least sensitive) latencies to response. Slight differences between bedding types were also seen in a moderate cold temperature preference assay. A modified tactile conditioned place preference chamber assay revealed that animals preferred TEK-Fresh to aspen bedding. Bedding type had no effect in a nonreflexive wheel running assay. In both acute (2 day) and chronic (5 week) inflammation induced by injection of complete Freund's adjuvant in the hindpaw, mechanical thresholds were reduced in all groups regardless of bedding type, but TEK-Fresh and Pure-o'Cel groups exhibited a greater dynamic range between controls and inflamed cohorts than aspen-housed mice. These findings indicate that the bedding type routinely used to house animals can markedly affect the dynamic range of mechanical and heat behavior assays under normal and tissue injury conditions. Among beddings tested, TEK-Fresh bedding resulted in the least sensitive baseline thresholds for mechanical and thermal stimuli and the greatest dynamic range after tissue injury. Therefore, selection of routine cage bedding material should be carefully considered for animals that will be tested in behavioral somatosensory assays.


B cell depletion therapy ameliorates autoimmune disease through ablation of IL-6-producing B cells.
B cells have paradoxical roles in autoimmunity, exerting both pathogenic and protective effects. Pathogenesis may be antibody independent, as B cell depletion therapy (BCDT) leads to amelioration of disease irrespective of autoantibody ablation. However, the mechanisms of pathogenesis are poorly understood. We demonstrate that BCDT alleviates central nervous system autoimmunity through ablation of IL-6-secreting pathogenic B cells. B cells from mice with experimental autoimmune encephalomyelitis (EAE) secreted elevated levels of IL-6 compared with B cells from naive controls, and mice with a B cell-specific IL-6 deficiency showed less severe disease than mice with wild-type B cells. Moreover, BCDT ameliorated EAE only in mice with IL-6-sufficient B cells. This mechanism of pathogenesis may also operate in multiple sclerosis (MS) because B cells from MS patients produced more IL-6 than B cells from healthy controls, and this abnormality was normalized with B cell reconstitution after Rituximab treatment. This suggests that BCDT improved disease progression, at least partly, by eliminating IL-6-producing B cells in MS patients. Taking these data together, we conclude that IL-6 secretion is a major mechanism of B cell-driven pathogenesis in T cell-mediated autoimmune disease such as EAE and MS.


Hemodynamic effects of procainamide and quinidine and the influence of beta-blockade before and after experimental myocardial infarction.
The use of antiarrhythmie drugs in combination has been limited because of possible side effects secondary to myocardial depression in the acute myocardial infarction patient. Therefore, we investigated in intact dogs (group I) the hemodynamic interaction of propranolol plus procainamide (subgroup A) or quinidine (subgroup B) and in dogs after experimental myocardial infarction produced by coronary artery ligation (group II). Infusion of procainamide (30 mg/kg over 5 min) in animals of group IA produced a significant (P less than 0.05) decrease of 30% in mean aortic pressure, a decrease of 40% in left ventricular dp/dt and 29% in cardiac output. When procainamide was reinfuse after propranolol (1 mg/kg), its hemodynamic effects were not significantly different from those observed before propranolol in both groups IA and IIA. Infusion of quinidine (10 mg/kg over 5 min) in animals of group IB (intact dogs) also produced significant decreases of 24% in mean aortic pressure and 38% in dp/dt while cardiac output was unchanged. However, these hemodynamic changes were seen only after beta-blockade and were significantly different from those obtained before propranolol, where heart rate increased by 14%, dp/dt by 30%, and cardiac output by 35%. These changes occurred despite a similar reduction in mean aortic pressure. This drug combination produced similar response in animals after coronary artery ligation (group IIB). In conclusion, we feel that the administration of propranolol does not prevent the depressive circulatory effects of procainamide. The combined use of quinidine and propranolol also has a negative circulatory effect although not as marked as the effects observed after procainamide with propranolol.


Potential of visible-near infrared spectroscopy combined with chemometrics for analysis of some constituents of coffee and banana residues.
Banana (stalk, leaf, rhizome, rachis and stem) and coffee (leaf and husks) residues are promising feedstock for fuel and chemical production. In this work we show the potential of near-infrared spectroscopy (NIR) and multivariate analysis to replace reference methods in the characterization of some constituents of coffee and banana residues. The evaluated parameters were Klason lignin (KL), acid soluble lignin (ASL), total lignin (TL), extractives, moisture, ash and acid insoluble residue (AIR) contents of 104 banana residues (B) and 102 coffee (C) residues from Brazil. PLS models were built for banana (B), coffee (C) and pooled samples (B+C). The precision of NIR methodology was better (p<0.05) than the reference method for almost all the parameters, being worse for moisture. With the exception of ash (B and C) and ASL (C) content, which was predicted poorly (R(2)<0.80), the models for all the analytes exhibited R(2)>0.80. The range error ratios varied from 4.5 to 16.0. Based on the results of external validation, the statistical tests and figures of merit, NIR spectroscopy proved to be useful for chemical prediction of banana and coffee residues and can be used as a faster and more economical alternative to the standard methodologies.


Rapid prediction of ochratoxin A-producing strains of Penicillium on dry-cured meat by MOS-based electronic nose.
The availability of rapid diagnostic methods for monitoring ochratoxigenic species during the seasoning processes for dry-cured meats is crucial and constitutes a key stage in order to prevent the risk of ochratoxin A (OTA) contamination. A rapid, easy-to-perform and non-invasive method using an electronic nose (e-nose) based on metal oxide semiconductors (MOS) was developed to discriminate dry-cured meat samples in two classes based on the fungal contamination: class P (samples contaminated by OTA-producing Penicillium strains) and class NP (samples contaminated by OTA non-producing Penicillium strains). Two OTA-producing strains of Penicillium nordicum and two OTA non-producing strains of Penicillium nalgiovense and Penicillium salamii, were tested. The feasibility of this approach was initially evaluated by e-nose analysis of 480 samples of both Yeast extract sucrose (YES) and meat-based agar media inoculated with the tested Penicillium strains and incubated up to 14 days. The high recognition percentages (higher than 82%) obtained by Discriminant Function Analysis (DFA), either in calibration and cross-validation (leave-more-out approach), for both YES and meat-based samples demonstrated the validity of the used approach. The e-nose method was subsequently developed and validated for the analysis of dry-cured meat samples. A total of 240 e-nose analyses were carried out using inoculated sausages, seasoned by a laboratory-scale process and sampled at 5, 7, 10 and 14 days. DFA provided calibration models that permitted discrimination of dry-cured meat samples after only 5 days of seasoning with mean recognition percentages in calibration and cross-validation of 98 and 88%, respectively. A further validation of the developed e-nose method was performed using 60 dry-cured meat samples produced by an industrial-scale seasoning process showing a total recognition percentage of 73%. The pattern of volatile compounds of dry-cured meat samples was identified and characterized by a developed HS-SPME/GC-MS method. Seven volatile compounds (2-methyl-1-butanol, octane, 1R-α-pinene, d-limonene, undecane, tetradecanal, 9-(Z)-octadecenoic acid methyl ester) allowed discrimination between dry-cured meat samples of classes P and NP. These results demonstrate that MOS-based electronic nose can be a useful tool for a rapid screening in preventing OTA contamination in the cured meat supply chain.


A comparison of primary nursing and team nursing in a geriatric long-term care setting.
The purpose of this study was to evaluate primary and team nursing on two 45-bed geriatric units. A 2 year longitudinal study with a quasi-experimental ABA cross-over design and a staff survey, permitted comparisons of the two nursing systems on indices of patient well-being, nursing practice, staff morale and costs. Differences in nursing practice, in selected measures of patient well-being and in responses to the staff survey were positively associated with primary nursing. No differences emerged in relation to staff morale or costs. The benefits of primary nursing and implications for further research are discussed.


Natural Orifice Translumenal Endoscopic Surgery: Review of Its Applications in Bariatric Procedures.
This review aims to summarise clinical applications of natural orifice translumenal endoscopic surgery (NOTES) in bariatric surgery. A review of data, until December 2014, was carried out regarding techniques and outcomes of bariatric NOTES procedures. Nine publications were included in the final analysis, with another six papers describing endolumenal procedures included for comparison. All NOTES studies adopted a hybrid procedure. Hybrid NOTES sleeve gastrectomy (hNSG) was described in four humans and two porcine studies. In humans, six subjects (23.1%) were converted to conventional laparoscopic methods, and one postoperative complication (3.8%) was reported. Mean excess weight loss was 46.6% (range 35.2-58.9). Transvaginal-assisted sleeve gastrectomy appears feasible and safe when performed by appropriately trained professionals. However, improvements must be made to overcome current technical limitations.


Mineral nutrition and leaf longevity in an evergreen shrub, Ledum palustre ssp. decumbens.
Effects of variable mineral nutrient status on evergreen leaf longevity were investigated in a field fertilization experiment, and by comparison of plants from several sites. The species studied was Ledum palustre spp. decumbens, with a normal leaf life expectancy of 2.06 years and a maximum leaf longevity of 4.5-5.0 years. Most leaf losses took place during the growing season, not during the winter. Fertilization increased leaf production but decreased leaf survivorship. Total number of leaves per stem was unchanged with fertilization. In a comparison among sites, there was a moderate negative correlation between plant N and P concentrations and leaf longevity. These intraspecific responses are similar to known interspecific changes along nutrient gradients, i.e. with high nutrient availability a vegetation should become more "deciduous" and less "evergreen".


Early changes in laboratory parameters are predictors of mortality and ICU admission in patients with COVID-19: a systematic review and meta-analysis.
Despite the growing knowledge of the clinicopathological features of COVID-19, the correlation between early changes in the laboratory parameters and the clinical outcomes of patients is not entirely understood. In this study, we aimed to assess the prognostic value of early laboratory parameters in COVID-19. We conducted a systematic review and meta-analysis based on the available literature in five databases. The last search was on July 26, 2020, with key terms related to COVID-19. Eligible studies contained original data of at least ten infected patients and reported on baseline laboratory parameters of patients. We calculated weighted mean differences (WMDs) for continuous outcomes and odds ratios (ORs) with 95% confidence intervals. 93 and 78 studies were included in quantitative and qualitative syntheses, respectively. Higher baseline total white blood cell count (WBC), C-reactive protein (CRP), lactate-dehydrogenase (LDH), creatine kinase (CK), D-dimer and lower absolute lymphocyte count (ALC) (WMDALC = - 0.35 × 109/L [CI - 0.43, - 0.27], p < 0.001, I2 = 94.2%; < 0.8 × 109/L, ORALC = 3.74 [CI 1.77, 7.92], p = 0.001, I2 = 65.5%) were all associated with higher mortality rate. On admission WBC, ALC, D-dimer, CRP, LDH, and CK changes could serve as alarming prognostic factors. The correct interpretation of laboratory abnormalities can guide therapeutic decisions, especially in early identification of potentially critical cases. This meta-analysis should help to allocate resources and save lives by enabling timely intervention.


Ensuring the Quality of Point-of-Care Testing in a Large and Decentralized Ambulatory Care Setting.
In this project, we assessed the breadth, quality, trends, and outcomes of point-of-care (POC) testing and regulatory compliance in 200 University of California, Los Angeles (UCLA) Health system outpatient clinics. We retrospectively extracted clinic POC test orders, results, and e-prescription data from the UCLA electronic health record over a 1-year period. Over 100,000 total tests were performed, encompassing 10 POC tests. Initially, 40% of clinics did not have complete licensure, but after implementation of the POC team, this metric improved to 100% licensure within 6 months. Most clinics used two or fewer POC tests, resulted fewer than 200 tests per year, and performed little to no external quality control measures. Our data analytics approach showed that peak POC testing occurred in January 2015, driven by influenza and urinalysis testing, and that both the testing and resulting clinical decision making do not routinely follow society guidelines. This decentralization of laboratory testing presents challenges to ensuring quality POC testing. Optimization and analysis of informatics data allow for the identification of POC test utilization trends, areas of improvement for clinical workflows, and increased education on national guidelines.


Interaction between biofilm development, structure and detachment in rotating annular reactors.
In biotechnology, composition of biofilms and suspended bioaggregates can be crucial for system performance or product quality. Consequently, understanding biofilm dynamics is important for any process optimisation. The aim of this study was to investigate biofilm development and detachment under different hydrodynamic conditions and varying glucose load. Confocal laser scanning microscopy proved to be a fast method providing information about structure, distribution and volume ratio of bacteria and extra cellular polymers (EPS) within biofilms and detached biomass. As a result, it could be shown that biofilm structure, in terms of density and EPS volume, was largely influenced by hydrodynamic conditions. Furthermore, it was demonstrated that the EPS:bacteria ratio and distribution was largely influenced by substrate load. Finally, the characteristics in biofilm structure and development were reflected in the composition and quantity of the detached biomass.


Advance care planning in COPD: guidance development for healthcare professionals.
To examine current practices, attitudes and levels of confidence related to advance care planning (ACP) in patients with chronic obstructive pulmonary disease (COPD) among healthcare professionals working in Ireland. This will inform future clinical guidance development. A cross-sectional survey of healthcare professionals. There were 143 participants (109 general practitioners, 25 nurses, 7 physiotherapists and 2 consultant physicians). The majority (82%, n=117) cared for patients with COPD weekly, but only 23% (n=33) had initiated ACP with a patient with COPD over the previous 6 months. Overall, 59% (n=85) answered ≥6 of 8 general knowledge questions correctly. Participants demonstrated positive attitudes towards ACP (mean score 3.6/5.0), but confidence levels were low (2.2/4.0). Most thought ACP was appropriate for patients with severe or very severe COPD (71%, n=101%, and 91%, n=130, respectively) but were unsure or felt that it was not appropriate for those with mild-moderate COPD. However, almost all participants (97%, n=139) stated that if a patient expressed a desire to have ACP discussions, they would comply. Topics most likely to be discussed related to diagnosis and treatment options. Death and end-of-life issues were rarely discussed. The death of a family member or friend and participation in support groups were identified as new 'triggers' for initiating ACP. Targeted education to improve general knowledge and confidence levels among healthcare professionals, together with initiatives to increase public awareness of ACP so that patients themselves might be more inclined to start the discussion, may help increase the uptake of ACP for this patient group.


Significance of screening for Fabry disease among male dialysis patients.
Fabry disease is an X-linked disorder resulting from a deficiency of the lysosomal enzyme alpha-galactosidase A(alpha-Gal A). Renal insufficiency is a very important manifestation and affects the prognosis of patients. Recently, a renal variant type that is characterized by low plasma alpha-Gal A activity and a milder phenotype, but which progresses to end-stage renal failure, has been reported. In this study, we clarified the incidence of this atypical variant of Fabry disease in hemodialysis patients. We measured plasma alpha-Gal A activity in 450 male dialysis patients who had never been diagnosed with Fabry disease. The mean of the alpha-Gal A activity of the patients was 9.75 +/- 3.20 nmol/h/ml, while the controls with classical Fabry (n = 3) were 0.52-1.04 nmol/h/ml. Among the patients, one patient was found to exhibit low alpha-Gal A activity in plasma (3.18 nmol/h/ml) and in leukocytes (0.639 nmol/h/mg). This patient was a 43-year-old Japanese man who had been on regular dialysis since the age of 23. He did not present typical clinical signs of classical Fabry, such as acroparesthesias or hypohidrosis, but did present renal insufficiency and severe left ventricular hypertrophy which had developed only recently, suggesting a variant form of Fabry disease. Sequencing of the DNA of this patient revealed a deletion of a single amino acid of valine in 10252. A case of an atypical variant of Fabry among 450 male dialysis patients (0.22%) was found in the survey. This indicates the potential for undiagnosed Fabry disease among dialysis patients. The results of this study indicate the significance of screening for Fabry disease among male dialysis patients.


Literature analysis on asparagus roots and review of its functional characterizations.
Asparagus root (AR) is utilized globally as a traditional herbal medicine because it contains various bioactive compounds, such as polyphenols, flavonoids, saponins, and minerals. The composition profiles of AR are strongly affected by its botanical and geographical origins. Although minerals and heavy metals are minor constituents of AR, they play a crucial role in determining its quality and efficacy. A comprehensive classification of AR, its phytochemistry, and its pharmacology were reviewed and interpreted herein. Potentially eligible articles (in English) were identified through an electronic search of the Web of Science database (2010-2022) and Google (2001-2022). We used the primary search term "Asparagus roots" combined with the words "pharmacology," "bioactive compounds," "physicochemical properties," and "health benefits" to find the relevant literature. We screened the titles, keywords, and abstracts of the publications obtained from the database. A full copy of the article was obtained for further assessment if deemed appropriate. Different asparagus species might potentially be used as herbal medicines and functional foods. Phytochemical studies have revealed the presence of various bioactive compounds as valuable secondary metabolites. The dominant class of bioactive compounds in AR is flavonoids. Furthermore, AR displayed significant pharmacological effects, such as antioxidant, antimicrobial, antiviral, anticancer, anti-inflammatory, and antidiabetic effects, as shown in animal and human studies. This review provides a valuable resource to enable a thorough assessment of the profile of Asparagus root as a functional ingredient for the pharmaceutical and food industries. In addition, it is anticipated that this review will provide information to healthcare professionals seeking alternative sources of critical bioactive compounds.


A Quality Improvement Initiative: Reducing Blood Culture Contamination in a Children's Hospital.
Blood culture contamination is a safety and quality concern in children's hospitals; it leads to increased unnecessary testing, admissions, antibiotic exposure, and cost. The standard benchmark for blood culture contamination is 3%. Our aim with the quality improvement project was to reduce the contamination rate at our children's hospital from a mean of 2.85% to <1.5% in 2 years. After initial unit-specific efforts, we formed a multidisciplinary team, created a process map and a cause-and-effect analysis, sent out surveys to nurses, and created observation sheets used to identify problem areas and record the most common deviations during the collection process. We also standardized the blood culture collection protocol and reemphasized nurse education in person and with online modules. During our project, we noted that nurses were collecting 1 to 3 mL of blood on all children regardless of weight. We developed optimal weight-based blood volumes and, after educating ordering providers, we updated our electronic medical record to reflect appropriate volumes in the order. Despite a steady increase in the number of blood cultures collected at our children's hospital, we were able to decrease the average contamination rate from 2.85% to 1.54%, saving the hospital an estimated average of $49 998 per month. By standardizing blood culture collection methods, optimizing blood volume, creating checklists, and reinforcing nurse education, we were able to develop a best practice for pediatric blood culture collection and reduce blood culture contamination to a sustainable low rate at our children's hospital.


Histopathology and histochemistry of insects treated with chemosterilants. VII. On the corpora cardiaca of Periplaneta americana (L) treated with hempa.
The neurosecretory granules are reduced and intrinsic cells are damaged in the corpora cardiaca of the last instar nymphs of P. americana treated with hempa.


Morphological and biochemical characterization of Procambarus clarki blood cells.
Morphological and cytochemical analysis of Procambarus clarki hemocytes demonstrated three cell types: hyaline, semigranular, and granular. Hyaline cells showed a higher nuclear/cytoplasmic ratio with few small electron-dense granules in the cytoplasm. Semigranular cells presented numerous round or oval eosinophilic granules (0.40-0.78 micron). Granular cell contained large eosinophilic granules (1.79-3.05 microns). Ultrastructurally, all cells showed microtubules near the borders, a poorly developed Golgi complex, and secretory-type electron-dense particles. No mitotic figures were seen. Cell monolayers showed three morphologically distinct cell types (composed of flattened and well-spread cells) depending on the presence and size of granules (hyaline, semigranular, and granular). No sex-related differences could be documented in cell features or proportions. Cytochemical studies showed that the three cell types were positive for acid phosphatase. Granular and semigranular cells were also positive for nonspecific esterase. Phenoloxidase activity was localized only in granular and semigranular hemocytes, and peroxidase activity was observed only in the granular hemocytes. These results may suggest that the semigranular and granular hemocytes participate in the prophenoloxidase system and also in phagocytic or cytotoxic function.


Gamification of a Mobile Applications Lecture in a Pharmacy Course.
This report describes a librarian's development of an interactive and competitive trivia game using Poll Everywhere, an audience response system software. The trivia game was implemented during a live lecture session on drug information mobile applications taught to first-year pharmacy students. To add a fun and engaging reference for students, the librarian decided to model the game after HQ, a free trivia gaming app. Development of the session, student response, changes to future iterations, and lessons learned by the librarian are described.


Nintedanib reduces radiation-induced microscopic lung fibrosis but this cannot be monitored by CT imaging: A preclinical study with a high precision image-guided irradiator.
Nintedanib has anti-fibrotic and anti-inflammatory activity and is approved for the treatment of idiopathic pulmonary fibrosis. The aim of this study was to noninvasively assess the efficacy of nintedanib in a mouse model of partial lung irradiation to prevent radiation-induced lung damage (RILD). 266 C57BL/6 adult male mice were irradiated with a single radiation dose (0, 4, 8, 12, 16 or 20Gy) using parallel-opposed fields targeting the upper right lung using a precision image-guided small animal irradiator sparing heart and spine based on micro-CT images. One week post irradiation, mice were randomized across nintedanib daily oral gavage treatment (0, 30 or 60mg/kg). CT density analysis of the lungs was performed on monthly acquired micro-CT images. After 39weeks, lungs were processed to evaluate the fibrotic phenotype. Although the CT density increase correlated with the radiation dose, nintedanib did not influence this relationship. Immunohistochemical analysis confirmed the ability of nintedanib to reduce the microscopic fibrotic phenotype, in particular interstitial edema, interstitial and perivascular fibrosis and inflammation, and vasculitis. Nintedanib reduces radiation-induced lung fibrosis after partial lung irradiation without adverse effects, however, noninvasive CT imaging measuring electron density cannot be applied for monitoring its effects.


The relationship between health-related quality of life and melancholic depressive symptoms is modified by brain insulin receptor gene network.
To investigate whether expression-based polygenic risk scores for the insulin receptor gene network (ePRS-IRs) modifiy the association between type of depressive symptoms and health-related quality of life (HRQoL). This cross-sectional study includes 1558 individuals from the Helsinki Birth Cohort Study. Between 2001 and 2004, the Short Form-36 questionnaire was employed to assess mental and physical components of HRQoL and Beck Depression Inventory (BDI) to assess depressive symptoms. Depressive symptoms were categorized into minimal (BDI < 10), non-melancholic and melancholic types of depression. The ePRS-IRs were calculated for the hippocampal (hePRS-IR) and the mesocorticolimbic (mePRS-IR) regions of the brain. General linear regression models adjusted for age, sex, population stratification, lifestyle factors and body mass index were applied to analyze the data. Both types of depressive symptoms were associated with lower HRQoL (p < 0.0001). HePRS-IR modified the association between the types of depression and mental HRQoL (p for interaction = 0.005). Melancholic type of depressive symptoms was associated with higher mental HRQoL compared to the non-melancholic symptoms among individuals with low hePRS-IR (adjusted mean 4.1, 95% CI 0.7-7.4, p = 0.018). However, no such difference was evident in moderate or high hePRS-IR groups as higher hePRS-IR was associated with lower mental HRQoL (B = - 3.4, 95% CI - 5.6 to - 1.2) in individuals with melancholic type of depressive symptoms. No direct associations were detected between the ePRS-IRs and type of depressive symptoms or HRQoL. Variations in the glucose-insulin metabolism can lower HRQoL in individuals with melancholic depressive symptoms.


Compound jetting from bubble bursting at an air-oil-water interface.
Bursting of bubbles at a liquid surface is ubiquitous in a wide range of physical, biological, and geological phenomena, as a key source of aerosol droplets for mass transport across the interface. However, how a structurally complex interface, widely present in nature, mediates the bursting process remains largely unknown. Here, we document the bubble-bursting jet dynamics at an oil-covered aqueous surface, which typifies the sea surface microlayer as well as an oil spill on the ocean. The jet tip radius and velocity are altered with even a thin oil layer, and oily aerosol droplets are produced. We provide evidence that the coupling of oil spreading and cavity collapse dynamics results in a multi-phase jet and the follow-up droplet size change. The oil spreading influences the effective viscous damping, and scaling laws are proposed to quantify the jetting dynamics. Our study not only advances the fundamental understanding of bubble bursting dynamics, but also may shed light on the airborne transmission of organic matters in nature related to aerosol production.


[Effect of pre-administered flurbiprofen axetil on the EC50 of propofol during anesthesia in unstimulated patients: a randomized clinical trial].
Preoperative use of flurbiprofen axetil (FA) is extensively adopted to modulate the effects of analgesia. However, the relationship between FA and sedation agents remains unclear. In this study, we aimed to investigate the effects of different doses of FA on the median Effective Concentration (EC50) of propofol. Ninety-six patients (ASA I or II, aged 18-65 years) were randomly assigned into one of four groups in a 1:1:1:1 ratio. Group A (control group) received 10 mL of Intralipid, and groups B, C and D received 0.5 mg.kg-1, 0.75 mg.kg-1 and 1 mg.kg-1 of FA, respectively, 10 minutes before induction. The depth of anesthesia was measured by the Bispectral Index (BIS). The "up-and-down" method was used to calculate the EC50 of propofol. During the equilibration period, if BIS ≤ 50 (or BIS > 50), the next patient would receive a 0.5 μg.mL-1-lower (or-higher) propofol Target-Controlled Infusion (TCI) concentration. The hemodynamic data were recorded at baseline, 10 minutes after FA administration, after induction, after intubation, and 15 minutes after intubation. The EC50 of propofol was lower in Group C (2.32 μg.mL-1, 95% Confidence Interval [95% CI] 1.85-2.75) and D (2.39 μg.mL-1, 95% CI 1.91-2.67) than in Group A (2.96 μg.mL-1, 95% CI 2.55-3.33) (p = 0.023, p = 0.048, respectively). There were no significant differences in the EC50 between Group B (2.53 μg.mL-1, 95% CI 2.33-2.71) and Group A (p ˃ 0.05). There were no significant differences in Heart Rate (HR) among groups A, B and C. The HR was significantly lower in Group D than in Group A after intubation (66 ± 6 vs. 80 ± 10 bpm, p < 0.01) and 15 minutes after intubation (61 ± 4 vs. 70 ± 8 bpm, p < 0.01). There were no significant differences among the four groups in Mean Arterial Pressure (MAP) at any time point. The MAP of the four groups was significantly lower after induction, after intubation, and 15 minutes after intubation than at baseline (p < 0.05). High-dose FA (0.75 mg.kg-1 or 1 mg.kg-1) reduces the EC50 of propofol, and 1 mg.kg-1 FA reduces the HR for adequate anesthesia in unstimulated patients. Although this result should be investigated in cases of surgical stimulation, we suggest that FA pre-administration may reduce the propofol requirement when the depth of anesthesia is measured by BIS.


Methods for handling missing data in serially sampled sputum specimens for mycobacterial culture conversion calculation.
The occurrence and timing of mycobacterial culture conversion is used as a proxy for tuberculosis treatment response. When researchers serially sample sputum during tuberculosis studies, contamination or missed visits leads to missing data points. Traditionally, this is managed by ignoring missing data or simple carry-forward techniques. Statistically advanced multiple imputation methods potentially decrease bias and retain sample size and statistical power. We analyzed data from 261 participants who provided weekly sputa for the first 12 weeks of tuberculosis treatment. We compared methods for handling missing data points in a longitudinal study with a time-to-event outcome. Our primary outcome was time to culture conversion, defined as two consecutive weeks with no Mycobacterium tuberculosis growth. Methods used to address missing data included: 1) available case analysis, 2) last observation carried forward, and 3) multiple imputation by fully conditional specification. For each method, we calculated the proportion culture converted and used survival analysis to estimate Kaplan-Meier curves, hazard ratios, and restricted mean survival times. We compared methods based on point estimates, confidence intervals, and conclusions to specific research questions. The three missing data methods lead to differences in the number of participants achieving conversion; 78 (32.8%) participants converted with available case analysis, 154 (64.7%) converted with last observation carried forward, and 184 (77.1%) converted with multiple imputation. Multiple imputation resulted in smaller point estimates than simple approaches with narrower confidence intervals. The adjusted hazard ratio for smear negative participants was 3.4 (95% CI 2.3, 5.1) using multiple imputation compared to 5.2 (95% CI 3.1, 8.7) using last observation carried forward and 5.0 (95% CI 2.4, 10.6) using available case analysis. We showed that accounting for missing sputum data through multiple imputation, a statistically valid approach under certain conditions, can lead to different conclusions than naïve methods. Careful consideration for how to handle missing data must be taken and be pre-specified prior to analysis. We used data from a TB study to demonstrate these concepts, however, the methods we described are broadly applicable to longitudinal missing data. We provide valuable statistical guidance and code for researchers to appropriately handle missing data in longitudinal studies.


The regulation of necroptosis and perspectives for the development of new drugs preventing ischemic/reperfusion of cardiac injury.
In the last 10 years, mortality from acute myocardial infarction (AMI) has not significantly decreased. This situation is associated with the absence in clinical practice of highly effective drugs capable of preventing the occurrence of reperfusion injury of the heart. Necroptosis inhibitors may become prototypes for the creation of highly effective drugs that increase cardiac tolerance to ischemic/reperfusion (I/R) and reduce the mortality rate in patients with AMI. Necroptosis is involved in I/R cardiac injury and inhibition of RIPK1 or RIPK3 contributes to an increase in cardiac tolerance to I/R. Necroptosis could also be involved in the development of adverse remodeling of the heart. It is unclear whether pre- and postconditioning could inhibit necroptosis of cardiomyocytes and endothelial cells. The role of necroptosis in coronary microvascular obstruction and the no-reflow phenomenon also needs to be studied. MicroRNAs and LncRNAs can regulate necroptotic cell death. Ca2+ overload and reactive oxygen species could be the triggers of necroptosis. Activation of kinases (p38, JNK1, Akt, and mTOR) could promote necroptotic cell death. The interaction of necroptosis, apoptosis, autophagy, ferroptosis, and pyroptosis is discussed. The water-soluble necroptosis inhibitors may be highly effective drugs for treatment of AMI or stroke. It is possible that microRNAs may become the basis for creating drugs for treatment of diseases triggered by I/R of organs.


Does complement factor B have a role in the pathogenesis of atypical HUS?
Atypical haemolytic uraemic syndrome (aHUS) is a disorder of complement dysregulation. Because complement factor B (fB) carries the catalytic site of the alternative pathway convertase we examined it as both a potential candidate gene and modifier in the pathogenesis of aHUS. No factor B gene (BF) mutations were found in 20 patients with aHUS. There was no statistical difference between controls and aHUS patients in either BF allele or haplotype frequency. In conclusion, in this small series of aHUS patients we found no evidence that fB has a major role in the pathogenesis of aHUS.


Use of a genetic marker to examine genetic interaction among subpopulations of pink salmon (Oncorhynchus gorbuscha).
In 1979 and 1981, a genetic marker was bred into one of the five identifiable subpopulations of pink salmon [Oncorhynchus gorbuscha (Walbaum)] in the Auke Lake drainage in Southeast Alaska. As a result of the marking effort, the frequencies of two malate dehydrogenase (MDH-B1, 2*) alleles were changed in the marked subpopulation, but not in other subpopulations that spawn at different times or places. Between 1983 and 1989, the marker allele frequencies were monitored in many of these subpopulations and in early- and late-run pink salmon spawning in nearby Waydelich Creek, located approximately 1 km away. Changes in allele frequencies at MDH-B1, 2*, used to obtain direct estimates of average migration rates (m) from the marked to the unmarked subpopulations, revealed little or no introgression into early subpopulations or into nearby Waydelich Creek. Moreover, spatially distinct late-run Auke Creek subpopulations were not immediately overrun by the more abundant marked subpopulation. These observations suggest that genetic isolation exists between temporally distinct spawning runs and that small temporal and spatial (or ecological) differences contribute to population structure. These observations should be considered in taking actions that affect conservation and harvest management or extensive culture of salmonids.


The influence of a nitric oxide synthase inhibitor and endothelin receptor blocker on the free sulfhydryl groups content in lung homogenates.
The aim of the study was to assess the influence of the nitric oxide synthase inhibitor L-NAME and the endothelin receptor blocker BQ123 on the free sulfhydryl (-SH) groups content in rat lung homogenates. Experiments were performed on Wistar-Kyoto rats divided into the following groups: group I (control) received (i.v.) saline; group II (ET-1) received (i.v.) endothelin 1 (3 g μg/kg b.w.); group III (BQ123+ET-1) received (i.v.) ET(A) receptor blocker (1 mg/kg b.w.) + endothelin 1 (3 g μg/kg b.w.); group IV (L-NAME+ET-1) received (i.v.) nitric oxide synthase inhibitor (5 mg/kg b.w.) + endothelin 1 (3 μg/kg b.w.). Administration of BQ123 at a dose of 1 mg/kg b.w. resulted in a statistically significant increase in the concentration of -SH groups (p<0.001 vs. ET-1). L-NAME (5 mg/kg b.w.) also significantly increased the level of -SH groups in the lungs of rats during oxidative stress induced ET-1 (p<0.001). The nitric oxide synthase inhibitor L-NAME at a dose of 5 mg/kg b.w. and the endothelin receptor blocker BQ123 at a dose of 1 mg/kg b.w. showed a significant increase in the concentration of -SH groups in the lungs, which may be associated with an increase in synthesis of proteins containing sulfhydryl groups.


Post-translational modifications on the retinoblastoma protein.
The retinoblastoma protein (pRb) functions as a cell cycle regulator controlling G1 to S phase transition and plays critical roles in tumour suppression. It is frequently inactivated in various tumours. The functions of pRb are tightly regulated, where post-translational modifications (PTMs) play crucial roles, including phosphorylation, ubiquitination, SUMOylation, acetylation and methylation. Most PTMs on pRb are reversible and can be detected in non-cancerous cells, playing an important role in cell cycle regulation, cell survival and differentiation. Conversely, altered PTMs on pRb can give rise to anomalies in cell proliferation and tumourigenesis. In this review, we first summarize recent findings pertinent to how individual PTMs impinge on pRb functions. As many of these PTMs on pRb were published as individual articles, we also provide insights on the coordination, either collaborations and/or competitions, of the same or different types of PTMs on pRb. Having a better understanding of how pRb is post-translationally modulated should pave the way for developing novel and specific therapeutic strategies to treat various human diseases.


Protocols and guides, tools.
The author describes in the first part of the review the definitions and relations of the occurring concepts. In the second part a short history of the topic is overviewed. The third part is dealing with the electronic patient record based development of guidelines in addition what are the relations among guidelines, protocols, tools, knowledge-based systems, diagnosis supporting systems, expert systems, outcome analysis and artificial intelligence. A short review of what was presented in the MIE '97 in this area is finally described and the Session Chairman's conclusion.


Modification of Glenn anastomosis for total cavopulmonary connection conversion after atriopulmonary Fontan.
As several complications can develop after the atriopulmonary Fontan procedure, total cavopulmonary connection conversion is often considered. We report two cases in which total cavopulmonary connection conversion was performed with a modified Glenn procedure. We used an expanded polytetrafluoroethylene graft between the superior vena cava and extracardiac conduit. This procedure ensures that a balanced hepatic blood flow is perfused into both lungs to avoid pulmonary arteriovenous malformations.


Love 2.0: a quantitative exploration of sex and relationships in the virtual world Second Life.
This study presents the quantitative results of a web-based survey exploring the experiences of those who seek sex and relationships in the virtual world of Second Life. The survey gathered data on demographics, relationships, and sexual behaviors from 235 Second Life residents to compare with U.S. General Social Survey data on Internet users and the general population. The Second Life survey also gathered data on interests in and experiences with a number of sexual practices in both offline and online environments. Comparative analysis found that survey participants were significantly older, more educated, and less religious than a wider group of Internet users, and in certain age groups were far less likely to be married or have children. Motivations for engaging in cybersex were presented. Analysis of interest and experience of different sexual practices supported findings by other researchers that online environments facilitated access, but also indicated that interest in certain sexual practices could differ between offline and online environments.


Influence of the COVID-19 outbreak in people with epilepsy: Analysis of a Spanish population (EPICOVID registry).
The aim of this study was to have a better understanding of the influence of the coronavirus disease 2019 (COVID-19) pandemic in people with epilepsy (PWE) and to assess whether there have been changes in seizure control during the current COVID-19 outbreak, exploring the possible causes thereof. This is an observational, retrospective study based on prospective data collection of 100 successive patients who attended an epilepsy outpatient clinic either face-to-face or telephonically during the months of the COVID-19 outbreak and national state of emergency. One hundred patients were included, 52% women, mean age 42.4 years. During the COVID-19 period, 27% of the patients presented an increase of >50% of seizure frequency. An increase of stress/anxiety (odds ratios (OR): 5.78; p = 0.008) and a prior higher seizure frequency (OR: 12.4; p = 0.001) were associated with worsening of seizures. Other risk factors were exacerbation of depression, sleep deprivation, less physical activity, and history of epilepsy surgery. Three patients had status epilepticus (SE) and one a cluster of seizures. Likewise, 9% of patients improved their seizure control. Reduction in stress/anxiety (OR: 0.05; p = 0.03) and recent adjustment of antiepileptics (OR: 0.07; p = 0.01) acted as protecting factors. A high proportion of PWE suffered a significant worsening of their seizure control during the months of the COVID-19 pandemic. Emotional distress due to home confinement was the main factor for the change in seizure control. Promoting physical activity and adequate sleep may minimize the potential impact of the pandemic in PWE. Ensuring correct follow-up can prevent decompensation in those PWE at high risk.


Dairy intake and long-term body weight status in German children and adolescents: results from the DONALD study.
To analyse the association between intake of total dairy (TD) and types of dairy [liquid dairy (LD), solid dairy (SD), low-fat dairy (LFD), high-fat dairy (HFD), high sugar dairy (HSD), low-sugar dairy (LSD), not fermented dairy (NFD), as well as fermented dairy (FD)] and long-term changes in body weight status and composition among children and adolescents in Germany. In total, 9999 3-day dietary records collected between 1985 and 2019 by 1126 participants (3.5-18.5 years; boys: 50.8%) of the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study were analysed. Polynomial mixed-effects regression models were used to examine whether changes (median follow-up: 9 years) in the intake of TD and dairy types (in 100 g/1000 kcal total energy intake) were associated with changes in body-mass-index-standard-deviation-score (BMI-SDS); fat mass index (FMI); fat-free mass index (FFMI) over time. An individual increase in TD intake was slightly but significantly associated with an increase in BMI-SDS (β = 0.0092; p = 0.0371), FMI (β = 0.022; p = 0.0162), and FFMI (β = 0.0156; p = 0.0417) after adjustment for potential confounder. Analyses for LD (BMI-SDS: β = 0.0139; p = 0.0052; FMI: β = 0.0258; p = 0.0125; FFMI: β = 0.0239; p = 0.0052) and LSD intake (BMI-SDS: β = 0.0132; p = 0.0041, FMI: β = 0.02; p = 0.0316, FFMI: β = 0.0183; p = 0.0189) showed similar results to TD. Both processing method and fat content showed no association with body composition in our analyses. Increases in TD, LD, and LSD intake showed small but significant increases in BMI and concomitant increases in fat mass and lean mass. However, the observed changes were too small to expect biological or physiological meaningful effects. Overall, our results showed that policies to promote dairy intake in childhood are to be welcomed, as no negative effects on body composition are expected, while the intake of important nutrients for growth is ensured. The type of dairy does not seem to matter.


Space and time resolved monitoring of airborne particulate matter in proximity of a traffic roundabout in Sweden.
Concerns over exposure to airborne particulate matter (PM) are on the rise. Currently monitoring of PM is done on the basis of interpolating a mass of PM by volume (μg/m(3)) but has the drawback of not taking the chemical nature of PM into account. Here we propose a method of collecting PM at its emission source and employing automated analysis with scanning electron microscopy associated with EDS-analysis together with light scattering to discern the chemical composition, size distribution, and time and space resolved structure of PM emissions in a heavily trafficated roundabout in Sweden. Multivariate methods (PCA, ANOVA) indicate that the technogenic marker Fe follows roadside dust in spreading from the road, and depending on time and location of collection, a statistically significant difference can be seen, adding a useful tool to the repertoiré of detailed PM monitoring and risk assessment of local emission sources.


Hsp70 expression and free radical release after exposure to non-thermal radio-frequency electromagnetic fields and ultrafine particles in human Mono Mac 6 cells.
The contemporary urban environment has become increasingly complex in its composition, leading to discussions regarding possible novel health effects. Two factors that recently have received considerable attention are ultrafine particles (UFP; <0.1 microm) produced by combustion processes and emissions from wireless communication devices like mobile phones that emit in the radio-frequency (RF) part of the spectrum. Several studies have shown biological effects of both these exposures in various cell systems. Here we investigate if exposure to UFP (12-14 nm, 100 microg/ml) and RF-electromagnetic fields (EMF; 2 W/kg specific absorption rate (SAR); continuous wave (CW) or modulated (217Hz or GSM-nonDTX)), alone or in combination influences levels of the superoxide radical anion or the stress protein heat-shock protein (Hsp70) in the human monocyte cell line Mono Mac 6. Heat treatment (42-43 degrees C, 1h) was used as positive control for both stress reaction and for heat development in the RF exposure setup. Our results clearly show that Mono Mac 6 cells are capable to internalise UFP, and that this phagocytic activity is connected to an increased release of free radicals. This increase (40-45% above negative control) is stronger than the effect of heat treatment. On the other hand, none of the employed RF exposures showed any effects on free radical levels. Co-exposure of RF and UFP did not potentiate the UFP effect either. Our investigations showed a significantly increased Hsp70 expression level by heat treatment in a time-dependent manner, whereas UFP, RF, or UFP+RF were without any effect. Therefore, we conclude that in the investigated Mono Mac 6 cells, RF exposure alone or in combination with UFP cannot influence stress-related responses.


A theoretical study of π-stacking interactions in C-substituted tetrazoles.
The π-stacking effects of benzene ring (Ben) with 1H- and 2H-tetrazole derivatives (1H-TZ-X and 2H-TZ-X) substituted at C5 (where X is Cl, COH, NO, NO2, CN, NH2, OH, OCH3, SH and H) has been investigated by the quantum mechanical calculations at the M06-2X/6-311++G** level. The results indicate the 1H-TZ-X||Ben complexes (|| donates π-stacking interaction) are more stable than 2H-TZ-X||Ben while in unstacked forms, 1H-TZ-X is less stable than 2H-TZ-X. All substituents enhance the π-stacking interaction relative to the unsubstituted ones and enhancement is higher for the electron-withdrawing substituents (EWSs). Also, investigation of the local and direct effect of substituents in stacking interaction showed that all substituents regardless of whether are electron donating or electron withdrawing have an additive effect in π-stacking interaction. Excellent correlations were found between the binding energies of the complexes and combination of substituent constant terms. The results showed that the electrostatic interaction alone is not responsible for stacking stabilization but charge penetration is important. Furthermore, analysis of aromaticity, AIM, ESP and NPA were investigated to obtain aromaticity index, non-bonding interactions, chemical reactivity and polarity (dipole moment), respectively.


The organization of the right-end early region of bacteriophage PRD1 genome.
Bacteriophage PRD1 is the only protein-primed DNA replication system known to operate in Escherichia coli. The left-genome end of PRD1 contains the early genes for the terminal protein and the DNA polymerase. These genes have been sequenced and the proteins have been produced separately. In this investigation we completed the analysis of the PRD1 early DNA regions by cloning and sequencing the right end genome containing early genes XII and XIX. We compared the structure of the right- and left-terminal regions. The genome organization of both ends was found to be rather uniform. The inverted terminal repeats, the first promoters and the first translation start codons are located almost exactly at the same distance from the genome ends. The PRD1 early gene products, P12 and P19, do not share similarities with proteins found in other protein-primed replication systems.


XP BOND in self-curing mode used for luting porcelain restorations. Part B: Placement and 6-month report.
The aim of this clinical study was to evaluate the postoperative hypersensitivity of Empress II inlays/onlays luted under clinical conditions with XP BOND in combination with SCA and Calibra cured in self-curing mode. Fifty-three restorations were placed in 38 patients in March and April 2006. No patient received more than two restorations. Luting procedures were performed following manufacturers' instructions. The restorations were evaluated after 2 weeks and 6 months for postoperative hypersensitivity, marginal discoloration, marginal integrity, secondary caries, maintenance of interproximal contact, and fracture. At the 2-week recall, the postoperative hypersensitivity was reported in only 10 and after 6 months in only 3 patients. All other parameters showed alpha scores. All the evaluated restorations were in place and acceptable. The postoperative hypersensitivity recorded after using XP BOND and Calibra in self-curing mode was clinically acceptable.


Determining Associations between Human Diseases and non-coding RNAs with Critical Roles in Network Control.
Deciphering the association between life molecules and human diseases is currently an important task in systems biology. Research over the past decade has unveiled that the human genome is almost entirely transcribed, producing a vast number of non-protein-coding RNAs (ncRNAs) with potential regulatory functions. More recent findings suggest that many diseases may not be exclusively linked to mutations in protein-coding genes. The combination of these arguments poses the question of whether ncRNAs that play a critical role in network control are also enriched with disease-associated ncRNAs. To address this question, we mapped the available annotated information of more than 350 human disorders to the largest collection of human ncRNA-protein interactions, which define a bipartite network of almost 93,000 interactions. Using a novel algorithmic-based controllability framework applied to the constructed bipartite network, we found that ncRNAs engaged in critical network control are also statistically linked to human disorders (P-value of P = 9.8 × 10(-109)). Taken together, these findings suggest that the addition of those genes that encode optimized subsets of ncRNAs engaged in critical control within the pool of candidate genes could aid disease gene prioritization studies.


Medico-legal issues for intensivists caring for children in a District General Hospital.
Anaesthetists and intensivists are often called upon to assist with the care of acutely unwell children presenting to district general hospitals. Treatment is usually provided with the consent of a parent but it may be required to treat the child using the doctrine of necessity. In this article we discuss aspects of the law, as it relates to children, to enable teams, who predominately treat sick adults, understand the legal framework surrounding the treatment of sick children.


Invasive cribriform carcinoma of the breast detected incidentally on computed tomography: A case report.
Invasive cribriform carcinoma is a rare type of invasive breast carcinoma, and a few cases have been reported. Its features are a cribriform pattern resembling the histological structures of cribriform ductal carcinoma in situ and an excellent prognosis. However, the extent of progress for intraductal extension must be carefully evaluated.


Neurocognitive functioning in patients undergoing coronary artery bypass graft surgery or percutaneous coronary intervention: evidence of impairment before intervention compared with normal controls.
Cognitive deficits have been reported to occur in a significant proportion of patients undergoing coronary artery bypass grafting (CABG), but the extent to which these deficits were preexistent or related to the natural history of cognitive decline in this patient population remains poorly defined. After excluding patients with conditions known to cause brain dysfunction (eg, hepatic dysfunction, stroke), a group of patients referred for percutaneous coronary intervention (PCI) or CABG (n = 82) was compared with an age- and education-matched control group that did not have clinical evidence of coronary artery disease (n = 41). These subjects underwent a battery of neurocognitive and emotional testing. Test score means for 5 of 14 different measures were significantly greater (impaired) in cardiac compared with control group subjects. Of cardiac subjects, 20% demonstrated clinical impairment (test result > or = 1 SD worse than mean for normative standards) in 6 of 14 tests, compared with 10% of the controls. By clinical standards, 46% of cardiac subjects would be considered to be impaired (score 1 SD or more below the control group mean) on 3 or more neuropsychologic measures, compared with 29% of the controls. By this (control group mean) standard, cardiac subjects demonstrated impaired scores on 3.06 +/- 2.6 tests compared with impairment in 2.0 +/- 2.35 tests for the control group (p = 0.01). Even excluding patients at high risk for brain dysfunction, cognitive impairment is found in patients with coronary artery disease before interventional therapy. Baseline impairment must be considered when evaluating outcomes after intervention.


Computed tomography and magnetic resonance imaging in late-onset globoid cell leukodystrophy (Krabbe disease).
A five-year-old white male presented with a history of progressive loss of vision that was subsequently followed by progressive corticospinal dysfunction. Evaluation revealed the presence of leukodystrophy which was confirmed by a deficiency of the enzyme, galactosylceramide beta-galactosidase. We present the clinical, computed tomographic, and magnetic resonance imaging features of this late-onset form of globoid cell leukodystrophy.


Evidence of insufficient genetic data and lack of regular genetic research on rabies virus in the Russian Federation: a study of the recent epizootic situation.
This paper attempts to point out a disparity between keeping rabies epidemiological statistics and rabies virus sequencing in the Russian Federation. While data on rabies prevention and laboratory detection are duly gathered, virus sequencing efforts remain insufficient. Along with a lack of public information and mass vaccination campaigns for wildlife and pets, this also might have an impact on the current rabies situation, which is of high risk in Russia. Additionally, drawing on GenBank data, it is suggested that some isolated rabies variants might be circulating in the country.


Design, synthesis and biological evaluation of substituted pyrrolo[2,3-d]pyrimidines as multiple receptor tyrosine kinase inhibitors and antiangiogenic agents.
Direct and indirect involvement of receptor tyrosine kinases (RTKs) in tumor growth and metastasis makes them ideal targets for anticancer therapy. A paradigm shift from inhibition of single RTK to inhibition of multiple RTKs has been recently demonstrated. We designed and synthesized eight N(4)-phenylsubstituted-6-(2-phenylethylsubstituted)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamines as homologated series of our previously published RTK inhibitors. We reasoned that increased flexibility of the side chain, which determines potency and selectivity, would improve the spectrum of RTK inhibition. These compounds were synthesized using a bis-electrophilic cyclization to afford substituted pyrrolo[2,3-d]pyrimidines followed by chlorination and substitution at the 4-position with various anilines. Five additional compounds of this series were previously reported by Gangjee et al.(1) with activities against IGFR only. Their synthesis, characterization and biological activities against a variety of other RTKs are reported in this study for the first time. The biological evaluation, in whole cell assays, showed several analogs had remarkable inhibitory activity against epithelial growth factor receptor (EGFR), vascular endothelial growth factor receptor-1 (VEGFR-1), platelet-derived growth factor receptor-beta (PDGFR-beta), the growth of A431 cells in culture, and in the chicken embryo chorioallantoic membrane (CAM) angiogenesis assay. The inhibitory data against the RTKs in this study demonstrate that variation of the 6-ethylaryl substituents as well as the N(4)-phenyl substituents of these analogs does indeed control both the potency and specificity of inhibitory activity against RTKs. In addition, homologation of the chain length of the 6-substituent from a methylene to an ethyl increases the spectrum of RTK inhibition. New multi-RTK inhibitors (8, 12) and potent inhibitors of angiogenesis (15, 19) were identified with the best compound, N(4)-(3-trifluromethylphenyl)-6-(2-phenylethyl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine (15), with an IC(50) value of 30nM in the CAM angiogenesis inhibition assay.


Specific target-directed axonal outgrowth from transplanted embryonic rodent retinae into neonatal rat superior colliculus.
We have investigated whether there is evidence of target-directed growth of retinal axons to the tectum, and whether the surface of the rostral brainstem is an obligatory substrate for growing optic axons by transplanting embryonic mouse retinae to the cerebral aqueduct of neonatal rats. Such retinae emit axons that grow dorsally through the brain parenchyma to reach the superficial layers of the superior colliculus either by running dorsally along the midline, or by following a dorsally directed, radially arching course through the brain parenchyma. Studies of the early outgrowth pattern from transplanted retinae, and comparison studies of the axonal outgrowth from similarly placed cortical grafts suggest that outgrowth of retinal axons is target-directed and specific to optic axons.


A simple technique for introducing bone graft during revision ACL surgery.
Bone grafting of the tibial tunnel is often required when performing revision ACL surgery. We describe a simple method of introducing bone graft which allows accurate delivery and is quick and easy to perform.


Variations in renal arteriolar diameter in deoxycorticosterone acetate-salt hypertensive rats. A microvascular cast study.
The relation between hypertensive glomerular damage and arteriolar diameter was examined in a microvascular cast study in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. The blood pressure and urinary protein excretion increased progressively in the DOCA rats. In controls afferent arteriolar diameters increased during the course of the experiment, and efferent arteriolar diameters remained unchanged. In the DOCA rats, however, afferent arteriolar diameters did not change significantly, while efferent arteriolar diameters increased. Histological studies showed severe arteriolosclerosis and glomerulosclerosis in the DOCA rats. The results show that these arteriolar changes might contribute to the reduction of glomerular capillary pressure in the development of DOCA-salt hypertension. However, they are not sufficient to protect glomeruli from hypertensive damage.


The electroencephalographic characteristics of the rhombencephalectomized cat.
The electroencephalographic responses in the rhombencephalectomized cat after the application of photic and epileptogenic agents resemble those phenomena in the normal animal. The spontaneous EEG of the motor region had fewer beta waves, a slower alpha but more delta components than the presection record. The response to photic stimulation in the occipital cortex was similar before and after the rhombencephalectomy, although the initial waves were slightly delayed. Epileptic activity upon topical application or intravenous administration of epileptogenic agents was demonstrated in the sensorimotor cortex.


Nursing education research in Finland--A review of doctoral dissertations.
The aim of this literature review was to describe the focus of nursing education research in Finnish doctoral dissertations in the field of nursing and caring sciences between the years 1979-2014. In addition, the characteristics (methods, study informants and reporting of validity, reliability, and research ethics) of the dissertations were described. A literature review was carried out. Altogether 51 Finnish doctoral dissertations of nursing and caring sciences focusing on nursing education research were included in the final analysis. The dissertations were published in 1990-2014. The data were analyzed by content analysis both deductively and inductively. Finnish nursing education research was focused on four main areas: structural factors in nursing education, nurse teacherhood, teaching activities, and learning and learning outcomes in nursing education. The most central focus was learning in nursing education whereas nurse teacherhood and structural factors in nursing education were studied the least. Students were the predominant study informant group while nurse staff including nurse mentors were next and nurse educators only the third. Surveys and interviews were the most common data collection methods. In the findings there were a lot of similarities with international nursing education research. Finnish nursing education research has been relatively student-centered yet studies focusing on the education of other nursing-based professions are rare. Future research about nurse teacherhood, curricula and structural factors in nursing education is recommended also. In addition, nursing education research should focus on the central phenomena of nursing education and working life. All in all, more nursing education research is needed. Nursing education dissertations cover only 12.3% of all the dissertations of nursing and caring sciences in Finland.


The long-term survival of the doublet regimen of concurrent chemoradiation therapy for locoregionally advanced nasopharyngeal carcinoma: a retrospective study.
This study introduces innovative strategies, the doublet regimen of concurrent chemoradiotherapy, to ensure longer survival for locoregionally advanced nasopharyngeal carcinoma. We retrospectively reviewed 104 locoregionally advanced nasopharyngeal carcinoma patients who underwent taxane combined platinum-based concurrent chemoradiotherapy in our center between January 2013 and December 2018. All statistical analyses were performed using the Kaplan-Meier method (SPSS 23.0). Different groups were compared with the Wilcoxon rank-sum test. Ultimately, 104 patients were selected for this study, including 18 and 86 who received either concurrent chemoradiation therapy alone or concurrent chemoradiation therapy plus adjuvant chemotherapy, respectively. The median follow-up time for progression free survival was 53.0 months (IQR 48.5-57.5). The 3-years progression-free survival (PFS), overall survival (OS), local-regional recurrence-free survival (LRRFS) and distant metastasis-free survival (DMFS) rates of the doublet regimen of concurrent chemotherapy for locoregionally advanced nasopharyngeal carcinoma were 85.9%, 96.0%, 96.0% and 90.8%, respectively. Additionally, we analyzed the subgroups and found that the 3-years PFS, OS, LRRFS and DMFS rates for stage III versus stage IVa were 97.8% versus 75.5% (P = 0.000), 100% versus 92.5% (P = 0.004), 100% versus 92.4% (P = 0.015) and 97.8% versus 82.8% (P = 0.002), respectively. During concurrent chemotherapy, acute chemotherapy adverse events of grade 3 or 4 was only 18.3%. Leukopenia was the most common acute chemotherapy adverse event (in 10 patients [9.6%]), followed by neutropenia (in 8 patients [7.6%]). The doublet regimen of taxane plus platinum concurrent chemoradiotherapy resulted in improved long-term survival of locoregionally advanced nasopharyngeal carcinoma patients, especially for local control rate and warrants further prospective evaluation.


Iron chelator induces MIP-alpha/CCL20 in human intestinal epithelial cells: implication for triggering mucosal adaptive immunity.
A previous report by this laboratory demonstrated that bacterial iron chelator (siderophore) triggers inflammatory signals, including the production of CXC chemokine IL-8, in human intestinal epithelial cells (IECs). Microarray-based gene expression profiling revealed that iron chelator also induces macrophage inflammatory protein 3 alpha (MIP-3alpha)/CC chemokine-ligand 20 (CCL20). As CCL20 is chemotactic for the cells involved in host adaptive immunity, this suggests that iron chelator may stimulate IECs to have the capacity to link mucosal innate and adaptive immunity. The basal medium from iron chelator deferoxamine (DFO)-treated HT-29 monolayers was as chemotactic as recombinant human CCL20 at equivalent concentrations to attract CCR6(+) cells. The increase of CCL20 protein secretion appeared to correspond to that of CCL20 mRNA levels, as determined by real-time quantitative RT-PCR. The efficacy of DFO at inducing CCL20 mRNA was also observed in human PBMCs and in THP-1 cells, but not in human umbilical vein endothelial cells. Interestingly, unlike other proinflammatory cytokines, such as TNF-alpha and IL-1beta, a time-dependent experiment revealed that DFO slowly induces CCL20, suggesting a novel mechanism of action. A pharmacologic study also revealed that multiple signaling pathways are differentially involved in CCL20 production by DFO, while some of those pathways are not involved in TNF-alpha-induced CCL20 production. Collectively, these results demonstrate that, in addition to some bacterial products known to induce host adaptive immune responses, direct chelation of host iron by infected bacteria may also contribute to the initiation of host adaptive immunity in the intestinal mucosa.


Color superposition: a new modality for contrast echocardiography.
To improve the estimation of endocardial borders in echocardiography, a technique has been developed to combine images from contrasted and noncontrasted echocardiograms of the same heart-phase using a color superposition mode. This method allows both experienced as well as less experienced examiners to define the endocardial borders more reproducibly and objectively. This is achieved by displaying tissue structures as gray level images while the ventricular cavity is marked selectively by the color display of the contrast material zone. Results of volume estimations of the left ventricle by different examiners using several imaging modes including color superposition display are presented.


Effect of Sleep Surgery on Inflammatory Cytokines in Adult Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis.
To evaluate whether sleep surgery is associated with inflammatory cytokine changes. This study hypothesizes cytokines may change after surgery in adult obstructive sleep apnea (OSA). Systematic review and meta-analysis. The study protocol was registered on PROSPERO (CRD42020154425). Two authors independently searched PubMed, Embase, and Cochrane review databases from their inception to June 2021. The keywords used were sleep apnea, inflammatory markers, cytokines, and surgery. The effects of sleep surgery on the apnea-hypopnea index (AHI) and inflammatory cytokines were evaluated using a random-effects model. Both mean difference (MD) and standardized mean difference (SMD) of the changes in cytokines were calculated. Nine studies with 235 adults were included (mean age: 43 years; 82% were men). After sleep surgery, AHI significantly reduced by -11.3 events/h (95% confidence interval [CI], -15.8 to -6.9). In total, 8 and 6 studies were pooled for examining tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) levels, respectively. Sleep surgery significantly reduced TNF-α levels, with an MD of -2.8 pg/ml (95% CI, -5.1 to -0.6) and an SMD of -0.56 (95% CI, -0.85 to -0.27). Furthermore, sleep surgery reduced IL-6 levels, with an MD of -0.6 pg/ml (95% CI, -1.0 to -0.2) and an SMD of -0.66 (95% CI, -0.89 to -0.43). No covariates were identified to be correlated with cytokine changes in subgroup and meta-regression analyses. Funnel plots showed possible publication bias in current data. In adults, OSA treatment with sleep surgery improves inflammatory cytokines. Laryngoscope, 132:2275-2284, 2022.


Investigating acute satiation and meal termination effects of a commercial lipid emulsion: A breakfast meal study.
Early clinical studies showed the commercial lipid emulsion Fabuless™ to decrease energy intake (EI) and prevent weight regain, but later studies have failed to confirm this finding. Where appetite suppression has been observed it is commonly attributed to the ileal brake, where emulsified fats pass undigested to the distal small intestine and promote later satiety, but satiety profiles suggest possible transient effects within 15 min. The aim of this study was to determine whether this emulsion promotes short-term satiation and meal termination. In a randomised cross-over intervention 18 lean men were given 4 lipid preloads immediately prior to a breakfast meal, during which ad libitum food consumption, time to meal termination and VAS-rated appetite scores were measured. Preloads were given as lipid emulsion and lipid control, both alone as a 'shot' and combined with a dairy yoghurt: (i) lipid emulsion alone (LE, Fabuless™ 4.2g lipid, 0.2MJ), (ii) lipid control alone (LC, 4.2g lipid, 0.2 MJ), (iii) LE+yoghurt (1.2 MJ), (iv) LC+yoghurt (1.2MJ). Whilst both yoghurt preloads suppressed EI at breakfast relative to the 'shots', as expected, neither lipid emulsion suppressed EI or triggered more rapid meal termination when compared to energy matched lipid controls (P>0.05). There was also no difference in VAS-assessed appetite scores between emulsion and control, for either preload. When consumed with a meal there was no evidence in lean men that this commercial lipid emulsion promotes satiation or suppresses short-term food intake.


Implementation of a model of bodily fluids regulation.
The classic model of blood pressure regulation by Guyton et al. (Annu Rev Physiol 34:13-46, 1972a; Ann Biomed Eng 1:254-281, 1972b) set a new standard for quantitative exploration of physiological function and led to important new insights, some of which still remain the focus of debate, such as whether the kidney plays the primary role in the genesis of hypertension (Montani et al. in Exp Physiol 24:41-54, 2009a; Exp Physiol 94:382-388, 2009b; Osborn et al. in Exp Physiol 94:389-396, 2009a; Exp Physiol 94:388-389, 2009b). Key to the success of this model was the fact that the authors made the computer code (in FORTRAN) freely available and eventually provided a convivial user interface for exploration of model behavior on early microcomputers (Montani et al. in Int J Bio-med Comput 24:41-54, 1989). Ikeda et al. (Ann Biomed Eng 7:135-166, 1979) developed an offshoot of the Guyton model targeting especially the regulation of body fluids and acid-base balance; their model provides extended renal and respiratory functions and would be a good basis for further extensions. In the interest of providing a simple, useable version of Ikeda et al.'s model and to facilitate further such extensions, we present a practical implementation of the model of Ikeda et al. (Ann Biomed Eng 7:135-166, 1979), using the ODE solver Berkeley Madonna.


[Alcohol in old age: Drinking habits, low risk drinking and alcohol-related disorders].
Alcohol abuse and health problems due to alcohol increase in the elderly. The functional impact is more pronounced than in younger people; nevertheless, alcohol abuse in the elderly is often overlooked. Early onset and late onset alcoholics differ with respect to previous problems, social and health status and therapy prognosis. The severity of withdrawal depends on addiction severity and comorbidities but not on calendar age. It is important to support patients in developing a motivation for change. Brief interventions are effective in elderly persons with an at-risk consumption of alcohol. Guidelines for low risk alcohol consumption recommend two alcohol-free days per week. There is no evidence for the popular hypothesis of the beneficial effects of light to moderate drinking. This hypothesis was drawn from former observational studies but recent large and more thorough methodical studies suggest that these former results were due to statistical bias. Alcohol consumption is a matter of pleasure and not a matter of medical treatment or prevention. The new German guidelines on "Screening, assessment and treatment of alcohol use disorders" contain for the first time a special chapter on the elderly.


Treatment of empyema and bronchopleural fistula by bovine pericardium and latissimus flap.
Management of empyema with bronchopleural fistula remains a challenge. A 38-year-old man who had bullous emphysema was hospitalized on account of a right-sided necrotizing pneumonia complicated by empyema that mandated a tube drainage. Persistent air leak from the chest tube was noted, and chest computed tomography confirmed an empyema cavity with a suspicious bronchopleural fistula. This complex condition was successfully treated using fibrin glue with buttressed bovine pericardium to seal the fistula, followed by obliteration of the empyema cavity using a pedicled muscle flap of the latissimus dorsi. There was no recurrence of empyema at a follow-up 5 years after this procedure.


Total skin electron irradiation therapy in mycosis fungoides using high-dose rate mode: a preliminary experience.
Total skin electron irradiation (TSEI) therapy is the treatment of choice for mycosis fungoides. However, conventional TSEI therapy is time consuming as well as patient unfriendly. Therefore we used high-dose rate (HDR) mode TSEI in these patients. High-dose rate mode of TSEI is a technological innovation attached to a Linear Accelerator (Philips, SL-20, Netherlands), which can deliver an electron beam of 30 Gy/min at the iso-center. The iso-center faces the patient, 100 cm away from the target of the linear accelerator. The patient is treated at a distance of 10 feet from the iso-center of the linear accelerator. The dose delivered to the skin was 1.13 Gy/min, making the treatment execution much easier and patient compliance much better. Seven male patients between 40 and 64 years in age having mycosis fungoides for 9-18 months were treated by TSEI using high-dose rate mode between 1998 and 2000. The TSEI was performed according to the Stanford technique, delivering a total dose of 36 Gy. Each patient received a dose of 1.2 Gy/field/day. There were six fields, i.e. anterior, posterior, left and right anterior obliques, and left and right posterior obliques in both the upper and lower parts of the body. The eyes and nails were shielded at each session of radiotherapy. The times taken at each session of the therapy and radiation-associated side-effects were determined in each patient. The patients were followed up to 26 months (median 9 months) to look for any relapse. Three patients had early stage disease (IB) whereas four patients had advanced disease (IIB). Six patients out of these had complete remission following TSEI while one patient died as a result of progression of the disease during treatment. The treatment time taken at each treatment session in each individual patient was approximately 15 min. Radiation-associated morbidity was seen in all patients. Cutaneous lesions relapsed in two patients after 4 and 10 months, respectively, while four patients were alive without the disease at the end of 2 years. Total skin electron irradiation using high-dose rate mode delivery of electrons is an easy, better, compliant and effective therapeutic modality for treatment of mycosis fungoides with an acceptable range of toxicities.


Allopurinol decreases serum uric acid level and intestinal glucose transporter-5 expression in rats with fructose-induced hyperuricemia.
High fructose consumption is considered to be related to the increasing prevalence of hyperuricemia (HUA). Glucose transporters (GLUT) 2 and 5 are crucial for fructose absorption and transporter. Effects of anti-HUA drugs, allopurinol (API) and benzbromarone (BBR), on expressions of GLUT5 and GLUT2 are not evaluated. Wistar rats were given 10% fructose in drinking water for 60 days to induce HUA, and 5mg/kg API and 10mg/kg BBR were intragastricly treated for 30 days. Serum level of uric acid and xanthine oxidase (XOD) activity in liver were determined. Expressions of GLUT2 and GLUT5 in intestine were analyzed by immunohistochemistry staining assay and Western blot assay. Treatment with API or BBR significantly decreased the serum level of uric acid in HUA rats induced by fructose. Meanwhile, API treatment significantly reduced the XOD activity in liver and GLUT5 expression in intestine. However, BBR treatment did not show inhibitory effects on hepatic XOD activity and intestinal GLUT5 expression. In addition, treatment with API or BBR did not show any effect on GLUT2 expression in intestine. API decreases serum level of uric acid in fructose-induced HUA rats. The mechanisms are associated with suppressing XOD activity in liver to reduce uric acid production, and inhibiting GLUT5 expression in intestine to reduce fructose absorption.


The mercury content of hair of Japanese immigrants in various locations in South America.
Hair mercury levels in four Japanese immigrant settlements in South America were determined by cold-vapor atomic absorption spectrometry. The levels in the two Bolivian settlements were relatively higher (6.22 and 3.53 ppm for males, 3.66 and 2.23 ppm for females) than those in Brazil (2.19 ppm for males, 1.57 ppm for females) and in Paraguay (2.40 ppm for males, 2.04 ppm for females). The levels in Bolivia were almost the same as recent Japanese levels. Dose-response relationships between frequency of eating fish and hair mercury level were found in all the settlements. However, even in the same fish-eating category, the content varied from place to place. Significant correlations between husbands and wives were demonstrated in three out of four settlements. These results imply that the mercury content of hair is regulated by the life style within each family. That is, inhabitants of Japanese settlements, especially in Bolivia, maintain their Japanese habit of fish eating. This results in a high hair mercury content, even when they live in a rural area and consume only fish from the head rivers of the Amazon.


Interaction of climate change and marine pollution in Southern India: Implications for coastal zone management practices and policies.
Climate change and marine litter are inextricably linked, and their interaction manifests differently depending on the specific environmental and biological characteristics, and other human activities taking place. The negative impacts resulting from those synergistic interactions are threatening coastal and marine ecosystems and the many goods and services they provide. This is particularly pervasive in the coastal zone of the Indian subcontinent. India is already experiencing severe climate change impacts, which are projected to worsen in the future. At the same time, the country is gripped by a litter crisis that is overwhelming authorities and communities and hindering the country's sustainable development goals. The coastal environment and communities of the southern states of Kerala and Tamil Nadu are particularly vulnerable to the impacts of climate change. While these state governments and authorities are stepping up efforts to improve the management of their coastal zones, the scale and severity of these issues are mounting. Here we review the combined effects of climate change and marine litter pollution in Southern India, focusing on the Gulf of Mannar Reserve in Tamil Nadu and the Malabar Coast in Kerala. Finally, we discuss effective management options that could help improve resilience and sustainability.


Cooling effect of the pocket park in the built-up block of a city: a case study in Xi'an, China.
Pocket parks, the green infrastructures with small sizes and flexible layouts, are suitable for thermal environment improvement in the urban built-up block with limited green space. To quantify the relationship between pocket parks and the thermal environment in western China, two parks in the built-up block of Xi'an were selected. By field measurement, the cooling effect could be extended 100 m from the park boundary, connecting two parks. Furthermore, the road and greening within the block demonstrate significant influence on the cooling diffusion by regression analysis. Based on ENVI-met simulation, the ratio of the tree and the grass, the layout of the tree and the grass, and the layout of the paving were analyzed at different proportions of greening and paving of the park. Finally, a combination of the daytime physiological equivalent temperature (PET) and nighttime air temperature (AT) was proposed to choose the optimum layouts: the trees concentrated in the center and the pavement with more roads. Results can provide insights for designing pocket parks based on the thermal environment improvement.


Penalty feet positioning rule modification and laterality effect on soccer goalkeepers' diving kinematics.
In 2019, a new rule was applied in soccer. It allows the goalkeeper to have only one foot or part of it on the goal line when the kicker hits the ball, unlike the previous rule that determined the goalkeeper should have both feet on the line. The purpose of the present study was to analyze how the change in the rule and the lower limbs laterality influences on the diving save kinematic performance in penalties. Six goalkeepers, two professionals and four amateurs, performed a total of 20 dives in the laboratory and had their force and impulse exerted by the lower limb and displacement/velocity data from the center of body mass collected through force plates and kinematic analysis. The side preference was collected through an inventory. The results showed that goalkeepers dive further (p < 0.001) and faster (p < 0.001) when diving according to the new rule. Dives for the non-dominant side presented higher values than the trials for the dominant side in mediolateral (p = 0.02) and resultant (p = 0.03) displacements. Concluding, the goalkeepers performed better with the new rule in the analyzed variables and the lower limb preference has influenced only the mediolateral and resultant displacement.


Renal function is associated with blood neurofilament light chain level in older adults.
Neurofilament light chain (NfL) is a novel biomarker of neurodegenerative diseases. It is detectable in the peripheral blood, allowing low-invasive assessment of early signs of neurodegeneration. The level of NfL gradually increases with age; however, what other factors affect it remains unclear. The present study examined the association between blood NfL level and renal function among healthy participants undergoing a health check (n = 43, serum NfL) and patients with diabetes mellitus (n = 188, plasma NfL). All participants were 60 years of age or older; none were diagnosed with dementia. In each group, levels of blood NfL and serum creatinine significantly correlated (coefficient r = 0.50, 0.56). These associations remained statistically significant even after adjustment for age, sex, and body mass index. These findings indicate that blood NfL level might be partially affected by renal function. We recommend measuring renal function for a more precise evaluation of neuroaxonal damage, in particular, among older adults.


Transport of two metal oxide nanoparticles in saturated granular porous media: role of water chemistry and particle coating.
The growing use of nanosized titanium dioxide (nTiO2) and zinc oxide (nZnO) in a large number of commercial products raises concerns regarding their release and subsequent mobility in natural aquatic environments. Laboratory-scale sand-packed column experiments were conducted with bare and polymer-coated nTiO2 and nZnO to improve our understanding of the mobility of these nanoparticles in natural or engineered water saturated granular systems. The nanoparticles are characterized over a range of environmentally relevant water chemistries using multiple complimentary techniques: dynamic light scattering, nanoparticle tracking analysis, transmission electron microscopy, and scanning electron microscopy. Overall, bare (uncoated) nanoparticles exhibit high retention within the water saturated granular matrix at solution ionic strengths (IS) as low as 0.1 mM NaNO3 for bare nTiO2 and 0.01 mM NaNO3 for bare nZnO. Bare nTiO2 and nZnO also display dynamic (time-dependent) deposition behaviors under selected conditions. In contrast, the polymer-coated nanoparticles are much less likely to aggregate and exhibit significant transport potential at IS as high as 100 mM NaNO3 or 3 mM CaCl2. These findings illustrate the importance of considering the extent and type of surface modification when evaluating metal oxide contamination potential in granular aquatic environments.


[The lymphocyte transformation test for detecting immunologic inner ear deafness].
The basis and performance of the lymphocyte transformation test for proving an immunologically induced inner ear hearing loss are described and documented. In 6 out of 14 patients with inner ear hearing loss of unknown origin an immunological etiology could be elaborated by using this test. The relevance of this test as well and its further application by using collagen type II as antigen are discussed.


Transportation Infrastructures and Socioeconomic Statuses: A Spatial Regression Analysis at the County Level in the Continental United States, 1970-2010.
There is a large body of literature examining transportation impacts on population and employment growth. However, the possible impacts that transportation infrastructures have on socioeconomic statuses are less clear. This study fills the gap in the literature by associating education and income-two socioeconomic status measures-with transportation infrastructures. In specific, this study examines the associations of railroads, highways, and airports collectively with high school, Bachelor's degree, graduate degree, and income change in the continental United States for the period between 1970 and 2010. Data come from various sources, such as National Transportation Atlas Database, Decennial Census, Cartographic Boundary Shapefiles, and Land Developability Index. Standard regression and spatial analysis are conducted at decade levels and at the entire study period to test the consistency of the associations between transportation infrastructures and education and income. The study shows that railroads have a distributive and highways have a facilitative association with both education and income. Airports behave as a growth factor with education and as a facilitator with income. The findings clearly show the increased complexity of the roles performed by transportation infrastructures and do not show straightforward behaviors as has been considered for a long time. This study provides new insights into the role of transportation infrastructures for transportation planning and decision making.