Effects of a beta3-adrenergic agonist on the immune response in diet-induced (cafeteria) obese animals.
Molecules with affinity for beta3-adrenoceptors are not only effective anti-obesity agents in rodent models, but may play a role in the regulation of the immune response. The aim of the current investigation was to analyse the effects of trecadrine on the immune response in diet-induced (cafeteria) obese rats. Male Wistar rats were divided into 2 groups, the control group (C, n=9) was fed with the standard pelleted chow laboratory diet, while the other group was fed with a high-fat (cafeteria) diet. Cafeteria-fed rats were divided into two new subgroups (n=9 each), which received either i.p. saline (obese, O) or trecadrine (1mg/kg/day) (obese+trecadrine, O+T) daily for 5 weeks. Lymphocyte subpopulations and the proliferative response were determined by validated procedures. The administration of trecadrine was able to prevent the onset of obesity in cafeteria-fed rats. Trecadrine-treatment to obese animals appeared to improve the number of lymphocyte subpopulations (CD4+ and CD8+) as compared to those animals only receiving the high-fat diet, being the values of the trecadrine-treated animals on the high-fat diet similar to the control rats. However, the lymphoproliferative response when stimulated with several mitogens was markedly reduced by the cafeteria intake and was further decreased by the beta3-adrenergic administration. The spleen mRNA expression level of UCP2, PPARgamma and Ob-Rb were not affected by the trecadrine treatment. Summing up, at the immune system level, trecadrine administration increased the proportion of CD4+ spleen lymphocytes, although it was not able to restore the lymphocyte proliferative response which was depressed.


Ethnopharmacology and systems biology: a perfect holistic match.
Traditional medical doctors often apply a holistic approach in prescribing medicines to the patient. Each individual patient gets his own optimalized medicine, usually a mixture of different ingredients. The present day paradigm of drug development of <single target, single compound>, is based on a super reductionist approach which involves mostly tests of compounds at the molecular level in, e.g., receptor binding assays. This approach is not the best for studies on traditional medicines. A more holistic approach using systems biology seems much more suited to proof efficacy and to obtain information that might lead to understanding the mode of action. Synergy, prodrugs, novel targets, all these might be detected by a systems biology approach whereas the reductioinist approach only will recognize activity on already known targets, and will not detect synergism and prodrugs. Metabolomics will be a major tool in recognizing compounds connected with activity in the traditional medicines, and will also be very useful in recognizing the effect on the test organism, which can be the patient in case of clinical trials with well established traditional medicines.


GROUP-BASED SYMPTOM TRAJECTORIES IN INDICATED PREVENTION OF ADOLESCENT DEPRESSION.
Adolescent depression prevention research has focused on mean intervention outcomes, but has not considered heterogeneity in symptom course. Here, we empirically identify subgroups with distinct trajectories of depressive symptom change among adolescents enrolled in two indicated depression prevention trials and examine how cognitive-behavioral (CB) interventions and baseline predictors relate to trajectory membership. Six hundred thirty-one participants were assigned to one of three conditions: CB group intervention, CB bibliotherapy, and brochure control. We used group-based trajectory modeling to identify trajectories of depressive symptoms from pretest to 2-year follow-up. We examined associations between class membership and conditions using chi-square tests and baseline predictors using multinomial regressions. We identified four trajectories in the full sample. Qualitatively similar trajectories were found in each condition separately. Two trajectories of positive symptom course (low-declining, high-declining) had declining symptoms and were distinguished by baseline symptom severity. Two trajectories of negative course (high-persistent, resurging), respectively, showed no decline in symptoms or decline followed by symptom reappearance. Participants in the brochure control condition were significantly more likely to populate the high-persistent trajectory relative to either CB condition and were significantly less likely to populate the low-declining trajectory relative to CB group. Several baseline factors predicted trajectory classes, but gender was the most informative prognostic factor, with males having increased odds of membership in a high-persistent trajectory relative to other trajectories. Findings suggest that CB preventive interventions do not alter the nature of trajectories, but reduce the risk that adolescents follow a trajectory of chronically elevated symptoms.


Computed tomography based 3D printed patient specific blocks for total knee replacement.
3D printing is an emerging technology and its use in orthopaedics is being explored. We discuss the role of computed tomography based 3D printed patient specific jigs in total knee replacement. We also discuss the various advantages of 3D printed patient specific jigs and the future scope of their use in total knee replacement. A search of English literature was done and articles discussing the role of CT scan based 3D printed patient specific jigs in total knee replacement were included in the study. The role of 3D printed jigs in total knee replacement have been found in the prediction of femoral valgus angle, component sizing and in retained hardware. They have shown promise with studies suggesting they might improve the overall mechanical alignment of the knee. There are studies which have also studied the combined role of patient specific instruments with navigation. 3D printed jigs hold promise in total knee replacement. Their use in total knee replacement in the presence of retained hardware is useful for the surgeon. They have also showed promise in improving prediction of component sizing and improving mechanical alignment of the knee. Further studies with longer follow up and larger sample size will help in establishing their role in total knee replacement.


Clinical and genetic factors associated with post-operative nausea and vomiting after propofol anaesthesia.
The incidence of post-operative nausea and vomiting (PONV) remains at about 30% despite all therapeutic efforts to reduce it. The clinical risk factors guiding the prophylactic treatment are well established, but genetic factors associated with PONV remain poorly known. The aim of this study was to explore clinical and genetic factors impacting PONV by performing a genome-wide association study (GWAS) together with relevant clinical factors as covariates, and systematically attempt to replicate previously reported PONV associations. Relevant clinical factors are explored with logistic regression model. This was an observational case control study in Helsinki University Hospital between 1 August 2006 and 31 December 2010. One thousand consenting women with elevated risk for PONV, undergoing breast cancer surgery with standardised propofol anaesthesia and antiemetics. After exclusions for clinical reasons and failed genotyping, 815 patients were included with 187 PONV cases and 628 controls. Emergence of PONV up to 7th post-operative day was recorded. PONV at 2-24 h after surgery was selected to be the primary outcome. The GWAS explored associations between PONV and 653 034 genetic variants. Replication attempts included 31 variants in 16 genes. The overall incidence of PONV up to 7th post-operative day was 35%, where 3% had PONV at 0-2 h and 23% at 2-24 h after surgery. Age, American Society of Anaesthesiologists status, the amount of oxycodone used in the post-anaesthesia care unit, smoking status, previous PONV, and history of motion sickness were statistically significant predictive factors in the logistic model. The receiver operating characteristic-area under the curve of 0.75 (95% CI 0.71-0.79) was calculated for the model. The GWAS identified six variants with suggestive association to PONV (p < 1 × 10-5 ). Of the previously reported variants, association with the DRD2 variant rs18004972 (TaqIA) was replicated (p = .028). Our GWAS approach did not identify any high-impact PONV susceptibility variants. The results provide some support for a role of dopamine D2 receptors in PONV.


Phenylpyruvic acid may be a direct precursor of mandelic acid without intermediate transamination of phenylalanine.
A series of compounds related to phenylalanine was administered to rats. Output of mandelic acid, a major but unexplained metabolite in phenylketonuria, was increased after the administration of phenylethanolamine or phenylpyruvic acid, whereas phenylethylamine or phenylalanine increased its excretion only marginally. Phenylacetic acid, previously suggested as a possible precursor in man, was almost without effect. It seems likely that mandelic acid can be formed from phenylpyruvic acid directly, without intermediate transamination to phenylalanine.


Lethal herpes simplex virus type 1 hepatitis in a normal adult.
A fatal case of human herpes simplex type 1 hepatitis is presented and compared with cases previously reported. The patient presented with fulminant hepatic necrosis, coagulopathy, leukopenia, thrombocytopenia, and absence of typical herpetic mucocutaneous lesions. Liver biopsy helped to establish a presumptive diagnosis in this patient and in one previously reported case. Theoretically, early diagnosis might enable application of specific antiviral therapy in future cases of this usually fatal infection.


Transcriptomic profile analysis of brain microvascular pericytes in spontaneously hypertensive rats by RNA-Seq.
Changes in the structure and function of micro-vessels is the pathogenic basis of organ damage in cardiovascular and cerebrovascular diseases. Microcirculation is primarily affected in hypertension, resulting in increased vascular resistance. Pericytes are contractile cells that are embedded in the basement membrane of capillaries, and regulate endothelial cell membrane maturation, capillary blood flow, cell debris removal, and stability of endothelial cells. However, the exact role of brain microvascular pericytes in the pathogenesis of hypertension has not been elucidated. Brain microvascular pericytes were isolated from spontaneously hypertensive rats (SHR) and wild type Wistar Kyoto (WKY) rats. The transcriptomes of SHR and WKY pericytes were analyzed by RNA-Seq, and the differentially expressed genes (DEGs) were screened by Ballgown, and Student's t test was used to be used to compare differences between groups. DAVID was used for the GO-enrichment analysis and KEGG pathway analysis of the DEGs, and an interaction network between the significant signaling pathways and DEGs was constructed. A total of 1356 DEGs were identified between the WKY and the SHR group pericytes (P value < 0.05, Fold change > 1.5), of which 733 were upregulated and 623 downregulated. The genes with greatest betweenness centrality values were Itgb1, Vcam-1 and MMP-9. Based on KEGG analysis, 34 interacting signaling pathways and 43 interacting genes were screened, and MAPK, p53, Wnt, Jak-STAT, TGF-beta, VEGF and PPAR signaling pathways were the key nodes. Several DEGs and signaling pathways were identified in the brain microvascular pericytes of SHR rats compared to the WKY rats. Our findings will lay the foundation to study the role of brain microvascular pericytes in the development of spontaneous hypertension.


Risk of advanced colorectal neoplasm by the proposed combined United States and United Kingdom risk stratification guidelines.
The U.K. guidelines for risk stratification after colon polypectomy differ from the U.S. guidelines in 2 ways: the U.K. guidelines consider ≥5 adenomas as high risk and do not consider histology (villous or high-grade dysplasia) in the assessment. Thus, we aimed to investigate the risk of advanced colorectal neoplasm (CRN) by categorized risk groups, considering both ≥5 adenomas and histology. A total of 2570 patients with ≥1 adenoma at index colonoscopy were included. The patients were divided into 6 groups: group 1, 1 to 2 non-advanced adenomas (non-AAs) ≥10 mm or high-grade dysplasia or villous adenoma; group 1A, 1 to 2 adenomas with ≥1 advanced adenoma (AA); group 2, 3 to 4 non-AAs; group 2A, 3 to 4 adenomas with ≥1 AA; group 3, ≥5 non-AAs; and group 3A, ≥5 adenomas with ≥1 AA. The risk of advanced CRN at 3 years was compared among the 6 groups. Group 3A showed a higher risk of advanced CRN (9.6%) than group 3 (4.5%; P = .03) and group 1A (4.6%; P < .001). The risk of advanced CRN in group 3 (4.5%) showed no difference compared with group 1A (4.6%; P = .91) or group 2A (6.8%; P = .25). There was no difference between group 1 and group 2 in the risk of advanced CRN (1.7% vs 2.2%; P = .22). More than 1 AA at index colonoscopy was an independent risk factor for advanced CRN. More-intensive surveillance than the 3-year interval for patients with ≥5 adenomas with ≥1 AA and less-intensive surveillance than the 3-year and 1-year intervals for those with 3 to 4 non-AAs and ≥5 non-AAs, respectively, might be suggested.


The reliability of physical examination in diagnosing arterial injury in penetrating trauma to extremities: A first look at different anatomical regions and injury mechanisms.
The accuracy of physical examination to exclude arterial injury in penetrating trauma to extremities has been well established. To determine whether the accuracy of physical examination to exclude arterial injury is similar to that of a computed tomography arteriogram (CTA) for different anatomical regions and mechanisms of injury, and in patients with concomitant fractures compared with those without. A retrospective review was conducted on all patients who underwent CTA for penetrating injuries to an extremity between 1 June 2016 and 30 June 2017. The presence of arterial injuries was noted, and these were grouped into anatomical areas. Clinical notes were reviewed for the presence of hard signs of arterial injury at initial examination. A total of 220 lower limb and 133 upper limb CTAs were included. The mean patient age was 28.9 years (range 11 - 68). The overall sensitivity of physical examination in detecting a CTA-confirmed arterial injury was 95.3% (95% confidence interval (CI) 88.4 - 98.7), with a specificity of 93.9% (95% CI 90.2 - 96.4). Physical examination of the thigh had the highest specificity of 96.4% (95% CI 91.8 - 98.8), followed by the lower leg at 94.4% (95% CI 81.3 - 99.3), the upper arm at 89.6% (95% CI 79.7 - 95.7) and the forearm at 77.8% (95% CI 40.0 - 97.2). For gunshot wounds the specificity was 96.1% (95% CI 92.4 - 98.3), while for stab wounds it was 86.8% (95% CI 74.7 - 94.5). This study agrees with current literature indicating that physical examination has high specificity in detecting arterial injury in the setting of penetrating trauma to an extremity. However, it shows that the specificity is not equal for all anatomical regions or mechanisms of injury.


Method for data analysis in different institutions: example of image guidance of prostate cancer patients.
Multi-institutional collaborations allow for more information to be analyzed but the data from different sources may vary in the subgroup sizes and/or conditions of measuring. Rigorous statistical analysis is required for pooling the data in a larger set. Careful comparison of all the components of the data acquisition is indispensable: identical conditions allow for enlargement of the database with improved statistical analysis, clearly defined differences provide opportunity for establishing a better practice. The optimal sequence of required normality, asymptotic normality, and independence tests is proposed. An example of analysis of six subgroups of position corrections in three directions obtained during image guidance procedures for 216 prostate cancer patients from two institutions is presented.


The immunohistochemical localization of nine peptides in the sacral parasympathetic nucleus and the dorsal gray commissure in rat spinal cord.
The sixth lumbar and first sacral spinal cord segments in the rat contain parasympathetic preganglionic neurons which innervate the pelvic viscera. There have been few studies, however, which have specifically considered the distribution of putative peptide neurotransmitters in these cord segments. The present paper describes and compares the immunohistochemical distribution of dynorphin (1-8)-, enkephalin-, somatostatin-, cholecystokinin octapeptide-, avian pancreatic polypeptide-, FMRF-NH2-, neurotensin-, and vasoactive intestinal polypeptide-like immunoreactivities in the dorsal gray commissure and sacral parasympathetic nucleus of the sixth lumbar and first sacral spinal cord segments in colchicine-treated rats. Antisera against all of the peptides, except avian pancreatic polypeptide, stained cells in the sacral parasympathetic nucleus. Dynorphin (1-8-), enkephalin-, and substance P-like immunoreactive cells were present in significantly greater numbers than somatostatin-, neurotensin-, cholecystokinin-, FMRF-NH2-, and vasoactive intestinal polypeptide-like immunoreactive cells. All of the antisera also stained fibers in the sacral parasympathetic nucleus in varying densities, and a fiber bundle which extended between the dorsal gray commissure and the sacral parasympathetic nucleus. Antisera against substance P and cholecystokinin stained a bundle of fibers that extended between the dorsal horn and the sacral parasympathetic nucleus. Antisera against somatostatin, cholecystokinin octapeptide, substance P and FMRF-NH2 stained an additional fiber bundle which extended between the lateral edge of the dorsal horn and the dorsal gray commissure. All the remaining antisera, except neurotensin, also stained fibers that extended between the sacral parasympathetic nucleus and the dorsal gray commissure, but in a sparser distribution. Immunoreactive cells were localized to the dorsal gray commissure in sections stained with each of the antisera. Dynorphin (1-8) and enkephalin antisera stained the greatest number of cells, followed by FMRF-NH2, neurotensin, somatostatin and avian pancreatic polypeptide. The smallest number of immunoreactive cells was present in substance P, cholecystokinin and vasoactive intestinal polypeptide immunostained sections. A significant difference was noted between the number of dynorphin, enkephalin, somatostatin, cholecystokinin, avian pancreatic polypeptide, FMRF-NH2, neurotensin and vasoactive intestinal polypeptide immunoreactive cells in the sacral parasympathetic nucleus and dorsal gray commissure.(ABSTRACT TRUNCATED AT 400 WORDS)


Analysis of Time to Treatment and Survival Among Adults Younger Than 50 Years of Age With Colorectal Cancer in Canada.
Colorectal cancer (CRC) is uncommon in adults younger than 50 years of age, so this population may experience delays to treatment that contribute to advanced stage and poor survival. To investigate whether there is an association between time from presentation to treatment and survival in younger adults with CRC. This retrospective cohort study used linked population-based data in Ontario, Canada. Participants included patients with CRC aged younger than 50 years who were diagnosed in Ontario between 2007 and 2018. Analysis was performed between December 2019 and December 2022. Administrative and billing codes were used to identify the number of days between the date of first presentation and treatment initiation (overall interval). The associations between increasing overall interval, overall survival (OS), and cause-specific survival (CSS) were explored with restricted cubic spline regression. Multivariable Cox proportional hazards models were also fit for OS and CSS, adjusted for confounders. Analyses were repeated in a subset of patients with lower urgency, defined as those who did not present emergently, did not have metastatic disease, did not have cross-sectional imaging or endoscopy within 14 days of first presentation, and had an overall interval of at least 28 days duration. Among 5026 patients included, the median (IQR) age was 44.0 years (40.0-47.0 years); 2412 (48.0%) were female; 1266 (25.2%) had metastatic disease and 1570 (31.2%) had rectal cancer. The lower-urgency subset consisted of 2548 patients. The median (IQR) overall interval was 108 days (55-214 days) (15.4 weeks [7.9-30.6 weeks]). Patients with metastatic CRC had shorter median (IQR) overall intervals (83 days [39-183 days]) compared with those with less advanced disease. Five-year overall survival was 69.8% (95% CI, 68.4%-71.1%). Spline regression showed younger patients with shorter overall intervals (<108 days) had worse OS and CSS with no significant adverse outcomes of longer overall intervals. In adjusted Cox models, overall intervals longer than 18 weeks were not associated with significantly worse OS or CSS compared with those waiting 12 to 18 weeks (OS: HR, 0.83 [95% CI, 0.67-1.03]; CSS: HR, 0.90 [95% CI, 0.69-1.18]). Results were similar in the subset of lower-urgency patients, and when stratified by stage. In this cohort study of 5026 patients with CRC aged younger than 50 years of age in Ontario, time from presentation to treatment was not associated with advanced disease or poor survival. These results suggest that targeting postpresentation intervals may not translate to improved outcomes on a population level.


An electron microscopic study of childhood dermatomyositis.
Muscle biopsies from 12 patients with a typical clinical picture of dermatomyositis have been examined by electron microscopy. Endothelial cells of intramuscular blood vessels, their basal lamina, pericytes, muscle fibers, and satellite cells show degenerative or regenerative alterations. In nine patients, tubular arrays were noted in the cisterns of endoplasmic reticulum of endothelial cells, pericytes, lymphocytes, macrophages and satellite cells. Other types of inclusions were also observed. The pathogenesis of the disease is discussed.


Time-lapse photography: a novel tool to study normal morphogenesis and the diseased hepatobiliary system in children.
The etiology of biliary atresia (BA) and many other childhood cholangiopathies remains unknown. To investigate the normal and diseased hepatobiliary system in vitro, we isolated and cultured biliary epithelial cells (BEC) from a number of species including man. Time-lapse video microscopy was used to study cell movements in vitro, and demonstrated the characteristic morphologic appearance of the BEC and their interactions with hepatocytes and other cell types on artificial biosynthetic materials. The cells remain attached and viable in routine culture conditions; however, when placed onto or within a source of extracellular matrix, the cells move off the surface and form characteristic morphologic patterns, which on time-lapse video are consistent with tube or duct formation. These findings suggest that time-lapse photography may be a useful tool for in vitro studies of normal morphogenesis of the hepatobiliary system and may enable us to better understand biliary atresia and other childhood cholangiopathies.


Pre-operative N-terminal pro-brain natriuretic peptide predicts outcome in type A aortic dissection.
Acute Stanford type A aortic dissection (AAD) is associated with substantial perioperative mortality and morbidity. N-terminal pro-brain natriuretic peptide (NT-proBNP) is a prognostic biomarker of outcome in cardiovascular disease. Its predictive power in patients undergoing emergency surgery for acute type A aortic dissection is yet unknown. We prospectively measured pre-operative NT-proBNP in 104 patients (39 female, 35%; median age 61 years) undergoing emergency surgery for AAD during a 6-year study period. European System for Cardiac Operative Risk Evaluation risk scores were recorded and patients were followed for 30-day mortality and major adverse events (MAEs) as defined by the need for rethoracotomy, occurrence of postoperative heart failure, neurologic deficit, lung failure, renal failure, or sepsis. Median logistic European System for Cardiac Operative Risk Evaluation in the cohort was 12 (interquartile range 7 to 19). During the first 30 days, 23 patients (22%) died, and 53 patients (51%) experienced MAEs. Median (interquartile range) NT-proBNP levels in survivors versus nonsurvivors were 328 pg/ml (157 to 569) versus 2,240 pg/ml (515 to 4,734; p < 0.001), and in patients without versus with MAEs, 227 pg/ml (107 to 328) and 719 pg/ml (442 to 2,287; p < 0.001), respectively. Adjusted odds ratios for increasing tertiles of NT-proBNP compared with the lowest tertile were 0.98 (95% confidence interval [CI] 0.18 to 5.33; p = 0.98) and 11.67 (95% CI 2.61 to 52.09; p = 0.001) for 30-day mortality and 9.07 (95% CI 2.58 to 31.83; p = 0.001) and 50.21 (95% CI 10.85 to 232.45; p < 0.001) for MAEs, respectively, indicating a significant association between pre-operative NT-proBNP levels and outcome. Pre-operative NT-proBNP predicts outcome in patients undergoing surgery of AAD.


Massive rupture of a hepatic hydatid cyst associated with mechanical ventilation.
An 80-yr-old woman with a complicated Echinococcus cyst of the liver underwent endotracheal intubation with a simple endotracheal tube and conventional mechanical ventilation that led to massive rupture of the cyst into the bronchi followed by fatal anaphylactic shock. We believe that the currently recommended use of a double-lumen endotracheal tube during surgery in the pulmonary hydatid cysts should be extended to hydatid cysts of the liver with thoracic involvement. We present a case of massive rupture of hepatic Echinococcus cyst associated with mechanical ventilation. We believe that the use of a double-lumen endotracheal tube could be crucial in the management of the hydatid cysts of the liver with thoracic involvement.


High-throughput screening for the identification of small-molecule inhibitors of retinoblastoma protein phosphorylation in cells.
The tumor suppressor protein, pRb, regulates progression through the G1 phase of the cell cycle by its ability to bind to and regulate the activity of a variety of transcription factors. This function of pRb is disabled through its phosphorylation by the cyclin-dependent kinase (CDK) family of serine/threonine kinases. In many human cancers, genetic alteration such as loss of CDK inhibitor function and deregulated G1 cyclin expression leads to inappropriate phosphorylation and hence inactivation of this tumor suppressor. Identification of cell-permeable small molecules that block pRb phosphorylation in these tumors could therefore lead to development of an effective anticancer treatment. As a result, we have developed a high-throughput assay to detect changes in the level of pRb phosphorylation in cells. Signal detection is by a time-resolved fluorescence-based cellular immunosorbant assay on a fixed monolayer of cells. This comprises a mouse monoclonal antibody that recognizes the phosphorylated form of serine 608 on pRb, a known site of CDK phosphorylation, and a Europium-labeled secondary antibody for signal detection. The assay is reproducible and amenable to automation and has been used to screen 2000 compounds in a search for cell-permeable small molecules that will block pRb phosphorylation.


Primary tuberculosis cutis orificialis; a different face of the same coin.
Primary tuberculosis cutis orificialis (TCO) is a rare form of extrapulmonary TB. The Lack of respiratory symptoms and similarity of the presentations to other oral lesions can pose a diagnostic dilemma. Hence, delaying treatment and potentially devastating consequences.


Pulmonary excretion of hydrogen sulfide, methanethiol, dimethyl sulfide and dimethyl disulfide in mice.
Neither hydrogen sulfide nor any other volatile sulfur metabolites were found in the expired breath of mice given sodium sulfide intraperitoneally in doses up to the LD50. The detection system was sensitive to less than 0.1% of the sulfur in the given dose. The intraperitoneal administration of dimethyl disulfide resulted in its appearance in the expired breath of mice as well as much smaller amounts of both methanethiol and dimethyl sulfide. The intraperitoneal administration of methanethiol resulted in its pulmonary excretion as well as that of dimethyl sulfide. Administration of dimethyl sulfide led to its appearance alone in expired breath. Mice pretreated with ammonium acetate and then injected with dimethyl disulfide excreted the same three compounds via the lungs as above, but there were complex changes in the proportions and in the time sequence of their appearance. The absolute amounts of all three were increased, and the peak excretion for each was delayed. The amount excreted as dimethyl sulfide was particularly increased.


Age-Dependent Carriage of Kingella kingae in Young Children and Turnover of Colonizing Strains.
In a longitudinal study, Kingella kingae carriage rate was nil below 6 months of age, 1.5% at 6 months, 9.6% at 12 months, remained stable between 10.4% and 12.0% during the second year of life, and decreased significantly to 5.3% at 30 months. Replacement of carried strains occurred over time.


Analysis of Dictyostelium discoideum plasma membrane fluidity by electron spin resonance.
Dictyostelium discoideum grown axenically in media containing polyunsaturated fatty acids exhibited normal growth rates but impaired differentiation (Weeks, G. (1976) Biochim. Biophys. Acta 450, 21--32). Since cell-cell contact is vital for differentiation but unnecessary for growth we have examined the isolated plasma membranes of these cells. The lipids of the plasma membranes of cells grown in the presence of polyunsaturated fatty acids contain considerable quantities of these acids, but the total phospholipid and sterol contents of the plasma membrane are close to normal. Electron spin resonance studies using 5-doxyl-stearic acid as the spin probe reveal two things. Firstly, there are no detectable characteristic transition temperatures in the plasma membranes of D. discoideum. Secondly, the plasma membranes of cell grown in the presence of polyunsaturated fatty acids have essentially the same fluidity as that of the control cells. The possible significance of this result to impaired cell-cell interaction is discussed.


Role of extracellular cues to trigger the metabolic phase shifting from acidogenesis to solventogenesis in Clostridium acetobutylicum.
Clostridium acetobutylicum exhibits a two-step metabolic pathway where substrates are first converted to organic acids accompanied by a decrease in pH. The acids are then assimilated to organic solvents. The transition from the acid-producing (acidogenesis) to the solvent-producing phase (solventogenesis) is controlled by integration of a number of cellular and environmental cues, whose precise mode of action are not well understood. In this study, a series of batch experiments were performed to understand the impact of extracellular cues in regulating the dynamics of acidogenesis and solventogenesis. It is demonstrated that the two phases operate independently of each other and the growth phase of the cell, i.e. the cues controlling a phase are not linked to the status of the other phase or the growth phase of the cell. Kinetic experiments demonstrated that there exist two previously uncharacterized negative feedback loops controlling the amounts of acids produced in the acidogenesis phase.


Nurse academics meeting the challenges of scholarship and research.
This research study explored nurse academics' perceptions and experiences of scholarship and research. Interviews were carried out with 20 nurse academics in four Australian states. A grounded theory approach was used to explore issues they faced. The paper discusses how academics engaged in research and scholarship integrate it into their work practices. The participants spoke of problems encountered, such as the difficulty of gaining higher degrees whilst undertaking additional research. They indicated they felt under significant pressure to publish. The organisational structures that a small number of institutions put in place to facilitate the development of a scholarly research culture are illustrated.


[Are conventional dental x-ray films a thing of the past?].
Dental x-ray film is still the most important medium for the detection and storage of x-ray images. However, just as the use of computers cannot be stopped, digital techniques will take over the role of dental x-ray films in dental radiology.


NEDD4-1 deficiency impairs satellite cell function during skeletal muscle regeneration.
Satellite cells are tissue-specific stem cells primarily responsible for the regenerative capacity of skeletal muscle. Satellite cell function and maintenance are regulated by extrinsic and intrinsic mechanisms, including the ubiquitin-proteasome system, which is key for maintaining protein homeostasis. In this context, it has been shown that ubiquitin-ligase NEDD4-1 targets the transcription factor PAX7 for proteasome-dependent degradation, promoting muscle differentiation in vitro. Nonetheless, whether NEDD4-1 is required for satellite cell function in regenerating muscle remains to be determined. Using conditional gene ablation, we show that NEDD4-1 loss, specifically in the satellite cell population, impairs muscle regeneration resulting in a significant reduction of whole-muscle size. At the cellular level, NEDD4-1-null muscle progenitors exhibit a significant decrease in the ability to proliferate and differentiate, contributing to the formation of myofibers with reduced diameter. These results indicate that NEDD4-1 expression is critical for proper muscle regeneration in vivo and suggest that it may control satellite cell function at multiple levels.


A penetrating ocular injury can affect the induction of anterior chamber-associated immune deviation.
To determine the effect of penetrating ocular injury on the induction of anterior chamber-associated immune deviation (ACAID). An injection of 5 mul ovalbumin (OVA, 20 mg/ml) into the anterior chamber (AC) of female BALB/c mice was performed to induce ACAID. A penetrating ocular injury was induced via the limbus on OVA-inoculated eyes at 24 h, 48 h, 72 h, and 120 h following AC injection. The mice receiving an OVA inoculation without the ocular injury served as the AC-injection group. Delayed type hypersensitivity (DTH) was examined to evaluate the induction of ACAID. The levels of transforming growth factor (TGF)-beta1, interleukin (IL)-10, and interferon (IFN)-gamma produced by splenocytes were detected by enzyme-linked immunosorbent assays (ELISA). The frequency of CD4(+)CD25(+)Foxp3(+)T cells in the splenocytes was detected by flow cytometry. A significantly decreased DTH response was observed in the AC-injection group as well as in mice that received a penetrating injury at 72 h and 120 h following AC-injection of OVA. The levels of TGF-beta1 and IL-10 produced by splenocytes of mice in the AC-injection group and in the 72-h and 120-h group were significant higher than those in the 24-h and 48-h group. However, the levels of IFN-gamma produced by splenocytes of the AC-injection group and the 72-h and 120-h group were significantly lower than those in the 24-h and 48-h group. An increased frequency of CD4(+)CD25(+)Foxp3(+)T cells was found in the AC-injection group and the 72-h and 120-h group. Penetrating ocular injury preformed shortly (24 h-48 h) after an AC injection of an antigen was able to abrogate ACAID and was associated with a decreased production of TGF-beta1 and IL-10, an increased production of IFN-gamma, and a decreased expression of CD4(+)CD25(+)Foxp3(+)T cells.


Making Sense of Jiese: An Interview Study of Members from a Porn-Free Self-Help Forum in China.
About 6 million men in China engage in jiese (abstaining from masturbation and porn) and call themselves jieyou (porn-free self-help community members). In this article, we sought to unpack how the idea of jiese took root in Chinese historical, social, and cultural contexts by interviewing 32 jieyou. Guided by the sensemaking theory, we conducted a critical discourse analysis of participants' responses and ended up identifying four major themes: embodied experiences, jiese as rational and noble, reconstructing the subjectivity of jieyou, and nationalistic sentiments. We found out that jieyou tended to justify their abstinence by seeking sources of legitimacy in traditional Chinese culture, the ideology of healthism, science, and patriotic discourses. We argue that jiese reflects young men's contradictory cultural practices of conservatism, self-medicalization, and neoliberal governmentality.


Inorganic nitrogen control in wastewater treatment ponds from a fish farm (Orbetello, Italy): denitrification versus Ulva uptake.
The aim of this study was to quantify the N removal efficiency of an Ulva-based phytotreatment system receiving wastewaters from a land-based fish farm (Orbetello, Italy), to identify the main biogeochemical pathways involved and to provide basic guidelines for treatment implementation and management. Fluxes of O2 and nutrients in bare and in Ulva colonised sediments were assessed by light/dark core incubations; denitrification by the isotope pairing technique and Ulva growth by in situ incubation of macroalgal disks in cages. O2 and nutrient budgets were estimated as sum of individual processes and further verified by 24-h investigations of overall inlet and outlet loads. Ulva uptake (up to 7.8 mmol Nm(-2) h(-1)) represented a net sink for water column and regenerated NH4+ whilst N removal via denitrification (10-170 micromol Nm(-2) h(-1)) accounted for a small percentage of inorganic nitrogen load (<5%). Laboratory experiments demonstrated a high potential for denitrification (over 800 microM Nm(-2) h(-1)) indicating that N loss could be enhanced. The control of Ulva standing stocks by optimised harvesting of surplus biomass may represent an effective strategy to maximise DIN removal and could result in the assimilation of approximately 50% of produced inorganic nitrogen.


Rapid suppression of bone resorption marker levels with ibandronate therapy in a bisphosphonate-naïve population.
This 6-mo open-label study assessed the pattern of bone turnover marker (BTM) level changes in bisphosphonate-naïve women with postmenopausal osteoporosis treated with monthly oral ibandronate 150mg and the correlation between month 1 and month 6 serum C-terminal cross-linking telopeptide of type I collagen (sCTX) levels. The following BTMs were monitored: sCTX, urinary N-terminal telopeptide of type I collagen (uNTX), serum procollagen type 1 N-terminal propeptide (PINP), serum osteocalcin (OC), and serum bone-specific alkaline phosphatase (bALP). BTM levels were measured immediately before dosing at baseline and months 1, 2, 3, and 6, and 7d after dosing at baseline and month 4. A multiple regression model was applied to determine whether month 1 sCTX response predicted month 6 sCTX change. sCTX levels declined 70% 7d after dosing at baseline and month 4. Predosing sCTX declined 55% at month 6. The pattern of uNTX reduction was similar to sCTX. Bone formation markers PINP, OC, and bALP declined gradually over time. Month 1 sCTX change was a significant predictor of Month 6 change (p=0.0001). Once monthly 150mg oral ibandronate treatment reduced BTMs in women with osteoporosis. sCTX reduction occurred within 7d and was sustained over 6mo. Month 1 sCTX predicted month 6 sCTX.


Computed tomography severity index is an early prognostic tool for acute pancreatitis.
Acute pancreatitis is a severe disease with unpredictable course and outcomes. It is especially hard to identify early those patients who will have a fulminant course. In a prospective observational study, we tested the hypothesis that the CT Severity Index (CTSI), established within 48hours after admission, is prognostic for morbidity and mortality and can predict the necessity for admission to an ICU. From January 1994 to October 2002, all patients with the diagnosis of first time acute pancreatitis underwent spiral CT with intravenous contrast within 48hours of admission. The extent of inflammation and necrosis was assessed to define the CTSI. Patients were initially managed in an ICU in a standardized fashion. Complications and mortality were registered in a systematic manner. Seventy-nine patients were admitted with acute pancreatitis. The overall complication rate was 57%; mortality was 9%. In patients with a CTSI of 0 to 3, these rates were 42% and 2%, respectively; in those with CTSI of 4 to 6, 81% and 19%, respectively; and in those with CTSI of 7 to 10, 100% and 33%, respectively. Outcomes of subsequent CT scans did not alter the initial prognosis. Early CTSI correlated well with the incidence of complications, sepsis, mortality, and necessity for ICU admission. Acute pancreatitis is associated with marked morbidity and mortality. Initial admission to an ICU and standardized conservative treatment are justified for all patients. Early establishment of the CTSI is an excellent prognostic tool for complications and mortality. Patients with a CTSI of 0 to 3 can safely be discharged from the ICU.


Adaptive laboratory evolution of ethanologenic Zymomonas mobilis strain tolerant to furfural and acetic acid inhibitors.
Furfural and acetic acid from lignocellulosic hydrolysates are the prevalent inhibitors to Zymomonas mobilis during cellulosic ethanol production. Developing a strain tolerant to furfural or acetic acid inhibitors is difficul by using rational engineering strategies due to poor understanding of their underlying molecular mechanisms. In this study, strategy of adaptive laboratory evolution (ALE) was used for development of a furfural and acetic acid-tolerant strain. After three round evolution, four evolved mutants (ZMA7-2, ZMA7-3, ZMF3-2, and ZMF3-3) that showed higher growth capacity were successfully obtained via ALE method. Based on the results of profiling of cell growth, glucose utilization, ethanol yield, and activity of key enzymes, two desired strains, ZMA7-2 and ZMF3-3, were achieved, which showed higher tolerance under 7 g/l acetic acid and 3 g/l furfural stress condition. Especially, it is the first report of Z. mobilis strain that could tolerate higher furfural. The best strain, Z. mobilis ZMF3-3, has showed 94.84% theoretical ethanol yield under 3-g/l furfural stress condition, and the theoretical ethanol yield of ZM4 is only 9.89%. Our study also demonstrated that ALE method might also be used as a powerful metabolic engineering tool for metabolic engineering in Z. mobilis. Furthermore, the two best strains could be used as novel host for further metabolic engineering in cellulosic ethanol or future biorefinery. Importantly, the two strains may also be used as novel-tolerant model organisms for the genetic mechanism on the "omics" level, which will provide some useful information for inverse metabolic engineering.


Treatment of pulmonary arterial hypertension due to scleroderma: challenges for the future.
Although progress has been made in treatment of pulmonary arterial hypertension, serious challenges remain. This article provides an overview of the challenges faced in treatment of PAH caused by scleroderma. It also provides a glimpse into the future, based on recent developments in the field that hold promise for enhancing the treatment of this disease.


Use of oral and intravenous fat tolerance tests to assess plasma chylomicron clearance in dogs.
The reduced clearance of chylomicrons from plasma results in an exaggerated post prandial lipaemia and fasting hypertriglyceridaemia. This study evaluated whether oral and intravenous fat tolerance tests are appropriate for the in vivo analysis of chylomicron clearance in dogs. Plasma and chylomicron triglyceride concentrations were measured in eight beagles after the administration of a cream-based meal of 2.35 g fat kg-1 bodyweight. The changes in each parameter were determined chiefly by the activity of lipoprotein lipase, which was measured in plasma collected after the intravenous injection of heparin and did not appear to be influenced by intestinal fat absorption. The inclusion of retinyl palmitate in the meal provided additional information on the metabolic fate of chylomicron remnants. After the intravenous injection of 0.1 g Intralipid kg-1 bodyweight, there was an initial linear decay in plasma triglyceride concentrations that represented the maximal elimination rate K1. This was followed by a second exponential component so that the plasma triglyceride concentration returned to baseline by 60 minutes. Lipoprotein lipase was the major determinant of K1 and the area under the curve of plasma triglycerides.


A case of emotional facial palsy with ipsilateral anterior inferior cerebellar artery territory infarction.
Emotional facial palsy (EFP) commonly results from anterolateral thalamic or striatocapsular infarcts. Its occurrence in brainstem lesions is uncommon, with previously reported cases being restricted to superior cerebellar artery infarction (3 cases). We report an unusual case of EFP ipsilateral to an anterior inferior cerebellar artery infarction, which opens new insights into the facial corticobulbar tract pathway.


Impact of method of endometrial preparation for frozen blastocyst transfer on pregnancy outcome: a retrospective cohort study.
To determine whether live birth rates differ by type of endometrial preparation in frozen embryo transfer (FET) cycles. Retrospective cohort study. Academic fertility center. Reproductive-aged women undergoing autologous vitrified-warmed blastocyst FETs. Comparison of two methods of endometrial preparation: programmed FET (known as group A: luteal phase GnRH agonist suppression, oral E2, and IM P starting 5 days before ET) versus unstimulated FET (known as group B: hormone and ultrasound monitoring for follicle collapse to time transfer). Live birth rates in group A and group B. Group A consisted of 923 cycles, and group B consisted of 105. When stratified by age at transfer, there was no difference in any of the measured outcomes, including live birth rates in adjusted models (adjusted odds ratio 1.0, 95% confidence interval 0.6-1.5), except in patients older than 40 years. These patients in group B had a 100% failure rate (n = 6). In most women, unstimulated endometrial preparation with luteal support before FET has similar success compared with exogenous hormone preparation. Women older than 40 years may benefit from programmed FETs owing to the challenges of increased cycle variability expected in that age group.


Effects of hsa_circ_0074854 on colorectal cancer progression, construction of a circRNA-miRNA-mRNA network, and analysis of immune infiltration.
Circular RNAs have been demonstrated to be closely associated with the onset and metastasis of colorectal cancer. However, the roles and clinical diagnostic value of most circRNAs in colorectal cancer remain unclear. We detected the differential expression of circRNAs in CRC tissues and cells and investigated their relationship in conjunction with clinical pathological features. Additionally, we performed cellular functional experiments in CRC cell lines to explore the functions of circRNAs. To further validate the potential ceRNA network, qPCR was performed to assess the expression of miRNA and mRNA in CRC cells after differential expression of circRNAs knockdown. Furthermore, database analysis was utilized to explore the relationship between the predicted mRNAs and immune infiltration in CRC. Our research findings indicate a positive correlation between hsa_circ_0074854 expression and advanced clinical pathological features, as well as an unfavorable prognosis. Knockdown of hsa_circ_0074854 was observed to inhibit proliferation and migration capabilities of colorectal cancer cells, affecting the cell cycle progression, and simultaneously promoting apoptosis. A competing endogenous RNA mechanism may exist among circRNAs, miRNAs, and mRNAs. Furthermore, the expression of target genes displayed correlations with the abundance of certain immune cells. We propose a novel ceRNA network and evaluate the interplay between target genes and immune cells, providing novel insights for the diagnosis and targeted therapy of CRC.


Medicinal plant diversity of Sitamata wildlife sanctuary, Rajasthan, India.
The present study has been carried out in Sitamata wildlife sanctuary of Chittorgarh and Udaipur district located in south-west region of Rajasthan. A field survey of the study area was carried out during 2002-2004 to document the medicinal utility of herbs occurring in this area. Two hundred fourty-three genera belonging to 76 families have been reported which are used by the tribals of about 50 villages around the sanctuary as means of primary health care to cure various ailments. The study revealed the new ethnobotanical uses of 24 plant species belonging to 20 genera. A list of plant species along with their local name, plant part/s used and mode of administration for effective control in different ailments of ethnomedicinal plants are given.


Repigmentation through Melanocyte Regeneration in Vitiligo.
Repigmentation in vitiligo is the process that replaces, in the epidermal basal layer of vitiligo skin, the mature melanocytes that have been killed by cytotoxic T cells specific for melanocyte antigens. It consists of mobilization of melanocyte precursors in the hair follicle bulge and infundibulum to proliferate, migrate, and differentiate into mature melanocytes, moving from the hair follicle bulge to the interfollicular epidermis. The most common clinical presentation of repigmentation in vitiligo is the perifollicular pattern. The most potent stimulus for repigmentation is the UV light.


Massive posterior mitral annular calcification causing dynamic left ventricular outflow tract obstruction: mechanism and management implications.
We report a case of massive posterior mitral annular calcification causing severe systolic anterior motion of the anterior mitral leaflet and dynamic left ventricular outflow tract obstruction. Mechanism of genesis of systolic anterior motion by this unusual mechanism is illustrated. Importance of recognizing this mechanism and its implications for surgical therapy are discussed. Our patient also had liquefaction necrosis of mitral annular calcification causing its extension into left ventricular myocardium mimicking a tumor.


Mucinous appendix intussusception: Case report.
Intussusception is an intestinal invagination of one bowel segment into another. It occurs mostly in children, but it can show in adults due to different etiologies. Appendiceal neoplasms are rare and can mimic an acute onset of appendicitis. Appendiceal mucinous neoplasm is one of the subtypes of appendiceal malignancies found in less than 1 % of appendectomies samples. We present the case of a 32-year-old woman with abdominal pain in the right upper quadrant, whose computed tomography revealed an ileocolic intussusception and a low-density tubular image in the distal loop. She underwent diagnostic laparoscopy and laparoscopic right colectomy. Biopsy results confirmed a LAMN with acute appendicitis and intussusception. Appendiceal intussusception (AI) is associated with the alteration of peristalsis, in addition to multiple inflammatory conditions and diseases such as parasites, foreign bodies, Crohn's disease, and lymphoid hyperplasia. The pathophysiology of AI is not fully established, but the main appendicular alteration that has been associated with it is the presence of a tumor. AI lead points are typically pathological in 90 % of cases, 65 % of which are neoplastic in nature. Right hemicolectomy should be performed for tumors involving the periappendicular area or in those larger than 2 cm in size. Follow-up and surveillance colonoscopy is suggested. Intussusception is a rare diagnosis in adults. However, malignancy should be suspected if identified.


Magnetic field assisted beam-scanning leaky-wave antenna utilizing one-way waveguide.
We propose a Leaky-Wave Antenna (LWA) based on one-way yttrium-iron-garnet (YIG)-air-metal waveguide. We first analyze the dispersion of the LWA, showing the one-way feature and the radiation loss. Owing to the unique one-way dispersive property, the beam radiated from the LWA can have very narrow beam width, at the same time having large scanning angle. The main beam angle obtained by full-wave simulation is consistent with our theoretical prediction with the aid of the dispersion. For a given frequency, we can realize continuous beam scanning by varying the magnetic field, where the 3 dB beam width is much narrower than previously demonstrated. Our results pave a new way to realize continuous angle scanning at a fix frequency for modern communications.


Testing the relation between dispositional optimism and conditioned pain modulation: does ethnicity matter?
Greater dispositional optimism has been related to less severe pain; however, whether optimism is associated with endogenous pain modulation has not yet been examined. The beneficial effects of dispositional optimism often vary according to cultural dynamics. Thus, assessing optimism-pain relationships across different ethnic groups is warranted. This study sought to examine the association between optimism and conditioned pain modulation (CPM), and test whether this association differs according to ethnicity. Optimism and CPM were assessed in a sample of healthy, ethnically diverse young adults. CPM was determined by comparing pressure pain thresholds obtained before and during exposure to a cold pressor task. All participants completed a validated measure of dispositional optimism. Greater reported optimism was significantly associated with enhanced CPM, and the strength of this association did not vary according to individuals' ethnic background. These findings suggest that an optimistic disposition may potentiate endogenous pain inhibition.


Pollination intensity and potential seed set in Passiflora vitifolia.
Initial seed set and fruit set were pollen-limited in a Costa Rican population of Passiflora vitifolia, a self-incompatible species with 200-350 ovules per flower. Pollination intensity was measured by counting the number of allogamous pollen grains on stigmas of the large one-day flowers. Hand-pollinations demonstrated that 25-50 pollen grains are required for fruit set, and >450 are needed for maximum seed set, with a pollen:seed ratio of about 1.6:1.0. Hummingbirds (Phaethornis superciliosus) delivered sufficient allogamous pollen for maximum seed set to only 28% of the flowers examined. Naturally pollinated flowers yielded fewer fruits and fewer seeds per fruit than those pollinated by hand. Most pollen transferred by humming-birds was self-incompatible; emasculated flowers yielded higher seed set than flowers with intact anthers. Visitation rates did not provide a good index of effective pollination.There were significant differences in ovule number, maximum seed set, and maximum per cent seed set among individual vines. More than half of an individual's flowers failed to set fruit, whether pollinated by birds or by hand. In this population, maximum reproductive potential may be limited by maternal resources for fruit development, but seed set varies with pollination intensity. Pollen-limited seed set may be a disadvantage of self-incompatibility, especially in species with many-seeded fruits.


Comparison of four clinical risk scores in comatose patients after out-of-hospital cardiac arrest.
Several different scoring systems for early risk stratification after out-of-hospital cardiac arrest have been developed, but few have been validated in large datasets. The aim of the present study was to compare the well-validated Out-of-hospital Cardiac Arrest (OHCA) and Cardiac Arrest Hospital Prognosis (CAHP)-scores to the less complex MIRACLE2- and Target Temperature Management (TTM)-scores. This was a post-hoc analysis of the Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest (TTM2) trial. Missing data were handled by multiple imputation. The primary outcome was discriminatory performance assessed as the area under the receiver operating characteristics-curve (AUROC), with the outcome of interest being poor functional outcome or death (modified Rankin Scale 4-6) at 6 months after OHCA. Data on functional outcome at 6 months were available for 1829 cases, which constituted the study population. The pooled AUROC for the MIRACLE2-score was 0.810 (95% CI 0.790-0.828), 0.835 (95% CI 0.816-0.852) for the TTM-score, 0.820 (95% CI 0.800-0.839) for the CAHP-score and 0.770 (95% CI 0.748-0.791) for the OHCA-score. At the cut-offs needed to achieve specificities >95%, sensitivities were <40% for all four scoring systems. The TTM-, MIRACLE2- and CAHP-scores are all capable of providing objective risk estimates accurate enough to be used as part of a holistic patient assessment after OHCA of a suspected cardiac origin. Due to its simplicity, the MIRACLE2-score could be a practical solution for both clinical application and risk stratification within trials.


Extraction of Sterile Leads: Is it Beneficial?
Extraction of sterile leads remains a controversial area. The risks and benefits of abandoning a lead are largely unknown, whereas the risks of lead extraction are better studied. Lead management decisions need to be made on a patient-by-patient basis, with important input from the patient and family. This article presents several representative cases and reviews the major considerations in making the decision of whether or not to extract a sterile lead that has become either no longer needed or no longer functional.


Chlorination and dechlorination rates in a forest soil - A combined modelling and experimental approach.
Much of the total pool of chlorine (Cl) in soil consists of naturally produced organic chlorine (Clorg). The chlorination of bulk organic matter at substantial rates has been experimentally confirmed in various soil types. The subsequent fates of Clorg are important for ecosystem Cl cycling and residence times. As most previous research into dechlorination in soils has examined either single substances or specific groups of compounds, we lack information about overall bulk dechlorination rates. Here we assessed bulk organic matter chlorination and dechlorination rates in coniferous forest soil based on a radiotracer experiment conducted under various environmental conditions (additional water, labile organic matter, and ammonium nitrate). Experiment results were used to develop a model to estimate specific chlorination (i.e., fraction of Cl(-) transformed to Clorg per time unit) and specific dechlorination (i.e., fraction of Clorg transformed to Cl(-) per time unit) rates. The results indicate that chlorination and dechlorination occurred simultaneously under all tested environmental conditions. Specific chlorination rates ranged from 0.0005 to 0.01 d(-1) and were hampered by nitrogen fertilization but were otherwise similar among the treatments. Specific dechlorination rates were 0.01-0.03d(-1) and were similar among all treatments. This study finds that soil Clorg levels result from a dynamic equilibrium between the chlorination and rapid dechlorination of some Clorg compounds, while another Clorg pool is dechlorinated more slowly. Altogether, this study demonstrates a highly active Cl cycling in soils.


Health and Healthcare Access for Essential, Nonessential, and Nonworkers During the COVID-19 Pandemic.
The aim of the study is to describe sociodemographic characteristics, healthcare access, and health status of low-income essential, nonessential, and nonworkers during the COVID-19 pandemic. Using survey data (2020-2021) from Wisconsin Medicaid enrollees ( N = 2528), we compared sociodemographics, healthcare access, and health status between essential, nonessential, and nonworkers. Essential workers had less consistent health insurance coverage and more problems paying medical bills than nonessential and nonworkers. They reported better health than nonessential and nonworkers. They reported fewer work-limiting conditions and less outpatient healthcare utilization than nonworkers but similar rates as nonessential workers. Essential workers reported masking less frequently than nonworkers but similar frequency to nonessential workers, and lower COVID-19 vaccine willingness than nonessential and nonworkers. Essential workers report better health, fewer protective behaviors, and more healthcare barriers than nonessential and nonworkers. Findings indicate essential worker status may be a social determinant of health.


Bone histomorphometry in children prior to commencing renal replacement therapy.
Renal osteodystrophy (ROD) develops early in the course of chronic kidney disease (CKD). With improving patient survival it's importance and relevance has increased. The last published bone biopsy data in children prior to renal replacement therapy (RRT) was in 1982, which demonstrated abnormal histology in all patients with a glomerular filtration rate (GFR) <20 ml/min per 1.73 m(2). Studies investigating the relationship between bone histology and parathyroid hormone levels (PTH) and/or growth in children with CKD are few (seven). These were mostly undertaken in patients already initiated on RRT-dialysis. We investigated the presence of ROD in children at the commencement of RRT and to investigate any relationship between histology, growth and PTH levels. Following double tetracycline labelling, bone biopsies were taken from patients at the time of RRT surgery. Histological classification was based on the newly proposed turnover/mineralisation/volume (TMV) system. Eleven patients underwent bone biopsy. Patients were followed for an average of 1.1 years (0.5-1.8) prior to biopsy over an average of eight clinic visits (3-14), when routine biochemical data were collected. Time-integrated median calcium, phosphate and PTH levels were calculated. PTH levels were within the normal range in two patients with low turnover, 1.1-1.4 times the upper limit of normal (ULN) in three with mixed osteodystrophy and >2.9 times the ULN in four patients with high bone turnover. There was no relationship between bone turnover and growth. The presence of ROD was universal in these children with severe CKD. Low bone turnover was associated with normal-range mean PTH levels, and high bone turnover occurred at lower PTH levels than current guidelines would suggest.


Hypotension, myocardial infarction, and coagulopathy following gila monster bite.
We report a 23-year-old man who developed life threatening hypotension, myocardial infarction, coagulopathy, and renal failure following the bite of a Gila monster (Heloderma suspectum). These are previously unreported complications in humans. The patient recovered after fluid resuscitation and treatment with pressor agents.


Effects of adenosine and epidermal growth factor on the growth of mouse mammary epithelial cells.
The objective of this study was to determine if adenosine alters growth of mammary epithelium. Mouse mammary epithelial cells (NMuMG) were cultured in DMEM supplemented with 10% fetal calf serum. After serum starvation for 24 h, EGF (0-100 ng/ml) and/or adenosine (0-100 microM) was added. Adenosine at concentrations of 1, 10 or 100 microM increased DNA synthesis significantly, when compared to control. Addition of epidermal growth factor (EGF) (10 ng/ml) into 1 or 10 microM adenosine showed the interaction in DNA synthesis between EGF and adenosine. A similar result was observed when 100 microM adenosine added to various concentrations of EGF (0-100 ng/ml). In the second mammary gland (thoracic) organ culture studies, mammary development scores were increased by adenosine (100 microM), EGF (100 ng/ml) and adenosine plus EGF. These results indicate that the purine nucleoside adenosine stimulates mammary epithelial cell growth and interacts with EGF in DNA synthesis of mouse mammary epithelial cells.


Modulation of cardiac interstitial noradrenaline levels through K(ATP) channels during ischemic preconditioning in rabbits: comparison of the effect of anesthesia between pentobarbital and ketamine + xylazine.
In rabbits, both the stimulation of alpha1-adrenoceptors and ischemic preconditioning (PC) reduce infarct size. One candidate for the mechanism of PC is noradrenaline (NA), which stimulates alpha1-adrenoceptors in the myocardium during PC. Opening of the K(ATP) channel is considered to be another candidate for PC, since a K(ATP) channel blocker, glibenclamide, blocks the infarct size-reducing effect of the PC of 5-min ischemia and 5-min reperfusion in rabbits anesthetized with ketamine + xylazine. However, in rabbits anesthetized with pentobarbital, the infarct size-reducing effect of PC was not blocked by glibenclamide. The effect of glibenclamide on the PC effect thus differs depending on the anesthesia used. Therefore, we speculated that the increase in cardiac interstitial NA levels induced by PC may be modified by the anesthesia used, thus regulating the effect of glibenclamide on the PC effect. In open-chest Japanese white male rabbits anesthetized with pentobarbital or ketamine + xylazine, myocardial interstitial NA levels were measured before and during the PC of 5-min ischemia and 5-min reperfusion in the presence or absence of the K(ATP) channel blocker, glibenclamide (0.3 mg/kg, i.v.), using a microdialysis technique. The NA levels were measured using high-performance liquid chromatography coupled with electrochemical detection. The PC of 5-min ischemia and 5-min reperfusion significantly elevated the interstitial NA level. This increase in the NA level was not blocked by glibenclamide under anesthesia with pentobarbital. Under anesthesia with ketamine + xylazine, the PC did not cause an increase in the myocardial interstitial NA level in either the absence or the presence of glibenclamide. In conclusion, PC elevates the myocardial interstitial NA level, and this elevation is not mediated through the opening of the K(ATP) channel under anesthesia with pentobarbital. Under anesthesia with ketamine + xylazine, PC does not cause an increase in the myocardial interstitial NA level. This may explain the discrepancy in the blocking effect of glibenclamide on the infarct size-reducing effect of PC between anesthesia with pentobarbital and ketamine + xylazine.


Speech intelligibility enhancement through maxillary dental rehabilitation with telescopic prostheses and complete dentures: a prospective study using automatic, computer-based speech analysis.
A completely edentulous or partially edentulous maxilla involving missing anterior teeth may impact speech production and lead to reduced speech intelligibility. The aim of this study was to prospectively evaluate the effect of a dental prosthetic rehabilitation on speech intelligibility in patients with a toothless or interrupted maxillary arch by means of an automatic, standardized speech recognition system. The speech intelligibility of 45 patients with complete tooth loss or a loss including missing anterior teeth in the maxilla was evaluated by means of a polyphone-based automatic speech recognition system that assessed the percentage of correctly recognized words (word accuracy). To replace inadequate maxillary removable dentures, 20 patients from the overall sample had been rehabilitated with complete dentures and 25 patients with telescopic prostheses. Speech recordings were made in four recording sessions (with and without existing prostheses and then at 1 week and 6 months after placement of newly fabricated prostheses). Significantly higher speech intelligibility was observed in both patient groups compared to the original results without the dentures inserted. After 6 months of adaptation, both groups had reached a level of speech quality that was comparable to the healthy control group. However, patients receiving new telescopic prostheses showed significantly higher levels of speech intelligibility compared to those receiving new complete dentures. Within 6 months, speech intelligibility did not significantly improve from the level found 1 week after insertion of new prostheses for both groups. Patients benefit from the fabrication of new dentures in terms of speech intelligibility, regardless of the type of prosthesis. However, telescopic crown prostheses yield significantly better speech quality compared to complete dentures.


Adjusting serum zinc concentration for inflammation based on the data of Malawian preschool children and women of reproductive age.
Serum zinc negatively reacts to inflammation yet to our knowledge only a few studies have attempted to adjust it for inflammation. The aim of this study, based on the data of Malawi Micronutrient Survey, was to correct zinc concentration for inflammation in preschool children (n = 1081) and women of reproductive age (n = 799) and to evaluate the effects of the adjustment on the prevalence of zinc deficiency (ZD). Based on C-reactive protein (CRP) and α-1-acid glycoprotein (AGP), inflammation status was grouped into four categories: no inflammation, incubation, early convalescence, and late convalescence. The association between zinc and inflammation was examined using linear regression analysis and correction was made by six approaches: exclusion, internal correction factor, and four regression adjustments. The unadjusted prevalence of ZD was 58.9% in children and 62% in women. Inflammation was observed in 57.6% of children and 17.1% of women. Zinc demonstrated negative correlations with inflammation markers (P < 0.05). Among children, zinc showed marginally insignificant (P = 0.072) decline during incubation (β= -8.25; 95% confidence interval [CI], -17.28 to 0.78) and significant decline during early convalescence inflammation (β= -4.92; 95% CI, -7.00 to -2.31). Among women, significant change was only observed in late convalescence inflammation (β= -4.10; 95% CI, -8.06 to -0.14). However, all the corrections resulted in modest decline in the prevalence of ZD (1.4-2.1 and 0-2.6 percentage points in children and women). The study observed statistically significant negative correlations between serum zinc concentration and inflammation markers (AGP and CRP). However, correction of serum zinc for inflammation using multiple options including exclusion, internal correction factor, and regression adjustment resulted in very marginal changes in the prevalence of ZD. Although inflammation adjustment may enable more precise estimation of ZD, it only resulted in modest changes in the actual prevalence of ZD in Malawi.


Use of inhaled nitric oxide in preterm vs term/near-term neonates with pulmonary hypertension: results of the PaTTerN registry study.
To evaluate inhaled nitric oxide (iNO) in preterm (PT) vs term/near-term (TNT) neonates with hypoxic respiratory failure (HRF) and pulmonary hypertension (PH) in an observational registry (PaTTerN). Non-inferiority study comparing PT neonates of GA ≥ 27 to <34 weeks vs TNT neonates of GA ≥ 34 to ≤40 weeks with HRF associated with PH, who received iNO for 24-96 h during the first 0-7 days after birth. Primary endpoint: Achieving ≥25% decrease in oxygenation index/surrogate oxygenation index during iNO treatment. Of 140 neonates (PT, n = 55; TNT, n = 85), the primary endpoint was achieved in 50 (90.9%) PT vs 75 (88.2%) TNT neonates (difference [95% CI]: 0.027 [-0.033, 0.087]); PT neonates achieved non-inferiority interval, and the study was stopped early based on prespecified criteria. Use of iNO for improving oxygenation in PT neonates with HRF associated with PH is at least as effective as in TNT neonates. #NCT03132428, registered April 27, 2017.


Genome flux in tomato cell clones cultured in vitro in different physiological equilibria. II. A RAPD analysis of variability.
An analysis of the effect of changing physiological conditions on genome evolution in tomato cell populations has been carried out on long-term in vitro cultured clones grown on different auxin-cytokinin equilibria or selected for low-high competence for active defense against Fusarium oxysporum f.sp. lycopersici. RAPD analysis, confirmed through pattern rehybridization, was used as a random tool to measure the genetic variability. Through the use of a modified ANOVA, variation was shown to depend on both the initial genotype and the physiological conditions. Pattern correlation analysis through a mutual information algorithm suggested the fixation of RAPD patterns specific to physiological equilibria. The results are discussed in view of the possible relevance for evolution at hierarchical levels higher than cell populations. Key words : tomato clones, somaclonal variation, RAPD, coadaptation.


[The detection of breast carcinoma micrometastases in axillary lymph nodes by reverse transcriptase-polymerase chain reaction].
To detect tumor micrometastases in axillary lymph nodes of breast carcinoma so as to obtain more reliable information about nodes status and its clinical significance. The expression of CK19 mRNA was measured in 61 axillary lymph nodes (LNs) of 15 breast carcinomas by using reverse transcriptase-polymerase chain reaction (RT-PCR). CK19 mRNA expression was detected in all 15 breast carcinomas, but not in 5 control LNs. Of 61 axillary LNs analysed by HE staining and CK19 RT-PCR, 7 LNs were found to have metastases by histological staining and CK19 RT-PCR. Of the remaining 54 axillary nodes, 12 were found to have metastases by using CK19 RT-PCR method. The CK19 RT-PCR method is more sensitive than histological study for the detection of micrometastases in LNs (P < 0.01). This new method is of value in differentiating breast cancer patients at high risk for relapse from those with negative lymph node.


Cytogenetic analysis of a mesenchymal hamartoma of the liver.
Cytogenetic analysis of a mesenchymal hamartoma of the liver in a 3-year-old child revealed a balanced translocation between chromosomes 15 and 19 as the sole chromosome change.


Bioethanol production from the macroalgae Sargassum spp.
Macroalgae, an abundant and carbon-neutral renewable resource, with several species rich in carbohydrates are suitable for bioethanol production. This study focused on the pretreatment, enzyme saccharification and fermentation of Sargassum spp., a brown macroalgae for bioethanol production. The optimal acid pretreatment condition achieved in terms of glucose and reducing sugar yields was 3.4-4.6% (w/v) H2SO4 concentration, 115°C and 1.50h. The pretreated biomass was hydrolyzed with cellulase enzyme system supplemented with β-glucosidase. After fermentation by Saccharomyces cerevisiae at 40°C, pH of 4.5 for 48 h, the ethanol conversion rate of the enzyme hydrolysate reached 89%, which was markedly higher than the theoretical yield of 51% based on glucose as substrate. Since all the glucose was consumed during fermentation, other sugar sources might be present in the hydrolysate. The macroalgae, Sargassum spp., showed significant potential as a renewable feedstock for the production of bioethanol.


[Experimental study on effect of curcumin on inhibiting injury of free radical in pulmonary fibrosis rats].
To study on the effect and mechanism of curcumin on inhibiting injury induced by free radical in pulmonary fibrosis. One hundred and forty-four male SD rats were randomly divided into 6 groups (24 rats in each group). Rats in the model control group, positive medicine group, and high, moderate and low curcumin groups were injected with a single dose of bleomycin by trachea, and rats in sham-model control group with same volume normal saline. One day after the injection, curcumin solution of different dosages (200,100,50 mg x kg(-1) x d(-1)) was respectively given to rats in the high, moderate and low curcumin group by daily gastrogavage, while equal volume of normal saline was given to those in the sham-model control group and model control group, and an equal volume of prednisone (0.56 mg x kg(-1) x d(-1)) was saline was given to those in positive medicine control group. On the 7, 14, 28 days, the contents of GSH-Px, SOD, MDA and iNOS in pulmonary tissues of different groups were measured. Curcumin can raise the content of SOD and GSH-Px and lessen the level of MDA and iNOS. Curcumin can regulate the level of free radical in the body of rats with pulmonary fibrosis and lessen the oxidative injury of pulmonary tissues caused by free radical, in the body of rats with pulmonary fibrosis. The mechanisms of curcumin on idiopathic pulmonary fibrosis lie in adjusting the level of free radical and inhibiting the injury of lung tissue induced by free radical.


Risk factors, clinical presentation, and neuroimaging findings of neonatal perforator stroke.
To date, studies on neonatal stroke have mainly focused on cortical stroke. We have focused on perforator strokes, noncortical strokes in the arterial vascular perforator area. We sought to identify risk factors and evaluate clinical presentation and neuroimaging findings for neonatal perforator stroke, which seems to be under-recognized. All infants admitted to our tertiary intensive care unit in ≈12 years, whose perforator stroke was diagnosed with postnatal brain imaging, were enrolled in this study. Demographic, perinatal, and postnatal data were evaluated. Seventy-nine perforator strokes were detected in 55 patients (28 boys), with a median gestational age of 37 1/7 weeks (range 24 1/7 to 42 1/7 weeks, 25 preterm). Perforator stroke was asymptomatic in most patients (58%). Initial diagnosis was predominantly made with cranial ultrasound (80%) in the first week of life (60%). Risk factors for stroke were present in all cases: maternal, fetal, and perinatal. Likely pathogenic mechanisms were prolonged birth asphyxia (16%), hypoxia or hypotension (15%), embolism (15%), infection (15%), acute blood loss (9%), and birth trauma (9%). Previously described risk factors for developing neonatal main artery stroke are probably also associated with neonatal perforator stroke. Perforator stroke is often asymptomatic, but cranial ultrasound is a reliable diagnostic tool in diagnosing perforator stroke.


Fluorometric high-performance liquid chromatography of N-acetyl- and N-glycolylneuraminic acids and its application to their microdetermination in human and animal sera, glycoproteins, and glycolipids.
A simple, rapid, and highly sensitive high-performance liquid chromatographic method is described for the determination of N-acetyl- and N-glycolylneuraminic acids in human and animal sera, glycoproteins, and glycolipids. The neuraminic acids, released by acid hydrolysis of these biological samples, are converted in dilute sulfuric acid with 1,2-diamino-4,5-methylene-dioxybenzene, a fluorogenic reagent for alpha-keto acids, to highly fluorescent derivatives. The derivatives are separated within 12 min on a reversed-phase column (Radial-Pak cartridge C18) with an isocratic elution and detected fluorometrically. The detection limits are 25 fmol (7.7 pg) for N-acetylneuraminic acid and 23 fmol (7.5 pg) for N-glycolylneuraminic acid in a 10-microliter injection volume at a signal-to-noise ratio of 2. This method permits precise determination of the neuraminic acids in 5 microliter of human and animal sera or in 0.25-2.5 micrograms of glycoproteins and glycolipids.


Simultaneous determination of scopolamine, hyoscyamine and littorine in plants and different hairy root clones of Hyoscyamus muticus by micellar electrokinetic chromatography.
Hyoscyamus muticus hairy root clones were established following infection with Agrobacterium rhizogenes strains A4, LBA-9402 and 15834 and with A. tumefaciens strain C58C1pRTGus104. The accumulation of tropane alkaloids hyoscyamine, littorine and scopolamine was evaluated by micellar electrokinetic capillary electrophoresis. Littorine was reported for the first time in these clones as well as in the roots of the intact plant and confirmed by collision induced dissociation-mass spectrometry. Tropane alkaloid content in hairy roots was compared with leaves and roots of normal plants at two vegetative stages. Significant differences appeared between the alkaloid contents of the different clones. In particular, all the hairy root clones and the roots of the intact plant produced 1.5-3 and 4.5-9 times more littorine than scopolamine, respectively. The only exception was clone KB7, carrying the h6h gene, which overproduced scopolamine. The aerial parts of H. muticus plants did not contain any littorine, thus indicating different transportation or translocation mechanisms of the various tropane alkaloids.


Partial purification and characterisation of the human skin fibroblast androgen receptor: detection of abnormal receptor complexes in cells from patients with androgen insensitivity syndromes.
After incubation of hGSF with [3H]5 alpha-dihydrotestosterone, 17 beta-hydroxy-7 alpha, 17 alpha-dimethyl-4-estrene-3-one, or 17 beta-hydroxy-17 alpha-methyl-4,9,11-estrien-3-one, androgen-receptor complexes were extracted with 0.5 M KCl and precipitated by 35% ammonium sulphate. Receptor complexes from control hGSF sedimented at approximately 4S on linear 5-20% sucrose gradients. The 4S peak was diminished or absent in cells from androgen insensitive patients exhibiting absent, deficient or unstable binding of androgens in intact hGSF. This procedure may be a useful means of distinguishing quantitative and qualitative defects in androgen binding to receptor, since one cell line found to have normal levels of androgen receptor complexes in whole cell assays had a profile resembling that of receptor negative cells on sucrose gradients. The complexes from one patient with complete androgen insensitivity having normal androgen binding in intact hGSF were indistinguishable from control complexes after sucrose gradient analysis and ADP-Sepharose chromatography. Receptor complexes were eluted from the ADP-Sepharose between 0.5-1.0 M KCl. HPLC-gel filtration of androgen receptor complexes at 22 degrees C revealed two peaks, the larger had a Mr of 60-65K, Stokes radius of 3.16 nm and a frictional ratio between 1.21 and 1.43. The second peak, Mr of 15K, was believed to represent a fragment of the receptor containing the steroid binding domain. On gel filtration at 22 degrees C the complexes from a patient with partial androgen insensitivity, who showed a diminished 4S receptor peak on sucrose gradients, revealed only the small "meroreceptor" fragment, suggesting that the mutation in this individual might render the androgen receptor more susceptible to proteolysis in vitro.


Construction and analysis of a Mannheimia haemolytica A1 luxS mutant.
Mannheimia haemolytica A1 is the causative agent of bovine pneumonic pasteurellosis, a major cause of sickness, death, and economic loss to the feedlot cattle industry. M. haemolytica A1 produces autoinducer-2 (AI-2) like molecules that are capable of inducing quorum sensing system 2 of Vibrio harveyi. This interspecies quorum sensing system has been shown to regulate the expression of virulence genes in several pathogenic bacteria. The protein central to the production of AI-2 is LuxS. To determine if quorum sensing is involved in the regulation of virulence genes in M. haemolytica A1, a luxS mutant was constructed by replacing luxS with a cat cassette. This mutant was verified by PCR analysis, Southern hybridization, as well as its inability to induce bioluminescence in the V. harveyi reporter strain. RT-PCR analysis showed there was no difference in leukotoxin (lktC) mRNA levels, however there were increased mRNA levels of putative virulence associated genes, transferrin binding protein B (tbpB), adhesin (ahs) and capsule biosynthesis (nmaA). Electron microscopy showed that the level of encapsulation in the mutant is higher than the parent. Additionally, the mutant was slightly more adherent to bovine tracheal cells than the parent. In vitro competition assays showed the mutant out-competed the parent under iron-restricted conditions. However, in a calf challenge, the parent was the dominant isolate recovered.


Physical exercise prevents and mitigates non-alcoholic steatohepatitis-induced liver mitochondrial structural and bioenergetics impairments.
Exercise is considered a non-pharmacological tool against several lifestyle disorders in which mitochondrial dysfunction is involved. The present study aimed to analyze the preventive (voluntary physical activity-VPA) and therapeutic (endurance training-ET) role of exercise against non-alcoholic steatohepatitis (NASH)-induced liver mitochondrial dysfunction. Sixty male Sprague-Dawley rats were divided into standard-diet sedentary (SS, n=20), standard-diet VPA (SVPA, n=10), high-fat diet sedentary (HS, n=20) and high-fat diet VPA (HVPA, n=10). After 9weeks of diet-treatment, half of SS and HS animals were engaged in an ET program (SET and HET) for 8weeks, 5days/week and 60min/day. Liver mitochondrial oxygen consumption and transmembrane-electric potential (ΔΨ) were evaluated in the presence of glutamate-malate (G/M), palmitoyl-malate (P/M) and succinate (S/R). Mitochondrial enzymes activity, lipid and protein oxidation, oxidative phosphorylation (OXPHOS) subunits, cytochrome c, adenine nucleotide translocator (ANT) and uncoupling protein-2 (UCP2) content were assessed. HS groups show the histological features of NASH in parallel with decreased ΔΨ and respiratory control (RCR) and ADP/O ratios (G/M and P/M). A state 3 decrease (G/M and S/R), FCCP-induced uncoupling respiration (S/R) and ANT content were also observed. Both exercise types counteracted oxygen consumption (RCR, ADP/O and FCCP-uncoupling state) impairments and improved ΔΨ (lag-phase). In conclusion, exercise prevented or reverted (VPA and ET, respectively) the bioenergetic impairment induced by NASH, but only ET positively remodeled NASH-induced liver structural damage and abnormal mitochondria. It is possible that alterations in inner membrane integrity and fatty acid oxidation may be related to the observed phenotypes induced by exercise.


Receiver operating characteristic (ROC) analysis of images reconstructed with iterative expectation maximization algorithms.
The quality of images reconstructed by means of the maximum likelihood-expectation maximization (ML-EM) and ordered subset (OS)-EM algorithms, was examined with parameters such as the number of iterations and subsets, then compared with the quality of images reconstructed by the filtered back projection method. Phantoms showing signals inside signals, which mimicked single-photon emission computed tomography (SPECT) images of cerebral blood flow and myocardial perfusion, and phantoms showing signals around the signals obtained by SPECT of bone and tumor were used for experiments. To determine signals for recognition, SPECT images in which the signals could be appropriately recognized with a combination of fewer iterations and subsets of different sizes and densities were evaluated by receiver operating characteristic (ROC) analysis. The results of ROC analysis were applied to myocardial phantom experiments and scintigraphy of myocardial perfusion. Taking the image processing time into consideration, good SPECT images were obtained by OS-EM at iteration No. 10 and subset 5. CONCLULSION: This study will be helpful for selection of parameters such as the number of iterations and subsets when using the ML-EM or OS-EM algorithms.


[Enhancement of expression of Escherichia coli uridine phosphorylase gene as a result of duplication].
The thymine-requiring (thy) Escherichia coli strains normally convert thymine to thymidine through the action of thymidine phosphorylase, an enzyme, whose synthesis is directed by tpp gene of the deo operon. Selection for efficient thymine utilization in the thy mutants carrying a deletion in the tpp gene allows to obtain clones with constitutive synthesis of an alternative enzyme, uridine phosphorylase coded by the udp gene. Such clones are usually formed, due to "promoter-up" constitutive udpP mutants. Further selection for increased expression of the udp gene was performed on the background of udpP1 and udpP18 "promoter-up" constitutive mutants isolated previously. Several lines of evidence obtained by using transposon insertions suggest that the increased synthesis of uridine phosphorylase in some newly isolated mutants is due to duplications of the udp gene. In two mutants the adjacent metE gene is involved in duplications simultaneously with the udp gene.


Mobilizing Carbon Dioxide Stores. An Experimental Study.
Rationale: Understanding the physiology of CO2 stores mobilization is a prerequisite for intermittent extracorporeal CO2 removal (ECCO2R) in patients with chronic hypercapnia.Objectives: To describe the dynamics of CO2 stores.Methods: Fifteen pigs (61.7 ± 4.3 kg) were randomized to 48 hours of hyperventilation (group "Hyper," n = 4); 48 hours of hypoventilation (group "Hypo," n = 4); 24 hours of hypoventilation plus 24 hours of normoventilation (group "Hypo-Baseline," n = 4); or 24 hours of hypoventilation plus 24 hours of hypoventilation plus ECCO2R (group "Hypo-ECCO2R," n = 3). Forty-eight hours after randomization, the current [Formula: see text]e was reduced by 50% in every pig.Measurements and Main Results: We evaluated [Formula: see text]co2, [Formula: see text]o2, and metabolic [Formula: see text]co2 ([Formula: see text]o2 times the metabolic respiratory quotient). Changes in the CO2 stores were calculated as [Formula: see text]co2 - metabolic V̇co2. After 48 hours, the CO2 stores decreased by 0.77 ± 0.17 l kg-1 in group Hyper and increased by 0.32 ± 0.27 l kg-1 in group Hypo (P = 0.030). In group Hypo-Baseline, they increased by 0.08 ± 0.19 l kg-1, whereas in group Hypo-ECCO2R, they decreased by 0.32 ± 0.24 l kg-1 (P = 0.197). In the second 24-hour period, in groups Hypo-Baseline and Hypo-ECCO2R, the CO2 stores decreased by 0.15 ± 0.09 l kg-1 and 0.51 ± 0.06 l kg-1, respectively (P = 0.002). At the end of the experiment, the 50% reduction of [Formula: see text]e caused a PaCO2 rise of 9.3 ± 1.1, 32.0 ± 5.0, 16.9 ± 1.2, and 11.7 ± 2.0 mm Hg h-1 in groups Hyper, Hypo, Hypo-Baseline, and Hypo-ECCO2R, respectively (P < 0.001). The PaCO2 rise was inversely related to the previous CO2 stores mobilization (P < 0.001).Conclusions: CO2 from body stores can be mobilized over 48 hours without reaching a steady state. This provides a physiological rationale for intermittent ECCO2R in patients with chronic hypercapnia.


Wearable device signals and home blood pressure data across age, sex, race, ethnicity, and clinical phenotypes in the Michigan Predictive Activity & Clinical Trajectories in Health (MIPACT) study: a prospective, community-based observational study.
Wearable technology has rapidly entered consumer markets and has health-care potential; however, wearable device data for diverse populations are scarce. We therefore aimed to describe and compare key wearable signals (ie, heart rate, step count, and home blood pressure measurements) across age, sex, race, ethnicity, and clinical phenotypes. In the Michigan Predictive Activity & Clinical Trajectories in Health (MIPACT) prospective observational study, we enrolled participants from Michigan Medicine, Ann Abor, MI, USA, and followed them up for at least 90 days. Patients were included if they were aged 18 years or older, were fluent in English, owned an iPhone 6 or newer model with a supported iOS version, and had regular access to the internet throughout the study period. All participants were provided with an Apple Watch Series 3 or 4, an Omron Evolv Wireless Blood Pressure Monitor, and the MyDataHelps study smartphone application. Participants were asked to wear their watch for 12 h per day or longer and to do daily or weekly tasks, including home blood pressure measurements and breathing tasks. Heart rate, blood pressure, step counts, and distance walked were collected. The study was divided into two phases: an intensive 45-day collection phase (phase 1); and a 3-year longitudinal monitoring phase (phase 2). Here we report the first 90 days of data for all participants, which includes all of phase 1 and the first 45 days of phase 2. Participants' electronic health records were used to establish clinical diagnoses for analysis. We enrolled 6765 eligible participants between Aug 14, 2018, and Dec 19, 2019, of whom 6454 participants from Michigan Medicine completed the phase 1 study protocol and were included in this analysis (3482 [54%] women and 2972 [46%] men; 3657 [57%] participants were White, with 1094 [17%] Asian and 1090 [17%] Black participants). On days when participants wore their smart watches, median daily watch wear time was 15·5 h (IQR 14-17). Participants contributed a total of 1 107 320 blood pressure and 202 198 347 heart rate measurements over 90 days, with 172 (SD 50) blood pressure and 31 329 (SD 24 620) heart rate measurements per participant. Mean systolic blood pressure was 122 mm Hg (SD 10) and mean diastolic blood pressure was 77 mm Hg (SD 8), with 167 312 (15%) measurements having a systolic blood pressure higher than 140 mm Hg or diastolic blood pressure higher than 90 mm Hg. Mean resting heart rate was 64 beats per min (SD 8). Blood pressure and resting heart rate varied by sex, age, race, and ethnicity, with higher blood pressures in males and lower heart rate in participants aged 65 years or older (p<0·0001). Participants took 7511 steps per day (SD 2805) and walked 6009 metres per day (SD 2608), varying across demographic and clinical subgroups. These data could inform clinical trial design, interpretation of wearable data in clinical practice, and health-care interventions. Apple, University of Michigan.


Echocardiogram calculations for the dog using Lotus 123.
A microcomputer (IBM-PC or compatible) program using the spreadsheet program, Lotus 123 was developed to calculate the 95% confidence intervals for the normal canine echocardiographic dimensions. Other cardiac function parameters are also calculated, but confidence intervals have not been determined.


Speckle disturbance limit in laser-based cinema projection systems.
In a multi-disciplinary effort, we investigate the level of speckle that can be tolerated in a laser cinema projector based on a quality of experience experiment with movie clips shown to a test audience in a real-life movie theatre setting. We identify a speckle disturbance threshold by statistically analyzing the observers' responses for different values of the amount of speckle, which was monitored using a well-defined speckle measurement method. The analysis shows that the speckle perception of a human observer is not only dependent on the objectively measured amount of speckle, but it is also strongly influenced by the image content. The speckle disturbance limit for movies turns out to be substantially larger than that for still images, and hence is easier to attain.


Natural history of human prostate gland: Morphometric and histopathological analysis of Japanese men.
To clarify the pathology of the development of prostatic disorders such as inflammation, cancer, and hyperplasia, we compared histopathological findings of the prostate according to age group. Whole-mount sections of prostates were used to assess the relationship between age and prostate weight (n=962), prostate histological composition in the transition zone (TZ) and in the peripheral zone (PZ) (n=68), prostate histopathological findings by zone (n=102), and comparison of latent tumor development by age group (n=1,815). A rapid increase in prostate weight from birth to the 20s was followed by a slow rise thereafter. Volume increases (P<0.01) were observed in all components of glandular epithelium, glandular lumen, and stroma in the TZ from the 40s to 70s inclusive. In the PZ, the epithelial and stromal volumes tended to decrease in an age-dependent manner (P<0.05). Calculi and lymphocyte infiltration were detected at a relatively early age, with a tendency towards an age-dependent increase. Glandular dilation and nodular hyperplasia were noted first in the 30s group, also with a tendency towards age-dependent increase. Latent tumors were first detected in the 30s group (5.6%), and slowly increased thereafter. There was an age-dependent trend towards prostate glandular dilation and prostate enlargement with inflammation. It was demonstrated that tumor and hyperplasia have a long natural history, usually starting in the fourth decade of life, accompanied by dynamic changes with age in glandular tissue composition as well as cell proliferation activity.


Isolation and comparison of tribe-specific centromeric repeats within Bovidae.
A taxonomic division of the family Bovidae (Artiodactyla) is difficult and the evolutionary relationships among most bovid subfamilies remain uncertain. In this study, we isolated the cattle satellite I clone BTREP15 (1.715 satellite DNA family) and autosomal centromeric DNAs of members of ten bovid tribes. We wished to determine whether the analysis of fluorescence in situ hybridization patterns of the cattle satellite I clone (BTREP15) and tribe-specific centromeric repeats isolated by laser microdissection would help to reveal some of the ambiguities occurring in the systematic classification of the family Bovidae. The FISH study of the presence and distribution of the cattle satellite I clone BTREP15 (1.715 satellite DNA family) within members of ten bovid tribes was not informative. FISH analysis of autosomal centromeric DNA probes in several species within one tribe revealed similar hybridization patterns in autosomes confirming tribal homogeneity of these probes. Sex chromosomes showed considerable variation in sequence composition and arrangement not only between tribes but also between species of one tribe. According to our findings it seems that Oreotragus oreotragus developed its own specific satellite DNA which does not hybridize to any other bovid species analysed. Our results suggest O. oreotragus as well as Aepyceros melampus may be unique species not particularly closely related to any of the recognized bovid tribes. This study indicates the isolation of tribe-specific centromeric DNAs by laser microdissection and cloning the sequence representing the main motif of these repetitive DNAs could offer the perspectives for comparative phylogenetic studies.