Predicting DUI recidivism: Personality, attitudinal, and behavioral risk factors.
To predict DUI recidivism using personality, attitudinal, and behavioral factors. We conducted cross-sectional analyses of survey data. Covariance structure modeling was used to identify unique predictors of driving after drinking (DAD), alcohol consumption, and high-risk driving. Two hundred and eighty individuals with multiple DUI convictions, predominately male and Hispanic. Participants were surveyed in the Rio Hondo Courthouse, Los Angeles County, California. The survey included measures of past year frequency of DAD, socially desirable response bias, sensation seeking, trait hostility, high-risk driving style, alcohol expectancies, and alcohol consumption. DAD was positively related with frequency of drinking and with positive alcohol expectancies. It was negatively associated with socially desirable response bias. Measures of high-risk driving and the personality variables were highly negatively associated with socially desirable response bias. Individuals who believe that they are affected positively by alcohol intoxication are not responding to the standard penalties for DUI and persist in driving after drinking. These beliefs may serve as an important point of intervention for programs designed to reduce drunk driving. The current research also suggests that self-report measures of DAD, as well as many hypothesized risk factors, are highly correlated with socially desirable response biases. Failure to control for such biases may be a significant threat to the validity of research in this field.


Biomechanics of cervical laminoplasty: kinetic studies comparing different surgical techniques, temporal effects and the degree of level involvement.
Laminoplasty is a common surgical technique used to treat cervical myelopathy. Both voids and contradictory information exist in the literature with regard to the initial and long-term biomechanical consequences of cervical laminoplasty. In order to clarify the existing literature, as well as provide clinically useful information, we identified three specific aims: (1) to measure the long-term differences in kinetics between the open door laminoplasty (ODL) and French door laminoplasty (FDL) techniques; (2) to delineate differences in primary and long-term cervical motion after laminoplasty; and (3) to determine whether inclusion of additional levels in the laminoplasty procedure results in a change in immediate cervical biomechanics. The study design involved both an animal (caprine) model and in vitro surgical simulation. We kinematically evaluated the cervical spine specimens (C2-C7) by applying pure bending moment loads to the cephalad vertebra (C2), while constraining the caudal vertebra (C7). Resultant intervertebral rotations (C3-C6) were determined via stereophotogrammetry. Overall, the data indicate that both FDL and ODL significantly reduce range of motion 6 months postoperatively, compared with the un-operated spine. There were no significant differences between the two techniques after 6 months. We also showed that ODL produces a significant reduction in motion 6 months postoperatively compared with the immediate postoperative condition. Finally, the data indicated that extending the laminoplasty from two to four levels did not significantly change range of motion. The choice of technique should be based upon the surgeon's experience with these technically demanding procedures. In addition, initial stability considerations should not affect the decision to extend the laminoplasty to adjacent levels. Finally, the data also suggest that early changes in biomechanics should not be a major factor when considering whether immobilization of the cervical spine is necessary after laminoplasty. In fact, our temporal study, as well as previously reported clinical data, indicates that one should expect significantly decreased intervertebral motion 6 months after laminoplasty. Therefore, early physical therapy should be considered to preserve a more physiologic pattern of cervical range of motion.


Characterization of negatively charged phospholipids and cell origin of microparticles in women with gestational vascular complications.
Gestational vascular complications (GVC) are a major cause of maternal and fetal morbidity which can be potentially reduced by LMWH. Microparticles (MPs) are involved in thrombosis and inflammation. However, characterization and role of MPs in GVC have not been elucidated. MPs were isolated from non-pregnant women, healthy pregnant women, women with GVC (hypertension or preeclamptic toxemia (PET)) and women with a history of pregnancy complications who were treated with LMWH. MP count, cell origin and expression of negatively charged phospholipids were evaluated. Total numbers of MPs were similar in the study cohorts, with a non-significant trend toward an increase in the pregnant groups, while percentage of MPs bearing negatively charged phospholipids was significantly reduced in all the pregnancy groups. Endothelial CD144-MPs were elevated in the GVC groups compared to the healthy pregnant cohort. Endothelial CD31+/CD41-MPs were decreased in the LMWH group compared to women with PET. Percentage of placental trophoblast MPs was similar in all pregnancy groups and platelet MPs were reduced in healthy pregnant compared to non-pregnant women. Notably, percent of MPs bearing negatively charged phospholipids correlated only with platelet MPs, but not with endothelial, trophoblast or leukocyte MPs. Presence of negatively charged phospholipids cannot be considered universal characteristics of MPs in pregnancy. MPs may reflect the vascular injury characterizing GVC pathology.


Radon levels and indoor air quality after application of thermal retrofit measures-a case study.
This study was conducted to evaluate the influence of thermal retrofit on radon levels in workrooms, and to determine whether the radon concentration in the building changes after the application of retrofit measures. In the first survey, digital Airthings Corentium Home radon detector was used for 1-month radon measurements during the heating season 2018/19. The daily averaged radon concentrations varied from 37 to 573 Bq/m3 for 10 selected workrooms, while hourly averaged radon measurements showed extreme variations from 6 to 1603 Bq/m3 due to radon fluctuations. In second survey, passive radon technique based on charcoal canister test kit was conducted in all basement workrooms in spring 2021. The averaged radon concentrations grouped according to flooring type in workrooms were 327 Bq/m3 for parquet, 227 Bq/m3 for ceramic tiles, 146 Bq/m3 for vinyl flooring and 71 Bq/m3 for laminate. Besides thermal insulation and airtight windows, noticeable differences in indoor radon concentration within the renovated building are primarily caused by different types of flooring. It includes various types of insulation from the ground/concrete slab: laminate, parquet (wood blocks), vinyl flooring, and ceramic tiles. Detailed analysis point out that laminate is more efficient way for radon protection than other types of flooring. An efficient ventilation system should be installed to avoid increasing occupational radon exposure and to provide healthy and comfortable indoor environment.


Kappa statistic considerations in evaluating inter-rater reliability between two raters: which, when and context matters.
In research designs that rely on observational ratings provided by two raters, assessing inter-rater reliability (IRR) is a frequently required task. However, some studies fall short in properly utilizing statistical procedures, omitting essential information necessary for interpreting their findings, or inadequately addressing the impact of IRR on subsequent analyses' statistical power for hypothesis testing. This article delves into the recent publication by Liu et al. in BMC Cancer, analyzing the controversy surrounding the Kappa statistic and methodological issues concerning the assessment of IRR. The primary focus is on the appropriate selection of Kappa statistics, as well as the computation, interpretation, and reporting of two frequently used IRR statistics when there are two raters involved. The Cohen's Kappa statistic is typically utilized to assess the level of agreement between two raters when there are two categories or for unordered categorical variables with three or more categories. On the other hand, when it comes to evaluating the degree of agreement between two raters for ordered categorical variables comprising three or more categories, the weighted Kappa is a widely used measure. Despite not substantially affecting the findings of Liu et al.?s study, the statistical dispute underscores the significance of employing suitable statistical methods. Rigorous and accurate statistical results are crucial for producing trustworthy research.


Sociodemographic disparities in choice of therapy and survival in advanced laryngeal cancer.
To determine if sociodemographic factors are associated with treatment choice and survival in patients with advanced stage laryngeal cancer in the U.S. Population-based, non-concurrent cohort study of 5381 patients diagnosed with stage III or IV laryngeal squamous cell carcinoma from 1992-2009. Data was extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Choice of therapy (surgical vs. non-surgical) and disease-specific survival (DSS). Age ≥60 years (odds ratio [OR]=0.78; 95% CI, 0.70-0.88) and more recent year of diagnosis (OR=0.89; 95% CI, 0.87-0.90) decreased the odds of receiving surgical therapy, while residing in a county with low median household income (OR=1.36; 95% CI, 1.17-1.57) increased the odds of receiving surgical therapy. Age ≥60 years (hazard ratio [HR]=1.45; 95% CI, 1.33-1.59) and Black race (HR=1.14; 95% CI, 1.02-1.27) were negatively associated with DSS, while female sex (HR=0.81; 95% CI, 0.72-0.90) and married status (HR=0.69; 95% CI, 0.63-0.75) were positively associated with DSS. For patients with advanced laryngeal cancer, younger age and residing in a low-income county increase the likelihood of receiving surgical therapy. Female sex and married status provide a survival benefit, while Black race appears to be a negative prognostic factor. This highlights the impact of sociodemographic factors on treatment strategies and outcomes and highlights areas for further research on health disparities.


A simple and reliable method for visualization of the arterial autonomic nerve plexus by scanning electron microscopy.
A simple and reproducible procedure is described by which the autonomic nerve plexus in rat mesenteric arteries is revealed at a three-dimensional level, using scanning electron microscopy after HC1-hydrolysis.


Magnetic resonance imaging and correlative gross anatomy of the ligamentum semicirculare humeri (rotator cable).
The purpose of this study has been to demonstrate macroscopic and MRI anatomy of the so-called rotator cable, otherwise known as the ligamentum semicirculare humeri (LSCH) of the superior shoulder joint capsule. Twelve shoulder joints from eight cadavers were dissected; seven of which, from four of the cadavers, were studied using MR arthrography (1.5-Tesla device Somatom Symphony, Siemens, Erlangen, Germany) prior to dissection. The MRI protocol included T1WI, PDWI, and DESS 3D WI standard sequences. The results of MRI were compared with gross anatomic dissection findings. The macroscopically recognizable capsular bundle of LSCH fibers was identified by anatomic dissection in all specimens. On MRI, the entire ligament or parts of it could be identified in six of seven cases. It was best visualized on axial images. In the evaluation of magnetic resonance images of superior shoulder joint structures, additional knowledge on the anatomy of the LSCH can be used by the radiologist to facilitate detailed interpretation of the shoulder MRI.


[Adult metachromatic leukodystrophy manifested as schizophrenic psychosis (author's transl)].
An autopsy case of adult metachromatic leukodystrophy (MLD) manifested clinically as schizophrenic psychosis is reported. A 50-year-old man developed progressive mental changes 10 years before his death, and later manifested a schizophrenic syndrome without neurologic deficits or EEG changes. After his death from uremia neuropathology disclosed MLD with demyelination accentuated in the frontal lobes and abundant metachromatic deposits in the preserved areas of cerebral white matter. Neurochemical examination of the demyelinated frontal area showed reduced concentration of cerebrosides and sulfatides, decreased amounts of total lipids in the tissue, and an increase of sulfatides, and particularly of their cerebron fractions in lipid extract. The problems of adult forms of MLD with prolonged course are discussed with special reference to cases showing mainly psychiatric syndromes.


High aspect ratio nanotubes assembled from macrocyclic iminium salts.
One-dimensional nanostructures such as carbon nanotubes and actin filaments rely on strong and directional interactions to stabilize their high aspect ratio shapes. This requirement has precluded making isolated, long, thin organic nanotubes by stacking molecular macrocycles, as their noncovalent stacking interactions are generally too weak. Here we report high aspect ratio (>103), lyotropic nanotubes of stacked, macrocyclic, iminium salts, which are formed by protonation of the corresponding imine-linked macrocycles. Iminium ion formation establishes cohesive interactions that, in organic solvent (tetrahydrofuran), are two orders of magnitude stronger than the neutral macrocycles, as explained by physical arguments and demonstrated by molecular dynamics simulations. Nanotube formation stabilizes the iminium ions, which otherwise rapidly hydrolyze, and is reversed and restored upon addition of bases and acids. Acids generated by irradiating a photoacid generator or sonicating chlorinated solvents also induced nanotube assembly, allowing these nanostructures to be coupled to diverse stimuli, and, once assembled, they can be fixed permanently by cross-linking their pendant alkenes. As large macrocyclic chromonic liquid crystals, these iminium salts are easily accessible through a modular design and provide a means to rationally synthesize structures that mimic the morphology and rheology of carbon nanotubes and biological tubules.


Ciprofloxacin resistance in the faecal carriage of patients undergoing transrectal ultrasound guided prostate biopsy.
WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Transrectal ultrasound guided prostate biopsies (TRUSBx) are associated with a spectrum of complications, including most significantly infection, which affects up to 5% of patients. In the most severe cases, infection leads to sepsis, a life-threatening complication. Escherichia coli is the primary responsible pathogen. Although antibiotic prophylaxis with fluoroquinolones is routinely used, there is evidence that the infection rate after TRUSBx is increasing, and this appears to be due to an increasing prevalence of ciprofloxacin-resistant rectal flora. This is the largest prospective clinical trial to date analysing the rectal flora of men undergoing prostate biopsies. We determined the microbial and antibiotic sensitivity profiles from 849 patients. Ciprofloxacin-resistant Gram-negative organisms were identified in the rectal flora of 19.0% of men. Furthermore, fluoroquinolone use within 6 months preceding a TRUSBx and the presence of a prosthetic heart valve were significant predictors of ciprofloxacin resistance on rectal swab. Determining the prevalence of rectal fluoroquinolone resistance has important implications in evaluation of the suitability of prophylactic regimens. Antimicrobial profiles derived from rectal swabs pre-biopsy may prove useful in guiding targeted antibiotic prophylaxis. To establish the prevalence of ciprofloxacin-resistant bacteria in patients undergoing transrectal ultrasound guided prostate biopsies (TRUSBx) and to determine whether this predicts subsequent infectious complications. To identify risk factors for harbouring ciprofloxacin-resistant flora. Any patient undergoing a TRUSBx from 2009 to 2011 was eligible for enrolment in this prospective study. Pre-biopsy rectal and urine cultures and post-biopsy urine cultures were obtained and antimicrobial susceptibility was determined. Univariate and multivariate analyses were performed to identify independent patient risk factors associated with ciprofloxacin-resistant rectal flora. A total of 865 patients underwent TRUSBx, of whom 19.0% were found to have ciprofloxacin-resistant Gram-negative coliforms. Escherichia coli was the most prevalent Gram-negative rectal isolate (80.9%) and accounted for 90.6% of ciprofloxacin resistance. Patient characteristics that conferred an increased risk of harbouring ciprofloxacin-resistant organisms included a history of a heart valve replacement (P < 0.05) and ciprofloxacin use in the past 3 months (P < 0.05). Infectious complications were observed in 3.6% (n = 31) of the patient population and 48% of these patients grew ciprofloxacin-resistant organisms on the pre-biopsy rectal swab (P < 0.001). Antimicrobial resistance to ciprofloxacin in the rectal flora was common, particularly in patients with recent ciprofloxacin use and a heart valve replacement. Despite a significant correlation between those patients who developed infections and the detection of ciprofloxacin-resistant organisms, only 9.0% (n = 15) of the total group with ciprofloxacin resistance developed an infectious complication. Future studies will need to evaluate the cost effectiveness and clinical utility of a pre-biopsy rectal culture in targeting antibiotic prophylaxis.


Multigenerational cadmium acclimation and biokinetics in Daphnia magna.
A Cd exposure (3 microg L(-1)) experiment was conducted for six successive generations to investigate the responses to chronic Cd stress in Daphnia magna. We observed a biphasic accumulation of Cd in the six generations and suggested a similar pattern with respect to daphnids' tolerance. Cd assimilation efficiencies, daphnid growth, and reproduction corresponded to the changes of tolerance, which was partially accounted for by metallothionein induction. When maternally exposed neonates grew in Cd-free water for one or two generations, their growth, MT concentration and biokinetic parameters partially or totally recovered. The rapid recovery suggests the high potential for ecological restoration from Cd pollution. Our results indicate that the tolerance of sensitive D. magna clones to Cd was dependent on long-term or multigenerational exposure. The tolerance developed within the first several generations might not be maintained, and the animals may become even more sensitive to Cd stress in subsequent generations.


Qualitative and quantitative variations of membrane lipid species in Acholeplasma laidlawii A.
In Acholeplasma laidlawii A, strain EF 22, the relative amounts of the membrane polar lipids vary as a consequence of different fatty acid supplements to the growth medium. The number of lipid species also varies; a new apolar monoglucolipid containing four fatty acid residues was present only when saturated fatty acids dominated in the growth medium. A new phosphoglucolipid, probably with a glycerophosphoryl-monoglucosyldiglyceride structure, was also found. The most pronounced variations occurred between the two dominating glucolipids, monoglucosyldiglyceride and diglucosyldiglyceride; the former being found in larger amounts when a saturated or a trans-unsaturated fatty acid was present in the medium. The amount of diglucosyldiglyceride decreased accordingly. A qualitative relationship between fatty acid properties and membrane lipid variations was established over a wide fatty acid concentration range. Incorporation of supplied fatty acids reached higher levels than normally found in other acholeplasmas. The ratio between membrane protein and lipids exhibited significant and coherent variations during growth and was to some extent influenced by the fatty acids in the medium. These changes indicate variations in lipid-protein organization in the membranes during growth.


The role of intestinal flora on the interactions between nonparenchymal cells and hepatocytes in coculture.
Kupffer cells are exposed directly to a number of factors in the portal circulation that can modify or regulate their responses to septic stimuli. The gut represents a potential source of a number of these factors including endotoxin, lymphokines, and prostaglandins. We examined Kupffer cells from germfree rats and germfree rats exposed to endotoxin or bacteria via their GI tracts to determine the importance of the intestinal flora in maintaining or modulating Kupffer cell responses. Kupffer cells from germfree animals were reduced in numbers and failed to respond to LPS in Kupffer cell: hepatocyte coculture. When germfree rats were exposed to bacterial endotoxin or bacteria via the gastrointestinal tract their Kupffer cells increased in numbers to normal and the cells responded to LPS in culture. Intestinal overgrowth with Escherichia coli for 2 days activated the Kupffer cells and significantly increased Kupffer cell sensitivity to LPS. These data suggest that the environment of the gastrointestinal tract is important for normal Kupffer cell responses and that intestinal bacterial overgrowth can modify Kupffer cell responses to septic stimuli.


Diversity in Orthopaedic Sports Medicine Societies.
The purpose of this study was to report demographic trends in terms of ethnicity/race and gender among the membership and leadership positions of the Arthroscopy Association of North America (AANA) and the American Orthopaedic Society of Sports Medicine (AOSSM). Over the years both AANA and AOSSM will increase in diversity through their committee membership and leadership positions. AANA and AOSSM membership and leadership were reviewed for the years 2010, 2015, and 2020. Race/ethnicity was divided into Caucasian, Asian, African American (AA), Hispanic/Latin/South American (HLSA), and Middle Eastern (ME). Gender was limited to male or female, based on name and photographic depiction. Diversity in AANA and AOSSM committee and leadership positions is summarized in Table 1 and Table 2, respectively. In 2010, 166/191 (87%) AANA committee members were Caucasian, as compared with 125/186 (67%) in 2020. Asian committee members were similar in 2010 (13/191, 7%) and 2015 (13/216, 6%) but increased to 17/186 (10%) in 2020. HLSA committee members increased from 5/191 (3%) 2010 to 11/186 (6%) in 2020. AA committee membership increased from 2/191 (1%) in 2010 to 5/186 (3%) in 2020. The diversity of AANA Board of Director leadership positions increased, with Caucasian representation decreasing from 14/14 (100%) 2010 to 11/12 (92%) in 2020 and Asian representation increasing from 0% in 2010 to 1/12 (8%) in 2020, with HLSA, AA and ME remaining the same with 0/12 (0%). In AANA, men comprised 181/191 (95%) committee members in 2010 and 166/186 (89%) in 2020. The percentage of female committee members increased from 10/191 (5%) in 2010 to 20/186 (11%) in 2020. In 2010, 73/79 (92%) AOSSM committee members were Caucasian compared to 62/81 (77%) in 2020 with AA having the largest increase in committee members from 0% in 2010 to 6/81 (7%) in 2020 (Table 2). Within AOSSM, men comprised 73/79 (92%) committee members in 2010 and 70/81 (86%) in 2020. The percentage of female committee members in AOSSM increased from 6/79 (8%) in 2010 to 11/81 (14%) in 2020. There has been a progressive trend toward increasing diversity in both committee membership and leadership positions in AANA and AOSSM from 2010 to 2020. Within AANA, there has been a decrease in the Caucasian representation from 87% in 2010 to 67% in 2020 and an increase in the female representation from 5% in 2010 to 11% in 2020. AOSSM demonstrated a similar trend, with Caucasian representation decreasing from 92% in 2010 to 77% in 2020, in addition to female percentage increasing from 8% in 2010 to 14% in 2020. Although there has been an increase in representation of minority and female orthopaedic surgeons within both societies, there is still room for more diversity and inclusion within committee membership and leadership. It is important to progress toward the understanding of the changes that need to be made and work to implement opening the field of orthopaedic sports medicine.


A mixed blessing for liver transplantation patients - Rapamycin.
Liver transplantation (LT) is an effective treatment option for end-stage liver disease. Mammalian target of rapamycin (mTOR) inhibitors, such as rapamycin, are widely used post LT. In this review, we focused on the anti-cancer activities and metabolic side effects of rapamycin after LT. The literature available on PubMed for the period of January 1999-September 2022 was reviewed. The key words were rapamycin, sirolimus, liver transplantation, hepatocellular carcinoma, diabetes, and lipid metabolism disorder. Rapamycin has shown excellent effects and is safer than other immunosuppressive regimens. It has exhibited excellent anti-cancer activity and has the potential in preventing hepatocellular carcinoma (HCC) recurrence post LT. Rapamycin is closely related to two long-term complications after LT, diabetes and lipid metabolism disorders. Rapamycin prevents HCC recurrence post LT in some patients, but it also induces metabolic disorders. Reasonable use of rapamycin benefits the liver recipients.


Age-related changes in glycerolipid formation in lean and obese Zucker rats.
Age-related changes in hepatic and adipose glycerolipid formation have been described in Zucker rats. Glycerolipid formation was measured in vitro in the presence of [14C]glycerol-3-phosphate, palmitate, ATP, CoA, and Mg2+ by using liver and adipose tissue homogenates derived from various age groups of animals. Hepatic glycerolipid formation increased after birth to reach a peak value at 1 day of age. This period was followed by a decline in the rates of glycerolipid formation. Hepatic glycerolipid formation increased again at the time of weaning and continued to rise up to 32 days in lean rats and 42-44 days in obese rats. Obesity in rats was recognizable at the age of 32 days and was associated with increased rates of glycerolipid formation in both liver and adipose tissue. As far as the changes in hepatic glycerolipid formation and triglyceride accumulation are concerned, obese rats showed more resemblance to 1-day-old rats than to lean animals of similar age groups. Glycerolipid formation decreased in liver and increased in adipose tissue with age in both lean and obese rats. These studies suggest that hepatic and adipose tissue glycerolipid formation is significantly influenced by age and obesity in Zucker rats.


Cross-talk between Janus kinase-signal transducer and activator of transcription pathway and transforming growth factor beta pathways and increased collagen1A1 production in uterine leiomyoma cells.
To characterize the potential interaction between interleukin-6 (IL6), Janus kinase (JAK)-signal transducer and activator of transcription (STAT)-3 (JAK/STAT3) pathway, and Transforming growth factor beta (TGFβ)-3 , and to determine whether such cross-talk was a contributing factor in the dysregulation of type I collagen production in leiomyomas. Laboratory study. University research laboratory. None. Exposure of leiomyoma and myometrial cell lines to IL6 and STAT3 activators/inhibitors. Western immunoblot analysis and immunohistochemistry. Expression of STAT3, pSTAT3, SOCS3, COL1A1, and TGFb3. We observed that IL6 increased pSTAT3 as well as collagen1A1 in uterine leiomyoma cells. Direct activation of the JAK/STAT3 pathway increased collagen1A1 production in leiomyoma cells, whereas inhibition of the pathway significantly decreased collagen1A1 production. We further observed that modulation of the JAK/STAT3 pathway also increased the expression of TGFβ3 protein. Leiomyoma cells exposed to TGFβ3 demonstrated a significant decrease in pSTAT3 protein. Myometrial cells demonstrated a less sensitive response to STAT3 modulation and collagen production. Cross-talk between the TGFβ pathway and JAK/STAT3 pathway contributes to the fibrotic nature of uterine leiomyomas.


The establishment of the hemangioma model in nude mouse.
Hemangioma is one of the most common benign tumors in children. Most of them could regress spontaneously; however, the pathogenesis and triggering of regression are still unknown. Here, we introduce a new means in which the specimen of human hemangioma was transplanted into nude mice subcutaneously. At the same time, high dose of estradiol was administered to the experimental nude mice intramuscularly to promote implantation and proliferation of hemangioma endothelial cells. By this means, a credible animal model of human hemangioma was established. Further studies on pathogenesis and medical intervention of hemangioma could be carried on with this model. The specimen of grafted hemangioma was taken from a 6-month-old girl, in whom the hemangioma grew rapidly, by surgery. The fresh estrogen receptor-positive strawberry hemangioma specimens were sliced and inoculated subcutaneously into 16 nude mice that were divided randomly into 2 groups, namely, group 1 (n = 8) with normal diet and group 2 (n = 8) with normal diet and 10(-7) mg estradiol administered intramuscularly every week additionally. The size of grafts was measured weekly. All of the experimental mice were killed at 90 days after graft. Hemangioma tissues were harvested and sliced into 4 to 5 microm sections. Living grafts were subjected to histopathologic examination and immunohistochemistry for CD34 and Ki-67. All of the sizes of hemangioma tissues in group 1 were diminished distinctly in 30 days. Thirteen samples of hemangioma were almost absorbed and disappeared completely in 90 days. The sizes of hemangioma in group 2 were larger than primary specimens. It was observed from the section of hemangioma that endothelial cells proliferate vividly and fresh capillary blood vessels grew up into the body of hemangioma. The mean positive cell rate of CD34 in group 2 was 48.49 +/- 3.90 and the Ki-67 was 15.04 +/- 2.44. The transplanted tumor cell retained the histologic characters of original tumor. The capillary hemangioma model established in nude mice retains almost all the biologic character of original human hemangioma and could be widely used in further study on hemangioma.


Energy footprint and carbon emission reduction using off-the-grid solar-powered mixing for lagoon treatment.
Mixing is the driver for the energy footprint of water resource recovery in lagoons. With the availability of solar-powered equipment, one potential measure to decrease the environmental impacts of treatment is to transition to an off-the-grid treatment. We studied the comparative scenarios of an existing grid-powered mixer and a solar-powered mixer. Testing was conducted to monitor the water quality, and to guarantee that the effluent concentrations were maintained equally between the two scenarios. Meanwhile, the energy consumption was recorded with the electrical energy monitor by the wastewater treatment utility, and the carbon emission changes were calculated using the emission intensity of the power utility. The results show that after the replacement, both energy usage and energy costs were significantly reduced, with the energy usage having decreased by 70% and its cost by 47%. Additionally, carbon-equivalent emission from electricity importation dropped by 64%, with an effect on the overall carbon emissions (i.e., including all other contributions from the process) decreasing from 3.8% to 1.5%.


Lassa virus glycoprotein nanoparticles elicit neutralizing antibody responses and protection.
The Lassa virus is endemic in parts of West Africa, and it causes hemorrhagic fever with high mortality. The development of a recombinant protein vaccine has been hampered by the instability of soluble Lassa virus glycoprotein complex (GPC) trimers, which disassemble into monomeric subunits after expression. Here, we use two-component protein nanoparticles consisting of trimeric and pentameric subunits to stabilize GPC in a trimeric conformation. These GPC nanoparticles present twenty prefusion GPC trimers on the surface of an icosahedral particle. Cryo-EM studies of GPC nanoparticles demonstrated a well-ordered structure and yielded a high-resolution structure of an unliganded GPC. These nanoparticles induced potent humoral immune responses in rabbits and protective immunity against the lethal Lassa virus challenge in guinea pigs. Additionally, we isolated a neutralizing antibody that mapped to the putative receptor-binding site, revealing a previously undefined site of vulnerability. Collectively, these findings offer potential approaches to vaccine and therapeutic design for the Lassa virus.


[Intra-uterine growth retardation and prenatal nutrition. I. Review of the literature].
The authors have carried out a review of the literature about the consequences of alimentary deficiency in the mother on the growth of the fetus. The effects of under nutrition in the animal kingdom are well known. In the human species studies have been made in developing countries and also in countries that are developed in times of food rationing. These show that when the ration is deficient in calories there is a drop in the birthweight of the newborn. All the same, the effects of moderate malnutrition are not well established. A discussion therefore is started on the methods by which the diet is examined and the patients have been selected. Whenever there is suspicion of failure of intra-uterine growth during pregnancy, the place of enquiring into the mother's diet is emphasized, together with the other methods of investigation of the causes.


Ultrasound measurements for evaluation of changes in upper airway during anaesthesia induction and prediction difficult laryngoscopy: a prospective observational study.
Upper airway collapsibility after anaesthesia induction may be associated with unpredictable difficult airway. However, most works on airway anatomy are tended to morphological description before anaesthesia. This study aimed to evaluate the changes of upper airway after anaesthesia induction and using pre-anesthetic ultrasound measurements to predict Difficult Laryngoscopy (DL). We included 104 eligible subjects with complete data, who were performed tracheal intubations under general anaesthesia in the study. The upper airway changes before and after anaesthesia induction were determined by seven neck ultrasound measurements, included as follow: (1) Distance from skin to under surface of Tongue (DT), (2) Thickness of the thickest part of Tongue body (TT), (3) Hyoid Mental Distance (HMD), (4) Depth of Hyoid (DH), (5) Width of Hyoid (WH), (6) Distance from Skin to Epiglottis (DSE), (7) Depth of the anterior combination of the Vocal Cords (DVC). DL was evaluated with Cormack-Lehane (CL). Data regarding HMD [from 45.3 (42.4-48.5) to 41.1 (38.5-44.9) mm], DH [from 8.7 (6.6-10.9) to 7.0 (5.3-9.1) mm], DSE [from 20.1 (16.6-22.5) to 19.5 (16.5-21.6) mm] and the DVC [from 7.1 (5.7-8.3) to 6.8 (5.7-7.9) mm] were decreased (P < 0.05), while the DT [from 15.9 (13.1-18.4) to 17.4 (14.5-19.8) mm] was increased (P > 0.05) after anaesthesia induction. Additionally, when cut-off value of DSE was 21.25 mm before anaesthesia, it may be better predicted to DL [sensitivity 80.0% (95% CI: 60.7-91.6%) and specificity 83.8% (95% CI: 73.0-91.0%)]. The upper airway after induction showed the propensity of collapsibility by ultrasound measurements. Compared with other indicators, the DSE assessed by ultrasound might be considered to a valuable predictor of DL.Trial registration: The study was registered in ClinicalTrials.gov on 23th Jan 2019, ChiCTR1900021123.


New constructions of decision evaluation functions in three-way decision spaces based on uninorms.
In 2014, Hu introduced the concept of three-way decision spaces and axiomatic definition of decision evaluation functions. In three-way decision spaces, decision evaluation function satisfies minimum element axiom, monotonicity axiom and complement axiom. Since then, the research on construction method of decision evaluation functions from commonly used binary aggregation functions becomes a research hotspot. Meanwhile, uninorms, as one class of binary aggregation functions, have been successfully applied in various application problems, such as in decision making, image processing, data mining, etc. This paper continues to consider this research topic and mainly explores the new construction methods of decision evaluation functions based on uninorms. Firstly, we show two novel transformation methods from semi-decision evaluation functions to decision evaluation functions based on uninorms. Secondly, using known semi-decision evaluation functions, we give some new construction methods of semi-decision evaluation functions. Thirdly, we give some novel construction methods of decision evaluation functions and semi-decision evaluation functions related to fuzzy sets, interval-valued fuzzy sets, fuzzy relations and hesitant fuzzy sets. Based on them, decision maker can obtain more useful decision evaluation functions, thereby more choices can be used for realistic decision-making problems. Finally, we consider two real evaluation problems to illustrate the results obtained in this paper. The three-way decisions results of evaluation problem show that the construction method proposed in this paper is superior to some existing construction methods under some conditions.


Interleukin-6 and interleukin-1 alpha production is associated with antigen-induced late nasal response.
Cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha, IL-6 and granulocyte macrophage-colony stimulating factor (GM-CSF) are able to potentiate allergic inflammation and seem to be implicated in the development of the late allergic reaction. To study the time course of cytokine production, sequential lavages were performed after nasal allergen challenge. Thirteen patients with allergic rhinitis and four healthy subjects were exposed to grass pollen (n = 6 and n = 2, respectively) or dust mite allergen (n = 7 and n = 2, respectively). Among the patients with allergic rhinitis, a single early response (single responders) developed in four, eight exhibited a dual response (dual responders) and one patient as well as the four healthy subjects did not respond. In addition to the measurement of IL-1 alpha, IL-6, TNF-alpha and GM-CSF concentrations by ELISA, the release of histamine, tryptase, and eosinophil cationic protein was also evaluated by radioimmunoassay performed on nasal lavage fluids. Concerning mediator levels in nasal lavage fluid, neither histamine release nor cytokine elevation were noted in healthy subjects. As previously described, histamine, tryptase and eosinophil cationic protein were released in single and dual responders. Concerning cytokines, TNF-alpha was undetectable in the majority of nasal lavages and an increase in GM-CSF concentration was occasionally observed whatever the type of response. In contrast, an increase in IL-1 alpha and IL-6 levels was observed for dual responders during the early period (12.6 +/- 3 and 9.2 +/- 2 pg/ml, respectively; p < 0.01 in both cases) and at a higher level during the late period (14.5 +/- 4, p not significant and 16.7 +/- 8 pg/ml, respectively; p < 0.01) when compared with baseline values (7.2 +/- 2.2 and 2 +/- 0.7 pg/ml, respectively). For single responders IL-1 alpha and IL-6 secretion was detected mainly during the early period. These data suggest a role for IL-1 alpha in the induction and perennisation of the inflammatory reaction in allergic rhinitis, whereas the role of IL-6 remains to be investigated.


Chemically modified tetracycline 3 prevents acute respiratory distress syndrome in a porcine model of sepsis + ischemia/reperfusion-induced lung injury.
Experimental pharmacotherapies for the acute respiratory distress syndrome (ARDS) have not met with success in the clinical realm. We hypothesized that chemically modified tetracycline 3 (CMT-3), an anti-inflammatory agent that blocks multiple proteases and cytokines, would prevent ARDS and injury in other organs in a clinically applicable, porcine model of inflammation-induced lung injury. Pigs (n = 15) were anesthetized and instrumented for monitoring. A "2-hit" injury was induced: (a) peritoneal sepsis-by placement of a fecal clot in the peritoneum, and (b) ischemia/reperfusion-by clamping the superior mesenteric artery for 30 min. Animals were randomized into two groups: CMT-3 group (n = 7) received CMT-3 (200 mg/kg); placebo group (n = 9) received the same dose of a CMT-3 vehicle (carboxymethylcellulose). Experiment duration was 48 h or until early mortality. Animals in both groups developed polymicrobial bacteremia. Chemically modified tetracycline 3 treatment prevented ARDS as indicated by PaO(2)/FIO(2) ratio, static compliance, and plateau airway pressure (P < 0.05 vs. placebo). It improved all histological lesions of ARDS (P < 0.05 vs. placebo). The placebo group developed severe ARDS, coagulopathy, and histological injury to the bowel. Chemically modified tetracycline 3 treatment prevented coagulopathy and protected against bowel injury. It significantly lowered plasma concentrations of interleukin 1β (IL-1β), tumor necrosis factor α, IL-6, IL-8, and IL-10. This study presents a clinically relevant model of lung injury in which CMT-3 treatment prevented the development of ARDS due in part to reduction of multiple plasma cytokines. Treatment of sepsis patients with CMT-3 could significantly reduce progression from sepsis into ARDS.


In vitro autoubiquitination activity of E3 ubiquitin ligases of the N-degron pathway.
As a part of the ubiquitin-proteasome system, E3 ubiquitin ligases play an important role in the regulation of the proteome in eukaryotic cells. These enzymes are extensively studied because of their crucial function, however it can be challenging to observe E3 ubiquitin ligases in action. Here, we outline a method for determining whether a known or potential E3 ubiquitin ligase exhibits autoubiquitination activity in vitro using PROTEOLYSIS1 (PRT1, AT3G24800), the first identified N-degron pathway E3 ubiquitin ligase from plants as an example. The approach provided here makes it possible to analyze mutations that could reduce or eliminate activity, to test for interaction with E2 ubiquitin conjugating enzymes, as well as to check for in vitro substrate ubiquitination.


Cyclophosphamide is contraindicated in patients with a history of transitional cell carcinoma.
Cyclophosphamide is a urotoxic agent that increases the incidence of malignant neoplasms of the urinary tract. The aim of this study was to evaluate the long-term impact of cyclophosphamide on patients with a history of superficial bladder cancer. Between July 1986 and January 1988, 58 consecutive patients with primary superficial transitional cell carcinoma of the bladder were included in this study. All patients had a transurethral R0 resection. Then 6 weekly intravesical instillations of 120 mg bacillus Calmette-Guérin (BCG) were performed. Until June 1987, 22 consecutive patients (group A) received an additional intravenous application of 700 mg/m(2) cyclophosphamide prior to the BCG immunotherapy, while from July 1987 36 patients were treated without cyclophosphamide. Survival was calculated using the Kaplan-Meier method and comparison of survival using the log rank test. Tumor staging, grading, and size were equally distributed in both groups. No significant difference could be observed regarding the 10-year overall survival rate (group A: 59%, group B: 58%), the 10-year tumor-specific survival rate (89 vs 94%), and the 10-year progression-free survival rate (85 vs 97%). There was a statistically significant deterioration of the 10-year recurrence-free survival rate in the cyclophosphamide group (44 vs 70%, log rank test: p < 0.05). Whereas there were no recurrences in the upper urinary tract among the patients of group B, 2 of the 22 patients from group A developed cancer of the renal pelvis. In patients with a history of superficial bladder cancer, a single dose of cyclophosphamide poses a significantly increased risk of tumor recurrence in the lower and in the upper urinary tract as well.


Gene Polymorphism of Xenobiotic Biotransformation Enzymes in Patients with Classical Ph-Negative Myeloproliferative Neoplasms.
The correlation of gene polymorphisms rs4025935 (large deletion), rs1695 (313A>G), rs71748309 (large deletion), and rs1800566 (609C>T) of GSTM1, GSTT1, and NQO1 genes encoding glutathione-S-transferases (GST) M1, P1, and T1 and NADPH-quinone oxidoreductase with the risk of development of classical Ph-negative myeloproliferative neoplasms (polycythemia vera, essential thrombocythemia, and primary myelofibrosis) was studied in the Caucasian ethnicity population of Vyatka region of the Russian Federation. It was found that NQO1*609T allele, NQO1*609T genotypes, and homozygous carriage of a deletion (null) allele of GSTT1 gene are associated with the risk of development of myeloproliferative neoplasms (OR=1.29, 95%CI=1.02-1.64, p=0.04; OR=1.39, 95%CI=1.04-1.85, p=0.03; and OR=1.48, 95%CI=1.03-2.12, p=0.03, respectively). However, no influence of GSTM1 and GSTP1 gene polymorphisms on the risk of development of myeloproliferative disorders was registered.


IDENTIFIABILITY OF INFECTION MODEL PARAMETERS EARLY IN AN EPIDEMIC.
It is known that the parameters in the deterministic and stochastic SEIR epidemic models are structurally identifiable. For example, from knowledge of the infected population time series I(t) during the entire epidemic, the parameters can be successfully estimated. In this article we observe that estimation will fail in practice if only infected case data during the early part of the epidemic (prepeak) is available. This fact can be explained using a well-known phenomenon called dynamical compensation. We use this concept to derive an unidentifiability manifold in the parameter space of SEIR that consists of parameters indistinguishable from I(t) early in the epidemic. Thus, identifiability depends on the extent of the system trajectory that is available for observation. Although the existence of the unidentifiability manifold obstructs the ability to exactly determine the parameters, we suggest that it may be useful for uncertainty quantification purposes. A variant of SEIR recently proposed for COVID-19 modeling is also analyzed, and an analogous unidentifiability surface is derived.


The mammalian heat shock (or stress) response: a cellular defense mechanism.
The response of mammalian cells to abrupt changes in their local environment entails a series of coordinated transcription and translation events leading to the accumulation of a group of proteins, the stress proteins. As evidenced by the high similarities in the structure of the stress proteins amongst different organisms, the stress response appears to be a well-conserved, pre-planned strategy by which cells protect themselves against changes in their environmental circumstance. In addition to their presumed protective role, most of the stress proteins are expressed at significant levels in cells grown under normal conditions and participate in a number of biological phenomenon apparently distinct from their role during stress. For example, we have described here the role of some of the stress proteins in clathrin coated vesicle assembly/disassembly, tyrosine kinase and steroid hormone receptor function, and cell proliferation. In this regard it seems likely that we have only touched the surface regarding the many different biological processes which occur normally in cells and which involve the participation of the individual stress proteins. Of particular importance, as well, is to understand the role of the stress proteins, both individually and collectively, in protecting the cell during and after recovery from physiological stress. A breakthrough in this endeavor has come from the recent observation demonstrating the structural and biochemical similarities of many of the stress proteins and notably their ability to bind ATP. In this regard, I have described the immunological and biochemical similarities of the 70 kDa heat shock proteins with that of the 80 kDa glucose regulated protein and suggest that this family of proteins serves basically similar functions but within different intracellular compartments: the 70 kDa proteins being cytosolic and nuclear and 80 kDa being present within the endoplasmic reticulum. That a general rule is emerging here comes from the recent observation of Sorger and Pelham (in press) describing a significant sequence homology of the 90 kDa heat shock protein with that of the other glucose-regulated protein, 100 kDa. Here again, however, the proteins are distributed differently: 90 kDa is a soluble cytoplasmic protein and 100 kDa is present within the Golgi and perhaps the plasma membrane (Welch et al., 1984). Might all of the stress proteins have evolved from only a few genes with selection having resulted in different compartmentalization of the stress proteins?(ABSTRACT TRUNCATED AT 250 WORDS)


Abnormalities of vertebral formation and Hox expression in congenital kyphoscoliotic rats.
Scoliosis is a condition that involves an abnormal curvature and deformity of the spinal vertebrae. The genetic background and key gene for congenital scoliosis in humans are still poorly understood. Ishibashi rats (ISR) have congenital malformation of the lumbar vertebrae leading to kyphoscoliosis similar to that seen in humans. To understand the pathogenesis of congenital scoliosis, we have studied the abnormality of vertebral formation and the associated gene expression in ISR. Almost all ISR showed kyphosis or scoliosis of the lumbar vertebrae. In ISR with severe kyphosis, some vertebral disks were missing and some vertebral bodies were fused. Of the ISR, 27% showed hemi-lumbarization of lumbar and sacral vertebrae. Homeotic transformation of the first sacral vertebra into the seventh lumbar vertebra and the resultant loss of the fourth sacral vertebra were seen in half of the ISR. We also found unilateral fusions and deformities of primary ossification centers of the lumbar vertebral column in fetal ISR. Moreover, we observed that the expression levels of Hox10 and Hox11 paralogs in lumbo-sacral transitional areas of ISR were extremely low compared with those of normal rats. These results suggest that fusion of primary ossification centers in lumbar vertebrae in the embryonic period causes scoliosis and kyphosis and that Hox genes are involved in the occurrence of homeotic transformation in lumbo-sacral vertebrae of congenital kyphoscoliotic ISR.


Discovery and optimization of a series of 3-(3-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amines: orally bioavailable, selective, and potent ATP-independent Akt inhibitors.
This paper describes the implementation of a biochemical and biophysical screening strategy to identify and optimize small molecule Akt1 inhibitors that act through a mechanism distinct from that observed for kinase domain ATP-competitive inhibitors. With the aid of an unphosphorylated Akt1 cocrystal structure of 12j solved at 2.25 Å, it was possible to confirm that as a consequence of binding these novel inhibitors, the ATP binding cleft contained a number of hydrophobic residues that occlude ATP binding as expected. These Akt inhibitors potently inhibit intracellular Akt activation and its downstream target (PRAS40) in vitro. In vivo pharmacodynamic and pharmacokinetic studies with two examples, 12e and 12j, showed the series to be similarly effective at inhibiting the activation of Akt and an additional downstream effector (p70S6) following oral dosing in mice.


Genome sequence of Comamonas testosteroni ATCC 11996, a representative strain involved in steroid degradation.
Comamonas testosteroni strains belong to the family of Comamonadaceae and are known for their ability to utilize steroid compounds as carbon source. Here, we present the draft genome sequence of strain ATCC 11996, with a G+C content of 61.48%.


Investigation of attributes of bourbon oil and cobalt nitrate constituted electrospun nanoscaffolds for blood compatibility and in vitro bone formation.
This work aims to fabricate scaffold using polyurethane (PU) integrated with bourbon oil (BB) and cobalt nitrate (CoNO3) using the electrospinning technique. Morphological investigation signified a fall in fibre diameter for the PU/BB and PU/BB/CoNO3 nanocomposite than the PU. Spectral analysis indicated that BB and CoNO3 were added within the PU matrix. Wettability analysis insinuated an increase in the hydrophobic nature of the PU/BB than the PU. PU/BB/CoNO3 turned to be hydrophilic due to the integration of CoNO3 in the polymer matrix. Mechanical testing of PU/BB and PU/BB/CoNO3 indicated an increase in the tensile strength of the fabricated composites. Atomic force microscopy (AFM) portrayed the reduction in the roughness of the PU/BB and PU/BB/CoNO3 compared to the PU. The coagulation studies invariably documented the improved anticoagulant behaviour and less toxic nature of the PU/BB and PU/BB/CoNO3 in comparison with the PU. Further, bone mineralization testing revealed the enhanced apatite formation of the nanocomposite. Nanocomposite scaffolds with the fore-mentioned properties hold good potential for bone tissue engineering.


hPSCs-derived Schwann cells serve for disease modeling and drug discovery.
In this issue, Majd et al.1 derive Schwann cells from human pluripotent stem cells (hPSCs), which can be used to study Schwann cell development and physiology and model diabetic neuropathy. hPSC-derived Schwann cells possess the molecular features of primary Schwann cells and are capable of myelination in vitro and in vivo.


Cardioselective peripheral noradrenergic deficiency in Lewy body synucleinopathies.
Lewy body (LB) synucleinopathies such as Parkinson's disease (PD) entail profound cardiac norepinephrine deficiency. The status of sympathetic noradrenergic innervation at other extracranial sites has been unclear. Although in vivo neuroimaging studies have indicated a cardioselective noradrenergic lesion, no previous study has surveyed peripheral organs for norepinephrine contents in LB diseases. We reviewed 18 F-dopamine (18 F-DA) positron emission tomographic images and postmortem neurochemical data across several body organs of controls and patients with the LB synucleinopathies PD and pure autonomic failure (PAF) and the non-LB synucleinopathy multiple system atrophy (MSA). 18 F-DA-derived radioactivity in the heart, liver, spleen, pancreas, stomach, kidneys, thyroid, and submandibular glands were analyzed from 145 patients with LB synucleinopathies (112 PD, 33 PAF), 74 controls, and 85 MSA patients. In largely separate cohorts, postmortem tissue norepinephrine data were reviewed for heart, liver, spleen, pancreas, kidney, thyroid, submandibular gland, and sympathetic ganglion tissue from 38 PD, 2 PAF, and 5 MSA patients and 35 controls. Interventricular septal 18 F-DA-derived radioactivity was decreased in the LB synucleinopathy group compared to the control and MSA groups (P < 0.0001 each). The LB and non-LB groups did not differ in liver, spleen, pancreas, stomach, or kidney 18 F-DA-derived radioactivity. The LB synucleinopathy group had markedly decreased apical myocardial norepinephrine, but normal tissue norepinephrine in other organs. The MSA group had normal tissue norepinephrine in all examined organs. By in vivo sympathetic neuroimaging and postmortem neurochemistry peripheral noradrenergic deficiency in LB synucleinopathies is cardioselective. MSA does not involve peripheral noradrenergic deficiency.


Cortical spreading depression modifies components of the inflammatory cascade.
As more information becomes available regarding the role of inflammation following stroke, it is apparent that some inflammatory mediators are detrimental and others are beneficial to the progression of ischemic injury. Cortical spreading depression (CSD) is known to impart some degree of ischemic tolerance to the brain and to influence the expression of many genes. Many of the genes whose expression is altered by CSD are associated with inflammation, and it appears likely that modulation of the inflammatory response to ischemia by CSD contributes to ischemic tolerance. Understanding which inflammatory processes are influenced by CSD may lead to the identification of novel targets in the effort to develop an acute treatment for stroke.


Role of caudate lobectomy in type III A and III B hilar cholangiocarcinoma: a 15-year experience in a tertiary institution.
Concomitant liver resection for type III hilar cholangiocarcinoma could improve the R0 resection rate and long-term outcome. In the present study, we examine the specific role of caudate lobectomy in liver resection for type III(A) and III(B) hilar cholangiocarcinoma and the prognostic factors for survival in this group of patients. We reviewed all patients with type III(A) and III(B) hilar cholangiocarcinoma who underwent liver resection in Samsung Medical Center from January 1995 to July 2010. Patients were divided into those with and without caudate lobectomy (CL). The log rank test and Cox regression analysis were employed to investigate for prognostic factors of survival. There were 127 patients in this cohort, 57 without CL (44.9%) and 70 with CL (55.1%). The demographics and symptoms of presentation were comparable. The median preoperative bilirubin level was significantly higher in the group undergoing CL (p = 0.017). Patients with CL had a significantly better overall survival (OS) (CL: 64.0 months vs without CL: 34.6 months) (p = 0.010) and disease-free survival (DFS) (CL: 40.5 months vs without CL: 27.0 months) (p = 0.031). Multivariate analysis showed that presence of symptoms (p = 0.025) and positive lymph node (LN) metastasis (p < 0.001) were negative prognostic factors for OS. Furthermore, multivariate analysis for DFS found that caudate lobectomy (p = 0.016) and positive LN metastasis (p = 0.001) were positive and negative prognostic factors, respectively. Caudate lobectomy contributed to improvement of DFS and OS in type III hilar cholangiocarcinoma. Other prognostic factors include positive LN metastasis and presence of symptoms.


Modified biblock versus monoblock mandibular advancement appliances for treatment of obstructive sleep apnea: A randomized controlled trial.
The high prevalence of obstructive sleep apnea represents a serious public health problem. Oral appliances have gained wide acceptance among patients diagnosed with obstructive sleep apnea, who should wear them every night. A comfortable oral appliance is mandatory for successful treatment outcomes. The purpose of this randomized controlled trial was the assessment of the influence of 2 different designs of the mandibular advancement appliance (MAA), modified biblock and monoblock, for the management of obstructive sleep apnea. The study was designed as a prospective 2-arm randomized controlled clinical trial conducted in parallel. Twenty participants (aged 40 ±7.5 years) diagnosed with moderate obstructive sleep apnea were randomly assigned to a control group (n=10), receiving monoblock MAA, and a study group (n=10), receiving modified biblock MAA with elastics. Both appliances were fabricated by using computer-aided design and computer-aided manufacture (CAD-CAM) technology at different mandibular advancement levels (MALs): 50% and 75% of maximum MAL. A total of 60 cone beam computed tomography scans, 60 overnight full polysomnography sleep tests, 60 STOP-Bang questionnaires, and 40 Usability of Sleep Apnea Equipment-Oral Appliance (USE-OA) questionnaires were collected and analyzed blindly at baseline (initial visit), 50% MAL (3 months), and 75% MAL (6 months). The main outcome measures were the upper airway volume, linear anteroposterior and cross-sectional airway measurements, Apnea Hypopnea Index, Respiratory Disturbance Index, STOP-Bang questionnaire scoring, and USE-OA questionnaire scoring. Nonparametric statistical analysis was performed by using a statistical software program (α=.05). With a beta error accepted of up to 20%, the power of the study was 80%. At 75% MAL, the percentage change in upper airway volumetric measurements showed a favorable increase: biblock group (115%) and monoblock group (42%), with a statistically significant difference (P=.001). The linear anteroposterior airway measurements and the percentage change in cross-sectional airway measurements were statistically similar: biblock group (80%) and (75%) monoblock group (60%), (54%) (P=.450, P=.151, respectively). The percentage change in the Apnea Hypopnea Index significantly decreased: biblock group (-89%) and monoblock group (-54%) (P<.001). The percentage change in the Respiratory Disturbance Index decreased: biblock group (-78%) and monoblock group (-62%) (P<.023). From the STOP-Bang questionnaire scoring, 100% of both groups showed low risk for obstructive sleep apnea at 75% MAL. From the satisfaction scoring on the USE-OA questionnaire, the biblock group was 100% strong satisfaction and the monoblock group was 50% satisfaction and 50% fairly satisfied. The modified biblock MAA with elastics showed significant improvements in patients diagnosed with obstructive sleep apnea regarding upper airway measurements and full polysomnography vital parameters when compared with monoblock MAA.


Enteral administration of the protease inhibitor gabexate mesilate preserves vascular function in experimental trauma/hemorrhagic shock.
Preserving vascular function is crucial for preventing multiorgan failure and death in ischemic and low-pressure states such as trauma/hemorrhagic shock (T/HS). It has recently been reported that inhibiting circulating proteases released from the bowel to the circulation during T/HS may preserve vascular function and improve outcomes following T/HS. This study aimed to evaluate the role of the serine protease inhibitor gabexate mesilate (GM) in preserving vascular function during T/HS when given enterally. We studied the vascular reactivity of mesenteric arteries from male Wistar rats treated with enteral GM (10 mg/kg) (GM-treated, n = 6) or control (Shock-control, n = 6) following (T/HS) using pressure myography. Concentration-response curves of endothelial-dependent and endothelial-independent agonists (e.g., acetylcholine, sodium nitroprusside) ranging from 10-10 to 10-5 M were performed. In a second set of experiments, ex-vivo arteries from healthy rats were perfused with plasma from shocked animals from both groups and vascular performance was similarly measured. Arteries from the GM-treated group demonstrated a preserved concentration-response curve to the α1 adrenergic agonist phenylephrine compared to arteries from Shock-control animals (- logEC50: - 5.73 ± 0.25 vs. - 6.48 ± 0.2, Shock-control vs. GM-treated, p = 0.04). When perfused with plasma from GM-treated rats, healthy arteries exhibited an even greater constriction and sensitivity to phenylephrine (- logEC50: - 6.62 ± 0.21 vs. - 7.13 ± 0.21, Shock-control vs. GM-treated, p = 0.02). Enteral GM also preserved the endothelium-dependent vascular response to agonists following T/HS and limited syndecan-1 shedding as a marker of glycocalyx compromise (41.84 ± 9 vs. 17.63 ± 3.97 ng/mL, Shock-control vs. GM-treated, p = 0.02). Syndecan-1 cleavage was correlated with plasma trypsin-like activity (r2 = 0.9611). Enteral gabexate mesilate was able to maintain vascular function in experimental T/HS, which was reflected by improved hemodynamics (mean arterial pressure 50.39 ± 7.91 vs. 64.95 ± 3.43 mmHg, Shock-control vs. GM treated, p = 0.0001). Enteral serine protease inhibition may be a potential therapeutic intervention in the treatment of T/HS.


Recognition and sensing of biologically relevant anions in alcohol and mixed alcohol-aqueous solutions using charge neutral cleft-like glycol-derived pyridyl-amidothiourea receptors.
In this paper, the synthesis and the spectroscopic investigation of new colorimetric receptors for anions 3-6, possessing a glycol chain at the 4-position of the pyridyl ring, and 1 and 2, which lack such a chain, and the X-ray crystal structure of 2 is presented. Structures 3-6 are able to bind to anions in competitive media, such as alcohol or in a mixture of methanol and water, where the anion recognition gives rise to changes in the absorption spectra, which is red-shifted, in 1:1 or 1:2 (sensor/anion) stoichiometry. The anion recognition for 1 and 2 was also investigated in organic solvents and in a 4:1 mixture of DMSO/H(2)O. The binding of 1 to anions such as acetate, phosphate, and fluoride was also evaluated using (1)H NMR in DMSO-d(6).


Non-pharmacological therapeutic strategy options for patients with dementia based on cognitive function-A Bayesian network meta-analysis of randomized controlled trials.
Dementia represents one of the most common neurodegenerative disorders in older adults. However, it is still unclear whether non-pharmacological therapies (NPTs) are effective or not and which treatment should be preferred. We applied a series of search strategies to identify eligible randomized controlled trials on 1st October, 2018, investigating the effects of NPTs of dementia in the older persons. Pairwise and network meta-analyses were sequentially performed. A total of 31 trials were included, which enrolled 1895 participants and 7 NPTs. Compared with control group, all the NPTs included were statistically beneficial to cognitive function, and our study indicated Comprehensive Therapy(CT) [the surface under the cumulative ranking curve (SUCRA = 92.42%)] might be the best choice for dementia patients. Our study suggests CT might be the optimal NPT for improving the cognitive function of dementia patients. However, the above conclusions need to be further analyzed.


Parallel microscope-based fluorescence, absorbance and time-of-flight mass spectrometry detection for high performance liquid chromatography and determination of glucosamine in urine.
A parallel microscope-based laser-induced fluorescence (LIF), ultraviolet-visible absorbance (UV) and time-of-flight mass spectrometry (TOF-MS) detection for high performance liquid chromatography (HPLC) was achieved and used to determine glucosamine in urines. First, a reliable and convenient LIF detection was developed based on an inverted microscope and corresponding modulations. Parallel HPLC-LIF/UV/TOF-MS detection was developed by the combination of preceding Microscope-based LIF detection and HPLC coupled with UV and TOF-MS. The proposed setup, due to its parallel scheme, was free of the influence from photo bleaching in LIF detection. Rhodamine B, glutamic acid and glucosamine have been determined to evaluate its performance. Moreover, the proposed strategy was used to determine the glucosamine in urines, and subsequent results suggested that glucosamine, which was widely used in the prevention of the bone arthritis, was metabolized to urines within 4h. Furthermore, its concentration in urines decreased to 5.4mM at 12h. Efficient glucosamine detection was achieved based on a sensitive quantification (LIF), a universal detection (UV) and structural characterizations (TOF-MS). This application indicated that the proposed strategy was sensitive, universal and versatile, and it was capable of improved analysis, especially for analytes with low concentrations in complex samples, compared with conventional HPLC-UV/TOF-MS.


A comparative immunofluorescent study of fixed decalcified tissue and frozen non-decalcified tissue from the guinea pig cochlea.
The immunofluorescence test (IF) is an important diagnostic laboratory tool for detecting immune-mediated sensorineural hearing loss (SNHL). The results of applying the IF to ethanol-fixed, paraffin-embedded, decalcified sections of guinea pig cochlea as compared with frozen non-decalcified preparations are presented. Sera from ten patients with SNHL were tested in addition to antibody-positive and negative human serum controls. Despite fixation and prolonged decalcification, deparaffinized cochlear sections showed a strong positive reaction with most of the positive serum controls. Anti-endothelial antibodies were detected in the serum of one patient and anti-nuclear antibodies in another. The fine cochlear structure was clearly delineated. However, the decalcified specimens failed to react with one serum model, which revealed a positive fluorescence when incubated with the frozen non-decalcified cochlear preparations. These latter findings denote possible leaching of the antigenic material from the sections. This study further shows that frozen nondecalcified cochlear tissue is a reliable tissue source for the interpretation of the results obtained with IF.


The regression of synapses formed by a foreign nerve in a mature axolotl striated muscle.
A study has been made of the factors which determine that the terminals of a foreign flexor nerve at synaptic sites in a unrodele extensor muscle regress on return of the original extensor nerve. The quantal content (m) of the endplate potential (EPP) at flexor nerve terminal synapses, during innervation of a previously denervated extensor muscle, increased in about 8 weeks to reach the same size as at normal extensor nerve terminals; the same time was taken for m to reach normal size at extensor nerve terminals when these reinnervated their own muscle. At flexor nerve terminals, m decreased eventually to zero if the extensor nerve terminals returned within about 6 weeks of synapse formation by the flexor nerve terminals to the same or an immediately adjacent synaptic site to that occupied by these terminals. During this decrease in m at flexor nerve terminals, stimulation of the flexor nerves in the presence of horseradish peroxidase (HRP) showed HRP-labelled flexor nerve terminals present only in those regions of the extensor muscle in which the electrical signs of flexor nerve terminals were observed, indicating that the decrease in m at regressing flexor terminals was accompanied by their vacating synaptic sites. However, flexor nerve terminals failed to regress from the extensor muscle on return of the original nerve supply if the flexor nerve allowed to form synapses for more than about 10 weeks before the return of the extensor nerve.


Genomic and signalling pathway characterization of the NZM panel of melanoma cell lines: A valuable model for studying the impact of genetic diversity in melanoma.
Melanoma is a disease associated with a very high mutation burden and thus the possibility of a diverse range of oncogenic mechanisms that allow it to evade therapeutic interventions and the immune system. Here, we describe the characterization of a panel of 102 cell lines from metastatic melanomas (the NZM lines), including using whole-exome and RNA sequencing to analyse genetic variants and gene expression changes in a subset of this panel. Lines possessing all major melanoma genotypes were identified, and hierarchical clustering of gene expression profiles revealed four broad subgroups of cell lines. Immunogenotyping identified a range of HLA haplotypes as well as expression of neoantigens and cancer-testis antigens in the lines. Together, these characteristics make the NZM panel a valuable resource for cell-based, immunological and xenograft studies to better understand the diversity of melanoma biology and the responses of melanoma to therapeutic interventions.


Effect of a flipped classroom course to foster medical students' AI literacy with a focus on medical imaging: a single group pre-and post-test study.
The use of artificial intelligence applications in medicine is becoming increasingly common. At the same time, however, there are few initiatives to teach this important and timely topic to medical students. One reason for this is the predetermined medical curriculum, which leaves very little room for new topics that were not included before. We present a flipped classroom course designed to give undergraduate medical students an elaborated first impression of AI and to increase their "AI readiness". The course was tested and evaluated at Bonn Medical School in Germany with medical students in semester three or higher and consisted of a mixture of online self-study units and online classroom lessons. While the online content provided the theoretical underpinnings and demonstrated different perspectives on AI in medical imaging, the classroom sessions offered deeper insight into how "human" diagnostic decision-making differs from AI diagnoses. This was achieved through interactive exercises in which students first diagnosed medical image data themselves and then compared their results with the AI diagnoses. We adapted the "Medical Artificial Intelligence Scale for Medical Students" to evaluate differences in "AI readiness" before and after taking part in the course. These differences were measured by calculating the so called "comparative self-assessment gain" (CSA gain) which enables a valid and reliable representation of changes in behaviour, attitudes, or knowledge. We found a statistically significant increase in perceived AI readiness. While values of CSA gain were different across items and factors, the overall CSA gain regarding AI readiness was satisfactory. Attending a course developed to increase knowledge about AI in medical imaging can increase self-perceived AI readiness in medical students.


Study on community structure and metabolic mechanism of dominant polyphosphate-accumulating organisms (PAOs) and glycogen-accumulating organisms (GAOs) in suspended biofilm based on phosphate recovery.
Biofilm sequencing batch reactor (BSBR) can achieve efficient phosphate (P) removal and enrichment, but its process performance and metabolic mechanisms for P removal and enrichment of municipal wastewater remain largely unclear. In the present study, we assessed the P removal and enrichment of municipal wastewater at influent P concentrations of 2.5 mg/L and 10 mg/L. The efficiency of P removal and enzyme activity in polyphosphate-accumulating organisms (PAOs) and glycogen-accumulating organisms (GAOs) were compared, and the growth and metabolic characteristics of dominant PAOs and GAOs at different influent P concentrations were studied with the macro-sequencing technology. The results showed that the P recovery efficiencies were 70.03% and 76.19% when the influent P concentration was 2.5 mg/L and 10 mg/L in BSBR, respectively, and the maximum P concentration of recovery liquid was 81.29 mg/L and 173.12 mg/L, respectively. There were no phosphate kinase (PPK) and phosphate hydrolase (PPX) in extracellular polymeric substances (EPS). The dominant PAOs were Candidatus_Contendobacter, Dechloromonas, and Flavobacterium, and the dominant GAO was Candidatus_Competibacter. The abundance of Candidatus_Contendobacter was the highest with the most potential contribution to P removal. PAOs had competitive advantages in carbon (C) source uptake, glycogen metabolism, P metabolism, and adenosine triphosphate (ATP) metabolism. HMP was unique to PAOs, EMP had the highest abundance in glycogen metabolism, and ED was contained in PAOs of BSBR. These results indicated that BSBR provided sufficient reducing power and ATP for PAOs through different glycogen decomposition pathways to promote P uptake and obtained competitive advantages in P metabolism, C source uptake, and ATP utilization to achieve efficient P removal and enrichment. Collectively, our current findings provided valuable insights into the P removal and enrichment mechanism of BSBR in municipal sewage.


Noncatalytic mono-N-methylation of aniline in supercritical methanol: the kinetics and acid/base effect.
Aniline is easily N-methylated in supercritical methanol without catalyst at 350 degrees C and 0.237 g cm-3 to give mono-N-methylaniline with high selectivity, and the reaction rate is increased by a small amount of base (LiOH, NaOH, KOH, and CH3ONa), indicating a difference in the reaction mechanism from the ordinary acid-catalyzed one.


Metallophilic interactions: observations of the shortest metallophilicinteractions between closed shell (d10d10, d10d8, d8d8) metal ions [MM' M = Hg(ii) and Pd(ii) and M' = Cu(i), Ag(i), Au(i), and Pd(ii)].
The salt metathesis reaction of two equivalents of 8-lithioquinoline (C6H6NLi) with HgBr2 afforded bis(quinoline-8-yl)mercury, [(C6H6N)2Hg]. Bis(quinoline-8-yl)mercury has been used for the synthesis of a series of heteronuclear complexes of the type [(C6H6N)2M·M']·X-n [M = Hg; {M' = Cu, X- = ClO4; X = I; X- = CF3SO3}, {M' = Ag, X- = ClO4; X- = CF3SO3; X- = BF4}, {M' = Au, X- = CF3SO3}; {M' = Pd, X- = CF3CO2}], [M = Pd; M' = Pd, X- = CF3CO2; n = 2]. All the complexes were well characterized by multinuclear NMR (1H, 13C, 19F, 11B, 199Hg) spectroscopic analysis. Their structures were determined by single crystal X-ray diffraction studies, which displayed the shortest HgM' (M' = Cu, Ag, Au, Pd) metallophilic interactions. The electronic properties of the molecular structures were determined by DFT calculations. ELF (Electron Localization Function) analysis provided the information about the localization of electrons between metalmetal bonds and dispersion of electron density around the metal ions. The AIM (Atoms in Molecule) analysis revealed the presence of electron density at the bond critical points (bcp) and the strengths of MM' [M = Hg, M' = Cu, Ag, Au, Pd; M, M'=Pd] interactions. The NBO (Natural Bond Orbital) analysis was used to identify the donor-acceptor character of the orbitals involved in the bonding.


A midrange theory of empowered holistic nursing education: a pedagogy for a student-centered classroom.
The purpose of this article is to propose Empowered Holistic Nursing Education (EHNE) as a midrange theory--developed through induction, explication, deduction, and retroduction--to help nurse educators teach holistically and create a student-centered classroom, to establish a theoretical basis for a nursing pedagogy reflecting nursing's foundational principles, and to guide future research. The model's 5 core concepts, how to use the model as a pedagogy for practice, and its application to research will be presented. Holistic nursing will be defined, and traditional holistic nursing, holistic pedagogy, and emancipatory pedagogy will each be described.


Polycystic ovary syndrome - a risk factor of pre-eclampsia after in vitro fertilisation.
Taking into account an increasing number of pregnancies after the assisted reproduction, we tried to evaluate the risk of pre-eclampsia for mono-foetal pregnancy after IVF and to determine the degree of risk factors. The study included 16,400 patients, while 15,874 of them were after spontaneous conception and 526 after conception using assisted reproductive technologies. For the basic statistical analysis, we used frequency tables and basic statistical characteristics for numeric and ordinary variables. To verify the statistical dependence, we used contingency tables, Fisher exact test and the odds ratio. In the group of women after in vitro fertilisation, a higher incidence of pre-eclampsia was recorded than in the group of women after spontaneous conception. Conception via in vitro fertilisation represents the 3.4-fold risk of pre-eclampsia development (OR 3.404 95% CI 2.407-4.8). The major causes of a higher incidence of pre-eclampsia in case of assisted reproduction include: polycystic ovary syndrome, insulin resistance, subfertility, age and obesity of patients. Assisted reproductive technologies are not the cause of a higher incidence of pre-eclampsia in case of the assisted reproduction (Tab. 4, Fig. 2, Ref. 22).


Cross-sectional and Test-Retest Characterization of PET with [(18)F]FP-(+)-DTBZ for β Cell Mass Estimates in Diabetes.
The vesicular monoamine transporter, type 2 (VMAT2) is expressed by insulin producing β cells and was evaluated as a biomarker of β cell mass (BCM) by positron emission tomography (PET) with [(18)F]fluoropropyl-dihydrotetrabenazine ([(18)F]FP-(+)-DTBZ). We evaluated the feasibility of longitudinal pancreatic PET VMAT2 quantification in the pancreas in two studies of healthy controls and patients with type 1 or 2 diabetes. VMAT2 binding potential (BPND) was estimated voxelwise using a reference tissue method in a cross-sectional study, followed by assessment of reproducibility using a test-retest paradigm. Metabolic function was evaluated by stimulated c-peptide measurements. Pancreatic BPND was significantly decreased in patients with type 1 diabetes relative to controls and the test-retest variability was 9.4%. Pancreatic VMAT2 content is significantly reduced in long-term diabetes patients relative to controls and repeat scans are sufficiently reproducible to suggest the feasibility clinically VMAT2 measurements in longitudinal studies of new onset diabetes.


Short-term treatment of spontaneously hypertensive rats with liver growth factor reduces carotid artery fibrosis, improves vascular function, and lowers blood pressure.
Liver growth factor (LGF), a mitogen for liver cells, reduces fibrosis in a rat model of cirrhosis. The present study assesses the possible vascular antifibrotic and antihypertensive effects of LGF treatment on spontaneously hypertensive rats (SHR). Six-month-old male SHR and normotensive Wistar Kyoto rats (WKY) were treated with LGF (4.5 microg LGF/rat i.p. twice a week for 2 weeks). Haemodynamic parameters were measured in anaesthetized rats. Vascular structure and function were studied in carotid arteries using optical and confocal microscopy, radioimmunoassay for desmosine, and isometric tension recording. LGF reduced systolic and diastolic blood pressure only in SHR. When compared to those of untreated SHR, carotid arteries from LGF-treated SHR showed: 1) a 50% reduction in collagen area and an increase in vascular smooth muscle cell number in the media, 2) no difference in total elastin content, but an increase in size of fenestrae in the internal elastic lamina, and 3) enhanced relaxation to acetylcholine, sodium nitroprusside, and forskolin. These effects were specific for SHR, since no changes were observed in LGF-treated WKY. Short-term treatment with a low dose of LGF induced a large improvement in vascular structure and function and significantly reduced blood pressure in a rat model of essential hypertension. The present results could open future research to explore the vascular effects of this endogenous factor in order to determine its potential as an antifibrotic and antihypertensive agent in humans.


Comparative sequence analysis and functional validation identified a retina-specific enhancer around zic5 and zic2a.
The spatiotemporal development of vertebrate retina is regulated by a variety of genes. The zinc finger transcription factors zic5 and zic2a are located close to each other in the chromosome. They have similar expression patterns, and both play important roles in the development of the retina and nervous system. Here, we used ECR browser and gfp fluorescence report experiment to identify a 290bp enhancer sequence ECR3, which is located at 3 kb upstream of zic5 and 10 kb downstream of zic2a, and it can drive the specific expression of gfp in the retina. pT2KXIGQ-ECR3 was used to construct a transgenic zebrafish line Tg(ECR3-290: gfp) which first exhibits specific green fluorescence in the whole retina area at 24hpf. Then the expression region was gradually limited to ganglion cell layer (GCL) and lasted through adulthood. This expression pattern is highly consistent with the zic5 and zic2a at retina. These results indicate that the 290bp enhancer might be an important element to regulate the expression of zic5 and zic2a genes in ganglion cells, and this transgenic line is an important tool for studying the development of retina.


Functional characterization of stem cell activity in the mouse mammary gland.
Any portion of the mouse mammary gland is capable of recapitulating a clonally derived complete and functional mammary tree upon transplantation into an epithelial divested mammary fat-pad of a recipient host. As such, it is an ideal model tissue for the study somatic stem cell function. This review will outline what is known regarding the function of stem/progenitor cells in the mouse mammary gland, including how progenitor populations can be functionally defined, the evidence for and potential role of selective DNA strand segregation, and the role of the niche in maintaining and controlling stem cell function.


Determinants of early case-fatality among stroke patients in Maputo, Mozambique and impact of in-hospital complications.
The burden of stroke is increasing in developing countries that struggle to manage it efficiently. We identified determinants of early case-fatality among stroke patients in Maputo, Mozambique, to assess the impact of in-hospital complications. Patients admitted to any hospital in Maputo with a new stroke event were prospectively registered (n = 651) according to the World Health Organization's STEPwise approach, in 2005-2006. We assessed the determinants of in-hospital and 28-day fatality, independently of age, gender and education, and computed population attributable fractions. In-hospital mortality was higher among patients with Glasgow score at admission ≤ 6 (more than fivefold) or needing cardiopulmonary resuscitation during hospitalization (approximately 2.5-fold). Pneumonia and deep vein thrombosis/other cardiovascular complications during hospitalization were responsible for 19.6% (95% confidence interval, 5.3 to 31.7) of ischaemic stroke and 15.9% (95% confidence interval, 5.8 to 24.9) of haemorrhagic stroke deaths until the 28th day. Ischaemic stroke patients with systolic blood pressure 160-200 mmHg had lower in-hospital mortality (relative risk = 0.32, 95% confidence interval, 0.13 to 0.78), and, for those with haemorrhagic events (haemorrhagic stroke), 28-day mortality was higher when systolic blood pressure was over 200 mmHg (hazard ratio = 3.42; 95% confidence interval, 1.02 to 11.51), compared with systolic blood pressure 121-140 mmHg. Regarding diastolic blood pressure, the risk was lowest at 121-150 mmHg for ischaemic stroke and at 61-90 mmHg for haemorrhagic stroke. Early case-fatality was mostly influenced by stroke severity and in-hospital complications. The allocation of resources to the latter may have a large impact on the reduction of the burden of stroke in this setting.


Choroidal morphologic features in central serous chorioretinopathy using ultra-widefield optical coherence tomography.
To analyze the choroidal morphological changes in central serous chorioretinopathy (CSC) using ultra-widefield (UWF)-optical coherence tomography (OCT). This single-center, case-control study included 65 CSC eyes (52 males; age, 55.6 ± 13.0 years) and 65 healthy eyes (50 males; age, 57.1 ± 17.9 years). UWF-OCT (viewing angle, 200°) with real-shape correction was used to create an automated choroidal thickness (CT) map. The CT map had three sub-areas: the central (0-30°), middle (30-60°), and peripheral areas (60-100°), and was divided by vertical and horizontal lines. Differences in the CT and the CT change rate (CTCR) from the central to peripheral areas were examined between the CSC and control groups after adjusting for subjects' demographic and clinical factors. Furthermore, we assessed the vortex veins dilation patterns (VVDP) in the macula and examined the CT and the CTCR differences between CSC patients and controls for each VVDP. CSC patients had greater CT than those of the controls in all sectors (CSC vs. controls, the peripheral area: supratemporal 284.4 ± 71.2 μm vs. 220.4 ± 71.2 μm, infratemporal 263.3 ± 69.2 μm vs. 195.3 ± 52.3 μm, supranasal 251.9 ± 70.3 μm vs. 189.5 ± 58.1 μm, infranasal 193.6 ± 71.2 μm vs. 146.3 ± 48.9 μm, P < 0.0001 for all sectors). The CTCR was apparently larger in CSC eyes than controls only for the upper-dominant type of VVDP (CSC patients vs. controls, supratemporal 32.1 ± 9.9% vs. 4.6 ± 23.1%, infratemporal 44.0 ± 11.2% vs. 25.6 ± 16.8%, supranasal 42.6 ± 9.8% vs. 22.2 ± 19.4%, infranasal 57.6 ± 41.2% vs. 41.2 ± 13.9%, P < 0.0001 for all sectors). CSC has a thicker choroid, even in the peripheral areas, and the macular choroidal thickening was more severe in the upper-dominant type of VVDP. VVDP may affect the location of excessive fluid.


The known unknowns of T cell immunity to COVID-19.
Tremendous progress has been made in understanding the role of T cell immunity in acute and convalescent COVID-19 infection. Here we shed light on the "known unknowns" of pre-existing and acquired T cell responses in relation to acute and convalescent SARS-CoV-2 infection.


Disintegration of Staphylococcus epidermidis biofilms under glucose-limiting conditions depends on the activity of the alternative sigma factor sigmaB.
To evaluate the role of the polysaccharide intercellular adhesin as an energy-storage molecule, we investigated the effect of nutrient limitation on S. epidermidis biofilms. The stability of established biofilms depends on sigma(B) activity; however, the slow decay of biofilms under conditions of nutrient limitation reveal its use as an energy-storage molecule to be unlikely.


Continuous spinal blockade: an old technique revisited.
In this paper we describe a technique for continuous spinal anesthesia, first described at the turn of the 20th century and long thought to have become obsolete. We discuss reasons for discontinuance and neglect of the technique, as well as its indications, applications, and specific advantages, and we report a significant illustrative case.


Are new-generation bisphosphonates effective for the inhibition of calcium oxalate stone formation in a rat model?
The effects of bisphosphonates on prophylaxis of stone formation are unclear. We evaluated the outcome of two new-generation bisphosphonates in a lithogenic rat model. 36 male rats were divided into three groups of 12 animals each. Both calcium and creatinine levels of plasma and urine were measured. Zinc discs of about 40 mg each were surgically placed into the bladder. The first group received no treatment and the second and third groups were treated with an intraperitoneal injection of weekly clodronate (20 mg/kg) and zoledronic acid (7.5 microg/kg), respectively. At the end of the 8th week, the weight increase in discs and biochemical changes were analyzed comparatively. The mean weight of discs in the control, clodronate and zoledronic acid groups was 109.65 +/- 80.97, 79.82 +/- 17.99 and 72.91 +/- 19.29 mg, respectively (p > 0.05). The percentage increase in weight of discs was 164% for control, 90% for clodronate and 71% for the zoledronic acid group. The increase of urinary calcium level in the zoledronic acid group was lower than the others (p < 0.05). When considering the percentage increase in weight of discs, the difference between control and bisphosphonate groups support the idea that these drugs may have a preventive role in stone formation.


Generation of hydrogen peroxide mediates hanging death-induced neuronal cell apoptosis in the dentate gyrus of the rat brain.
Present study was aimed to find out whether hanging death (HD) induces generation of reactive oxygen species (ROS) and neuronal cell apoptosis in the dentate gyrus (DG) region of rat brain. Permanent global brain ischemia was generated by HD in experimental rats and the brain was isolated after 0, 1, 2, 3, 4, 5, 6, 9, 12 and 24h post- HD and cervical dislocation (CD). The histology, hydrogen peroxide (H2O2) concentration, catalase, caspase-9 and caspase-3 activities and DNA fragmentation were analyzed in neuronal cells of DG region of the brain. Permanent global brain ischemia generated due to HD induced generation of H2O2 as well as catalase activity. The increased level of H2O2 was associated with the increased caspase-9 and caspase-3 activities. The increased caspase-3 activity induced neuronal cell apoptosis during early period (0-9h) of HD as compare to CD group. The neuronal cells necrosis was observed only 12h post-HD, while CD induced necrosis as early as 3h post-CD and the histoarchitecture of DG region was gradually disrupted after 6h of CD. In conclusion, data of the present study suggest that the permanent global brain ischemia induces neuronal cell apoptosis during early period of HD through ROS-mediated pathway, while CD induces neuronal cell necrosis and disruption of the histoarchitecture of the DG region. Thus, neuronal cell apoptosis may be used to develop a cellular marker to find out the exact timing of HD.


Observation of long supershear rupture during the magnitude 8.1 Kunlunshan earthquake.
The 2001 Kunlunshan earthquake was an extraordinary event that produced a 400-km-long surface rupture. Regional broadband recordings of this event provide an opportunity to accurately observe the speed at which a fault ruptures during an earthquake, which has important implications for seismic risk and for understanding earthquake physics. We determined that rupture propagated on the 400-km-long fault at an average speed of 3.7 to 3.9 km/s, which exceeds the shear velocity of the brittle part of the crust. Rupture started at sub-Rayleigh wave velocity and became supershear, probably approaching 5 km/s, after about 100 km of propagation.


Corticomotorneuronal hyper-excitability in amyotrophic lateral sclerosis.
We have analysed how the behaviour of a voluntarily activated motor unit changes when subjected to 100-150 threshold cortical stimuli using peristimulus time histograms (PSTHs). This is a measure of the integrity of the corticomotoneuronal core innervating a single anterior horn cell. One hundred and thirty units in 29 patients with ALS and 35 units in eight age-matched normal controls were studied. PSTHs were constructed using 1-ms bins of stimulus triggered sweeps with a total analysis time of 250 ms (50 ms before and 200 ms after the stimulus). In ALS the primary peak of the PSTH was delayed in onset and prolonged in duration. The primary peak was further analysed by finer 0.2-ms bins, which showed in ALS there were more sub-components than normally occur. Additional sub-components in the PSTH primary peak implies a hyper-excitable corticomotoneuron that fires excessively. Excitability could be glutamate induced and/or due to failure of GABA inhibitory mechanisms. Some glutamate antagonsits may be therapeutic in ALS because of their anticonvulsant or GABergic properties rather than their anti-glutamate properties. GABA(B) agonists might have a role in future therapeutic combined therapies for ALS.


Receptor-mediated endocytosis of galactose and mannose exposing ligands: an electron microscopic study on adult and neonatal cultured rat hepatocytes.
We compared the receptor-mediated endocytosis for galactose and mannose exposing ligands in primary cultures of hepatocytes from newborn and adult rats. The endocytic pathway was revealed ultrastructurally using colloidal gold particles coupled to lactosylated bovine serum albumin and invertase. The binding activity on the cell surfaces is observed by keeping the cells at 4 degrees C. For both ligands used, the binding capacity for hepatocytes from adult rats was greater than for neonatal cultured cells. Increasing the temperature to 37 degrees C, we observed that the protein-gold complexes entered the intracellular endocytic organelles. Within 5-15 min, the marker was confined in vesicles close to the cell surface and in the endosome, while after 60 min, the marker is found in lysosome-like compartments. We found that the process of endocytosis is similar for galactose and mannose exposing ligands. The organelles involved in the process of endocytosis in newborn cultured hepatocytes are not different in shape from those of cultured cells of adult rats, but the process of internalization is slower.


Comparison of different brown and white layer hybrid embryonic development and uptake of nutrients in the egg.
The objective of this study was to evaluate the comparison of different brown and white layers in embryonic development and uptake of nutrients in the egg. A total of 360 fertilized eggs obtained from two brown (Atak-S and Brown Nick) and two white (Atabey and Nick) layer breeders at 28 wk old. Hatching eggs from each genotype were examined on the day of setting for fresh egg analysis and then at the beginning of the embryonic day (E19) and embryonic day (E21) for egg, embryo and villus analysis. Differences in egg weight, shell percentages, relative weight of yolk and albumen, relative weight and length of embryo, villus height, some values of shell, yolk and albumen and relative chick weight in examined hybrids were significant. Yolk sac utilization of embryos during the incubation in the white layer hybrids was greater than that in the brown layer hybrids. Villus heights in the duodenum, jejenum and ileum of embryos in the brown layer hybrids was greater than that in the white layer hybrids. Genotype is important parameter to determine the egg composition at the same age and in animals being fed the same diet. It was observed that the consumption of yolk and shell nutrients from the embryos during the incubation was not related to whether embryos were from the brown or white layer hybrids. Only uptake of the yolk sac and villus height in the embryo among examined variables varied depending on whether the embryos were from the brown or white layer hybrids.