Biosynthesis of a substituted cellulose from a mutant strain of Xanthomonas campestris.
In Xanthomonas campestris the genes involved in polysaccharide (xanthan) biosynthesis are located in a gene cluster (gum) of 16 kb. A Tn5 insertion mutant with a reduced slimy phenotype has been characterized. This mutant failed to produce the pentasaccharide repeating-unit of xanthan. Only three sugars were transferred to the prenyl phosphate intermediate. Several lines of evidence suggested that the lipid-associated saccharide was the trisaccharide reducing end of the pentasaccharide from the wild-type strain. This trisaccharide was built up from UDP-Glc and GDP-Man, and a glucose residue was at the reducing end, linked to an allylic prenol through a diphosphate bridge. Results from one- or two-stage reactions showed that the trisaccharide-P-P-polyprenol was the precursor of the polymer. This new polymer, a polytrisaccharide, was detected also in vivo. The transposon responsible for the mutation was located within gumK gene. Therefore, this gene encodes for the glycosyltransferase IV, which catalyses the transfer of glucuronic acid to the lipid-linked beta-D-Manp-(1-->3)-beta-D-Glcp-(1-->4)-beta-D-Glcp trisaccharide. A recombinant plasmid with the whole gum cluster restored the wild type phenotype.


Are Elevated Vancomycin Serum Trough Concentrations Achieved Within the First 7 Days of Therapy Associated With Acute Kidney Injury in Children?
In 2008, the empiric vancomycin dosing recommendation in children at our institution was changed from 40 to 60 mg/kg per day. Subsequently, an increased incidence of acute kidney injury (AKI) in patients receiving vancomycin was suspected. The objective of this study was to evaluate AKI in children receiving vancomycin and to determine risk factors for AKI development. Medical records of patients aged 30 days through 17 years who received vancomycin for at least 72 hours between January and December 2007 (40 mg/kg per day) and January and December 2010 (60 mg/kg per day) were reviewed. Patients with cystic fibrosis, an elevated baseline serum creatinine, or without a serum creatinine concentration obtained after receipt of vancomycin were excluded. Acute kidney injury was defined using adapted pediatric RIFLE criteria as an increase in serum creatinine from baseline of 50% or more. Acute kidney injury occurred in 19.4% of the 859 children included, with no difference between the 2007 and 2010 periods (18.8% vs 20%, respectively; P = .636). Intensive care unit admission (odds ratio [OR], 1.86; 95% confidence interval [CI], 1.20-2.94) and an initial vancomycin trough concentration ≥15 mg/L (OR, 2.18; 95% CI, 1.21-3.92) were determined to be significantly associated with AKI. These results suggest an initial vancomycin serum trough concentration of ≥15 mg/L and intensive care unit admission are predictors of AKI in this pediatric population.


Differential binding of Sin3 interacting repressor domains to the PAH2 domain of Sin3A.
The Sin3 interacting domain (SID), originally described in the Mad family of repressors, is a novel transcriptional repressor domain that binds the PAH2 domain of corepressors Sin3A and Sin3B with high affinities. The conserved SID-like domains are reportedly present in five KLF proteins. However, the KLF SIDs and the Mad SIDs can be classified into two subtypes according to sequence similarity. Here, we report the finding from computational and experimental studies that the two subtypes of SID domains bind differentially to Sin3A. This finding offers insights into a mechanism of cell growth regulation by interactions of different subtypes of SID-containing repressor proteins with Sin3. It also provides the structural basis for developing selective modulators of Sin3.


Cholesterol and Inflammation in Atherosclerosis: An Immune-Metabolic Hypothesis.
Atherosclerotic cardiovascular disease (ASCVD) is a major cause of morbidity and mortality worldwide [...].


The effect of acupressure on sleep quality of older people: A systematic review and meta-analysis of randomized controlled trials.
The effects of acupressure on sleep quality and insomnia symptoms have been studied in various groups of haemodialysis patients, those undergoing surgery, and those living in elderly care homes. The aim of this study is to determine the effect of acupressure on sleep quality in elderly people. This study was conducted with a systematic review and meta-analysis. In this study, electronic databases of PubMed, Science Direct, National Thesis centre, Google Scholar, Web of Science, EBSCO were systematically scanned between December 2020 and February 2021 using the keywords "older, elderly, sleep quality, acupressure". The study included 11 articles published in English and Turkish languages without any year limitation. This systematic review and meta-analysis were done by following the PRISMA reporting system. The total sample size of 11 randomized controlled trials included in this systematic review and meta-analysis was 722 (experiment: 363 and control: 359), and the mean duration of acupressure interventions applied was 19.65 ± 11.28 days. The sleep quality of the acupressure group in the elderly was significantly increased compared to the control group (MD: -1.71,%95 CI: -2.31 to -1.11, Z = 5.60, p< 0.00001, I2 = 91%). After the subjects received training for acupressure application and applied acupressure themselves, their sleep quality improved compared to the control group (MD: -0.86, 95% CI: -1.39 to -0.32, p <0.001). We have utilized meta-analysis to try to reveal statistical significance by pooling small studies with high quality. This meta-analysis provided a potentially effective intervention on the quality of sleep in elderly people.


Mechanism of arterial remodeling in chronic allograft vasculopathy.
Chronic allograft vasculopathy (CAV) remains a major obstacle for long-term survival of grafts even though therapeutic strategies have improved considerably in recent years. CAV is characterized by concentric and diffuse neointimal formation, medial apoptosis, infiltration of lymphocyte or inflammatory cells, and deposition of extracellular matrix both in arteries and veins. Recent studies have shown that stem cells derived from the recipient contribute to neointimal formation under the regulation of chemokines and cytokines. Arterial remodeling in allografts eventually causes ischemic graft failure. The pathogenesis is multi-factorial with both immunologic and non-immunological factors being involved. The immunological factors have been discussed extensively in other articles. This review focuses mainly on the arterial remodeling that occurs in 3 layers of vessel walls including intimal injury, accumulation of smooth muscle-like cells in the neointimal, medial smooth muscle cell apoptosis, adventitial fibrosis, and deposition of extracellular matrix.


Characterizing providers' immunization communication practices during health supervision visits with vaccine-hesitant parents: a pilot study.
To determine the feasibility of using direct observation of provider-parent immunization discussions and to characterize provider communication practices with vaccine-hesitant parents. Over a 6 month period in 2010, we videotaped immunization discussions between pediatric providers and vaccine-hesitant parents during health supervision visits involving children 2-15 months old (N=24) in the Seattle area, Washington, USA. Videotapes were analyzed using the qualitative method of conversation analysis. We approached 96 parents seen by 9 different providers. Of those who were eligible (N=56), we enrolled 43% (N=24). Four videotaped visits were excluded from analysis for failure to obtain parental HIPAA authorization. Of the remaining 20 visits, there were ≥2 visits each that involved children aged 2, 4, 6, 9, 12, and 15 months, and all videotaped visits contained at least a brief immunization discussion. We identified 6 communication practices and several behavior types within each practice relevant to immunization: Practice 1, providers' initiations of the topic of vaccination; Types: participatory or presumptive format; Practice 2, parents' responses to providers' topic initiations; Types: strong or weak acceptance or resistance; Practice 3, providers' follow-ups to parent's responses; Types: no, immediate, or delayed pursuit; Practice 4, parents' vaccine-related questions or statements; Types: fact- or concern-based; Practice 5, providers' explicit solicitations of parent's questions/concerns; Types: designed to discourage or encourage discussion; and Practice 6, parents' responses to providers' solicitations of questions/concerns; Types: no question or fact- or concern-based inquiry. Direct observation of immunization discussions in the primary care pediatric setting is feasible and yields insight into several provider-parent immunization communication practices that are worthy of further study to determine which are effective at improving parental acceptance of immunization.


Clinicians' perceptions of opioid error-contributing factors in inpatient palliative care services: A qualitative study.
Opioid errors are a leading cause of patient harm and adversely impact palliative care inpatients' pain and symptom management. Yet, the factors contributing to opioid errors in palliative care are poorly understood. Identifying and better understanding the individual and system factors contributing to these errors is required to inform targeted strategies. To explore palliative care clinicians' perceptions of the factors contributing to opioid errors in Australian inpatient palliative care services. A qualitative study using focus groups or semi-structured interviews. Three specialist palliative care inpatient services in New South Wales, Australia. Inpatient palliative care clinicians who are involved with, and/or have oversight of, the services' opioid delivery or quality and safety processes. Deductive thematic content analysis of the qualitative data. The Yorkshire Contributory Factors Framework was applied to identify error-contributing factors. A total of 58 clinicians participated in eight focus groups and 20 semi-structured interviews. Nine key error contributory factor domains were identified, including: active failures; task characteristics of opioid preparation; clinician inexperience; sub-optimal skill mix; gaps in support from central functions; the drug preparation environment; and sub-optimal clinical communication. This study identified multiple system-level factors contributing to opioid errors in inpatient palliative care services. Any quality and safety initiatives targeting safe opioid delivery in specialist palliative care services needs to consider the full range of contributing factors, from individual to systems/latent factors, which promote error-causing conditions.


Structural characterisation of the polysaccharides from endemic Mongolian desert plants and their effect on the intestinal absorption of ovalbumin.
Using successive extractions with water and 0.7% aqueous ammonium oxalate, pectic polysaccharides were isolated from the following plants growing in the arid climate of Mongolia (Gobi): saxaul Haloxylon ammodendron Maxim., rhubarb Rheum nanum Sievers, Nitraria sibirica Pall., Peganum harmala L. and almond Amygdalus mongolica Maxim. The data obtained exhibited the primary synthesis of the cell wall pectic polysaccharides but not the middle lamellae water-soluble pectins in plants growing in the dry climatic zone. Both α-(1→4)-D-galacturonan and α-(1→4)-D-galacturonan, which was substituted with methyl groups, were found to be backbone of pectins. The L-arabinofuranose residues were identified as the main components of ramified regions. The pectins from almond differed from other pectins due to a high arabinose content. The data from NMR spectroscopy and methylation analyses demonstrated that pectic polysaccharides from almond included terminal, (1→5)-, (1→3)-linked and 3,5-substituted L-arabinofuranose residues and a small terminal D-galactopyranose and 2,5- and 2,3,5-substituted L-arabinofuranose residue content. The pectic polysaccharides were found to decrease the absorption of ovalbumin (OVA) in the blood from the gut lumen. The serum OVA level was lower in mice fed with OVA mixed with the pectins compared with the control group, which was administered OVA alone.


Not Just Another Methanation Catalyst: Depleted Uranium Meets Nickel for a High-Performing Process Under Autothermal Regime.
Ni-based catalysts prepared through impregnation of depleted uranium oxides (DU) have successfully been employed as highly efficient, selective, and durable systems for CO2 hydrogenation to substituted natural gas (SNG; CH4 ) under an autothermal regime. The thermo-physical properties of DU and the unique electronic structure of f-block metal-oxides combined with a nickel active phase, generated an ideal catalytic assembly for turning waste energy back into useful energy for catalysis. In particular, Ni/UOx stood out for the capacity of DU matrix to control the extra heat (hot-spots) generated at its surface by the highly exothermic methanation process. At odds with the benchmark Ni/γ-Al2 O3 catalyst, the double action played by DU as a "thermal mass" and "dopant" for the nickel active phase unveiled the unique performance of Ni/UOx composites as CO2 methanation catalysts. The ability of the weakly radioactive ceramic (UOx ) to harvest waste heat for more useful purposes was demonstrated in practice within a rare example of a highly effective and long-term methanation operated under autothermal regime (i. e., without any external heating source). This finding is an unprecedented example that allows a real step-forward in the intensification of "low-temperature" methanation with an effective reduction of energy wastes. At the same time, the proposed catalytic technology can be regarded as an original approach to recycle and bring to a second life a less-severe nuclear by-product (DU), providing a valuable alternative to its more costly long-term storage or controlled disposal.


[Practice of hygienic standardization of industrial allergens in the air of the work area and ways of its improvement].
Proceeding from the results of 8-year practical experience in hygienic standardization of industrial allergens (IA) in the workplace air it is pointed out that only substances for which sensitizing effect is a limiting criterion should be regarded as IA. It is demonstrated that IA are attributed to different hazardous classes according to which differential selection of safety factor is recommended. Highlighted is the necessity of developing new methods of IA hygienic standardization.


Inhibitory activity of four demethoxy fluorinated anthracycline analogs against five human-tumor cell lines.
Four anthracycline analogs synthesized in our laboratory were evaluated in comparison with adriamycin (doxorubicin) for their growth-inhibitory effect against five human-tumor cell lines, including lung carcinoma, colon adenocarcinoma, breast adenocarcinoma, melanoma, and glioblastoma. The compounds included 4-demethoxy-7-O-(2,6-dideoxy-2-fluoro--l-talopyranosyl)daunomycinone (2), its 3',4'-diacetate (1), its 14-bromo derivative 3, and its 14-hydroxy analog, namely 4-demethoxy-7-O-(2,6-dideoxy-2-fluoro-α-l-talopyranosyl)adriamycinone (4). Compounds 1, 2, and 3 showed moderate cytotoxic effect in most of the cell lines, while compound 4 had a strong effect, comparable to or better than that of adriamycin in most of the cell lines.


Inclusive intervention to enhance the fundamental movement skills of children without hearing: a preliminary study.
The purpose of this study was to assess an intervention program on the fundamental movement skill of students with and without hearing impairment, using the Test of Gross Motor Development-2 (TGMD-2) standardized Turkish norm. Preschool children with and without hearing impairment participated in this study. At the beginning of the study, most of the children with hearing impairment demonstrated developmental delay on the Locomotor subscale (6/7), as did about one-third (4/11) of the children without hearing impairment. For the Object control subscale, 4/7 of children with hearing impairment and none without hearing impairment showed developmental delay prior to the intervention program. After the intervention program, 3/7 children with hearing impairment had developmental delay on the Locomotor subscale. On the Object control subscale, 2/7 children with hearing impairment and none without hearing impairment showed developmental delay. The six-week intervention program improved TGMD-2 scores of children with hearing impairment, yet did not yield statistically significant improvement of fundamental movement skills.


Kinetic analysis of arm reaching movements during voluntary and passive rotation of the torso.
Reaching movements made to targets during exposure to passive constant velocity rotation show significant endpoint errors. By contrast, reaching movements made during voluntary rotation of the torso are accurate. In both cases, as a consequence of the simultaneous motion of the arm and the torso, Coriolis forces are generated on the arm tending to deflect its path. Our goal in the present paper was to determine whether during voluntary torso rotations arm movement accuracy is preserved by feed forward compensations for self-generated Coriolis forces. To test this hypothesis we analyzed and quantified the contribution of torso rotation and translation to arm dynamics and compared the kinematics and kinetics of pointing movements during voluntary and passive torso rotation. Coriolis torques at the shoulder increase nearly sixfold in voluntary turn and reach movements relative to reaches made without torso rotation, yet are equally accurate. Coriolis torques during voluntary turn and reach movements are more than double those produced by reaching movements during passive body rotation at 60 degrees /s. Nevertheless, the endpoints of the reaches made during voluntary rotation are not deviated, but those of reaches made during passive rotation are deviated in the direction of the Coriolis forces generated during the movements. We conclude that there is anticipatory pre-programmed compensation for self-generated Coriolis forces during voluntary torso rotation contingent on intended torso motion and arm trajectory.


Magnetic gold-nanorod/ PNIPAAmMA nanoparticles for dual magnetic resonance and photoacoustic imaging and targeted photothermal therapy.
Nanomedicine can provide a multi-functional platform for image-guided diagnosis and treatment of cancer. Although gold nanorods (GNRs) have been developed for photoacoustic (PA) imaging and near infra-red (NIR) photothermal applications, their efficiency has remained limited by low thermal stability. Here we present the synthesis, characterization, and functional evaluation of non-cytotoxic magnetic polymer-modified gold nanorods (MPGNRs), designed to act as dual magnetic resonance imaging (MRI) and PA imaging contrast agents. In addition, their high magnetization allowed MPGNRs to be actively localized and concentrated by targeting with an external magnet. Finally, MPGNRs significantly enhanced the NIR-laser-induced photothermal effect due to their increased thermal stability. MPGNRs thus provide a promising new theranostic platform for cancer diagnosis and treatment by combining dual MR/PA imaging with highly effective targeted photothermal therapy.


Enzymic properties of thermopsin.
The specificity of thermopsin, a thermostable acid protease from Sulfolobus acidocaldarius, was studied using oxidized insulin B chain as substrate followed by peptide isolation and identification. The following bonds were hydrolyzed: Leu-Val, Leu-Tyr, Phe-Phe, Phe-Tyr, and Tyr-Thr. Thus, the specificity of thermopsin is similar to that of pepsin, that is, it prefers large hydrophobic residues at both sides of the scissile bond. We confirmed this by the use of a synthetic substrate, Lys-Pro-Ala-Glu-Phe-p-nitro-phenylalanyl-Ala-Leu, which was cleaved by thermopsin between Phe and p-nitro-phenylalanyl. Using this substrate, enzyme inhibition and kinetic properties of thermopsin have been studied. Thermopsin optimally hydrolyzes this substrate at 75 degrees C and pH 2 with Km and kcat values under these conditions of 5.3 x 10(-5) M and 14.3 s-1, respectively. Pepstatin competitively inhibits thermopsin with a Ki of 2 x 10(-7) M. Other known aspartic protease inhibitors, diazoacetylnorleucine ethyl ester and 1,2-epoxy-3-(p-nitrophenoxy)propane inhibited thermopsin only slowly and with nonspecific reactions. Although thermopsin contains a single cysteine, iodoacetic acid and p-chloromercuric benzoate had no effect on activity. Mercuric chloride inhibited the enzyme, and the inhibition was reversible by mercaptoethanol. However, the enzyme was not labeled by [14C]iodoacetic acid either before or after sodium dodecyl sulfate denaturation. Thus, the thiol group is likely blocked, and the inhibition effect of mercuric ion is unrelated to the thiol group. These observations suggest that thermopsin has a different active site than the aspartic protease family but may have a similar transition state structure. The temperature dependence of Km and kcat was studied for thermopsin hydrolysis of the synthetic substrate between 26-78 degrees C. Both parameters increased with temperature, and the rise of kcat value was particularly sharp above 65 degrees C. Hydrolysis activity measured at high substrate concentration has a maximum at 76 degrees C, which is near the physiological temperature for the optimal growth of this organism. Thus, thermopsin appears to function best at high temperature and high substrate concentration. It may be utilized by the organism to response to the presence of high substrate concentration in the medium. Thermopsin is also competitively inhibited by urea, acetamide, and phenylalaninamide with Ki values of 0.5, 0.4, and 0.01 M, respectively.


Epidemiology of Cutaneous Lupus Erythematosus Among Adults Over Four Decades (1976-2018): A Lupus Midwest Network (LUMEN) Study.
To characterize the epidemiological trends and mortality of cutaneous lupus erythematosus (CLE) between 1976 and 2018 in Olmsted County, Minnesota. In this retrospective population-based cohort study, all incident and prevalent CLE cases among adult residents in Olmsted County, Minnesota, between January 1, 1976, and December 31, 2018, were identified and categorized by subtype through medical record review using the resources of the Rochester Epidemiology Project. The overall incidence rate of CLE between 1976 and 2018 was 3.9 (95% CI, 3.4 to 4.5) per 100,000. The incidence of CLE was relatively stable, with no major trend across sexes or age groups. The age- and sex-adjusted prevalence of CLE was 108.9 per 100,000 on January 1, 2015. Mortality in CLE patients was similar to that of the general population, with a standardized mortality ratio of 1.23 (95% CI, 0.88 to 1.66) with no observed trends in mortality over time. In the past 4 decades, the incidence of CLE remained stable. Patients with CLE have mortality comparable to that of the general population.


Small threat and contraband detection with TNA-based systems.
The detection of small threats, such as explosives, drugs, and chemical weapons, concealed or encased in surrounding material, is a major concern in areas from security checkpoints to UneXploded Ordnance (UXO) clearance. Techniques such as X-ray and trace detection are often ineffectual in these applications. Thermal neutron analysis (TNA) provides an effective method for detecting concealed threats. This paper shows the effectiveness of Ancore's SPEDS, based on TNA, in detecting concealed liquid threats and differentiating live from inert mortar shells.


Respiratory patient experience of measures to reduce risk of COVID-19: findings from a descriptive cross-sectional UK wide survey.
To assess the experience of people with long-term respiratory conditions regarding the impact of measures to reduce risk of COVID-19. Analysis of data (n=9515) from the Asthma UK and British Lung Foundation partnership COVID-19 survey collected online between 1 and 8 April 2020. Community. 9515 people with self-reported long-term respiratory conditions. 81% female, age ranges from ≤17 years to 80 years and above, from all nations of the UK. Long-term respiratory conditions reported included asthma (83%), chronic obstructive pulmonary disease (10%), bronchiectasis (4%), interstitial lung disease (2%) and 'other' (<1%) (eg, lung cancer and pulmonary endometriosis). Study responses related to impacts on key elements of healthcare, as well as practical, psychological and social consequences related to the COVID-19 pandemic and social distancing measures. 45% reported disruptions to care, including cancellations of appointments, investigations, pulmonary rehabilitation, treatment and monitoring. Other practical impacts such as difficulty accessing healthcare services for other issues and getting basic necessities such as food were also common. 36% did not use online prescriptions, and 54% had not accessed online inhaler technique videos. Psychosocial impacts including anxiety, loneliness and concerns about personal health and family were prevalent. 81% reported engaging in physical activity. Among the 11% who were smokers, 48% reported they were planning to quit smoking because of COVID-19. COVID-19 and related social distancing measures are having profound impacts on people with chronic respiratory conditions. Urgent adaptation and signposting of services is required to mitigate the negative health consequences of the COVID-19 response for this group.


A musculoskeletal finite element model of rat knee joint for evaluating cartilage biomechanics during gait.
Abnormal loading of the knee due to injuries or obesity is thought to contribute to the development of osteoarthritis (OA). Small animal models have been used for studying OA progression mechanisms. However, numerical models to study cartilage responses under dynamic loading in preclinical animal models have not been developed. Here we present a musculoskeletal finite element model of a rat knee joint to evaluate cartilage biomechanical responses during a gait cycle. The rat knee joint geometries were obtained from a 3-D MRI dataset and the boundary conditions regarding loading in the joint were extracted from a musculoskeletal model of the rat hindlimb. The fibril-reinforced poroelastic (FRPE) properties of the rat cartilage were derived from data of mechanical indentation tests. Our numerical results showed the relevance of simulating anatomical and locomotion characteristics in the rat knee joint for estimating tissue responses such as contact pressures, stresses, strains, and fluid pressures. We found that the contact pressure and maximum principal strain were virtually constant in the medial compartment whereas they showed the highest values at the beginning of the gait cycle in the lateral compartment. Furthermore, we found that the maximum principal stress increased during the stance phase of gait, with the greatest values at midstance. We anticipate that our approach serves as a first step towards investigating the effects of gait abnormalities on the adaptation and degeneration of rat knee joint tissues and could be used to evaluate biomechanically-driven mechanisms of the progression of OA as a consequence of joint injury or obesity.


Heterogeneity of soil bacterial and bacteriophage communities in three rice agroecosystems and potential impacts of bacteriophage on nutrient cycling.
As genetic entities infecting and replicating only in bacteria, bacteriophages can regulate the community structure and functions of their host bacteria. The ecological roles of bacteriophages in aquatic and forest environments have been widely explored, but those in agroecosystems remains limited. Here, we used metagenomic sequencing to analyze the diversity and interactions of bacteriophages and their host bacteria in soils from three typical rice agroecosystems in China: double cropping in Guangzhou, southern China, rice-wheat rotation cropping in Nanjing, eastern China and early maturing single cropping in Jiamusi, northeastern China. Enterobacter phage-NJ was isolated and its functions on soil nitrogen cycling and effect on soil bacterial community structure were verified in pot inoculation experiments and 16S rRNA gene sequencing. Soil bacterial and viral diversity and predicted functions varied among the three agroecosystems. Genes detected in communities from the three agroecosystems were associated with typical functions: soil bacteria in Jiamusi were significantly enriched in genes related to carbohydrate metabolism, in Nanjing with xenobiotics biodegradation and metabolism, and in Guangzhou with virulence factors and scarce in secondary metabolite biosynthesis, which might lead to a significant occurrence of rice bacterial diseases. The virus community structure varies significantly among the three ecosystems, only 13.39% of the total viral species were shared by the three rice agroecosystems, 59.56% of the viral species were specific to one agroecosystem. Notably, over-represented auxiliary carbohydrate-active enzyme (CAZyme) genes were identified in the viruses, which might assist host bacteria in metabolizing carbon, and 67.43% of these genes were present in Jiamusi. In bacteriophage isolation and inoculation experiments, Enterobacter bacteriophage-NJ reduced the nitrogen fixation capacity of soil by lysing N-fixing host bacteria and changed the soil bacterial diversity and community structure. Our results showed that diversity and function predicted of paddy soil bacteria and viruses varied in the three agroecosystems. Soil bacteriophages can affect nutrient cycling by boosting host metabolism through the carried auxiliary metabolic genes (AMGs) and lysing the host bacteria that are involved in biogeochemical cycles. These findings form a basis for better understanding bacterial and bacteriophage diversity in different rice agroecosystems, laying a solid foundation for further studies of soil microbial communities that support ecofriendly production of healthy rice.


Genetic equidistance at nucleotide level.
The genetic equidistance phenomenon shows complex taxa to be all approximately equidistant to a less complex species in amino acid percentage identity. The overlooked mystery was re-interpreted by the maximum genetic diversity hypothesis (MGD). Here, we studied 14 proteomes and their coding DNA sequences (CDS) to see if the equidistance phenomenon also holds at the CDS level. We found that the outgroup taxon was equidistant to the two more complex taxa species. When two sister taxa were compared to human as the outgroup, the more complex taxon was closer to human, confirming species complexity to be the primary determinant of MGD. Finally, we found the fraction of overlap sites to be inversely correlated with CDS conservation, indicating saturation to be more common in less conserved DNAs. These results establish the genetic equidistance phenomenon to be universal at the DNA level and provide additional evidence for the MGD theory.


[Medicine of pet birds].
This article describes the demands made upon the veterinarian and equipment of a practice for companion birds. The case history of an avian patient is also described.


Expression of AKT and p-AKT protein in lung adenocarcinoma and its correlation with PD-L1 protein and prognosis.
The PI3K/AKT/mTOR signaling pathway were significantly associated with EGFR mutation in lung adenocarcinoma (LUAD), but its correlation with PD-L1 protein and prognosis are not clear. The aim of this study was to evaluate the expression of AKT and phosphorylated AKT (p-AKT) in LUAD and its correlation with programmed death ligand-1 (PD-L1); and to analyze the factors affecting LUAD prognosis. The expression of AKT, p-AKT, and PD-L1 was examined using immunohistochemistry in LUAD tissues from 110 patients who underwent surgical treatment. AKT protein expression was examined in 64.5% (71/110) of the LUAD samples, and p-AKT protein expression was examined in 44.5% (49/110) of the LUAD samples. The positive rate of PD-L1 at TC1/2/3 was 38.2% (42/110). AKT and p-AKT expression was significantly associated with epidermal growth factor receptor (EGFR) mutation (P=0.016, P=0.014 respectively). Pearson's correlation analysis indicated a negative correlation of p-AKT with PD-L1 protein (P=0.022). Out of the 62 patients with EGFR mutation, the expression of PD-L1 was negatively correlated with that of p-AKT protein (P=0.032). The expressions of AKT and p-AKT were not associated with prognosis. Multivariate analysis showed that tumor-node-metastasis (TNM) stage (P=0.013) and differentiation (P=0.046) were independent prognostic factors for overall survival. PI3K/AKT/mTOR in the downstream pathway of EGFR may negatively regulate the expression of PD-L1, which may partly explain why patients with EGFR mutation respond poorly to PD-1/PD-L1 inhibitors.


Coronary arteries of the European bison (Bison bonasus).
The European bison (Bison bonasus) is an endangered species. More information on its anatomy is needed as only few studies have been published. This study is the first report on the morphology of the coronary vessels. Given the anatomical similarity between the European bison and other ruminants, the results of this study can be applied to other species, including endangered ones. The study was conducted on 70 hearts of European bisons of both sexes, aged 5-20 years, with an average body weight of 449 kg. A distinct view of subepicardial arterial vessels was obtained by filling them with dyed synthetic latex (LBS 3060) and Plastogen G. There was a division of the common trunk of the left coronary artery into the interventricular paraconal branch and the left circumflex branch in 63 individuals (90 %). In five individuals (7.1 %), the presence of a third vessel, which was a branch of the interventricular septum, was observed. There was a lack of a common trunk in two individuals (2.9 %). Ramifications of the interventricular paraconal branch to the wall of the left ventricle were significantly larger than those to the wall of the right ventricle. In 17 individuals (24.3 %), the right coronary artery extended into the subsinuosal interventricular branch. The blood supply to the heart in bisons is provided by the left and right coronary arteries. In all the studied specimens, the left coronary artery was better developed than the right coronary artery.


Bordetella pertussis as a trigger of migraine without aura.
This report describes a 10-year-old child in whom the clinical and serologic appearance of pertussis coincided with new-onset migraine without aura. The child's mother, who had a history of migraine, also complained of exacerbation of symptoms and was found to be positive for Bordetella pertussis. The migraine improved in both mother and child concomitant with the clinical improvement of symptoms of the pertussis infection. The possible molecular basis of pertussis as a trigger for migraine is discussed.


Unusual coordination of tetrylenes to molybdenum carbonyl fragments.
Reactions of the tetrylenes Ge(SAr(Me6))2 (1) (Ar(Me6) = C6H3-2,6(C6H2-2,4,6-Me3)2), and Sn(SAr(Me6))2 (2) with (Mo(CO)4(NBD) (NBD = bicyclo[2.2.1]hepta-2,5-diene) gave three new, unusual complexes [Mo(THF)(CO)3{Ge(SAr(Me6))2}] (3), [Mo(THF)(CO)3{Ge(SAr(Me6))2}] (4) and [Mo(CO)4{Sn(SAr(Me6))2}] (5) which display no significant Ge/Sn-Mo bonding. Instead the ligands are coordinated to molybdenum in a bidentate fashion via the thiolato sulfurs.


Dieulafoy's lesion of the upper GI tract: a comprehensive nationwide database analysis.
We sought to determine the incidence, risk factors, and treatment outcomes of Dieulafoy's lesion of the upper GI tract (UDL) hemorrhage among adult patients in the United States. UDL and non-Dieulafoy upper GI bleeding (UGIB) were identified from the Nationwide Inpatient Sample and Nationwide Readmission Database using International Classification of Diseases, Tenth Revision, Clinical Modification and Procedure Coding System codes. Multivariate logistic (binary) and linear (continuous) regressions were used to model dependent variables. The incidence of UDL hemorrhage was 1.6 of 100,000 persons. Patients with UDL and UGIB who required endoscopic therapeutic intervention had similar in-hospital (adjusted odds ratio [aOR], .77; 95% confidence interval [CI], .42-1.43; P = .41) mortality rates. UDL was associated with more severe systemic illness, including higher rates of mechanical ventilation (aOR, 1.52; 95% CI, 1.07-2.15; P < .05), hypovolemic shock (aOR, 1.50; 95% CI, 1.08-2.08; P < .05), acute kidney injury (aOR, 1.25; 95% CI, 1.02-1.54; P < .05), and multiple endoscopies (aOR, 1.57; 95% CI, 1.28-1.93; P < .05) compared with other UGIB patients who required endoscopic therapeutic intervention. UDL was also associated with higher 30-day all-cause (aOR, 1.23; 95% CI, 1.12-1.35; P < .05) and recurrent bleeding-related (aOR, 1.73; 95% CI, 1.45-2.06; P < .05) readmissions. The rate of successful endoscopic treatment was 96.81%. UDL hemorrhage is an uncommon but highly morbid condition. Current UDL treatment modalities are effective in reducing mortality. Further investigations are warranted to lower recurrent bleeding rates.


Embolisation of internal carotid artery aneurysm using the double microcatheter technique - a case report.
A wide-necked aneurysm is defined as the one with a neck greater than 4 mm in diameter. Embolisation of wide-necked aneurysms is a great challenge for neuroradiologists. To overcome possible complications of endovascular treatment of this type of aneurysms, methods like intracranial stents, balloon remodelling, the double microcatheter and the microcatheter protective technique have been developed. We report a case of embolisation of a 63-year-old woman with a wide-necked aneurysm using the double microcatheter technique. Introduction of the second microcatheter into the aneurysm allowed for crossing two coils and prevented protrusion into the parent vessel, which resulted in successful treatment without postprocedural complications. Both postembolic and follow-up angiography showed complete exclusion of the aneurysm. The double microcatheter technique, owing to creation of a stable coil frame across the neck of the aneurysm, is suitable for treatment of aneurysms with an adverse dome-to-neck ratio. This technique is easy to perform for an experienced neuroradiologist.


Bilateral adhesive bone conduction devices in patients with congenital bilateral conductive hearing loss.
This study aims to characterize the hearing benefits and sound localization accuracy of bilateral adhesive bone conduction devices (aBCDs) compared to unilateral devices in patients with congenital bilateral conductive hearing loss (BCHL). Sixteen children and adolescents with congenital BCHL were enrolled and tested under four listening conditions: (1) unaided, (2) R aided: aided with a right-side aBCD, (3) L aided: aided with a left-side aBCD, and (4) B aided: aided with aBCDs on both sides. The sound field hearing threshold (SFHT, in dB hearing level [HL]) and the word recognition score (WRS) were measured. The mean absolute error (MAE) of sound source localization was calculated to assess the sound localization accuracy. The performance in SFHT and WRS was significantly higher in the B aided condition than that in the unaided, R and L aided conditions; moreover, no significant difference was observed between the R and L aided conditions. Concerning sound source localization, the accuracy of localization exhibited a sharp decline when using a single aBCD, while the application of bilateral aBCDs (B aided condition) resulted in a significantly improved localization accuracy as compared to the unilaterally aided conditions (both R and L); however, no significant difference was found between the unaided and B aided condition. Patients with congenital BCHL experienced suboptimal hearing benefits and manifested significant challenges in sound source localization when utilizing a single aBCD, as compared to the utilization of bilateral aBCDs.


Natural killer cells in normal horses and specific-pathogen-free foals infected with equine herpesvirus.
Peripheral blood mononuclear cells (PBMC) from an adult horse and from foals demonstrated natural killer (NK)-type cytotoxicity against a range of xenogeneic and allogeneic cell targets. The human tumour cell line, Chang liver was consistently the most susceptible. Chang liver, rabbit kidney (RK-13), equine sarcoid (ES) and embryonic equine kidney (EEK) cells were more susceptible when presented to horse PBMC than monolayer cultures. Embryonic equine lung (EEL) and murine YAC-1 cells conversely, were more susceptible in a trypsinized state. Horse PBMC demonstrated higher levels of NK-type activity against EEK, EEL and RK-13 cells infected with equine herpesvirus 1 (EHV-1) compared with uninfected cells. Similarly, EEK and EEL cells infected with Semliki forest virus (SFV) were more susceptible. Cytotoxicity against EHV-1-infected EEK cells developed faster, between 4 and 8 h of incubation and reaching a maximum at 24 h. By contrast, cytotoxicity against uninfected fibroblasts was not significant until approximately 16 h of incubation with maximum cytotoxicity observed between 32 h and 48 h. Specific pathogen-free (SPF) foals were inoculated with live EHV-1. PBMC isolated from these foals at different days after inoculation did not display appreciably reduced or elevated NK cytotoxicities against Chang liver cells and EHV-1-infected EEK targets, when compared with that of a PBMC reference from a healthy adult horse.


Fatal adult-onset diaphragmatic hernia in the context of the COVID-19 pandemic.
Late-presenting or "Adult-Onset" Diaphragmatic Hernia is uncommon, especially in individuals with no history of trauma. The non-traumatic diaphragmatic hernia may be a Congenital Diaphragmatic Hernia [CDH] lately manifested as a sequela to an iatrogenic intervention or prolonged infections. We aim to explore the genetic correlations in "adult-onset" CDH, with an insight into the indirect contribution of the COVID-19 pandemic towards the fatal outcome.In this report, we present a case of an adult female who died from the complications of an undiagnosed adult-onset diaphragmatic hernia, deemed completely preventable, if not for the global COVID-19 pandemic. There was no prior history of physical trauma or medical history of any relevance.Early diagnosis and rapid surgical intervention remain the keystone management for successfully treating individuals affected by this entity. The decedent in question presented with symptoms demanding hospital stay for investigations that would have aided in timely diagnosis and prevented death. However, the excessive fear of COVID-19 prevented the patient from undergoing hospitalization and follow-up, delaying the diagnosis and leading to death.


LI-RADS and transplantation: challenges and controversies.
Patients with early stage hepatocellular carcinoma (HCC) can be cured by liver transplantation. HCC imaging features on CT or MRI are specific enough to allow for definitive diagnosis and treatment without the need of confirmatory biopsy. When applied to the appropriate at-risk population the Liver Imaging Reporting and Data System (LI-RADS) imaging criteria achieve high specificity and positive predictive value for the diagnosis of HCC. The Organ Procurement and Transplantation Network (OPTN) is the United States organization that aims to assure the adequate and fair distribution of livers across candidates. Given the importance of fair organ allocation, OPTN also provides stringent imaging criteria for the diagnosis of HCC aiming to avoid false positive diagnosis. Although most imaging criteria are identical for both systems, discrepancies between LI-RADS and the current OPTN classification system for HCC diagnosis exists. Main differences include, but are not limited to, the binary approach of OPTN to classify lesions as HCC or not, versus the probabilistic algorithmic approach of LI-RADS, technical and interpretation considerations, and the approach towards treated lesions. The purpose of this article is to highlight the similarities and discrepancies between LI-RADS and the current OPTN criteria for HCC diagnosis and the implications that these differences may have on the management of patients who are transplant candidates.


A tale of two cities: the cost, price-differential and affordability of current and healthy diets in Sydney and Canberra, Australia.
The perception that healthy foods are more expensive than unhealthy foods has been reported widely to be a key barrier to healthy eating. However, assessment of the relative cost of healthy and unhealthy foods and diets is fraught methodologically. Standardised approaches to produce reliable data on the cost of total diets and different dietary patterns, rather than selected foods, are lacking globally to inform policy and practice. This paper reports the first application, in randomly selected statistical areas stratified by socio-economic status in two Australian cities, of the Healthy Diets Australian Standardized Affordability and Pricing (ASAP) method protocols: diet pricing tools based on national nutrition survey data and dietary guidelines; store sampling and location; determination of household incomes; food price data collection; and analysis and reporting. The methods were developed by the International Network on Food and Obesity/NCD Research, Monitoring and Action Support (INFORMAS) as a prototype of an optimum approach to assess, compare and monitor the cost and affordability of diets across different geographical and socio-economic settings and times. Under current tax policy in Australia, healthy diets would be 15-17% less expensive than current (unhealthy) diets in all locations assessed. Nevertheless, healthy diets are likely to be unaffordable for low income households, costing more than 30% of disposable income in both cities surveyed. Households spent around 58% of their food budget on unhealthy food and drinks. Food costs were on average 4% higher in Canberra than Sydney, and tended to be higher in high socioeconomic locations. Health and fiscal policy actions to increase affordability of healthy diets for low income households are required urgently. Also, there is a need to counter perceptions that current, unhealthy diets must be less expensive than healthy diets. The Healthy Diets ASAP methods could be adapted to assess the cost and affordability of healthy and unhealthy diets elsewhere.


Estimating solid waste generation and suitability analysis of landfill sites using regression, geospatial, and remote sensing techniques in Rangpur, Bangladesh.
Municipal solid waste (MSW) management has been a growing problem in fast-developing cities. A considerable amount of solid waste is generated daily and disposed anywhere, which creates an unhealthy environment. This study aims to develop a model to determine household solid waste (HSW) generation using multiple linear regression and identify suitable landfill sites to ensure proper MSW disposal in Rangpur City, Bangladesh. Socioeconomic variables data like average monthly income, educational level, family size, age of family head, and average HSW generation per day were collected from 381 respondents through stratified random sampling with a 95% confidence level. Multi-criteria decision analysis (MCDA) was performed using variables like surface water, slope, road network, and land use through GIS and remote sensing to find suitable landfill sites. Results of the model show no multicollinearity as the variance inflation factor was estimated to be less than 2 for each independent variable. Furthermore, the model provides a moderate overall fit because of the coefficient of determination (R2 = 0.661), which denotes the independent variables' predictive capability. The results also demonstrate that family size and education are the most critical variables in predicting waste generation because of the values of coefficients 122.39 and - 184.72, respectively. This study also illustrated suitable landfill sites through MCDA, which can be a useful resource for the city authority to ensure environmental sustainability by implementing effective strategies for proper MSW management.


Steroid in Chronic Subdural Hematoma: An Updated Systematic Review and Meta-Analysis Post DEX-CSDH Trial.
Chronic subdural hematoma (CSDH) is a neurologic condition characterized as a hematoma in the subdural space with a period >3 weeks that primarily affects the elderly. Glucocorticoid, especially dexamethasone, either alone or combined with surgery, has been used to manage CSDH. We aimed to perform an updated systematic review and meta-analysis of the literature regarding the role of steroids in CSDH. We searched the electronic databases PubMed, PubMed Central, Scopus, and Embase for relevant articles until December 2020. Study characteristics, quality, and end points were extracted, and analysis was performed by RevMan 5.4. The odds for subdural hematoma recurrence were decreased by 61% in the steroid group (odds ratio [OR], 0.39; confidence interval [CI], 0.19-0.79) compared with the control group. There was no significant difference in mortality during the study period (OR, 0.66; CI, 0.20-2.18), modified Rankin Scale score 0-3 (OR, 0.87; CI, 0.31-2.40), and modified Rankin Scale score 4-6 (OR, 1.15; CI, 0.42-3.18) between the 2 groups. However, pooling data from 3 studies showed 2.7 times higher odds of occurring adverse effects in steroid groups using the fixed-effect model (OR, 2.70; CI, 1.71-4.28). The treatment success was similar between the steroid and control groups (OR, 2.39; CI, 0.94-6.04). Treatment with steroids was associated with a lesser recurrence of CSDH. However, there was no benefit of steroid treatment in CSDH compared with nonsteroid treatment in terms of mortality and treatment success and some but significantly increased risk of adverse events.


A critical role of toll-like receptor 4 (TLR4) and its' in vivo ligands in basal radio-resistance.
Toll-like receptor-4 (TLR4) plays a critical role in innate and acquired immunity, but its role in radio-resistance is unknown. We used TLR4 knockout (KO,(-/-)) mice and gut commensal depletion methods, to test the influence of TLR4 and its' in vivo agonist on basal radio-resistance. We found that mice deficient in TLR4 were more susceptible to IR-induced mortality and morbidity. Mortality of TLR4-deficient mice after IR was associated with a severe and persistent bone marrow cell loss. Injection of lipopolysaccharide into normal mice, which is known to activate TLR4 in vivo, induced radio-resistance. Moreover, TLR4 in vivo ligands are required for basal radio-resistance. We found that exposure to radiation leads to significant endotoxemia that also confers endogenous protection from irradiation. The circulating endotoxins appear to originate from the gut, as sterilization of the gut with antibiotics lead to increased mortality from radiation. Further data indicated that Myd88, but not TRIF, may be the critical adaptor in TLR4-induced radio-resistance. Taken together, these data strongly suggest that TLR4 plays a critical role in basal radio-resistance. Our data suggest, it is important not to give antibiotics that may sterilize the gut before the whole body irradiation. Further, these data also suggest that management of gut flora through antibiotic or possibly probiotic therapy may alter the innate response to the total body irradiation.


Tetratrichomonads from the oral cavity and respiratory tract of humans.
To clarify the taxonomy of trichomonads associated with human respiratory diseases, we examined a collection of axenic trichomonad strains isolated from the oral cavity and bronchi of patients from pulmonary diseases clinics in Tallin, Estonia. The oral and bronchial strains were compared mutually as well as with a reference strain of Trichomonas tenax, a common inhabitant of the human oral cavity, and other trichomonad species from humans and animals. Unexpectedly, the morphological studies, as well as DNA sequencing of ITS1-5.8S rRNA-ITS2 regions revealed that the Estonian strains belong to the genus Tetratrichomonas, with a high similarity to the avian species Tetratrichomonas gallinarum. None of the strains belonged to Trichomonas tenax. DNA fingerprinting using the RAPD method separated Estonian strains into 2 distinct groups: 'bronchial' consisting of 5 and 2 strains isolated from bronchi and 'oral' cavity, respectively, and oral consisting of 3 oral strains. Consistent differences between 'bronchial' and 'oral' groups were confirmed by analysis of ITS1-5.8S rRNA-ITS2 sequences. Our results have revealed novel trichomonad species of the human oral cavity and bronchi.


Should We Operate on Thoracic Aortic Aneurysm of 5-5.5cm in Bicuspid Aortic Valve Disease Patients?
This study aims to determine the long-term outcomes and rate of reoperation among BAV patients with aortic diameter of 5-5.5cm who underwent immediate surgical repair versus surveillance. A total of 148 BAV patients with aortic aneurysm measuring 5-5.5cm were identified between 1993 to 2019. Patients were categorized into two groups: immediately operated (n=89), versus watched group (n=59) i.e., monitored until either symptomatic, aortic diameter ≥ 5.5 cm or operated at surgeons' discretion/patient preference. Compared to the immediately operated group the watched group had significantly lower proportion of proximal aorta replacement (86% vs 100%). The mean size of proximal thoracic aorta at initial encounter, including aortic root, ascending, and arch, for the watched group was 52.1 ± 1.62mm and 52.6 ± 1.81mm in the immediately operated group, p=0.06. There was no significant difference in 10-year survival between the watched group 94% (95% CI: 79%, 99%) vs immediately operated group 96.5% (95% CI: 86%, 99%), p=0.90. Initial operation rate for the watched group during 10-year follow-up was 85%. The operative mortality in both groups was 0%. The 10-year reoperation rate between groups was similar: 3.5% (95% CI: 0.9%, 9.1%) in the immediately operated group vs 7.7% (95% CI: 2.4%, 17.1%) in the patients who eventually had surgery in the watched group, p= 0.30. Our study showed that the rate of reoperation was similar between groups and survival outcomes were acceptable in observed asymptomatic BAV patients without significant family history and with proximal aortic diameter of 5-5.5cm.


Ecological and life-history correlates of erythrocyte size and shape in Lepidosauria.
Blood oxygen-carrying capacity is shaped both by the ambient oxygen availability as well as species-specific oxygen demand. Erythrocytes are a critical part of oxygen transport and both their size and shape can change in relation to species-specific life-history, behavioural or ecological conditions. Here, we test whether components of the environment (altitude), life history (reproductive mode, body temperature) and behaviour (diving, foraging mode) drive erythrocyte size variation in the Lepidosauria (lizards, snakes and rhynchocephalians). We collected data on erythrocyte size (area) and shape (L/W: elongation ratio) from Lepidosauria across the globe (N = 235 species). Our analyses show the importance of oxygen requirements as a driver of erythrocyte size. Smaller erythrocytes were associated with the need for faster delivery (active foragers, high-altitude species, warmer body temperatures), whereas species with greater oxygen demands (diving species, viviparous species) had larger erythrocytes. Erythrocyte size shows considerable cross-species variation, with a range of factors linked to the oxygen delivery requirements being major drivers of these differences. A key future aspect for study would include within-individual plasticity and how changing states, for example, pregnancy, perhaps alter the size and shape of erythrocytes in Lepidosaurs.


Color doppler flow analysis of uterine and ovarian arteries before and after tubal sterilization: electrocautery versus pomeroy.
To compare the changes in uterine and ovarian artery blood flow following laparoscopic sterilization via bipolar cautery with Pomeroy tubal ligation via mini-laparotomy in patients who had voluntary surgical sterilization. Ninety consecutive fertile women applying for voluntary tubal ligation were recruited in this prospective study. Patients were allocated for either laparoscopic tubal ligation via bipolar electrocoagulation (group 1) or Pomeroy tubal ligation via mini-laparotomy (group 2) according to their preference. Color Doppler flow analysis of uterine and ovarian arteries were carried out on the 3rd day of the cycle prior to the procedure (D(0)), on the 3rd postoperative day (D(1)) and on the 3rd day of the cycle, 3 months (D(3)) following the surgery. The significance of difference between the three measurements was analyzed by using analysis of variance. Prior to surgery, the mean pulsatility index of the uterine artery, left and right ovarian arteries were 1.9 +/- 0.3, 1.8 +/- 0.3, 1.8 +/- 0.2 in group 1 and 1.8 +/- 0.08, 1.8 +/- 0.08, 1.8 +/- 0.07 in group 2, respectively. There was no statistically significant difference between group 1 and group 2 in terms of D(0) values (p > 0.05). 3rd postoperative day and 3rd month measurements of both uterine and ovarian arteries in group 1 and group 2 did not show any statistically significant difference from that of preoperative values (p > 0.05). No alternation in the flow of either ovarian or uterine arteries following tubal sterilization performed by bipolar electrocautery and Pomeroy's technique was determined both in the immediate postoperative period and 3 months after the surgery.


Efficacy and safety of oral low-dose glucocorticoids in patients with estrogen-dependent primary osteoarthritis.
Estrogen-dependent osteoarthritis (EDPOA) is a disease of perimenopausal-age women. Their manifestations are polyarticular pain with common co-morbidities (carpal tunnel syndrome, insomnia, fatigue, depression, and fibromyalgia). Based on dual role of glucocorticoids, its trophic action on the chondrocyte and its anti-inflammatory effect, we conducted a prospective interventional cohort study where we evaluate the efficacy and safety of oral low-dose GC in one hundred women with EDPOA. The pain intensity, number of tender joints as well as impact in co-morbidities were analyzed. We conclude that the use of low-dose GC in patients with EDPOA can be an effective and a safe therapeutic option.


Digital position determination system for electron microscopy.
The precise determination of object positions within a specimen grid is important for many applications in electron microscopy. For example, real-time position determination is necessary for current statistical approaches and the efficient mapping and relocation of objects. Unfortunately, precise real-time position determination is not available on many older electron microscopes with manual stage controls. This report demonstrates the cost-effective and flexible implementation of a digital position determination system that can be adapted to many hand-operated electron microscopes. A customized solution that includes the hardware and software to accomplish position determination is presented. Lists of required parts, instructions for building the hardware, and descriptions of the developed programs are included. Two LED-photodiode assemblies detect x and y movements via an optical wheel that is in physical contact with the mechanical x and y stage control elements. These detector assemblies are interfaced with an integrated circuit that converts movement information into serial port-compatible signals, which are interpreted by a computer with specialized software. Two electron microscopes, a Philips CM12 (S)TEM and a Philips 201 TEM, were equipped with the described digital position determination system. The position fidelity and position fidelity after reloading of grids were determined for both microscopes. The determined position deviation was 1.06 microm in the x axis and 0.565 microm in the y axis for the Philips CM12 (S)TEM, and 0.303 microm in the x axis and 0.545 microm in the y axis for the Philips 201 TEM. After reloading and computational realigning, the determined average position variation was 2.66 microm in the x axis and 2.61 microm in the y axis for the Philips CM12 (S)TEM, and 1.13 microm in the x axis and 1.27 microm in the y axis for the Philips 201 TEM.


Growth and development of haemopoietic cells: a deterministic process?
The in vitro methods used to study haemopoiesis fall into two distinct categories. Short-term colony forming assays have identified a number of potent soluble factors capable of maintaining survival, proliferation and differentiation of haemopoietic cells but not their self-renewal. In contrast, in long-term bone marrow culture, extensive self-renewal occurs in the absence of exogenous factors and direct physical contact between haemopoietic cells and cells of the adherent stromal layer seems to be important. Obviously, LTBMC more closely resembles the situation in haemopoietic tissues but the potency of growth factors imply that they too play a role. Our data suggest that this may be at an earlier stage of haemopoietic development than previously appreciated. Primitive multipotent cells have the potential to respond to CSFs which were previously thought to stimulate only committed progenitor cells. This response is only seen, however, when the cells are exposed to a combination of factors which include either IL-1 or G-CSF. Thus, a combination of factors is able to recruit cells which are not already committed and determine the lineage along which they will differentiate. While it remains to be conclusively demonstrated that growth factors regulate normal "steady state" haemopoiesis in vivo it is clear that contact with stromal cells is important. The mechanisms by which the adherent layer influences haemopoietic development, however, are less obvious. We have shown that a component of stroma, heparan sulphate, is able to bind growth factors and present them to haemopoietic cells in a way that stimulates haemopoiesis.(ABSTRACT TRUNCATED AT 250 WORDS)


Improvement of left atrial function is associated with lower incidence of atrial fibrillation and mortality after cardiac resynchronization therapy.
Left atrial (LA) volume is a predictor of cardiovascular events in patients with heart failure. Improvement of LA function and reverse remodeling was observed after cardiac resynchronization therapy (CRT). The purpose of this study was to explore the clinical significance of improvement in LA function after CRT. Echocardiographic studies were performed before and 3 months after CRT in 97 patients (72 men and 25 women; age 63.8 +/- 13.3 years) with standard CRT indication but no history of atrial fibrillation (AF). LA active emptying fraction based on the change in volumes (LAV-EF) were calculated, and significant improvement in LA function (LA responder) was defined as a relative increase >/=50% from baseline LAV-EF. The primary end-points were newly developed AF detected by ECG or device and all-cause mortality. After 1,200 +/- 705 days of follow-up, LA responders (n = 47 [48.5%]) had a significantly lower incidence of AF (12.8% vs 40%, P = .002) and mortality (17% vs 44%, P = .004) than did LA nonresponders. In Cox proportional hazard analysis, LA responders was the only independent predictor of lower risk of new-onset AF (hazard ratio 0.22, 95% confidence interval 0.08-0.61, P = .003), whereas both LA responders (hazard ratio 0.22, 95% confidence interval 0.09-0.53, P <.001) and left ventricular reverse remodeling (>10% reduction in left ventricular end-systolic volume at 3 months; hazard ratio 0.96, 95% confidence interval 0.93-0.99, P = .03) were independent predictors of lower risk of death after CRT. Improvement of LA function after CRT was associated with a lower incidence of AF and mortality in AF naïve patients with severe heart failure.


Integration sites for genetic elements in prokaryotic tRNA and tmRNA genes: sublocation preference of integrase subfamilies.
Most classical integrases of prokaryotic genetic elements specify integration into tRNA or tmRNA genes. Sequences shared between element and host integration sites suggest that crossover can occur at any of three sublocations within a tRNA gene, two with flanking symmetry (anticodon-loop and T-loop tDNA) and the third at the asymmetric 3' end of the gene. Integrase phylogeny matches this classification: integrase subfamilies use exclusively either the symmetric sublocations or the asymmetric sublocation, although tRNA genes of several different aminoacylation identities may be used within any subfamily. These two familial sublocation preferences imply two modes by which new integration site usage evolves. The tmRNA gene has been adopted as an integration site in both modes, and its distinctive structure imposes some constraints on proposed evolutionary mechanisms.


Current clinical practice and outcome of neoadjuvant chemotherapy for early breast cancer: analysis of individual data from 94,638 patients treated in 55 breast cancer centers.
Neoadjuvant chemotherapy (NACT) is frequently used in patients with early breast cancer. Randomized controlled trials have demonstrated similar survival after NACT or adjuvant chemotherapy (ACT). However, certain subtypes may benefit more when NACT contains regimes leading to high rates of pathologic complete response (pCR) rates. In this study we analyzed data using the OncoBox research from 94,638 patients treated in 55 breast cancer centers to describe the current clinical practice of and outcomes after NACT under routine conditions. These data were compared to patients treated with ACT. 40% of all patients received chemotherapy. The use of NACT increased over time from 5% in 2007 up to 17.3% in 2016. The proportion of patients receiving NACT varied by subtype. It was low in patients with HR-positive/HER2-negative breast cancer (5.8%). However, 31.8% of patients with triple-negative, 31.9% with HR-negative/HER2-positive, and 26.5% with HR-positive/HER2-positive breast cancer received NACT. The rates of pCR were higher in patients with HR-positive/HER2-positive, HR-negative/HER2-positive and triple-negative tumors (36, 53 and 38%) compared to HR-positive/HER2-negative tumors (12%). PCR was achieved more often in HER2-positive and triple-negative tumors over time.This is the largest study on use and effects of NACT in German breast cancer centers. It demonstrates the increased use of NACT based on recommendations in current clinical guidelines. An improvement of pCR was shown in particular in HER2-positive and triple-negative breast cancer, which is consistent with data from randomized controlled trails.


Giant basal cell carcinoma of the thoracic wall: a case report and review of the literature.
Giant basal cell carcinoma is a rare skin tumour with aggressive biological behaviour, and deep invasion and metastasis have been reported. The authors describe a giant basal cell carcinoma involving the anterior chest wall. The lesion infiltrated the mediastinum, occluding the left brachiocephalic vein. Vascular invasion caused venous occlusion affecting the left upper limb. Neither surgical treatment nor radiotherapy were practicable.


"Breast is best": The evidence.
Although the benefits of breastfeeding in reducing morbidity and mortality from gastrointestinal and respiratory infections, sudden infant death syndrome, and (in preterm infants) necrotizing enterocolitis are well-established, long-term health effects are more controversial. The evidence is conflicting concerning the "programming" effect of breastfeeding in protecting against child obesity, hyperlipidemia, hypertension, type 2 diabetes, and atopic disease. Accelerated neurocognitive development has been associated with breastfeeding in many studies, although doubts remain about the potential for residual confounding due to cognitive and behavioural differences between mothers who breastfeed (or those who breastfeed for a longer duration or more exclusively) and those who do not. Most of this paper will summarize the methods and results of a large, cluster-randomized trial of a breastfeeding promotion intervention in the Republic of Belarus. Its experimental design and intention-to-treat analysis have yielded important findings bearing on several of these longer-term health and developmental outcomes.


Arthroscopic modified Broström procedure achieved similar favorable short term outcomes to open procedure for chronic lateral ankle instability cases with generalized joint laxity.
To compare the short-term clinical outcomes of the open versus arthroscopic modified Broström procedure in generalized joint laxity (GJL) patients. From January 2018 to January 2020, 64 consecutive patients with chronic lateral ankle instability (CLAI) and GJL (Beighton score ≥ 4) were prospectively enrolled into two groups: those who underwent the open modified Broström procedure (open group, n = 32) and those who underwent the arthroscopic modified Broström procedure (arthroscopic group, n = 32). Patients underwent an open or arthroscopic modified Broström procedure based on the time when they attended the clinic for consultation. All patients were followed-up at 3, 6, 12, and 24 months postoperatively. The clinical outcomes were evaluated using the visual analogue scale (VAS), American Orthopaedic Foot and Ankle Society (AOFAS) score, and Karlsson score, and the radiographic outcomes were assessed using stress radiography at 24 months postoperatively. The time to return to work and the failure rate were also evaluated and compared. Follow-up was completed for 31 patients in the open group and 30 patients in the arthroscopic group. No significant differences were found between the two groups in terms of demographic characteristics, Beighton score (6.2 ± 1.9 vs. 5.5 ± 1.4, n.s.), or duration of symptoms. There were no significant differences in the functional scores before surgery and at 6, 12 and 24 months postoperatively or in the mean anterior translation of the talus and talar tilt angle on stress radiography at 24 months postoperatively between the open and arthroscopic groups. Compared to the open group, the arthroscopic group showed a significantly earlier return to work (6.8 ± 2.1 vs. 8.1 ± 2.4 weeks, p = 0.006). There was no significant difference in terms of the failure rate between the open and arthroscopic groups (16.1% vs. 23.3%, n.s.). Arthroscopic modified Broström procedure achieved similar short-term outcomes to the open procedure for GJL patients. Arthroscopic modified Broström procedure showed an earlier return to work than the open modified Broström procedure and was an alternative to open surgery for CLAI patients with GJL. III. This study is a prospective study NCT05284188.


Levels of human cytomegalovirus miR-US25-1-5p and miR-UL112-3p in serum extracellular vesicles from infants with HCMV active infection are significantly correlated with liver damage.
Human cytomegalovirus (HCMV)-encoded microRNAs (miRNAs) are involved in posttranscriptional regulation of gene expression. Extracellular vesicles (EVs) can incorporate miRNAs. Relationship between HCMV infection and miRNAs in EVs remains unknown. EVs were isolated from supernatants of human embryonic lung fibroblasts (HELF) cells. Profiles of miRNAs in EVs were analyzed by deep sequencing. Dynamics of candidate viral miRNAs transportation via EVs was investigated using TaqMan PCR. Levels of candidate viral miRNAs in serum EVs from infants with HCMV active infection were detected and analyzed with their clinical index levels. A total of 16 HCMV miRNAs were found in EVs from infected HELF. Levels of miR-US25-1-5p and miR-UL112-3p in EVs increased at 6 h post-infection and were correlated with those in cells (for miR-US25-1-5p: r2 = 0.9375, p value < 0.05; for miR-UL112-3p: r2 = 0.7557, p value < 0.05). Viral miRNAs were transported into recipient cells at 2 h post-incubation. Moreover, levels of miR-US25-1-5p in serum EVs showed positive correlations with serum levels of γ-glutamyl transpeptidase, direct bilirubin, and total bile acid. Levels of miR-UL112-3p in serum EVs showed a positive correlation with serum levels of direct bilirubin. HCMV miRNAs could be transported to uninfected cells via EVs. Levels of miR-US25-1-5p and miR-UL112-3p in serum EVs from infants with HCMV active infection were significantly correlated with liver damage.


Reserved Bed Program Reduces Neurosciences Intensive Care Unit Capacity Strain: An Implementation Study.
Neurosciences intensive care units (NICUs) provide institutional centers for specialized care. Despite a demonstrable reduction in morbidity and mortality, NICUs may experience significant capacity strain with resulting supraoptimal utilization and diseconomies of scale. We present an implementation study in the recognition and management of capacity strain within a large NICU in the United States. Excessive resource demand in an NICU creates significant operational issues. To evaluate the efficacy of a Reserved Bed Pilot Program (RBPP), implemented to maximize economies of scale, to reduce transfer declines due to lack of capacity, and to increase transfer volume for the neurosciences service-line. Key performance indicators (KPIs) were created to evaluate RBPP efficacy with respect to primary (strategic) objectives. Operational KPIs were established to evaluate changes in operational throughput for the neurosciences and other service-lines. For each KPI, pilot-period data were compared to the previous fiscal year. RBPP implementation resulted in a significant increase in accepted transfer volume to the neurosciences service-line (P = .02). Transfer declines due to capacity decreased significantly (P = .01). Unit utilization significantly improved across service-line units relative to theoretical optima (P < .03). Care regionalization was achieved through a significant reduction in "off-service" patient placement (P = .01). Negative externalities were minimized, with no significant negative impact in the operational KPIs of other evaluated service-lines (P = .11). Capacity strain is a significant issue for hospital units. Reducing capacity strain can increase unit efficiency, improve resource utilization, and augment service-line throughput. RBPP implementation resulted in a significant improvement in service-line operations, regional access to care, and resource efficiency, with minimal externalities at the institutional level.


Altered responses to modulators of guanine nucleotide binding protein activity in endotoxin tolerance.
The effects of cholera toxin or pertussis toxin and nonhydrolyzable GTP analogs on Salmonella enteritidis endotoxin stimulation of iTxB2 and i6-keto-PGF1 alpha synthesis in control and endotoxin tolerant rat peritoneal macrophages were determined. Pretreatment with pertussis toxin alone had no effect on basal macrophage iTxB2 or i6-keto-PGF1 alpha production, but pertussis toxin (0.1, 1.0 and 10 ng/ml) significantly inhibited endotoxin-stimulated iTxB2 and i6-keto-PGF1 alpha synthesis. Pretreatment with cholera toxin, which did not affect basal iTxB2 or i6-keto-PGF1 alpha synthesis, significantly enhanced endotoxin-induced synthesis of iTxB2 and i6-keto-PGF1 alpha. The effects of pertussis and cholera toxin with or without endotoxin were significantly (P less than 0.05) less in macrophages from endotoxin tolerant rats compared to control macrophages. GTP[gamma-S] (100 microM) significantly increased iTxB2 synthesis and significantly augmented endotoxin-stimulated iTxB2 synthesis in control macrophages (P less than 0.05). However, in macrophages from endotoxin tolerant rats the effect of GTP[gamma-S] on iTxB2 synthesis was significantly less (P less than 0.05) compared to control macrophages. Collectively, these data suggest that: (1) guanine nucleotide binding regulatory proteins mediate endotoxin-stimulated arachidonic acid metabolism in rat peritoneal macrophages; and (2) endotoxin tolerance induces alterations in guanine nucleotide binding protein activity.


[Errors in the diagnosis of early forms of syphilis].
Reviews the results of diagnostic errors made by physicians of various specialties during examinations of patients with early syphilis. Suggests measures to improve timely diagnosis of this disease.


The effect of a first-generation H1-antihistamine on postural control: a preliminary study in healthy volunteers.
First-generation H1-antihistamines are known to cause fatigue and drowsiness, due to their poor receptor selectivity and their high penetration rate of the blood-brain barrier. However, little is known about the effects of first-generation H1-antihistamines on postural stability. The purpose of this study was to evaluate the effects of d-chlorpheniramine on postural stability using posturography with and without foam rubber. A double-blind study with three parallel groups was conducted. Twenty-seven healthy young volunteers (mean age 21.9 years) were recruited and orally administered d-chlorpheniramine, 2 or 4 mg, or placebo. Postural sway was measured every hour up to 8 h after administration. Two-legged stance tasks were performed by each subject in four conditions: eyes open or eyes closed and with or without foam rubber. Inter-group comparisons showed that the group receiving 4-mg d-chlorpheniramine showed significantly larger sway in the eyes open with foam rubber condition (visual and vestibular information available, somatosensory information reduced). Inter-subject analysis in the 4-mg d-chlorpheniramine group showed that the effect of d-chlorpheniramine on postural control was variable. Our results suggest that among the three main sensory systems responsible for postural control (visual, vestibular, and somatosensory), d-chlorpheniramine may have a larger effect on the visual and/or vestibular systems in susceptible individuals.


Research progress of anthocyanin prebiotic activity: A review.
Anthocyanins are a kind of flavonoids and natural water-soluble pigments, which endow fruits, vegetables, and plants with multiple colors. They are important source of new products with prebiotic activity. However, there is no systematic review documenting prebiotic activity of anthocyanins and their structural analogues. This study aims to fill this gap in literature. The objective of this review is to summarize and evaluate the prebiotic activity of anthocyanin's, and discuss the physical and molecular modification methods to improve their biological activities. In this review, the databases (PubMed, Google Scholar, Web of Science, Researchgate and Elsevier) were searched profoundly with keywords (anthocyanin's, prebiotics, probiotics, physical embedding and molecular modification). A total of 34 articles were considered for reviewing. These studies approved that anthocyanins play an important role in promoting the proliferation of probiotics, inhibiting the growth of harmful bacteria and improving the intestinal environment. In addition, physical embedding and molecular modification have also been proved to be effective methods to improve the prebiotic activity of anthocyanins. Anthocyanins could promote the production of short chain fatty acids, accelerate self degradation and improve microbial related enzyme activities to promote the proliferation of probiotics. They inhibited the growth of harmful bacteria by inhibiting the expression of harmful bacteria genes, interfering with the role of metabolism related enzymes and affecting respiratory metabolism. They promoted the formation of a complete intestinal barrier and regulated the intestinal environment to keep the body healthy. Physical embedding, including microencapsulation and colloidal embedding, greatly improved the stability of anthocyanins. On the other hand, molecular modification, especially enzymatic modification, significantly improved the biological activities (antioxidant, prebiotic activity and so on) of anthocyanins. All these research results displayed by this review indicate that anthocyanins are a useful tool for developing prebiotic products. The better activities of the new anthocyanins formed by embedding and modification may make them become more effective raw materials. Our review provides a scientific basis for the future research and application of anthocyanins.


Effect of Drug-Coated Balloons in Native Coronary Artery Disease Left With a Dissection.
The authors sought to understand the clinical and angiographic outcomes of dissections left after drug-coated balloon (DCB) angioplasty. Second-generation DCB may be an alternative to stents in selected populations for the treatment of native coronary lesions. However, the use of these devices may be hampered by a certain risk of acute vessel recoil or residual coronary dissection. Moreover, stenting after DCB has shown limited efficacy. Little is known about when a non-flow-limiting dissection is left after DCB angioplasty. This was a prospective observational study whose aim was to investigate the outcome of a consecutive series of patients with native coronary artery disease treated with second-generation DCB and residual coronary dissection at 2 Italian centers. We evaluated patient clinical conditions at 1 and 9 months, and angiographic follow up was undertaken at 6 months. Between July 2012 and July 2014, 156 patients were treated with DCB for native coronary artery disease. Fifty-two patients had a final dissection, 4 of which underwent prosthesis implantation and 48 were left untreated and underwent angiographic follow-up after 201 days (interquartile range: 161 to 250 days). The dissections were all type A to C, and none determined an impaired distal flow. Complete vessel healing at angiography was observed in 45 patients (93.8%), whereas 3 patients had persistent but uncomplicated dissections, and 3 had binary restenosis (6.2%). Late lumen loss was 0.14 mm (-0.14 to 0.42). Major adverse cardiovascular events occurred in 11 patients in the entire cohort and in 4 of the dissection cohort (7.2% vs. 8.1%; p = 0.48). We observed 8 and 3 target lesion revascularizations, respectively (5.3% vs. 6.2%; p = 0.37). In this cohort of consecutive patients treated with new-generation DCB and left with a final dissection, this strategy of revascularization seemed associated with the sealing of most of dissections and without significant neointimal hyperplasia.


Adenoviral vector-mediated transfer of the Indian hedgehog gene modulates lymphomyelopoiesis in vivo.
Indian hedgehog (Ihh) plays an essential role in angiogenesis, hematogenesis, and epiphysis formation during embryogenesis. In the present study, we injected an adenoviral vector (Adv) carrying the mock-control (Adv-control) or Ihh (Adv-Ihh) gene into severe combined immunodeficiency (SCID) or BALB/c mice to evaluate the effects of lhh on the regulation of postnatal hematopoiesis in vivo. After the i.v. injection of Adv-Ihh, the expression of vector-derived Ihh mRNA was detected in the liver. Four weeks after administration of Adv-Ihh to SCID mice, we observed an increase in the number of c-Kit+ cells and clonogenic cells per 10(5) mononuclear cells in the bone marrow compared with Adv-control-administered mice. Moreover, after administration of Adv-Ihh to BALB/c mice, the number of splenic B220+IgM(low)CD23(int)CD21(int) B lymphocytes and CD4+ T lymphocytes was strongly increased. Furthermore, the number of thymic double-negative (DN)2, DN3, CD8+ immature single-positive, and CD4+/CD8- cells was significantly elevated relative to the number in mice that received the control Adv vector. Our results suggest that enhanced signaling by Ihh can modulate the proliferation and differentiation of splenic B lymphocytes and thymic T lymphocytes during bone marrow hematopoiesis in vivo. Thus, modulation of the hedgehog signaling pathway may provide a therapeutic strategy to stimulate lymphomyelopoiesis in vivo.


Extracellular Matrix-Mimetic Immunomodulatory Hydrogel for Accelerating Wound Healing.
Macrophages play a crucial role in the complete processes of tissue repair and regeneration, and the activation of M2 polarization is an effective approach to provide a pro-regenerative immune microenvironment. Natural extracellular matrix (ECM) has the capability to modulate macrophage activities via its molecular, physical, and mechanical properties. Inspired by this, an ECM-mimetic hydrogel strategy to modulate macrophages via its dynamic structural characteristics and bioactive cell adhesion sites is proposed. The LZM-SC/SS hydrogel is in situ formed through the amidation reaction between lysozyme (LZM), 4-arm-PEG-SC, and 4-arm-PEG-SS, where LZM provides DGR tripeptide for cell adhesion, 4-arm-PEG-SS provides succinyl ester for dynamic hydrolysis, and 4-arm-PEG-SC balances the stability and dynamics of the network. In vitro and subcutaneous tests indicate the dynamic structural evolution and cell adhesion capacity promotes macrophage movement and M2 polarization synergistically. Comprehensive bioinformatic analysis further confirms the immunomodulatory ability, and reveals a significant correlation between M2 polarization and cell adhesion. A full-thickness wound model is employed to validate the induced M2 polarization, vessel development, and accelerated healing by LZM-SC/SS. This study represents a pioneering exploration of macrophage modulation by biomaterials' structures and components rather than drug or cytokines and provides new strategies to promote tissue repair and regeneration.


Neurovesical dysfunction in children after surgery for high or intermediate anorectal malformations.
To evaluate problems with bladder dysfunction in patients operated on for imperforate anus. All patients (11M, 25F) with high or intermediate imperforate anus seen in this institution between 1987 and 1997 were subjected to the investigation. They had all undergone a posterior sagittal anorectoplasty procedure with the aim of preserving as much as possible of the fistula. Hospital charts were reviewed. A detailed and structured interview regarding micturition habits was performed. If the results of this were abnormal the patients were also subjected to flow registration, measurements of residual urinary volume and in some cases also cystometry. Micturition habits were normal in 30 out of 36 children. The remaining six, considered to have neurovesical dysfunction (NVD), had difficulties in emptying their bladder and exhibited pathological residual volumes. Two were boys with rectourethral fistulae, two were girls with cloacal malformations and two were girls with rectovestibular fistulae. Four out of six children with NVD had sacral anomalies. NVD may occur even in the absence of sacral anomalies. A 4 h micturition observation is recommended in all newborns with intermediate or high anorectal anomalies to recognize the occurrence of NVD at an early stage.


Effects of trypsin on the in situ identification of epidermal cell membrane antigens.
In this work the role of trypsin in revealing epidermal cell surface antigens, with the use of immunological markers, was investigated. Two monoclonal antibodies (MCA) were used, the first: D47, belongs to the first cluster of differentiation and recognizes a membrane antigen of human thymocytes; the second HLA-ABC-m3, is an anti-HLA-B27 MCA. Preliminary treatment with various concentrations of trypsin was performed on frozen skin sections and followed by indirect immunofluorescence. D47 reacted with epidermal dendritic cells only after trypsin pretreatment of skin sections. In addition a mild preliminary trypsinization was shown to increase in situ immunoreactivity of MCA HLA-ABC-m3 with epidermal cells. Best results were obtained when trypsin concentrations ranging from 2.5 to 5 micrograms/ml were applied for 10 min at 37 degrees C. Preliminary trypsinization may be of interest for a better exposure of some surface antigens to immunohistochemical markers.


The effect of substrate bulk stiffness on focal and fibrillar adhesion formation in human abdominal aortic endothelial cells.
Endothelial cell (EC) dysfunction contributes to atherosclerosis, which is associated with arterial stiffening and fibronectin (FN) deposition, by ECs and smooth muscle cells (SMCs). The effect of stiffness on the EC/FN interaction and fibrillar adhesion formation has been poorly studied. An in vitro model was prepared that included FN-coated polydimethylsiloxane (PDMS) films with similar hydrophobicity and roughness but distinct Young's modulus values, mimicking healthy (1.0 MPa) and atherosclerotic (2.8 MPa) arteries. Human aortic abdominal endothelial cells (HAAECs) seeded on 1.0 MPa PDMS films spread over time and reached their maximum surface area faster than on 2.8 MPa PDMS films. In addition, HAAECs appeared to organize focal adhesion more rapidly on 1.0 MPa PDMS films, despite the similar cell binding domain accessibility to adsorbed FN. Interestingly, we also observed up to a ~5-fold increase in the percentage of HAAECs that had a well-developed fibrillar adhesion on 1.0 MPa compared to 2.8 MPa PDMS films as verified by integrin α5 subunits, tensin, and FN staining. This variation did not affect EC migration. These results suggest that there are favourable conditions for FN matrix assembly by ECs in early atherosclerosis rather than at advanced stages. Our in vitro model will therefore be helpful to understand the influence of bulk stiffness on cells involved in atherosclerosis.


Tissue-dependent VEGF and GLUT1 induction in a rat hemorrhage model: With regard to diagnostic application of mRNA quantification in forensic pathology.
Systemic hypoxia is inevitably involved in the death process to a varying extent. Hypoxia-response factors proved useful in forensic pathology in previous studies; however, fundamental investigations using animal models are expected to reinforce the findings from autopsy practice. An animal experiment using a rat model of fixed-volume hemorrhage was performed to apply basic insight into quantitative mRNA analyses in forensic pathology. Male Sprague-Dawley rats (n=5) were anesthetized, bled from the femoral artery (24ml/kg; about 30% of total circulating blood volume), and decapitated after 1 or 2h. Tissue samples of the heart, brain (hippocampus), kidney, liver, lung and skeletal muscle were collected for RNA and protein analyses. Quantitative analyses of VEGF, GLUT1 and GAPDH mRNAs were performed with TaqMan real-time RT-PCR assay. In the sham control without bleeding, mRNA quantification revealed the tissue-dependent mRNA levels in physiological condition. Relative quantification of VEGF and GLUT1 showed significant inductions under hemorrhage at the mRNA level, using GAPDH as endogenous reference. In conclusion, tissue-dependent induction patterns of VEGF and GLUT1 were revealed in the volume-fixed hemorrhage rat model. This study could practically guide the selection of mRNA markers and tissue samples in forensic pathology related to tissue ischemia and cellular hypoxia for autopsy cases.


Intraoperative transesophageal echocardiography in orthotopic liver transplantation in a patient with hypertrophic cardiomyopathy.
With improvements in the surgical technique for orthotopic liver transplantation, patients with significant underlying systemic disease are considered candidates for transplantation, thus increasing the complexity of the medical management of these patients and necessitating additional monitoring in order to minimize the anesthetic risk. We describe the anesthetic management of orthotopic liver transplantation for a patient with severe hypertrophic cardiomyopathy and mitral insufficiency. In this case, transesophageal echocardiography proved useful in the management of the postreperfusion period of the surgical procedure.


Redundant nerve roots of the cauda equina. A report of five cases.
Five personally examined cases of redundant nerve roots of the cauda equina are added to the 13 hitherto on record. Except for segmental neurological deficits, intermittent claudication-like symptoms of the cauda equina dominated the histories of four of our five cases. The diagnosis was confirmed at surgical exploration, which included laminal and dural decompression. At follow-up (two months--three years) the neurological deficit, or the intermittent claudication, or both, had improved in all our patients. The pathogenesis of root redundancy is obscure. It seems that the symptoms arise through the action of at least two factors viz compression of the spinal content and the existence of one or more redundant roots. Wider use of diagnostic aids and surgical exploration would probably show that redundant roots are more common than hitherto supposed.


Solvent-free directed patterning of a highly ordered liquid crystalline organic semiconductor via template-assisted self-assembly for organic transistors.
Highly ordered organic semiconductor micropatterns of the liquid-crystalline small molecule 2,7-didecylbenzothienobenzothiophene (C10 -BTBT) are fabricated using a simple method based on template-assisted self-assembly (TASA). The liquid crystallinity of C10 -BTBT allows solvent-free fabrication of high-performance printed organic field-effect transistors (OFETs).


Skeletal muscle properties in a transgenic mouse model for amyotrophic lateral sclerosis: effects of creatine treatment.
The present study was undertaken to identify the metabolic and contractile characteristics of fast- and slow-twitch skeletal muscles in a transgenic mouse model of amyotrophic lateral sclerosis (ALS). In addition, we investigated the effects of oral creatine supplementation on muscle functional capacity in this model. Transgenic mice expressing a mutant (G93A) or wild type human SOD1 gene (WT) were supplemented with 2% creatine monohydrate from 60 to 120 days of age. Body weight, rotorod performance and grip strength were evaluated. In vitro contractility was evaluated on isolated m. soleus and m. extensor digitorum longus (EDL), and muscle metabolites were determined. Body weight, rotorod performance and grip strength were markedly decreased in G93A compared to WT mice, but were unaffected by creatine supplementation. Muscle ATP content decreased and glycogen content increased in G93A versus WT in both muscle types, but were unaffected by creatine supplementation. Muscle creatine content increased following creatine intake in G93A soleus. Twitch and tetanic contractions showed markedly slower contraction and relaxation times in G93A versus WT in both muscle types, with no positive effect of creatine supplementation. EDL but not soleus of G93A mice showed significant atrophy, which was partly abolished by creatine supplementation. It is concluded that overexpression of a mutant SOD1 transgene has profound effects on metabolic and contractile properties of both fast- and slow-twitch skeletal muscles. Furthermore, creatine intake does not exert a beneficial effect on muscle function in a transgenic mouse model of ALS.


Biosorption of heavy metals in upflow sludge columns.
The present study was carried out for evaluating the retention behavior of sanitary sewage and sand in relation to chromium and nickel ions in upflow reactors. It was found that the sludge presented a greater assimilation of the metals studied when compared to the inert material, probably due to the presence of anionic groups, which favors adsorption and complexation processes. Thermal analyses of the samples showed a shift in the decomposition peaks of the "in natura" sludge, when compared with those of the samples spiked with the metals, confirming the possibility of interactions between the heavy metals and the anionic groups present in the sludge.


Prospective analysis of life-sustaining therapy discussions in the surgical intensive care unit: a housestaff perspective.
Prospective data addressing end-of-life care in the surgical ICU are lacking. We determined factors surrounding life-sustaining therapy discussions (LSTDs) in our surgical ICU as experienced by housestaff. Housestaff were interviewed daily about the occurrence of an LSTD between themselves and either a patient or surrogate. Patients for whom at least one LSTD occurred were compared with patients for whom an LSTD never occurred. Housestaff also completed a standardized questionnaire that captured events surrounding each LSTD. Eighty LSTDs occurred among 50 patients. Lack of decision-making capacity (p = 0.04), age (p = 0.02), and acuity (p = 0.01) predicted independently the occurrence of an LSTD. Housestaff were significantly more likely to both report recent clinical deterioration (p < 0.01) and to assign a worse prognosis (p < 0.01) to patients for whom an LSTD occurred. Housestaff initiated the majority of LSTDs (70.0%) and usually did so because of clinical deterioration (60.7%); patient surrogates were most commonly believed to initiate LSTDs because of lack of improvement (60.1%). In no instance did a patient initiate an LSTD. For 39 of 50 patients (78.0%), changes in end-of-life care plans were eventually enacted as proposed originally. Housestaff reported that the likelihood of enactment depended on both the preexisting end-of-life care plan and the proposed change in end-of-life care plan. Age, acuity, and lack of decision-making capacity were the most important factors involved in the initiation of an LSTD. Housestaff reported that they initiated LSTDs for different reasons and proposed different end-of-life care plans relative to both patients and their surrogates. These disparities can contribute to failed enactment of proposed changes in end-of-life care plans.


Effects of preceding context on discrimination of voice onset times.
When discriminating pairs of speech stimuli from an acoustic voice onset time (VOT) continuum (for example, one ranging from /ba/ to /pa/), English-speaking subjects show a characteristic performance peak in the region of the phonemic category boundary. We demonstrate that this "category boundary effect" is reduced or eliminated when the stimuli are preceded by /s/. This suppression does not seem to be due to the absence of a phonological voicing contrast for stop consonants following /s/, since it is also obtained when the /s/ terminates a preceding word and (to a lesser extent) when broadband noise is substituted for the fricative noise. The suppression is stronger, however, when the noise has the acoustic properties of a syllable-initial /s/, all else being equal. We hypothesize that these properties make the noise cohere with the following speech signal, which makes it difficult for listeners to focus on the VOT differences to be discriminated.