A single-blind field intervention study of whether increased bedroom ventilation improves sleep quality.
A four-week-long field intervention experiment was conducted in twenty-nine bedrooms with extract ventilation systems and air inlet vents. During the first week no interventions took place. In the three weeks that followed, each participant slept for one week under a low, moderate, and high ventilation rate condition in a balanced order. These conditions were established by covertly altering the fan speed of the exhaust ventilation system without changing other settings. Participants were not informed when or even whether the changes to bedroom ventilation would be executed. The bedroom environmental quality was monitored continuously and sleep quality was monitored using wrist-worn trackers. Tests of cognitive performance were conducted in the evening and morning. In twelve bedrooms where clear differences between the three ventilation conditions occurred, as indicated by the measured CO2 concentrations, participants had significantly less deep sleep, more light sleep and more awakenings at lower ventilation rate conditions. In twenty-three bedrooms where a clear difference in ventilation rate between the high and low ventilation conditions was observed, as confirmed by the measured CO2 concentrations, the deep sleep was significantly shorter in the low ventilation rate condition. No differences in cognitive performance between conditions were observed. At lower ventilation rate conditions, the concentrations of CO2 increased, as did the relative humidity, while bedroom temperatures remained unchanged. The present results, which were obtained in actual bedrooms, confirm the findings in previous studies of a positive effect of increased ventilation on sleep quality. Further studies with larger populations and better control of bedroom conditions, particularly ventilation, are required.


Diffusion of Anisotropic Colloids in Periodic Arrays of Obstacles.
Colloidal suspensions in confined geometries exhibit rich diffusion dynamics governed by particle shapes and particle-confinement interactions. Here, we propose a colloidal system, consisting of ellipsoids in periodic array of obstacles, to investigate the confined diffusion of anisotropic colloids. From the obstacle density-dependent diffusion, we discover a decoupling of translational and rotational diffusion in which only rotational motion is localized while translational motion remains diffusive. Moreover, by evaluating the probability distributions of displacements, we found Brownian but non-Gaussian diffusion behaviors with increasing the obstacle densities, which originates from the shape anisotropy of the colloid and the multiplicity of the local configurations of the ellipsoids with respect to the obstacle. Our results suggest that the shape anisotropy and spatial confinements play a vital role in the diffusion dynamics. It is important for understanding the transportations of anisotropic objects in complex environments.


Molecular Epidemiology of Human Astrovirus in Stool Samples From Patients With Acute Gastroenteritis in Korea, 2013-2017.
Human astroviruses (HAstVs) are one of the major causes of acute gastroenteritis. Classic HAstVs can be classified into eight genotypes. We investigated the positive rate of HAstVs and the distribution of HAstV genotypes in strains isolated from patients with acute gastroenteritis in Hwaseong, Korea, in 2013-2017. Between November 2013 and December 2017, 3,519 stool samples were collected from patients with symptoms of acute gastroenteritis and tested for HAstV using multiplex PCR. For HAstV-positive samples, the ORF2 gene, which encodes a capsid protein, was genotyped by reverse-transcription PCR and sequencing. Phylogenetic analysis was performed to determine whether the sequences of the HAstVs differed by year. The positive rate of HAstV was 1.9% (67 samples). HAstV Type 1 was the most prevalent genotype (82.4%), and Types 4, 5, and 8 were also detected. Infection occurred year-round, with no distinct seasonal variation. Infection occurred at nearly all ages (55 days-81 years; median: 3 years), and the positive rate was substantially higher in children younger than five years. Phylogenetic analysis revealed three distinct clades of HAstV Type 1 according to the collection time. Our results provide recent epidemiological data on HAstVs in Korea between 2013 and 2017. The finding of three distinct clades of HAstV Type 1 according to collection time suggests genetic evolution of HAstVs. These findings can enhance our knowledge on HAstV infection and viral evolution.


Association between surgical volume and failure of primary total hip replacement in England and Wales: findings from a prospective national joint replacement register.
To investigate the association of volume of total hip arthroplasty (THA) between consultants and within the same consultant in the previous year and the hazard of revision using multilevel survival models. Prospective cohort study using data from a national joint replacement register. Elective THA across all private and public centres in England and Wales between April 2003 and February 2017. Patients aged 50 years or more undergoing THA for osteoarthritis. The volume of THA conducted in the preceding 365 days to the index procedure. Revision surgery (excision, addition or replacement) of a primary THA. Of the 579 858 patients undergoing primary THA (mean baseline age 69.8 years (SD 10.2)), 61.1% were women. Multilevel survival found differing results for between and within-consultant effects. There was a strong volume-revision association between consultants, with a near-linear 43.3% (95% CI 29.1% to 57.4%) reduction of the risk of revision comparing consultants with volumes between 1 and 200 procedures annually. Changes in individual surgeons (within-consultant) case volume showed no evidence of an association with revision. Separation of between-consultant and within-consultant effects of surgical volume reveals how volume contributes to the risk of revision after THA. The lack of association within-consultants suggests that individual changes to consultant volume alone will have little effect on outcomes following THA.These novel findings provide strong evidence supporting the practice of specialisation of hip arthroplasty. It does not support the practice of low-volume consultants increasing their personal volume as it is unlikely their results would improve if this is the only change. Limiting the exposure of patients to consultants with low volumes of THA and greater utilisation of centres with higher volume surgeons with better outcomes may be beneficial to patients.


Improvement of a continuous ethanol fermentation from sweet sorghum stem juice using a cell recycling system.
The process variables (aeration rate and recycle ratio) of a continuous ethanol fermentation with a cell recycling system (CRS) by Saccharomyces cerevisiae NP 01 from sweet sorghum stem juice were optimized using response surface methodology (RSM). The relationship between intracellular composition and fermentation efficiency was also investigated. RSM results revealed that the optimum aeration rate and recycle ratio were 0.25vvm and 0.625, respectively. The validation experiment under the optimum conditions indicated high precision and reliability of the experiment, achieving an actual ethanol concentration (PE) of 99.28g/l, which was very close to the predicted value (98.01g/l), and a very high ethanol productivity (QP) of 7.94g/lh. The intracellular composition of the yeast cells (i.e., unsaturated fatty acids (UFAs), total fatty acids (TFAs), ergosterol and trehalose) was positively related to the fermentation efficiency and yeast adaptive response under ethanol stress. A higher ratio of UFAs/TFAs and ergosterol strongly promoted yeast viability and ethanol fermentation. Additionally, high trehalose content was observed when the yeast was subjected to stress conditions.


Anti-immunoglobulin stimulation of human B lymphocytes is inhibited by anti-class II major histocompatibility complex antibodies.
The effect of murine monoclonal antibodies binding monomorphic epitopes of Class II, HLA-DR molecules on responding human B lymphocytes stimulated by anti-immunoglobulin M (IgM) antibodies was studied. Goat F(ab')2 anti-human IgM coupled to Sepharose beads (insoluble), or in solution, was added to macrophage-depleted B cells in culture with, or without, anti-human HLA-DR monoclonal antibodies. The addition of monoclonal anti-HLA-DR antibodies to anti-human IgM-stimulated B lymphocytes inhibited this T-independent B-cell proliferation by 82-94%. The role of Class II, HLA-DR molecules on B cells may therefore exceed that of antigen presentation alone, to include responding B-cell activation induced by anti-immunoglobulin.


Deep venous thrombosis after laparoscopic cholecystectomy and prevention with nadroparin.
Postoperative thromboembolic disease has been suggested to occur with higher frequency during laparoscopic cholecystectomy than during other laparoscopic procedures or conventional cholecystectomy. The aim of this prospective study was to evaluate the occurrence of deep vein thrombosis (DVT) in laparoscopic cholecystectomy patients, whether they were treated with low-molecular-weight heparins or not. All 238 laparoscopic cholecystectomy patients included in the study underwent pre- and postoperative venous duplex scanning of both legs. Subcutaneous Nadroparin was administred to 105 patients. The remaining 133 patients did not receive pharmacologic prophylaxis. The different risk factors for thromboembolic disease were distributed evenly between the two groups, except for the duration of general anesthesia. No patient had postoperative clinical manifestations of DVT or pulmonary embolism. In five patients, DVT was detected at duplex scan approximately 10 days after surgery. Four DVTs were found among the 133 patients who did not receive Nadroparin (1.68%). In the group with pharmacologic prevention, one patient manifested a DVT (0.42%), giving a total DVT incidence of 2.10% after laparoscopic cholecystectomy. The difference between the two groups was not significant (p = 0.27), but the results seem to indicate a tendency toward a lower incidence in the Nadroparine group. In the light of the study results, it seems advisable to use thromboembolic prophylaxis during laparoscopic cholecystectomy.


Evaluation of free hydroxyl radical scavenging activities of some Chinese herbs by capillary zone electrophoresis with amperometric detection.
Due to the severe damage caused by free hydroxyl radicals (OH.) to cells and tissues, there is much interest in finding and studying effective and non-toxic OH. scavengers, including traditional Chinese herbs. In this paper, the simple and highly-sensitive technique of capillary zone electrophoresis with amperometric detection (CZE-AD) was used to study the OH. scavenging activities of aqueous extracts from some traditional Chinese herbs. Salicylic acid (SAL) was used as an OH. trap, and the content of OH. could be determined by assaying their products, 2,3-dihydroxybenzoic acid (2,3-DHBA) and 2,5-dihydroxybenzoic acid (2,5-DHBA). The optimum conditions for CZE-AD for the determination of 2,3-DHBA and 2,5-DHBA were explored. The linearity ranges of 2,3-DHBA and 2,5-DHBA were 1.0 x10(-7) approximately 1.0 x10(-4) mol L(-1), and their detection limits were as low as 2 x 10(-8) mol L(-1), which were much better than the CE-UV method often used. The traditional Chinese herbs studied included Radix angelicae sinensis, Rhizoma coptidis, Ligustrum lucidum, Ligusticum wallichii, Radices glycyrrhizae and Semen plantaginis. The experiments showed that the aqueous extracts from all of the above traditional Chinese herds had free OH. scavenging activities, although to different degrees.


Disposition of monodesethylamodiaquine after a single oral dose of amodiaquine and three regimens for prophylaxis against Plasmodium falciparum malaria.
The disposition of monodesethylamodiaquine was studied in four healthy subjects after a single oral dose of 10 mg/kg amodiaquine base. Amodiaquine was not found in any sample, but the major metabolite monodesethylamodiaquine was detected and was assumed to be the sole derivative that contributed significantly to antimalarial activity in the blood. The best fit for the decay of the metabolite was obtained with a three-compartment model. The half-lives of the first two phases were 3.2 to 11.4 h for t1/2 alpha 1 and 22.7 to 50.3 h for t1/2 alpha 2 in plasma. The half-life of the terminal phase (t1/2 beta) was between 9 and 18.2 days. The concentration in whole blood was 4- to 6-times higher than in plasma. Three schedules (alternate days, weekly, daily) of the conventional prophylactic dose of 10 mg/kg per week were compared in six other healthy subjects. There were significant differences in the plasma monodesethylamodiaquine levels between the three schedules.


The inhibition of ribonucleic acid synthesis by the thiol-oxidizing agent, diamide, in Escherichia coli.
The thiol-oxidizing agent, diamide, has been used to convert glutathione to glutathione disulfide within the cells of a stringent strain of Escherichia coli (CP 78), leading to a cessation of 14C-leucine incorporation (protein synthesis) and 3H-uracil incorporation (RNA synthesis). Parallel experiments with an isogenic relaxed strain (CP 79) gave similar results, providing evidence that glutathione is closely linked to RNA synthesis indepently of the link previously shown to protein synthesis.


[Effect of preoperative chemotherapy on apoptosis and tissues of pancreatic adenocarcinoma].
To investigate the apoptosis and tissues change of pancreatic adenocarcinoma with or without preoperative chemotherapy and discuss the effect of preoperative regional chemotherapy on pancreatic adenocarcinoma cell. Using the method of TUNEL and microscope, we determined the apoptosis of tumor cells and tissues changes in 30 pancreatic adenocarcinoma patients with or without preoperative chemotherapy. The ratio of apoptosis was much higher in the preoperatively treated group than in the untreated group (44.87 +/- 27.78) and (3.6 +/- 3.76)/HP, (P < 0.01). The ratio of apoptosis was related to the tissue type of pancreatic adenocarcinoma. The ratio of apoptosis in the highly differentiated adenocarcinoma group was much higher than that in the middle or low differentiated adenocarcinoma group (P < 0.05, P < 0.01). The inflammatory reaction and the proliferous intima of vessels were more obvious in the preoperatively treated group than in the untreated group (P < 0.05, P < 0.01). Preoperative regional chemotherapy can effectively inhibit pancreatic adenocarcinoma by inducing the apoptosis of tumor cells.


Studies on the partial structure of the O-antigen of Vibrio cholera Ogawa G-2102.
Detailed information was obtained regarding the partial structure of the lipopolysaccharide (LPS), containing glucose, glucuronic acid, 2-amino-2-deoxy-glucose, L-glycero-D-gluco-heptose, and small proportions of L-glycero-D-manno-heptose, mannose, and galactose, isolated from Vibrio cholera Ogawa G-2102. Structures of three oligosaccharides were determined. Results of deamination experiments established the sequence of the linkages between the amino sugar and heptose residues in the O-antigenic polysaccharide.


Efficacy of off-label augmentation in unipolar depression: A systematic review of the evidence.
Treatment of unipolar depression with currently available antidepressants is still unsatisfactory. Augmentation with lithium or second generation antipsychotics is an established practice in non-responders to antidepressant monotherapy, but is also associated with a substantial non-response rate and with non-tolerance. Based on a systematic review of the literature, including meta-analyses, randomized controlled trials (RCTs), non-randomized comparative studies and case studies, off-label augmentation agents (administered in addition to an antidepressant, without FDA approval for treatment of MDD) were identified and evaluated regarding their efficacy using levels of evidence. The agents had to be added to an existing antidepressant regime with the aim of achieving an improved clinical response to an ongoing antidepressant treatment (augmentation) or an earlier onset of effect when starting antidepressant and augmentation agent simultaneously (acceleration). Five substances, modafinil, ketamine, pindolol, testosterone and estrogen (the latter two in hormone-deficient patients) were shown to be clinically effective in high evidence studies. For the six drugs dexamethasone, mecamylamine, riluzole, amantadine, pramipexole and yohimbine clear proof of efficacy was not possible due to low levels of evidence, small sample sizes or discordant results. For the two agents methylphenidate and memantine only studies with negative outcomes could be found. Overall, the quality of study designs was low and results were often contradictory. However, the use of pindolol, ketamine, modafinil, estrogen and testosterone might be an option for depressed patients who are not responding to antidepressant monotherapy or established augmentation strategies. Further high quality studies are necessary and warranted.


A review of evidence from short-term studies leading to the prediction that diazoaminobenzene (1,3-diphenyltriazine) is a carcinogen.
The National Toxicology Program (NTP) is responsible for providing comprehensive toxicology evaluations of substances, while at the same time incorporating approaches to reduce, refine or replace laboratory animals in routine toxicity/carcinogenicity studies. Consistent with this, a series of metabolism studies in rodents and human liver slices, electron spin resonance spectroscopy (ESR) studies, short-term dermal toxicity studies in rodents, and acute bone marrow micronucleus studies in mice were performed on diazoaminobenzene (DAAB, also known as 1,3-diphenyltriazine). These studies demonstrated that DAAB is metabolized and shares similar genotoxic and toxicological properties to the known human carcinogen, benzene, and the known rodent carcinogen, aniline. These data were used to evaluate the potential carcinogenicity of DAAB without doing a 2-year rodent bioassay. Based on this analysis, DAAB was predicted to be carcinogenic if evaluated in a 2-year rodent bioassay. These data were evaluated to support listing DAAB in the NTP Report on Carcinogens as a substance 'reasonably anticipated to be a human carcinogen'. The purpose of this article is to review the data developed for predicting the carcinogenicity of DAAB.


Critical Care and Postoperative Management of the Head and Neck Patient.
Head and neck surgical patients, at times, can represent a challenging population to manage in the intensive care unit postoperatively. Close interaction between the critical care and surgical teams, awareness of potential surgery-specific complications, and utilization of protocol-driven care can reduce risk of morbidity significantly in this population and enhance outcomes. Given the relative complexity of otolaryngologic surgery and the unique risk that head and neck pathologies can pose to patient airway, breathing, and circulation, these collective circumstances warrant detailed discussion in the interest of minimizing patient morbidity and mortality.


Acceptability of a 7-day higher-carbohydrate, lower-fat menu: the Beltsville Diet study.
For 13 weeks, 20 men (aged 23 to 56), 19 premenopausal (aged 21 to 48), and 14 postmenopausal women (aged 49 to 65) consumed a 7-day rotation menu conforming to dietary recommendations of several research and health organizations. The diets were designed to make minimal changes in the standard American diet by the use of well-accepted normal foods. The average daily composition of the diet was 50% carbohydrate (complex 35%, simple 15%), 35% fat (P:S 0.7), and 15% protein; it contained 100 mg cholesterol, 1 gm sodium, and 14.5 gm neutral detergent fiber per 1,000 kcal. The acceptability of the menus was examined through questionnaires administered after the experimental diet period. Subjects rated the menus and individual foods and made recommendations for improvement of the menus. Most subjects (33 of 41 responding) rated the menu better than or almost as good as their usual diet. Few (9) were ever hungry during the 13-week period. During the study, a number of biochemical parameters were measured; the measurements indicated beneficial results. Blood pressure, cholesterol levels, and glucose responses were all improved after consumption of the menu. The results indicate that with minimal changes in the normal U.S. diet, acceptable menus that have beneficial effects on risk factors for heart disease and diabetes can be developed.


KRAS, MYC, and ARF6: inseparable relationships cooperatively promote cancer malignancy and immune evasion.
Mutations in the KRAS gene and overexpression of protein products of the MYC and ARF6 genes occur frequently in cancer. Here, the inseparable relationships and cooperation of the protein products of these three genes in cancer malignancy and immune evasion are discussed. mRNAs encoded by these genes share the common feature of a G-quadruplex structure, which directs them to be robustly expressed when cellular energy production is increased. These three proteins are also functionally inseparable from each other, as follows. 1) KRAS induces MYC gene expression, and may also promote eIF4A-dependent MYC and ARF6 mRNA translation, 2) MYC induces the expression of genes involved in mitochondrial biogenesis and oxidative phosphorylation, and 3) ARF6 protects mitochondria from oxidative injury. ARF6 may moreover promote cancer invasion and metastasis, and also acidosis and immune checkpoint. Therefore, the inseparable relationships and cooperation of KRAS, MYC, and ARF6 appear to result in the activation of mitochondria and the driving of ARF6-based malignancy and immune evasion. Such adverse associations are frequent in pancreatic cancer, and appear to be further enhanced by TP53 mutations. Video Abstract.


Follicular dendritic cells: origin, function, and different disease-associated patterns.
Follicular dendritic cells (FDCs) are a specialized type of antigen-presenting dendritic cells that are largely restricted to lymphoid follicles. They form dense three-dimensional meshwork patterns within benign follicles, which maintain the follicular architecture. The FDC function is to bind and retain antigens by linking to complement and immune complexes and then present these antigens to germinal center B cells that start the secondary immune response. FDCs aid in the rescue of bound B cells from apoptosis, and induce the differentiation of B cells into long-term memory B cell clones or plasma cells. We will discuss the different patterns of the FDC meshwork observed in different types of reactive and neoplastic disorders, which may be due to underlying different roles that FDCs may play in these disorders and whether changes in the architecture of the FDC meshwork can be useful in routine diagnostic practice or have a prognostic value.


A proximal promoter element in the hamster desmin upstream regulatory region is responsible for activation by myogenic determination factors.
The muscle-specific intermediate filament protein desmin is up-regulated during skeletal muscle differentiation. When myoblasts leave the cell cycle and fusion into multinucleated myotubes starts, genes associated with myogenesis become activated. The activation is believed to be mediated by the muscle-specific determination factors. We present evidence that both MyoD and myogenin are able to activate the transcription of the hamster desmin gene. A proximal promoter fragment of 89 base pairs is sufficient for this transactivation process. The single E-box in this region is essential for desmin promoter activity in mouse C2 skeletal muscle cells and upon co-transfection of a myogenin expression vector also in human primary fibroblasts. Mutation of this MyoD binding site abrogates desmin transcription, and transactivation of the promoter no longer occurs. By using gel electrophoretic mobility shift assays, we were able to demonstrate that nuclear proteins from C2 muscle cells and myogenin/E12 glutathione S-transferase fusion proteins are able to bind to the functional E-box consensus sequence. A second E-box, situated in a more upstream regulatory region, which also binds to purified Helix-Loop-Helix proteins in vitro is only moderately affected by site-directed in vitro mutagenesis.


Synthesis of a novel class of non-peptide NK-2 receptor ligand, derived from 1-phenyl-3-pyrrol-1-ylindan-2-carboxamides.
A series of trans,trans-1-phenyl-3-pyrrol-1-ylindan-2-carboxamide derivatives has been synthesized in eight steps starting from cinnamic acid or 3,3-diphenylpropionic acid. The trans,trans configuration of these carboxamides has been established by X-ray analysis and by NOE experiments in NMR. These new compounds were evaluated for their potential NK-1, NK-2 and NK-3 receptors binding affinity. The N,N-disubstituted carboxamides bound selectively on NK-2 receptors.


Estimates of nitrogen fixation by trees on an aridity gradient in Namibia.
Nitrogen (N2) fixation was estimated along an aridity gradient in Namibia from the natural abundance of 15N (δ15N value) in 11 woody species of the Mimosacease which were compared with the δ15N values in 11 woody non-Mimosaceae. Averaging all species and habitats the calculated contribution of N2 fixation (N f ) to leaf nitrogen (N) concentration of Mimosaceae averaged about 30%, with large variation between and within species. While in Acacia albida N f was only 2%, it was 49% in Acacia hereroensis and Dichrostachys cinerea, and reached 71% in Acacia melifera. In the majority of species N f was 10-30%. There was a marked variation in background δ15N values along the aridity gradient, with the highest δ15N values in the lowland savanna. The difference between δ15N values of Mimosaceae and non-Mimosaceae, which is assumed to result mainly from N2 fixation, was also largest in the lowland savanna. Variations in δ15N of Mimosaceae did not affect N concentrations, but higher δ15N-values of Mimosaeae are associated with lower carbon isotope ratios (δ13C value). N2 fixation was associated with reduced intrinsic water use efficiency. The opposite trends were found in non-Mimosaceae, in which N-concentration increased with δ15N, but δ13C was unaffected. The large variation among species and sites is discussed.


Induction of ROS generation by fluconazole in Candida glabrata: activation of antioxidant enzymes and oxidative DNA damage.
In this study, we assessed the generation of reactive oxygen species (ROS) induced by subinhibitory concentration of fluconazole in susceptible and resistant Candida glabrata strains at stationary growth phase and measured their oxidative responses parameters: glutathione peroxidase (GPx), superoxide dismutase (SOD), glutathione-S-transferase (GST), consumption of hydrogen peroxide, and total glutathione, as well as oxidative damage in lipids, proteins, and DNA. Data showed that fluconazole increased generation of ROS and GPx and SOD enzymatic activity in treated cells; however, these enzymatic activities did not differ between resistant and susceptible strains. Susceptible strains exhibited higher GST activity than resistant, and when susceptible cells were treated with fluconazole, GST activity decreased. Fluconazole treatment cause oxidative damage only in DNA. There are a possible participation of ROS, as organic peroxides and O2(•-), in antifungal mechanism of fluconazole, which results in higher GPx and SOD enzymatic activities and oxidative DNA damage in C. glabrata.


Risk-prone territories for spreading tuberculosis, temporal trends and their determinants in a high burden city from São Paulo State, Brazil.
To identify risk-prone areas for the spread of tuberculosis, analyze spatial variation and temporal trends of the disease in these areas and identify their determinants in a high burden city. An ecological study was carried out in Ribeirão Preto, São Paulo, Brazil. The population was composed of pulmonary tuberculosis cases reported in the Tuberculosis Patient Control System between 2006 and 2017. Seasonal Trend Decomposition using the Loess decomposition method was used. Spatial and spatiotemporal scanning statistics were applied to identify risk areas. Spatial Variation in Temporal Trends (SVTT) was used to detect risk-prone territories with changes in the temporal trend. Finally, Pearson's Chi-square test was performed to identify factors associated with the epidemiological situation in the municipality. Between 2006 and 2017, 1760 cases of pulmonary tuberculosis were reported in the municipality. With spatial scanning, four groups of clusters were identified with relative risks (RR) from 0.19 to 0.52, 1.73, 2.07, and 2.68 to 2.72. With the space-time scan, four clusters were also identified with RR of 0.13 (2008-2013), 1.94 (2010-2015), 2.34 (2006 to 2011), and 2.84 (2014-2017). With the SVTT, a cluster was identified with RR 0.11, an internal time trend of growth (+ 0.09%/year), and an external time trend of decrease (- 0.06%/year). Finally, three risk factors and three protective factors that are associated with the epidemiological situation in the municipality were identified, being: race/brown color (OR: 1.26), without education (OR: 1.71), retired (OR: 1.35), 15 years or more of study (OR: 0.73), not having HIV (OR: 0.55) and not having diabetes (OR: 0.35). The importance of using spatial analysis tools in identifying areas that should be prioritized for TB control is highlighted, and greater attention is necessary for individuals who fit the profile indicated as "at risk" for the disease.


Meningitis complicating an occult infected nasal epidermoid cyst in a child.
Congenital nasal epidermoid cyst without associated facial dysmorphism is an uncommon anomaly that is often asymptomatic. We report a case of occult nasal epidermoid cyst in a 12-year-old boy with initial nonspecific symptoms of fever, headache, abdominal pain, vomiting, and diarrhea. An enhanced magnetic resonance imaging (MRI) showed a cystic lesion in the frontal skull base with expansion of the foramen cecum and the perpendicular plate of the ethmoid bone, accompanied with meningitis. An emergent surgical intervention was undertaken, and an infected epidermoid cyst was confirmed by pathology. He recovered uneventfully during a 4-week treatment with parentally-administered antibiotics. This significant case report demonstrates the importance of MRI in the early diagnosis of a life-threatening intracranial infection from an otherwise occult infected congenital nasal epidermoid cyst in children.


The effects of a housing mobility experiment on participants' residential environments.
We used the Moving to Opportunity (MTO) housing experiment to inform how housing choice vouchers and housing mobility policies can assist families living in high-poverty areas to make opportunity moves to higher quality neighborhoods, across a wide range of neighborhood attributes. We compared the neighborhood attainment of the three randomly-assigned MTO treatment groups (Low Poverty voucher, Section 8 voucher, Control group) at 1997 and 2002 locations (4-7 years after baseline), by using survey reports, and by linking residential histories to numerous different administrative and population-based datasets. Compared to controls, families in Low-Poverty and Section 8 groups experienced substantial improvements in neighborhood conditions across diverse measures, including economic conditions, social systems (e.g., collective efficacy), physical features of the environment (e.g., tree cover) and health outcomes. The Low-poverty voucher group moreover achieved better neighborhood attainment compared to Section 8. Treatment effects were largest for New York and Los Angeles. We discuss the implications of our findings for expanding affordable housing policy.


Prostate-specific antigen doubling time is a reliable predictor of imageable metastases in men with biochemical recurrence after radical retropubic prostatectomy.
To examine the incidence of imageable metastases at the time of biochemical recurrence after radical prostatectomy and to determine whether prostate-specific antigen doubling time (PSADT) reliably predicts these imageable metastases. Between October 2000 and October 2005, 1112 men underwent open radical retropubic prostatectomy by a single surgeon. All men were advised to undergo bone scintigraphy and an abdominal/pelvic imaging study at the time of biochemical recurrence. We ascertained the sensitivity, specificity, and positive and negative predictive values of a PSADT cut-point of 3 months to predict the presence of imageable metastases. Seventy-four (6.7%) men developed a biochemical recurrence and imageable metastases were demonstrable in 7 cases. Imageable metastases were identified in 11.3% and 7.5% of men undergoing bone scans and abdominal/pelvic imaging, respectively. Extracapsular extension, and older age positive surgical margins, and PSADT were associated with a significantly greater risk of exhibiting imageable metastases. The sensitivity, specificity, and positive and negative predictive values of a PSADT cut-point of 3 months for predicting imageable metastasis were 100%, 98.0%, 87.5%, and 100%, respectively. A relatively small proportion of men at the time of developing biochemical recurrence after radical prostatectomy exhibit imageable metastasis. The 100% sensitivity and negative predictive value of a PSADT cut-point of 3 months strongly suggests that PSADT can be used as an excellent proxy for imageable metastasis. Omitting routine bone scintigraphy and body imaging at the time of biochemical recurrence minimizes the costs, inconvenience, and anxiety associated with these studies.


Prospective evaluation of optical coherence tomography in lower limb arteries compared with intravascular ultrasound.
To compare in a prospective noninferiority study optical coherence tomography (OCT) and intravascular ultrasound (IVUS) in popliteal and infrapopliteal vessels. OCT and IVUS images of 112 popliteal and infrapopliteal arterial segments were prospectively obtained from 16 patients with peripheral arterial occlusive disease. Three observers evaluated the corresponding OCT and IVUS images for image quality, artifact frequency, discriminability of vessel wall layers, and plaque composition. Measurements of the lumen, vessel, and plaque areas were compared for both modalities. The intrareader and interreader reproducibility of plaque tissue discrimination (0.88 vs 0.75), overall image quality, and vessel wall layer discriminability were significantly higher for OCT (all P < .001). Artifact frequency was higher in OCT, constraining the imaging of the tibioperoneal trunk. The results of measurements of the lumen and vessel area were comparable for both modalities (correlation > 0.9, P < .001). Plaque area measurements differed (correlation 0.8, P < .01) because OCT underestimated it. The OCT procedure caused vessel spasms in two patients. OCT imaging of infrapopliteal arteries is feasible and safe and provides high image quality. It enables an accurate assessment of vessel lumen, wall, and plaque. Compared with IVUS, OCT images provide excellent image quality and superior visualization of vessel wall layers and different plaque components. The penetration depth of OCT restricts its use to suitable vessel regions.


The Drosophila SR protein RBP1 contributes to the regulation of doublesex alternative splicing by recognizing RBP1 RNA target sequences.
The SR proteins represent a family of splicing factors several of which have been implicated in the regulation of sex-specific alternative splicing of doublesex (dsx) pre-mRNA in Drosophila. The dsx gene is involved in Drosophila sex determination. We have identified two RNA target sequence motifs recognized by the SR protein RBP1 from Drosophila using an in vitro selection approach. Several copies of these RBP1 target sequences were found within two regions of the dsx pre-mRNA which are important for the regulation of dsx alternative splicing, the repeat region and the purine-rich polypyrimidine tract of the regulated female-specific 3' splice site. We show that RBP1 target sequences within the dsx repeat region are required for the efficient splicing of dsx pre-mRNA. Moreover, our studies reveal that RBP1 contributes to the activation of female-specific dsx splicing in vivo by recognizing the RBP1 target sequences within the purine-rich polypyrimidine tract of the female-specific 3' splice site.


Haptoglobin phenotyping of bloodstains by horizontal electrophoresis on a compact polyacrylamide gradient gel.
A method is described for phenotyping haptoglobin by horizontal electrophoresis on a small polyacrylamide gradient gel. This method employs the same apparatus used in the separation of many red cell enzyme phenotypes and thereby eliminates the necessity for specialized vertical electrophoresis equipment.


First report of a permanent breast 103Pd seed implant as adjuvant radiation treatment for early-stage breast cancer.
A new technique of adjuvant partial breast irradiation using 103Pd permanent breast seed implants (PBSI) is presented. The procedure is performed in a single 1-hour session under local anesthesia. Patients referred to a single institution for adjuvant radiotherapy after lumpectomy for an infiltrating ductal carcinoma < or = 3 cm in diameter, surgical margin > or = 2 mm, no extensive in situ carcinoma, no lymphovascular invasion, and minimal or negative lymph node involvement were offered a PBSI. Between May and December 2004, 31 eligible patients underwent CT scan and ultrasound simulations assessing PBSI feasibility. Fifteen were excluded because of feasibility issues, and 16 received PBSI. A minimal peripheral dose of 90 Gy was prescribed to the planning target volume corresponding to the clinical target volume identified on the CT scan plus a margin of 1 cm. The procedure was well tolerated; 56% of the patients reported no pain during the procedure, and 46% of the patients developed National Cancer Institute Common Toxicity Criteria Grade 1 acute reaction. None experienced toxicity Grade 2 or 3. Permanent breast seed implantation seems feasible and well tolerated on these preliminary clinical data and represents an ultimate step in the reduction of treatment fraction for partial breast irradiation.


SPTLC1 p.Leu38Arg, a novel mutation associated with childhood ALS.
Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neuromuscular disease. Recently, several gain-of-function mutations in SPTLC1 were associated with juvenile ALS. SPTLC1 encodes for a subunit of the serine-palmitoyltransferase (SPT) - the rate-limiting enzyme in the de novo synthesis of sphingolipids (SL). SPT activity, and thus SL de novo synthesis, is tightly controlled by a homeostatic feedback mechanism mediated by ORMDL proteins. Here we report a novel SPTLC1p.L38R mutation in a young Chinese girl with a signature of juvenile ALS. The patient presented with muscular weakness and atrophy, tongue tremor and fasciculation, breathing problems and positive pyramidal signs. All SPTLC1-ALS mutations including the SPTLC1 p.L38R are located within a single membrane-spanning domain of the protein and impede the interaction with the regulatory ORMDL subunit of SPT. Pertinent to the altered homeostatic control, lipid analysis showed overall increased SL levels in the patient plasma. An increased SPT activity and SL de novo synthesis was confirmed in p.L38R expressing HEK293 cells. Particularily dihydro-sphingolipids (dhSL) were signficantly increased in patient plasma and p.L38R mutant expressing cells. Increased dhSL formation has been previously linked to neurotoxicity and may be involved in the pathomechanism of SPTLC1-ALS mutations.


V-doped porous CoP nanoarrays grown on carbon cloth with optimized electronic structure for the hydrogen evolution reaction.
As an efficient, renewable and clean energy, hydrogen is expected to replace traditional fossil fuel energy in the future. Currently, platinum-based materials (Pt) are excellent electrocatalysts for hydrogen evolution reaction (HER), but their high cost and low natural abundance limit their widespread application. Therefore, it is urgent to develop low-cost, highly efficient and earth-abundant electrocatalysts to replace the precious platinum-based materials. In this study, a Co-based organic framework (ZIF-67) was grown on a flexible substrate carbon cloth (CC), and a V-doped CoP nanoarray (V-CoP/CC) was prepared using a simple in situ ion exchange/phosphating method. Due to its unique porous structure, effective doping of V atoms and the in situ electrode construction, the V-CoP/CC exhibited high electrolytic hydrogen evolution reaction (HER) performance, with an overpotential of 98 mV at a current density of 10 mA cm-2. This work has important theoretical and practical significance for in situ construction of heteroatom-doped CoP electrodes.


Percutaneous transluminal intervention and antiplatelet therapy following endovascular graft exclusion for Stanford B thoracic aortic dissection.
To evaluate the safety and feasibility of percutaneous coronary intervention and antiplatelet therapy in patients who have undergone endovascular graft exclusion. From January 2005 to July 2007, percutaneous transluminal intervention (PCI) was performed in 13 patients who had undergone endovascular graft exclusion for the treatment of either acute or chronic Stanford B aortic dissection. Anticoagulant and antiplatelet treatments were administered according to the standard protocol. Patients were followed up for a mean period of 11 months. Clinical characteristics, false lumen thrombosis and angiographic data were collected. PCI was technically successful in all 13 patients and no severe complications, including death, paraplegia or renal failure occurred during hospitalization. Complete false lumen thrombosis was observed in all patients within 6 months. There were no major complications such as death, dissection rupture, or aneurysm development during the follow-up period. Our data suggested that PCI and standard antiplatelet therapy are feasible and safe in patients who have undergone endovascular stent graft exclusion for Stanford B aortic dissection.


Methodological considerations in determining sex steroids in children: comparison of conventional immunoassays with liquid chromatography-tandem mass spectrometry.
In laboratory medicine, external quality assessment (EQA) schemes have become versatile tools for detecting analytical flaws. However, EQA schemes are lacking for pediatric sex steroid levels. We aimed to investigate the suitability of different estradiol and testosterone immunoassays in a pediatric setting in comparison with clinical liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays. The study was conducted by staff and the advisory group on endocrinology at Equalis, the Swedish provider of EQA schemes for laboratory medicine. The test material consisted of five pooled serum samples from children who were either prepubertal or in puberty. Clinical laboratories enrolled in Equalis EQA schemes for estradiol and testosterone were invited to participate, as were clinical laboratories using LC-MS/MS-assays. Samples were analyzed by either routine immunoassays (n=18) or in-house LC-MS/MS assays (n=3). For estradiol, LC-MS/MS assays showed a high degree of conformity with interlaboratory coefficients of variation (CV) below 24.2 %. Reported levels were between 4.9 ± 1.2 and 33.9 ± 1.6 pmol/L (group mean ± standard deviation). The direct immunoassays had lower precision; their CVs were up to 81.4 %. Reported concentrations were between 25.3 ± 18.1 and 45.7 ± 19.4 pmol/L, an overestimation compared to LC-MS/MS. Testosterone LC-MS/MS also showed a high degree of conformity, CVs were below 13.4 %, and reported concentrations were from 0.06 ± 0.00 to 1.00 ± 0.11 nmol/L. The direct immunoassays had a larger discrepancy between results; CVs were up to 95.8 %. Concentrations were between 0.12 ± 0.11 and 0.85 ± 0.23 nmol/L. For the safe diagnosis and determination of sex steroids in children, analysis with mass spectrometry-based methods is recommended.


Amelioration of liver injury by ischaemic preconditioning.
Ischaemic preconditioning, i.e. preparatory brief ischaemia before subsequent long ischaemia, can effectively protect the heart from ischaemia-reperfusion injury in animals. The purpose of this study was to demonstrate the same phenomenon in the liver. Using warm ischaemia-reperfusion of 70 per cent of the liver followed by resection of the non-ischaemic portion in rats, livers with 10 min of ischaemic preconditioning, i.e. 10 min of warm ischaemia and reperfusion, were compared with those that had not been subjected to such a manoeuvre. At 120 min after reperfusion following 40 min of warm ischaemia, the livers with 10 min of ischaemic preconditioning had a significantly lower mean(s.d.) serum alanine aminotransferase level (492(217) versus 1236(695) units/l; P < 0005) and lactic dehydrogenase level (7905(4002) versus 15066(9201) units/l; P< 0.05), as well as a higher bile output (0.12(0.03) versus 0.09(0.04) ml per g liver; P < 0.05) and liver tissue adenosine 5'-triphosphate level (78(13) versus 61(11) per cent; P< 0.05) than the control livers. The necrosis rate, histologically defined as the percentage of necrotic area in given liver sections, was reduced significantly by this manoeuvre (mean(s.d.) 1.3(1.3) versus 5.3(1.7) per cent; P< 0.05). Ischaemic preconditioning exerts a protective effect on hepatic warm ischaemia-reperfusion injury. Such a manoeuvre may be useful for hepatic resection in the clinical setting.


Intracoronal incisal splint.
An intracoronal incisal splint for the stabilization of mobile anterior teeth is described. Advantages of the technique are good esthetics, open embrasures and no disturbance of occlusion.


Development and Life Table Parameters of Phenacoccus madeirensis Green (Hemiptera: Pseudococcidae) on Four Ornamental Plants.
The development, reproduction, and life table parameters of the Phenacoccus madeirensis Green (Hemiptera: Pseudococcidae) on four ornamental plant species, namely Pelargonium zonale (Geraniaceae), Hibiscus rosa-sinensis, Hibicus syriacus (Malvaceae), and Cestrum nocturnum (Solanaceae) were investigated under controlled conditions (25 ± 2°C, 60 ± 10% R.H., and 16 h photophase). Life table data were analyzed by using an age-stage two-sex life table. The shortest total immature developmental time of females and males for P. madeirensis was obtained on C. nocturnum (20.42 and 21.90 days, respectively). The highest fecundities were 233 and 232 eggs on C. nocturnum and H. syriacus, respectively. The intrinsic rate of increase (r = 0.1511 day(-1)) and finite rate of increase (λ = 1.1631 day(-1)) were the greatest when mealybugs were reared on C. nocturnum. Net reproductive rate (R 0 = 129.5 offspring) was the greatest when reared on H. syriacus, but this value was not statistically different from that on C. nocturnum. The shortest mean generation time (T = 31.3 days) was calculated on C. nocturnum. These results indicate that C. nocturnum and H. syriacus are more suitable hosts than H. rosa-sinensis and P. zonale for P. madeirensis.


Categories of manual asymmetry and their variation with advancing age.
Manual asymmetries were analyzed in 18- to 63-year-old right-handers in different motor tasks. This analysis aimed at describing the asymmetry profile for each task and assessing their stability across ages. For this purpose, performance of the right and left hands were analyzed in the following aspects: simple reaction time, rate of sequential finger movements, maximum grip force, accuracy in anticipatory timing, rate of repetitive tapping, and rate of drawing movements. In addition, stability of manual preference across ages was assessed through the Edinburgh inventory (Oldfield, 1971). The results indicated different profiles of manual asymmetry, with identification of three categories across tasks: symmetric performance (asymmetry indices close to zero), inconsistent asymmetry (asymmetry indices variable in magnitude and direction), and consistent asymmetry (asymmetry indices favoring a single hand). The different profiles observed in the young adults were stable across ages with two exceptions: decreased lateral asymmetry for maximum grip force and increased asymmetry for sequential drawing in older individuals. These results indicate that manual asymmetries are task specific. Such task specificity is interpreted to be the result of different sensorimotor requirements imposed by each motor task in association with motor experiences accumulated over the lifetime. Analysis of manual preference showed that strength of preference for the right hand was greater in older individuals.


Effects of decitabine on allogeneic immune reactions of donor lymphocyte infusion via activation of dendritic cells.
Successful prevention of post-transplantation relapse after donor lymphocyte infusion (DLI) depends on its capability to mediate an effective graft-versus-leukemia (GVL) response while minimizing DLI-related toxicity, including graft-versus-host disease (GVHD). We assessed the effects of decitabine (DEC), a hypomethylating agent, upon allogeneic immune reaction in a murine model of DLI. Significantly greater tumor growth retardation and survival prolongation occurred in mice administered with 1.0 mg/kg DEC for 5 days (DEC-1.0) than in control or DEC-0.1 mice. Upon prompt DEC and DLI co-administration, dendritic cells (DCs) were activated; DEC-1.0/DLI induced severe GVHD, and survival was significantly lower than with DLI alone or DEC-0.1/DLI treatments. IFN-γ and CD28 levels were higher in splenic DCs of DEC-1.0 mice than in those of control mice. Assessment of delayed DLI co-administration with DEC, when IFN-γ levels were normalized to control levels, revealed that DEC-1.0/DLI successfully facilitated tumor management without causing severe GVHD. Our results suggest that DEC primes allogeneic immune reactions of DLI via DC activation, and GVHD and GVL effects are separable through optimal DLI timing based on DEC-induced increase in IFN-γ expression levels.


A prospective randomized study of different retainer types.
In recent years, fixed lingual retainers have been gaining importance in relapse prevention. The aim of this prospective, randomized study was to compare different types of fixed retainers used for stabilization of the lower anterior segment with respect to detachment rate, relapse, periodontal and oral hygiene problems, as well as subjective patient discomfort. Two types of fixed, customized canine-to-canine retainers (attached to six teeth) with wire diameters of 0.0215" and 0.0195" as well as one type of prefabricated canine-and-canine retainer (bonded to two teeth) were investigated in a total of 103 patients. Some retainers were inserted under dry field conditions using a rubber dam, and the others under relatively dry conditions using cotton rolls. In addition, two types of composite, Heliosit and Concise, were compared. The canine-and-canine retainer displayed an 18% detachment rate, a value significantly lower than the 29% determined for the 0.0195" canine-to-canine retainers. The 0.0215" canine-to-canine retainer had the highest detachment rate (53%). The 37% detachment rate with dry field bonding was slightly higher than the 32% with relatively dry field bonding. Comparison of the composites showed a significantly higher detachment rate for Heliosit (73%) than for Concise (27%). Plaque accumulation increased with all retainer types in the course of the study, but with no significant inter-group differences. Tooth position with canine-to-canine retainers showed a good degree of stability. The canine-and-canine retainer induced frequent relapse of incisors not bonded to the retainer. In view of their higher rate of subjective discomfort, canine-and-canine retainers were given a significantly poorer rating than their canine-to-canine counterparts.


Iron-calcium reinforced solidification of arsenic alkali residue in geopolymer composite: Wide pH stabilization and its mechanism.
Arsenic-alkali residue (AAR) from antimony production can pose significant health and environmental hazards due to the risk of arsenic (As) leaching. In this study, geopolymer composite synthesized from fly ash (FA) was investigated for efficient stabilization of high-arsenic-containing AAR (As2O3 of 22.74 wt%). Two industrial wastes, e.g., granulated blast furnace slag (GBFS) with active calcium composition and water-quenched slag (WQS) from lead-zinc smelting with active iron composition, were investigated for the reinforcement of AAR geopolymer solidification. A wide pH stabilization (from pH = 3-pH = 12) of AAR with the geopolymer composite was successfully achieved, and As leaching concentration of geopolymer with the addition of 5 wt% AAR was significantly reduced from 2343.73 mg/L (AAR) to that below 0.18 mg/L, which successfully meet the regulatory limit of Chinese domestic waste landfill (GB, 18598-2019, 1.2 mg/L) and hazardous waste landfill (GB16889-2008, 0.3 mg/L). Johnbaumite (Ca5(AsO4)3(OH)) was formed in geopolymer composite and leached samples with initial pH from 2.6 to 6 (final pH from 5.54 to 13.15). Magnetite and iron hydroxide phases with strong adsorption and/or As co-precipitation capability were also observed. As stabilization was also achieved with iron oxidation from As(III) to As(V). This study solves the problem of unstable As leaching at different pH for the solidification of arsenic-bearing solid waste, and provides a promising and practical strategy for efficient solidification/stabilization of AAR as well as other similar arsenic-bearing solid wastes with geopolymer composite.


Studies on the interaction of microwave radiation with cholinesterase.
The significance of the enzyme cholinesterase in studies on the biological effects of microwaves is discussed. Experiments were performed on the direct effect of microwave radiation on the enzyme activity in aqueous solution, and in rabbit blood. Microwave radiation was found to have an effect only when the temperature increase was great enough to denature the enzyme.


Colorectal cancer in Crohn's disease evaluated with genes belonging to fibroblasts of the intestinal mucosa selected by NMF.
Crohn's disease (CD) is a type of chronic, inflammatory bowel disease (IBD) which affects any part of the gastrointestinal tract. This study aims to understand the mechanism which activate mucosal fibroblasts in the microenvironment of the colon in CD and colorectal carcinomas and to extract fibroblasts phenotypes via a novel framework based on non-negative factorization of matrix (NMF). The results identify a fibroblast phenotype characterized by intense pro-inflammatory activity ensured by the presence of genes belonging to the APOBEC1 family, such as APOBEC3F and APOBEC3G. These results demonstrated that there is a difference in fibroblast response in producing a pro-tumorigenic effect in CD. The different activation mechanisms could represent useful biomarkers in controlling CD development without generalizing its significance as IBD.


Impaired layer specific retinal vascular reactivity among diabetic subjects.
To investigate layer specific retinal vascular reactivity (RVR) in capillaries of diabetic subjects without DR or with only mild non-proliferative diabetic retinopathy (NPDR). A previously described nonrebreathing apparatus was used to deliver room air, 5% CO2, or 100% O2 to 41 controls and 22 diabetic subjects (with mild or no NPDR) while simultaneously acquiring fovea-centered 3x3mm2 Swept-Source Optical Coherence Tomography Angiography (SS-OCTA) images. Vessel skeleton density (VSD) and vessel diameter index (VDI) were calculated for each gas condition for the superficial retinal layer (SRL) and deep retinal layer (DRL). The superficial layer analysis excluded arterioles and venules. Data analysis was performed using mixed factorial analysis of covariance stratified by diabetic status. All models were adjusted for age, gender, and hypertension, and statistical significance for multiple comparisons from posthoc comparisons were defined at p<0.017. Among controls, there was a significant difference in capillary VSD between all gas conditions (p<0.001). This difference was present in both the SRL and DRL. Among diabetics, there was no significant difference in response to CO2 conditions in the SRL (p = 0.072), and a blunted response to both CO2 (p = 0.9) and O2 in the DRL (p = 0.019). A significant gas effect was detected in the capillary VDI in the SRL of controls (p = 0.001), which was driven by higher VDI in the oxygen condition compared to that of carbon dioxide. Impairment in RVR in diabetic subjects is characterized by a paradoxical response to CO2 in both the SRL and DRL as well as an attenuated response to O2 in the DRL. These layer and gas specific impairments in diabetics seem to occur early in the disease and to be driven primarily at the capillary level.


Building Connections with Families: Implementation of a Video-Messaging Service in the Neonatal Intensive Care Unit.
Family involvement is vital to optimize the care of infants in the neonatal intensive care unit (NICU). Various technologies have been used to support communication with parents in the NICU. The purpose of this study was to evaluate the parent and staff experience and perception of the use of a cloud-based video-messaging service in our NICU. This study was a single center observational study conducted at Mount Sinai Hospital, Toronto, Canada. Following the implementation of a video-messaging service, parent and staff surveys were distributed to evaluate their experience and perception. Parent responses were positive with respect to how the service helped them feel: closer to their infant (100%) and reassured about their infant's care (100%). Nursing staff responses indicated that they perceived a benefit to parents (100%) and to their building a relationship with families (79%). However, they also identified time constraints (85%) and the use of the technology hardware (24%) as challenges. The use of an asynchronous video-messaging service was perceived as beneficial to both parents and staff in the NICU. Complaints pertained to the impact of the technology on nursing workflow and the difficulty using the hardware provided for use of the service.


Central nervous system effects of lactate infusion in primates.
The concentration of total lactate in cisternal fluid increased threefold, from 12.3 +/- 2.1 to 37.6 +/- 8.9 mg/dl, during a 20-min intravenous infusion of 1 M racemic sodium lactate (10 mEq/kg) in 3 anesthetized, mechanically ventilated baboons. Rises in cisternal lactate lagged behind arterial lactate increases, but occurred during the time interval in which susceptible humans typically panic in response to lactate infusion. Subsequent to cisternal lactate increases, cisternal pH and HCO3- concentration progressively increased during a 105-min interval following lactate infusion. No consistent changes in cisternal pCO2 occurred during or subsequent to lactate infusion. These preliminary findings fail to support the hypothesis that lactate-induced panic is mediated by increasing central nervous system pCO2. Instead, these data demonstrate that lactate can rapidly increase in the central nervous system during lactate infusion, suggesting new lines of investigation for studying the mechanisms responsible for lactate-induced panic.


Adult bone marrow-derived stem cells and the injured heart: just the beginning?
Coronary artery disease leading to ischaemia of the human myocardium is one of the chief causes of morbidity and mortality in the western world. Cellular transplantation has recently been proposed as a novel alternative treatment modality. Adult bone marrow-derived autologous cells are one of the key cell types under investigation in both the experimental and clinical setting. A range of theories has been proposed with regard to the observed myocardial function improvement in both human and animal studies. A concerted interest in scientific questions needs to be constructed on the regenerative information made available throughout the last years. It is only now that we begin to fully understand this fast growing body of research and how it may have wide ranging implications for the treatment of ischemic heart disease.


Vaginal douching in teenagers attending a family planning clinic.
This study assessed the knowledge and usage patterns of vaginal douching in sexually active teenagers attending a family planning clinic. A questionnaire was administered consecutively to 94 black, 36 Hispanic, and 12 Anglo females ranging in age from 13 to 19 years. The survey showed that vaginal douching is a common practice, with almost two thirds learning about douching from their mother. The technique is primarily used for hygienic reasons with few using it to prevent pregnancy or infection. Age of first douche correlated with age of first intercourse (p less than 0.001). Almost 23% had douched within 2 days of the clinic visit, and 56% reported douching one or more times a week.


An intra-cultural investigation of susceptibility to 'perspective' and 'non-perspective' spatial illusions.
Conventional Müller-Lyer and modified Müller-Lyer (without 'perspective' cues) illusions were presented to two samples of children aged between eight and 19, matched in education, but living in 'carpentered' and 'uncarpentered' environments in Zambia. Traditional differences in susceptibility have been obtained with both the variations of the Müller-Lyer illusion. In view of the lack of perspective cues in one of these, it is concluded that the perspective theory as presented within the 'carpentered world hypothesis' is inadequate. Since these differences are intra-cultural, they also do not support the hypothesis which suggests that cross-cultural variations in illusion susceptibility are due to genetic factors--such as macular (or retinal) pigmentation.


Cartilage type IX collagen-proteoglycan contains a large amino-terminal globular domain encoded by multiple exons.
Type IX collagen in cartilage consists of molecules composed of three genetically distinct polypeptide subunits. One of the subunits, alpha 2(IX), contains a covalently attached glycosaminoglycan side chain whereas a second subunit, alpha 1(IX), contains a large noncollagenous, amino-terminal domain called NC4. In this report, we describe for the first time the complete primary structure of this noncollagenous domain, based on cloning and sequencing of cDNA and genomic DNA as well as amino acid sequencing of tryptic peptides. Analysis of genomic clones has also allowed determination of the exon structure of NC4. Our results demonstrate that the noncollagenous, amino-terminal domain of alpha 1(IX) chains contains 266 amino acid residues (including the signal peptide) with 5 cysteinyl residues forming two disulfide bridges. The domain is basic with an estimated pI of 9.7, thus supporting the idea that it may participate in ionic interactions with polyanionic glycosaminoglycans in cartilage. Both the sequence and exon structure of the NC4 domain is unique among collagens and there is no obvious homology with the noncollagenous domains of other types of collagen, including the propeptides of fibrillar collagens.


[Standardized clinical characteristic of the injured persons, suffering pelvic bones fractures as a consequence of a traffic accident].
The problem of the pelvic portion trauma was discussed in the investigation as a significant component of a multicomponent polysystemic trauma, for characterization of which a standard system of the injury severity estimation ISS (Injury Severity Score) was applied.


Carbon ions-induced apoptosis in hematopoietic tumor cell lines.
The purpose of this study was to assess apoptosis in hematopoietic tumor cells irradiated with carbon ions, in order to define its contribution to the cytotoxicity of these high-LET radiations. RDM4 (murine T lymphoma), MOLT-4, TK6 and WTK1 (human lymphoblastoid) cells were irradiated with 12C or 13C. Apoptosis was assessed by flow cytometry. Cell growth and activities of caspases were determined during the same periods. The ability of carbon ions to induce apoptosis markedly varied according to the cell line. MOLT-4 and TK6 cells underwent apoptosis at 1 Gy within 12 hours post-irradiation, whereas RDM4 and WTK1 showed little apoptosis under the same conditions. These results indicate that apoptosis contributes to the overall cytotoxicity of carbon ions towards hematopoietic tumor cells although other death mechanisms must also account for this cytotoxicity.


Binding of chloroquine to DNA.
Three diverse mechanisms have been proposed to explain the antimalarial activity of chloroquine: binding to DNA, binding to hemin, or alkalinizing parasite lysosomes. In order to assess the importance of DNA binding, we have measured the affinity of DNA for chloroquine by equilibrium dialysis using tritiated chloroquine. The dissociation constant of the DNA-chloroquine complex varied from 27 microM to 2.6 mM, depending on the ionic strength of the buffer. Our results suggest that chloroquine binding to DNA is highly dependent on salt concentration. Nevertheless, because of the large number of sites present, binding to parasite DNA may still account for the antimalarial activity of chloroquine.


Analysis of dosimetric factors associated with temporal lobe necrosis (TLN) in patients with nasopharyngeal carcinoma (NPC) after intensity modulated radiotherapy.
The radiation tolerance dose-volume in brain remains unclear for nasopharyngeal carcinoma (NPC) patients treated with intensity modulated radiotherapy (IMRT). We performed this study to investigate dosimetric factors associated with temporal lobe necrosis (TLN) in NPC patients treated with IMRT. From 2001 to 2008, 870 NPC patients were treated with IMRT. For the whole group, 40 patients have developed MRI-diagnosed TLN, and 219 patients were followed-up more than 60 months. Predictive dosimetric factors for TLN were identified by using univariate and multivariate analysis in these 259 patients. By univariate analyses, rVX ( percent of temporal lobes receiving ≥ X Gy) and aVX ( absolute volumes of temporal lobes receiving ≥ X Gy, values of X considered were 10, 20, 30, 40, 50, 60, 66 and 70) were all significantly associated with TLN. Multivariate analysis by logistic regression showed that rV40 and aV40 were significant factors for TLN. All dosimetric factors in current serials were highly correlated one another (p < 0.001). The 5-year incidence of TLN for rV40 <10% or aV40 <5 cc is less than 5%. The incidence for rV40 ≥ 15% or aV40c ≥ 10c is increased significantly and more than 20%. In this study, all dosimetric factors were highly correlated, rV40 and aV40 were independent predictive factors for TLN, IMRT with rV40 <10% or aV40 <5 cc in temporal lobe is relatively safe.


Neutrophil taurine in psoriasis.
Neutrophil taurine was measured in 30 subjects presenting with chronic stable plaque-type psoriasis. The taurine concentration expressed per 5 x 10(6) cells was significantly lower (p < 0.002) in these subjects compared to neutrophil taurine measured in 20 control subjects. In view of increasing evidence proposing possible roles for taurine in maintaining normal neutrophil function coupled with previously observed anti-inflammatory effects of taurine in vitro, an assessment of possible roles of taurine in the aetiology of psoriasis is discussed.


Fetal pulmonary cyst treated by repeated thoracocentesis.
This is a report of prenatal diagnosis and successful therapy of a septated fetal pulmonary cyst by repeated puncturing. This treatment was performed under ultrasonographic guidance for signs of fetal cardiac decompensation. This made normal development of the lungs possible.


Genomic search for prostate cancer predisposition loci in Utah pedigrees.
We report a genome linkage scan in extended Utah pedigrees, utilizing a pedigree-splitting approach to reduce intra-familial heterogeneity. Fifty-nine pedigrees with at least four Prostate cancer (PrCa) cases and no more than two meioses separating PrCa cases were analyzed using the CIDR genomic search STRP marker set. Parametric linkage analyses using dominant and recessive models were performed on four datasets resulting from a pedigree splitting algorithm. In addition, age at diagnosis subset analyses were performed. Four regions of interest (LODs>1.9) were identified on chromosomes 1p, 3q, 5q, and 22q. The linkage peaks on 1p, 3q, and 22q have been previously implicated for PrCa, though not significantly. The 1p region was supported by a single large Utah pedigree with a multipoint LOD score of 3.1. An additional 10 regions gave LOD scores>1.22 (nominal linkage evidence), including moderate evidence supporting the HPC20 region with a recessive model. Our genome-wide search in the informative, extended Utah pedigrees continues to illustrate an ability to identify and replicate linkage peaks, and supports four regions of interest for PrCa predisposition genes.


Isolated congenital absence of posterior cruciate ligament? A case report.
A rare case of a 28-year-old Asiatic male with the isolated absence of a posterior cruciate ligament is reported. Clinical features, diagnostic steps, therapeutic strategies and follow-up are described. A review of the literature is also presented.


A unique cytotoxic CD4+ T cell-signature defines critical COVID-19.
SARS-CoV-2 infection causes a spectrum of clinical disease presentation, ranging from asymptomatic to fatal. While neutralising antibody (NAb) responses correlate with protection against symptomatic and severe infection, the contribution of the T-cell response to disease resolution or progression is still unclear. As newly emerging variants of concern have the capacity to partially escape NAb responses, defining the contribution of individual T-cell subsets to disease outcome is imperative to inform the development of next-generation COVID-19 vaccines. Immunophenotyping of T-cell responses in unvaccinated individuals was performed, representing the full spectrum of COVID-19 clinical presentation. Computational and manual analyses were used to identify T-cell populations associated with distinct disease states. Critical SARS-CoV-2 infection was characterised by an increase in activated and cytotoxic CD4+ lymphocytes (CTL). These CD4+ CTLs were largely absent in asymptomatic to severe disease states. In contrast, non-critical COVID-19 was associated with high frequencies of naïve T cells and lack of activation marker expression. Highly activated and cytotoxic CD4+ T-cell responses may contribute to cell-mediated host tissue damage and progression of COVID-19. Induction of these potentially detrimental T-cell responses should be considered when developing and implementing effective COVID-19 control strategies.


Leucine-rich repeat kinase 2 interacts with p21-activated kinase 6 to control neurite complexity in mammalian brain.
Leucine-rich repeat kinase 2 (LRRK2) is a causative gene for Parkinson's disease, but the physiological function and the mechanism(s) by which the cellular activity of LRRK2 is regulated are poorly understood. Here, we identified p21-activated kinase 6 (PAK6) as a novel interactor of the GTPase/ROC domain of LRRK2. p21-activated kinases are serine-threonine kinases that serve as targets for the small GTP binding proteins Cdc42 and Rac1 and have been implicated in different morphogenetic processes through remodeling of the actin cytoskeleton such as synapse formation and neuritogenesis. Using an in vivo neuromorphology assay, we show that PAK6 is a positive regulator of neurite outgrowth and that LRRK2 is required for this function. Analyses of post-mortem brain tissue from idiopathic and LRRK2 G2019S carriers reveal an increase in PAK6 activation state, whereas knock-out LRRK2 mice display reduced PAK6 activation and phosphorylation of PAK6 substrates. Taken together, these results support a critical role of LRRK2 GTPase domain in cytoskeletal dynamics in vivo through the novel interactor PAK6, and provide a valuable platform to unravel the mechanism underlying LRRK2-mediated pathophysiology. We propose p21-activated kinase 6 (PAK6) as a novel interactor of leucine-rich repeat kinase 2 (LRRK2), a kinase involved in Parkinson's disease (PD). In health, PAK6 regulates neurite complexity in the brain and LRRK2 is required for its function, (a) whereas PAK6 is aberrantly activated in LRRK2-linked PD brain (b) suggesting that LRRK2 toxicity is mediated by PAK6.


Apolipoprotein E deficiency and a mouse model of accelerated liver aging.
The liver is the central metabolic organ which regulates several key aspects of lipid metabolism. The liver changes with age leading to an impaired ability to respond to hepatic insults and an increased incidence of liver disease in the elderly. Apolipoprotein E (ApoE) null mice have proved to be a very popular model to study spontaneous atherosclerosis, but recently it has been demonstrated that in ApoE-/- mice liver there are enzymatic and structural alterations, normally linked to the age. The purpose of this study was to consider ApoE-/- mice as a model for oxidative stress induced hepatic disease and to clarify how ApoE inactivation accelerates the aging process and causes liver disease.We used ApoE null mice and control mice at different ages (6 weeks and 15 months).Liver morphological damage as well as proteins involved in oxidative stress and liver ageing were all analyzed.Our study showed that ApoE null mice develop important age-related changes including oxidative stress, pseudocapillarization, increased polyploidy, decreased hepatocyte number and increased nuclear size. Our findings provide evidence that hypercholesterolemic ApoE-/- mice are more likely to develop severe liver injury, suggesting that in addition to vascular disease, increased cholesterol products and oxidative stress may also play a role in accelerating the progression of aging in the liver.


Validation of local review for the identification of contributory factors and potentially avoidable perinatal deaths.
Reporting on perinatal mortality commenced 2006 in New Zealand through the Perinatal and Maternal Mortality Review Committee (PMMRC). Following review of international models, a process was developed for use in local review to identify contributory factors and potentially avoidable perinatal deaths. Local review of 720 perinatal deaths in 2009 found contributory factors in 24% of deaths and 14% to be potentially avoidable. To validate the process of local review for identification of contributory factors and potentially avoidable perinatal deaths. Records of 48 perinatal deaths were reviewed by an independent multidisciplinary panel using the same methodology as local review to determine agreement between local and independent review for identification of contributory factors and potentially avoidable perinatal death. Independent review found contributory factors in 54% of deaths compared to 40% by local review. Independent review identified eight deaths and local review identified one death with contributory factors not identified by the other review. Kappa statistic for agreement for identifying contributory factors was substantial [0.63 (0.42, 0.84)]. Independent review found 42% of deaths potentially avoidable compared to 23% by local review. Independent review identified 10 deaths and local review identified one death not identified by the other review. Kappa statistic for agreement for identifying potentially avoidable deaths was moderate [0.50 (0.26, 0.73)]. This study provides validation of local review for identification of contributory factors in perinatal death. The higher proportion of potentially avoidable perinatal deaths identified by independent review compared to local review requires further exploration.


The use of chemical occurrence data at European vs. national level in dietary exposure assessments: a methodological study.
A typical EFSA approach to assess dietary exposure is to combine data from national consumption surveys with chemical occurrence data that have been pooled across the EU Member States (pooled approach). This approach was compared to the case where occurrence data were stratified by country and used for food categories where national data were abundant (semi-pooled approach), using cadmium as a case study. Some differences in estimated dietary exposure were observed between the pooled and semi-pooled approach. They were explained by differences, between the national and the European occurrence data, with respect to (1) contamination values and (2) sample proportions of food items classified in the food categories the assessment was based on. The latter aspect highlighted the sensitivity of the approach of directly aggregating monitoring data into food categories. Both the pooled and semi-pooled approach tended to be conservative relative to approaches used at national level. This appears to be attributed to differences in the way the available occurrence data is aggregated. Refinement of the studied methodologies would include a better separation of the food items with high concentration from those with low concentration.


Tissue inhibitor of metalloproteinases levels in patients with chronic heart failure: an independent predictor of mortality.
Matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) are involved in cardiac remodelling. The prognostic utility of TIMP is unknown in chronic heart failure (CHF). We investigated the association of plasma levels of soluble MMP-9 and TIMP-1 with clinical, laboratory and echocardiographic parameters and estimated their prognostic value in the prediction of all-cause death. MMP-9, TIMP-1, tumour necrosis factor-alpha, and amino-terminal pro-brain natriuretic peptide were measured in 249 consecutively enrolled CHF patients and 74 healthy individuals. After adjustment for age, sex and creatinine, levels of TIMP-1 (1640 vs. 735 ng/ml, P<0.001) but not MMP-9 were elevated in CHF patients compared to controls. During a median follow-up period of 2.5 years, 66 patients (27%) died. In multivariable Cox regression models TIMP-1 but not MMP-9 emerged as an independent predictor of all-cause death (hazard ratio per tertile, 3.5; 95% confidence interval [CI], 2.2-5.1). In addition to the full set of univariately predictive clinical and serological markers, information on TIMP-1 significantly increased the area under the receiver operating characteristic curve from 0.77 (95% CI, 0.71-0.84) to 0.87 (95% CI, 0.82-0.92). In stable CHF patients, TIMP-1 but not MMP-9 is of independent and incremental value regarding the prediction of all-cause death.


Folic acid-conjugated fluorescent polymer for up-regulation folate receptor expression study via targeted imaging of tumor cells.
Thoroughly investigation of folate receptor (FR) expression related to targeting drug delivery in tumor cells has been intensively pursued in recent years. Herein, a simple and versatile strategy for determination of FR expression based on targeted imaging of tumor cells with fluorescent nano-conjugates was developed. The fluorescent nano-conjugates were composed of poly 2-vinyl-4,4-dimethyl azlactone (PVDMA) as the linker, folic acid as the targeting unit and amino-Rhodamine B as the fluorescent ligand. Owing to possessing dimethyl azlactone groups in polymer framework, PVDMA could easily reacted with amines or alcohols, and form water soluble materials. Fluorescent imaging studies indicated that the prepared nano-conjugates could specifically target tumor cells and monitor the over expressing of FR. Moreover, the FR expression up-regulation in HeLa cells through medicines regulation has been further explored. This new protocol opens an effective way through synthesis and design of novel fluorescent nano-conjugates for FR expression investigation in tumor cells via targeted imaging, showing great potential in drug delivery mechanism study and cancer therapy.


Substantially improving the enantioconvergence of PvEH1, a Phaseolus vulgaris epoxide hydrolase, towards m-chlorostyrene oxide by laboratory evolution.
Epoxide hydrolase can regioselectively catalyze the oxirane ring-opening hydrolysis of rac-epoxides producing the corresponding chiral diols. In our laboratory, a gene named pveh1 encoding an EH from Phaseolus vulgaris was cloned. Although the directed modification of PvEH1 was carried out, the mutant PvEH1Y3 showed a limited degree of enantioconvergence towards racemic (rac-) m-chlorostyrene oxide (mCSO). PvEH1 and PvEH1Y3 were combinatively subjected to laboratory evolution to further enhance the enantioconvergence of PvEH1Y3 towards rac-mCSO. Firstly, the substrate-binding pocket of PvEH1 was identified using a CAVER 3.0 software, and divided into three zones. After all residues in zones 1 and 3 were subjected to leucine scanning, two E. coli transformants, E. coli/pveh1Y149L and /pveh1P184L, were selected, by which rac-mCSO was transformed into (R)-m-chlorophenyl-1,2-ethanediol (mCPED) having 55.1% and 27.2% eep. Secondly, two saturation mutagenesis libraries, E. coli/pveh1Y149X and /pveh1P184X (X: any one of 20 residues) were created at sites Y149 and P184 of PvEH1. Among all transformants, both E. coli/pveh1Y149L (65.8% αS and 55.1% eep) and /pveh1P184W (66.6% αS and 59.8% eep) possessed the highest enantioconvergences. Finally, the combinatorial mutagenesis was conducted by replacements of both Y149L and P184W in PvEH1Y3, constructing E. coli/pveh1Y3Z2, whose αS reached 97.5%, higher than that (75.3%) of E. coli/pveh1Y3. In addition, the enantioconvergent hydrolysis of 20 mM rac-mCSO was performed by E. coli/pveh1Y3Z2, giving (R)-mCPED with 95.2% eep and 97.2% yield. In summary, the enantioconvergence of PvEH1Y3Z2 was successfully improved by laboratory evolution, which was based on the study of substrate-binding pocket by leucine scanning. Our present work introduced an effective strategy for the directed modification of enantioconvergence of PvEH1.


Optimizing Fertility Treatment With Nutrition Guidance: Exploring Barriers and Facilitators to Healthful Nutrition Among Female Cancer Survivors With Fertility Challenges.
Young women diagnosed with cancer are at an increased risk for infertility compared to women without a cancer diagnosis. Consuming a healthful diet comprised of whole grains, fruits, vegetables, and unsaturated fats has been found to improve both fertility and cancer survivorship. Given this reason, dietary interventions tailored to support female cancer survivors with fertility challenges are of immense importance. Therefore, the aim of this study was to explore barriers and facilitators to healthful nutrition among female cancer survivors with fertility challenges, to inform the development of dietary interventions for this population. Using a formative research design, interview, survey, and dietary intake data were collected from 20 female cancer survivors of reproductive age. Participant-check focus group discussions were conducted to validate findings. All interviews were recorded and transcribed verbatim. Transcripts were coded and analyzed using a thematic analysis approach. Quantitative data were analyzed using means, standard deviations, ranges, frequencies, and percentages. The average age of respondents was 31.47 ± 3.5 years and the average BMI was 24.78 ± 4.1 kg/m2. All participants were college educated, 45% identified as White, 50% as Black, and 10% as Hispanic or Latinx. Cancer diagnoses included breast, thyroid, ovarian, leukemia, and gastrointestinal cancers. The following themes were identified: (1) Lack of nutrition-related resources and detailed guidance, (2) Work-life balance, (3) Perceived rigidity of dietary guidance, (4) Treatment-related fatigue, (5) Having trust in healthcare providers, (6) Higher motivation to change nutrition behavior, and (7) Recognizing the additional benefits of nutrition. These findings indicate a sought-after yet unmet need for post-cancer treatment fertility nutrition recommendations. Interventions should be tailored to women's needs and focus on improving their self-efficacy to make healthful dietary choices.


Dimeric HER2-specific affibody molecules inhibit proliferation of the SKBR-3 breast cancer cell line.
HER2-specific affibody molecules in different formats have previously been shown to be useful tumor targeting agents for radionuclide-based imaging and therapy applications, but their biological effect on tumor cells is not well known. In this study, two dimeric ((Z(HER2:4))(2) and (Z(HER2:342))(2)) and one monomeric (Z(HER2:342)) HER2-specific affibody molecules are investigated with respect to biological activity. Both (Z(HER2:4))(2) and (Z(HER2:342))(2) were found to decrease the growth rate of SKBR-3 cells to the same extent as the antibody trastuzumab. When the substances were removed, the cells treated with the dimeric affibody molecules continued to be growth suppressed while the cells treated with trastuzumab immediately resumed normal proliferation. The effects of Z(HER2:342) were minor on both proliferation and cell signaling. The dimeric (Z(HER2:4))(2) and (Z(HER2:342))(2) both reduced growth of SKBR-3 cells and may prove therapeutically useful either by themselves or as carriers of radionuclides or other cytotoxic agents.


Draft Whole-Genome Sequence of Triparma laevis f. inornata (Parmales, Bolidophyceae), Isolated from the Oyashio Region, Western North Pacific Ocean.
We present the first draft whole-genome sequence for the Parmales (Bolidophyceae, Heterokonta), a picoplanktonic sister group of diatoms, using a Triparma laevis f. inornata strain that was isolated from the Oyashio region in the western North Pacific Ocean.


Safety, Effect and Feasibility of Percutaneous SI-Screw with and without Augmentation-A 15-Year Retrospective Analysis on over 640 Screws.
Minimally invasive sacroiliac-screw (SI-screw) fixation of the pelvis is used in energy trauma (Arbeitsgemeinschaft für Osteosynthesefragen (AO) classified) and fragility fractures (Fragility Fracture of the Pelvis (FFP) classified). However, available clinical data are based on small case series and biomechanical data seem to be contradictory. The present single center retrospective cohort study investigated percutaneous SI-screw fixation and augmentation over 15 years. Groups were compared concerning the general epidemiological data, mobilization, complication rates, duration of stay, and safety of SI-screw insertion. Multivariable analyses were performed using logistic regression. Between 2005 and March 2020, 448 patients with 642 inserted SI-screws were identified. Iatrogenic neurological impairment was documented in 2.47% and correlated with screw misplacement. There was an increased complication risk in patients with AO type C over patients with AO type B and in FFP II over FFP III/IV patients. Cement-augmented FFP patients showed a 25% reduced stay in hospital and a reduced complication risk. Cement-associated complications were seen in 22% without correlation to neurologic impairment. The present study confirms the safety and usability of percutaneous SI-screw fixation, despite specific risks. Cement augmentation seems to reduce the complication risk in FFP patients and shorten hospital stay for some reasons, without increased specific complications or correlated neurological impairment.


Urban birdsongs: higher minimum song frequency of an urban colonist persists in a common garden experiment.
Environmental changes caused by urbanization and noise pollution can have profound effects on acoustic communication. Many organisms use higher sound frequencies in urban environments with low-frequency noise, but the developmental and evolutionary mechanisms underlying these shifts are generally unknown. We used a common garden experiment to ask whether changes in minimum song frequency observed 30 years after a songbird colonized an urban environment are a consequence of behavioural flexibility. We captured male juvenile dark-eyed juncos, Junco hyemalis thurberi, from two populations (urban and mountain) soon after they reached independence (aged 25-40 days), raised them in identical indoor aviaries and studied their songs at an age of 3 years. We found that the large population difference in minimum frequency observed in the field persisted undiminished in the common garden despite the absence of noise. We also found some song sharing between the common garden and natal field populations, indicating that early song memorization before capture could contribute to the persistent song differences in adulthood. These results are the first to show that frequency shifts in urban birdsong are maintained in the absence of noise by genetic evolution and/or early life experiences.


An individually moulded insole with 5-mm medial arch support reduces peak impact and loading at the heel after a one-hour treadmill run.
Foot pain experienced by long-distance runners could be relieved by functional insoles which aim at evenly distributing the plantar pressure. We hypothesised that an individually moulded insole with medial arch support would reduce the impact and loading under the heel and metatarsal regions. Twelve male recreational runners ran on a treadmill at 10 km/h for 1 hour with flat insoles and medial arch supported insoles. A pressure insole system (Novel Pedar, Germany) was used to obtain the peak pressure, peak force, time normalised pressure-time integrals, and the percentage of the total force-time integrals under 10 regions. Medial arch supported insoles reduced the peak force under the heel (medial: -15.3%, p = 0.001; lateral: -19.2%, p = 0.037) during the initial run, and reduced peak pressure under the heel (medial: -13.3%, p = 0.005; lateral: -9.9%, p = 0.006), and peak force under the medial heel (-17.8%, p = 0.006) after the run. The percentage of the total force-time integrals under the heel was reduced (medial: -23.8%, p = 0.004; lateral: -13.6%, p = 0.022) after the run. No significant difference was found under the metatarsal regions. There is shift of load from the metatarsal regions to the medial mid-foot as indicated by the change of the percentage of total force-time integrals. Medial arch supported insoles were effective in reducing the impact and loading under the heel region in prolonged running on a treadmill. Controlled laboratory study, Level V.


Vegetation and soil nutrient restoration of cut slopes using outside soil spray seeding in the plateau region of southwestern China.
Outside soil spray seeding (OSSS) is used widely for road cut revegetation, and the artificial soil used in OSSS can improve slope soil conditions and nutrients, and help promote plant growth and succession. Three different slopes was investigated to evaluate the effectiveness of OSSS for restoration, including a natural slope (NS), a cut slope without any artificial recovery treatment (CSW) and a cut slope treated with OSSS (CSO). The recovery of cut slopes was determined by evaluating a number of factors, including indices associated with plants on the slopes, soil enzyme activities (urease and sucrase), and soil nutrient content (soil organic matter (SOM), total phosphorous (TP), total potassium (TK), available nitrogen (AN), available phosphorous (AP), available potassium (AK), potassium (K+), calcium (Ca2+), magnesium (Mg2+), and sulphate (SO42-)). The results indicated that the vegetation and soil conditions differed between the three slopes. The Shannon-Wiener index (H), the Simpson index (D), and the Margalef index (R) values from the CSO and NS were lower than those of the CSW, whilst the Pielou index (E) value and vegetation canopy cover were higher for the CSO and NS than for the CSW. The content of SOM and AN in soil from the CSO was lower than in soil from the NS and CSW, and content of many nutrients were higher in soil from the CSO than in soil from the NS and CSW. This suggests that the restoration of vegetation and soil nutrients on the CSO was relatively successful. Our results indicated that the use of OSSS to restore cut slopes is effective in plateau areas. However, despite improvements in soil nutrient levels, there were still nutritional imbalances. Therefore, more attention should be paid to balancing nutrients in the later stage of OSSS implementation for the recovery of cut slopes at high altitudes.


Comparative pulmonary surfactant-inducing effect of three corticosteroids in the near-term rat.
Equivalent doses of dexamethasone, prednisolone, and betamethasone were given intraperitoneally to pregnant rats on day 20. Six dosage levels were selected: 0.4, 0.8, 1.6, 3.2, 6.4, and 12.8 mg/kg. Corticosteroids were diluted in saline solution containing 300 microCi of 3Hcholine. Twenty-four rats (18 experimental, six control) were killed on day 21, four viable fetuses were removed from each, and the four pairs of fetal lungs from each rat were pooled. Phospholipids were extracted and separated by thin-layer chromatography. Incorporation of 3Hcholine represented amounts of newly induced pulmonary lecithin and sphingomyelin. Results were expressed in terms of percentage change from control. Betamethasone appeared to be the most potent, with a statistically significant greater effect at the 6.4 mg/kg dosage level (two-factor analysis of variance, p = 0.03). There appeared to be a suppressive effect of all corticosteroids at the 12.8 mg/kg dosage level. If similar responses were observed in primates, the results would suggest that higher dosage levels of betamethasone (up to four times the presently recommended dose of approximately 0.34 mg/kg) might be more efficacious.


Antioxidant defenses at transcriptional and enzymatic levels and gene expression of Nrf2-Keap1 signaling molecules in response to acute zinc exposure in the spleen of the large yellow croaker Pseudosciaena crocea.
We evaluated the effects of acute Zn exposure (4 and 8 mg L(-1) Zn) on lipid peroxidation, and activities and mRNA levels of antioxidant enzyme genes (Cu/Zn-SOD, CAT, GPx, and GR), and gene expression of the Nrf2-Keap1 signaling molecule at different exposure times (0, 6, 12, 24, 48, and 96 h) in the spleen of large yellow croaker. Lipid peroxidation remained relatively constant during 6-48 h and 6-24 h and sharply increased at 96 h and during 48-96 h in fish exposed to 4 and 8 mg L(-1) Zn, respectively. Activities of all tested enzymes increased during the early stage of exposure and decreased towards the end of the exposure in both groups. However, mRNA levels of antioxidant enzyme genes were dramatically up-regulated by 4 and 8 mg L(-1) Zn during the late stage of exposure. During the early stage of exposure for 6 h, the 8 mg L(-1) Zn exposure sharply increased mRNA levels of Cu/Zn-SOD, CAT, GPx1b, Nrf2, and Keap1, whereas, the 4 mg L(-1) Zn exposure did not significantly affect the expression of these genes. Our data also showed positive relationships between Nrf2 expression and mRNA levels of its target genes, suggesting that Nrf2 was required for the protracted induction of these genes. Furthermore, a sharp increase in Keap1 expression levels was observed in fish exposed to 4 mg L(-1) at 96 h, and 8 mg L(-1) at 6, 48, and 96 h. In conclusion, the present study demonstrated that Zn-induced antioxidant defenses were involved in modifications at enzymatic and transcriptional levels and the transcriptional regulation of the Nrf2-Keap1 signaling molecule; these results may contribute to the understanding of mechanisms that maintain the correct redox balance in the immune organ of the large yellow croaker.


GC1118, a novel anti-EGFR antibody, has potent KRAS mutation-independent antitumor activity compared with cetuximab in gastric cancer.
EGFR overexpression in gastric cancer (GC) has been reported in about 30% of patients. However, the anti-EGFR antibodies cetuximab and panitumumab have failed to improve overall survival of GC patients in combination with cytotoxic chemotherapy compared with chemotherapy alone. GC1118, a novel anti-EGFR antibody with a distinct binding epitope compared with cetuximab or panitumumab, has not been tested in GC. GC cell lines, SNU-1, SNU-5, SNU-16, SNU-216, SNU-484, SNU-601, SNU-620, SNU-638, SNU-668, SNU-719, AGS, MKN-45, NCI-N87, and KATO-III, were employed to test the effect of cetuximab or GC1118 alone, and combined with the cytotoxic agent cisplatin or 5-fluorouracil (5-FU). Cells were also treat with or without high-affinity ligands EGF 20 ng/ml or HB-EGF 100 ng/ml. GC1118 exhibited a more potent growth inhibition effect in the majority of cell lines than cetuximab in MTT assay, regardless of the KRAS mutation status of cell lines. Co-treatment of GC1118 and cisplatin or 5-FU inhibited colony formation and migration to a greater extent, even following EGFR ligand stimulation. Ligand-induced p-AKT and p-ERK upregulation were more potently inhibited by combination treatment with GC1118 and chemotherapeutic agents compared with cetuximab plus chemotherapeutic agents. GC1118 also showed more potent anti-tumor effects compared with cetuximab in a mouse xenograft model. Taken together, GC1118 alone or in combination with cytotoxic chemotherapeutic agents exerted more potent anti-tumor effects than cetuximab in GC cells, regardless of KRAS status. These findings support the further clinical development of GC1118 for the treatment of GC.