Eukaryotic cell encystation and cancer cell dormancy: is a greater devil veiled in the details of a lesser evil?
Cancer cell dormancy is the main cause of cancer recurrence and failure of therapy as dormant cells evade not only the anticancer drugs but also the host immune system. These dormant cells veil themselves from detection by imaging and/or using biomarkers, which imposes an additional problem in targeting such cells. A similar form of hibernation process known as encystation is studied in detail for pathogenic unicellular eukaryotic microorganisms. By examination using microarray gene expression profiles, immunocytochemistry tools, and siRNAs during the process of encystation, understanding the covert features of cancer cell dormancy as proposed could be possible. This knowledge can be extended to dormant cancer cells to uncover the mechanisms that underlie this ghost, yet dangerous state of human cancers. We propose a strategy to induce dormancy and exit this state by application of knowledge gained from the encystation induction and retrieval processes in pathogenic eukaryotic microorganisms. Given that early detection and characterization of dormant malignant tumor cells is important as a general strategy to monitor and prevent the development of overt metastatic disease, this homology may enable the design of therapies that could either awake the dormant cell from dormancy to make it available for therapies or prolong such a phase to make cancer appear as a chronic disease.


Monitoring phase transformations in intact tablets of trehalose by FT-Raman spectroscopy.
The purpose of this study is to monitor phase transformations in intact trehalose tablets using FT-Raman spectroscopy. Tablets of trehalose dihydrate, amorphous trehalose (obtained by freeze-drying aqueous trehalose solutions), and anhydrous trehalose (beta-trehalose) were prepared. The tablets were exposed to different conditions [11% and 0% RH (60 degrees C); 75% RH (25 degrees C)] and monitored periodically over 96 h using Raman spectroscopy. Within 96 h of storage, the following phase transformations were observed: (1) trehalose dihydrate-->beta-trehalose (11% RH, 60 degrees C), (2) trehalose dihydrate-->alpha-trehalose (0% RH, 60 degrees C), (3) beta-trehalose-->trehalose dihydrate (75% RH, 25 degrees C), and (4) amorphous trehalose-->trehalose dihydrate (75% RH, 25 degrees C). FT-Raman spectroscopy was a useful technique to identify the solid form and monitor multiple-phase transformations in intact trehalose tablets stored at different conditions.


Tubular gastric adenocarcinoma: machine learning-based CT texture analysis for predicting lymphovascular and perineural invasion.
Lymphovascular invasion (LVI) and perineural invasion (PNI) are associated with poor prognosis in gastric cancers. In this work, we aimed to investigate the potential role of computed tomography (CT) texture analysis in predicting LVI and PNI in patients with tubular gastric adenocarcinoma (GAC) using a machine learning (ML) approach. Sixty-eight patients who underwent total gastrectomy with curative (R0) resection and D2-lymphadenectomy were included in this retrospective study. Texture features were extracted from the portal venous phase CT images. Dimension reduction was first done with a reproducibility analysis by two radiologists. Then, a feature selection algorithm was used to further reduce the high-dimensionality of the radiomic data. Training and test splits were created with 100 random samplings. ML-based classifications were done using adaptive boosting, k-nearest neighbors, Naive Bayes, neural network, random forest, stochastic gradient descent, support vector machine, and decision tree. Predictive performance of the ML algorithms was mainly evaluated using the mean area under the curve (AUC) metric. Among 271 texture features, 150 features had excellent reproducibility, which were included in the further feature selection process. Dimension reduction steps yielded five texture features for LVI and five for PNI. Considering all eight ML algorithms, mean AUC and accuracy ranges for predicting LVI were 0.777-0.894 and 76%-81.5%, respectively. For predicting PNI, mean AUC and accuracy ranges were 0.482-0.754 and 54%-68.2%, respectively. The best performances for predicting LVI and PNI were achieved with the random forest and Naive Bayes algorithms, respectively. ML-based CT texture analysis has a potential for predicting LVI and PNI of the tubular GACs. Overall, the method was more successful in predicting LVI than PNI.


Construction of NotI restriction map of the Streptococcus mutans genome.
Streptococcus mutans and Streptococcus sobrinus are the major causative organisms of human dental caries. Pulsed-field gel electrophoresis (PFG) showed that the restriction enzyme NotI produced ten and six DNA fragments from the genomes of S. mutans strain MT8148 and S. sobrinus strain 6715, respectively. The sizes of the chromosomes of S. mutans and S. sobrinus were each estimated to be about 2200 kb. The NotI restriction map of S. mutans MT8148 genome was constructed by Southern blot analysis with probes that overlapped two adjacent NotI fragments. Several virulence-associated genes of S. mutans were placed on the NotI restriction map. In addition, unique 'fingerprints' of S. mutans chromosomal DNA digested with NotI were produced by PFG, and these may be useful for epidemiological studies.


Survey of Clinician Perspectives and Practices Regarding Swallowing-Related Fatigue.
Introduction Fatigue is commonly identified by clinicians who evaluate and treat swallowing impairment despite a lack of research in this area. The purpose of this study was to understand the current role of swallowing-related fatigue in dysphagia evaluation with respect to (a) clinician practices, (b) perspectives, and (c) desire for resources regarding swallowing-related fatigue. Method A survey was conducted by licensed speech-language pathologists who evaluate and treat adult dysphagia. The survey was distributed via dysphagia-focused groups on Facebook and Special Interest Group 13. Data were analyzed descriptively and by thematic analysis for free-text response questions. Results Out of 426 prospective respondents, 311 completed the survey (response rate = 73.0%). While 86% of respondents agreed that fatigue may be a concern for individuals with swallowing impairment, there was wide variability in how clinicians define and evaluate swallowing-related fatigue, and the majority (62%) define fatigue in two or more ways. Explicit evaluation of fatigue was reportedly conducted by 45% of respondents during the Clinical Swallowing Evaluation, by 38% during videofluoroscopic swallowing study, and by 53% during Flexible Endoscopic Evaluation of Swallowing. The most common methods for identifying fatigue were general declines in performance over the course of the assessment. Respondents reported much more reliance on patient report during Clinical Swallowing Evaluation (41%) compared to videofluoroscopic swallowing study (7%) and fiberoptic endoscopic evaluation of swallowing (5%). Only 7% of respondents reported being aware of any standardized methods for assessing fatigue, while 97% of respondents affirmed interest in incorporating standardized methods for assessing swallow-related fatigue. Conclusions Our results demonstrated wide variability in how currently practicing clinicians define and evaluate swallowing-related fatigue, despite the vast majority considering fatigue to be an important factor in dysphagia evaluation. This study highlights a critical gap in the clinical evaluation of swallowing and requires significant further study to guide clinical practice.


Senior services in US hospitals and readmission risk in the Medicare population.
There is a little understanding of the association between hospital organizational characteristics and hospital readmissions. We previously developed a Senior Care Services Scale (SCSS) that describes hospital availability of services relevant to the care of older adults. Determine whether hospitals' SCSS scores were associated with risk of readmission among Medicare beneficiaries. Retrospective cohort analysis. Medicare beneficiaries ≥65 years of age (n = 3 553 367), admitted to 5568 US acute-care hospitals in 2006, discharged alive. Medicare data were linked to the American Hospital Association database of hospital characteristics. All-cause non-elective hospital readmission, or death without readmission, within 30 days of hospital discharge. We examined the association between high and low scores of each of two hospital SCSS service groups: inpatient specialty care (IP) and post-acute (PA) community care. There was no association between high IP scores and readmission (RR 1.00, 95% CI 0.98-1.02). Older adults admitted to hospitals with high PA scores had lower risk of experiencing hospital readmission when compared to older adults admitted to hospitals with low PA scores (RR 0.97, 95% CI 0.95-0.98). High PA scores were associated with increased mortality (RR 1.09, 95% CI 1.06-1.13). In sensitivity analyses exploring relationships at 90 days, both the IP and PA subcomponents were associated with older adults' reduced risk of hospital readmission (IP: RR 0.97, 95% CI 0.95-0.99; PA: RR 0.97, 95% CI 0.95-0.99). Senior services at the hospital-level represents a modifiable risk factor with important impact. Employing organization-level characteristics in readmission risk prediction tools should be expanded.


Scale-up synthesis of lipase-catalyzed palm esters in stirred-tank reactor.
Lipase-catalyzed production of palm esters by alcoholysis of palm oil with oleyl alcohol in n-hexane was performed in 2L stirred-tank reactor (STR). Investigation on the performance of reactor operation was carried out in batch mode STR with single impeller mounted on the centrally located shaft. Rushton turbine (RT) impellers provide the highest reaction yield (95.8%) at lower agitation speed as compared to AL-hydrofoil (AL-H) and 2-bladed elephant ear (EE) impellers. Homogenous enzyme particles suspension was obtained at 250 rpm by using RT impeller. At higher impeller speed, the shear effect on the enzyme particles caused by agitation has decreased the reaction performance. Palm esters reaction mixture in STR follows Newtons' law due to the linear relation between the shear stress (tau) and shear rate (dupsilon/dy). High stability of Lipozyme RM IM was observed as shown by its ability to be repeatedly used to give high percentage yield (79%) of palm esters even after 15 cycles of reaction. The process was successfully scale-up to 75 L STR (50 L working volume) based on a constant impeller tip speed approach, which gave the yield of 97.2% after 5h reaction time.


Application of phase-to-amplitude conversion technique to linear birefringence measurements.
A novel technique that measures the linear birefringence of crystal quartz within the configuration of a Soliel-Babinet compensator (SBC) is proposed. A characteristic of this technique is that phase retardation introduced by quartz is amplitude modulation (AM) instead of phase modulation (PM). The linear birefringence is measured regardless of the azimuth angle of the SBC and the orientation of the linear polarization laser beam. Compared with the single-wedge method, the SBC is similar to a parallel plate that allows for a wider range of refracttive index of the test material to be measured. This proposed method uses a conventional amplitude demodulation method in conjunction with an optical heterodyne technique and a bandpass filter to produce a better signal-to-noise ratio. Although the SBC configuration is more complex than a single element, the independence of azimuth angle and the orientation of the linear polarized laser beam can enhance the sensitivity of the linear birefringence measurement.


Antidiabetic Therapy during Pregnancy: The Prescription Pattern in Italy.
Pregestational and gestational diabetes mellitus are relevant complications of pregnancy, and antidiabetic drugs are prescribed to obtain glycemic control and improve perinatal outcomes. The objective of this study was to describe the prescription pattern of antidiabetics before, during and after pregnancy in Italy and to evaluate its concordance with the Italian guideline on treatment of diabetes mellitus. A multi-database cross-sectional population study using a Common Data Model was performed. In a cohort of about 450,000 women, the prescribing profile of antidiabetics seemed to be in line with the Italian guideline, which currently does not recommend the use of oral antidiabetics and non-insulin injection, even if practice is still heterogeneous (up to 3.8% in the third trimester used oral antidiabetics). A substantial variability in the prescription pattern was observed among the Italian regions considered: the highest increase was registered in Tuscany (4.2%) while the lowest was in Lombardy (1.5%). Women with multiple births had a higher proportion of antidiabetic prescriptions than women with singleton births both in the preconception period and during pregnancy (1.3% vs. 0.7%; 3.4% vs. 2.6%) and used metformin more frequently. The consumption of antidiabetics in foreign women was higher than Italians (second trimester: 1.8% vs. 0.9%, third trimester: 3.6% vs. 1.8%).


Cost-effectiveness of malaria preventive treatment for HIV-infected pregnant women in sub-Saharan Africa.
Malaria is a leading cause of morbidity and mortality among HIV-infected pregnant women in sub-Saharan Africa: at least 1 million pregnancies among HIV-infected women are complicated by co-infection with malaria annually, leading to increased risk of premature delivery, severe anaemia, delivery of low birth weight infants, and maternal death. Current guidelines recommend either daily cotrimoxazole (CTX) or intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTp-SP) for HIV-infected pregnant women to prevent malaria and its complications. The cost-effectiveness of CTX compared to IPTp-SP among HIV-infected pregnant women was assessed. A microsimulation model of malaria and HIV among pregnant women in five malaria-endemic countries in sub-Saharan Africa was constructed. Four strategies were compared: (1) 2-dose IPTp-SP at current IPTp-SP coverage of the country ("2-IPT Low"); (2) 3-dose IPTp-SP at current coverage ("3-IPT Low"); (3) 3-dose IPTp-SP at the same coverage as antiretroviral therapy (ART) in the country ("3-IPT High"); and (4) daily CTX at ART coverage. Outcomes measured include maternal malaria, anaemia, low birth weight (LBW), and disability-adjusted life years (DALYs). Sensitivity analyses assessed the effect of adherence to CTX. Compared with the 2-IPT Low Strategy, women receiving CTX had 22.5% fewer LBW infants (95% CI 22.3-22.7), 13.5% fewer anaemia cases (95% CI 13.4-13.5), and 13.6% fewer maternal malaria cases (95% CI 13.6-13.7). In all simulated countries, CTX was the preferred strategy, with incremental cost-effectiveness ratios ranging from cost-saving to $3.9 per DALY averted from a societal perspective. CTX was less effective than the 3-IPT High Strategy when more than 18% of women stopped taking CTX during the pregnancy. In malarious regions of sub-Saharan Africa, daily CTX for HIV-infected pregnant women regardless of CD4 cell count is cost-effective compared with 3-dose IPTp-SP as long as more than 82% of women adhere to daily dosing.


Purification and characterization of a serine proteinase from senescent sporophores of the commercial mushroom Agaricus bisporus.
A proteinase has been purified from the stipes of senescent sporophores of the mushroom Agaricus bisporus. The proteinase was inhibited by PMSF. It has a broad pH optimum, 6.5-11.5, and a narrow substrate specificity, requiring both a hydrophobic amino acid in the P1 position and a minimum peptide chain length. The apparent molecular mass of the proteinase was 27 kDa when determined by SDS-PAGE and 14.1 kDa when measured by gel filtration. The isoelectric point of the proteinase was 9.0. Polyclonal antibodies have been raised to the proteinase. The proteinase from A. bisporus has similar properties to, and 60% N-terminal sequence identity with, proteinase K from the fungus Tritirachium album.


Postnatal dynamics of Zeb2 expression in rat brain: analysis of novel 3' UTR sequence reveals a miR-9 interacting site.
ZEB2 is a transcription factor with established roles in neurogenesis but no defined function in postnatal brain despite extensive neuronal expression in telencephalic structures. Multiple, incompletely annotated transcripts derive from the Zeb2 locus; the purpose of the present study was to structurally characterize rat brain Zeb2 transcripts with respect to 3' untranslated (UTR) sequence in order to understand Zeb2 transcript regulation including possible interactions with regulatory molecules such as neuronal miRNAs. We cloned a 5054-nucleotide Zeb2 3' UTR that is included in the most abundant Zeb2 transcript in neonatal rat brain. Unique features of the distal 3' UTR region included a number of brain-specific miRNA target sites; a highly conserved miR-9 target site at 3' UTR position 4097 was selected for functional verification in transfection experiments. Parallel analysis of Zeb2 transcript, ZEB2 protein and miR-9 levels across postnatal brain cortical development revealed a significant accumulation of ZEB2 protein levels only between postnatal days P2 and P5 that was associated with an acute loss of postnatal miR-9 expression in cortex. These studies demonstrate novel features of Zeb2 gene expression in postnatal rat brain and highlight the importance of full transcript annotation for identifying the complement of potential transcript-interacting regulators.


Natural variation in CDC28 underlies morphological phenotypes in an environmental yeast isolate.
Morphological differences among individuals in a species represent one of the most striking aspects of biology, and a primary aim of modern genetics is to uncover the molecular basis of morphological variation. In a survey of meiosis phenotypes among environmental isolates of Saccharomyces cerevisiae, we observed an unusual arrangement of meiotic spores within the spore sac in a strain from Ivory Coast, West Africa. We mined population genomic data to identify CDC28 as the major genetic determinant of meiotic and budding cell shape behaviors in this strain. Molecular genetic methods confirmed the role of the Ivory Coast variant of CDC28 in the arrangement of spores after meiosis, in the shape of budding cells in rich medium and in the morphology of filamentous growth during nitrogen limitation. Our results shed new light on the role of CDC28 in yeast cell division, and our work suggests that with the growing availability of genomic data sets in many systems, a priori prediction of functional variants will become an increasingly powerful strategy in molecular genetics.


The accessory heads of the quadriceps femoris muscle may affect the layering of the quadriceps tendon and potential graft harvest lengths.
The aim of the study was to assess the quadriceps femoris system for the presence of additional layers. One hundred and twenty-eight lower limbs fixed in 10% formalin were examined. Five types of quadriceps tendon layering were found based on the accessory heads of the quadriceps muscle. Type I (55%)-represented by four heads and four layers, and it was something new because standard orthopaedic textbooks described quadriceps tendon as a structure composed of only three layers. Type II (27.4%)-the first four layers were the same as in Type 1, but the accessory tendon of the fifth head of the quadriceps femoris muscle had the deepest attachments. Type III (10.9%)-this type included 6 heads of quadriceps femoris. It consisted of five layers. Type IV (3.1%)-this type included 7 quadriceps femoris heads. This type consisted of only four layers. Type V (3.1%)-this type included 8 heads of the quadriceps femoris heads. This type consist of 5 layers. The findings of this study provide a detailed anatomy of the quadriceps tendon including the accessory tendons of the accessory heads of the quadriceps tendon. The accessory heads of the quadriceps femoris muscle contribute to the layering of the quadriceps tendon. The second conclusion of this study is the development of safe distances depending on the types. Not all types are perfect for harvesting-Type IV seems to be the safest type, in turn Type V the most dangerous.


Regional variation of microtubule flux reveals microtubule organization in the metaphase meiotic spindle.
Continuous poleward movement of tubulin is a hallmark of metaphase spindle dynamics in higher eukaryotic cells and is essential for stable spindle architecture and reliable chromosome segregation. We use quantitative fluorescent speckle microscopy to map with high resolution the spatial organization of microtubule flux in Xenopus laevis egg extract meiotic spindles. We find that the flux velocity decreases near spindle poles by approximately 20%. The regional variation is independent of functional kinetochores and centrosomes and is suppressed by inhibition of dynein/dynactin, kinesin-5, or both. Statistical analysis reveals that tubulin flows in two distinct velocity modes. We propose an association of these modes with two architecturally distinct yet spatially overlapping and dynamically cross-linked arrays of microtubules: focused polar microtubule arrays of a uniform polarity and slower flux velocities are interconnected by a dense barrel-like microtubule array of antiparallel polarities and faster flux velocities.


[Biological rhythms in psychopathology (biological patterns in psychiatry)].
On the basis of a clinical follow-up study of regularities of 486 cycles (phases and intervals) in the course of a disease in 80 endogenous and exogenous nosological patients the author established the principal resemblance in the rhythm of cycles and the coincidence of the curves in the regularity of attacks with a sharp displacement of the peaks of regularities in IV-VI and IX-X months (for epilepsy in VIII and XII months). The author tries to explain the latter fact by the influences of geophysical factors on synchronization, in periods of vernal and autumnal equinox, of the processes of metabolism and the reactivity of separate neuronal structures and endocrine structures.


Health enhancing physical activity in patients with hip or knee osteoarthritis - an observational intervention study.
Osteoarthritis is one of the leading causes of inactivity worldwide. The recommended level of health enhancing physical activity (HEPA) is at least 150 min of moderate intensity physical activity per week. The purpose of this study was to explore how the proportion of patients, who reached the recommended level of HEPA, changed following a supported osteoarthritis self-management programme in primary care, and to explore how reaching the level of HEPA was influenced by body mass index (BMI), gender, age and comorbidity. An observational study was conducted using data from a National Quality Registry in which 6810 patients in primary care with clinically verified hip or knee osteoarthritis with complete data at baseline, 3 and 12 months follow-up before December 31st 2013 were included. HEPA was defined as self-reported physical activity of at least moderate intensity either a) at least 30 min per day on four days or more per week, or b) at least 150 min per week. HEPA was assessed at baseline, and again at 3 and 12 months follow-up. Cochran's Q test was used to determine change in physical activity over time. The association between reaching the level of HEPA and time, age, BMI, gender, and Charnley classification was investigated using the generalized estimation equation (GEE) model. The proportion of patients who reached the level of HEPA increased by 345 patients, from 77 to 82%, from baseline to 3 months follow-up. At 12 months, the proportion of patients who reached the level of HEPA decreased to 76%. Not reaching the level of HEPA was associated with overweight, obesity, male gender and Charnley category C, i.e. osteoarthritis in multiple joint sites (hip and knee), or presence of any other disease that affects walking ability. Following the supported osteoarthritis self-management programme there was a significant increase in the proportion of patients who reached the recommended level of HEPA after 3 months. Improvements were lost after 12 months. To increase physical activity and reach long-lasting changes in levels of physical activity, more follow-up sessions might be needed.


The frequency of restricted range of movement in individuals with self-reported shoulder pain: results from a population-based survey.
Prevalence studies suggest that shoulder pain is very common (7-20%) in the adult population, though little is known about the severity and impact of such pain. Disability results, in part, from the restriction of movement and we therefore determined the frequency of restricted shoulder movement in individuals in a general population sample reporting shoulder pain and associated disability. In all, 232 individuals were interviewed about shoulder pain and related disability, and their range of shoulder movement in the following planes was measured: elevation, forward flexion, backward flexion, external rotation and internal rotation, together with the minimum difference achieved between the tip of a thumb and the spinous process of C7. In total, 48 (21%) subjects reported current pain and disability in one or both shoulders. Using receiver operating characteristic (ROC) analysis, cut-offs for restricted movements were selected at the point of maximal discrimination between painful and pain-free shoulders. There was considerable overlap in the distribution of range of movement, at all six sites, between these two groups. The highest positive predictive value for pain was observed in restriction of the thumb to cervical spine movement (53%), but this also had the lowest negative predictive value. By contrast, the highest negative predictive value was observed for restriction of external rotation (96%). Restriction in any plane was observed in 77% of those individuals with pain, but was also present in half of those without pain. In summary, most people with self-reported shoulder pain in the community do not have widespread restriction of movement. Reduction in external rotation was the most discriminatory, but it is necessary to examine movement in multiple planes to assess the true burden of shoulder pain in the community.


Targeting Lipid Metabolism for the Treatment of Age-Related Macular Degeneration: Insights from Preclinical Mouse Models.
Age-related macular degeneration (AMD) is a major leading cause of irreversible visual impairment in the world with limited therapeutic interventions. Histological, biochemical, genetic, and epidemiological studies strongly implicate dysregulated lipid metabolism in the retinal pigmented epithelium (RPE) in AMD pathobiology. However, effective therapies targeting lipid metabolism still need to be identified and developed for this blinding disease. To test lipid metabolism-targeting therapies, preclinical AMD mouse models are needed to establish therapeutic efficacy and the role of lipid metabolism in the development of AMD-like pathology. In this review, we provide a comprehensive overview of current AMD mouse models available to researchers that could be used to provide preclinical evidence supporting therapies targeting lipid metabolism for AMD. Based on previous studies of AMD mouse models, we discuss strategies to modulate lipid metabolism as well as examples of studies evaluating lipid-targeting therapeutics to restore lipid processing in the RPE. The use of AMD mouse models may lead to worthy lipid-targeting candidate therapies for clinical trials to prevent the blindness caused by AMD.


Surgical Smoke: Putting the Pieces Together to Become Smoke-Free: 1.6 www.aornjournal.org/content/cme.
Surgical smoke is generated when tissue vaporizes from the use of various energy-generating devices (eg, electrosurgery units, lasers). Surgical smoke contains toxic gases and vapors that can be hazardous to patients and perioperative staff members. In addition to ocular and upper respiratory tract irritation, surgical smoke can have mutagenic potential. Although many regulatory agencies agree that surgical smoke is dangerous, they have been slow to commit to a firm standard to address the inhalation hazards related to surgical smoke. With the clear evidence supporting the need to filter surgical smoke, perioperative nurses and surgical technologists at our facility implemented a plan to protect patients and staff members. The plan included identifying and evaluating in-house equipment and the perceived barriers to becoming smoke-free. Perioperative personnel tested multiple smoke-evacuating products to determine which best met the needs of our staff members and facility, and our ORs are now smoke-free.


[Clinical aspects, diagnosis and therapy of Yersinia enterocolitica infections].
The predominant form (65% of all patients) of yersiniosis is mesenteric adenitis, resulting in enteritis, pseudo-appendicular syndromes, ileitis or colitis. The severity of this form depends to some degree on the age. Extra-mesenteric forms (in 20-25%), focal infections by dissemination, the septic form and the lymphadenopathy syndrome may occur after or without previous enteritis. Persistence of Y. enterocolitica in lymphnodes and the GALT is responsible for chronic and recurrent forms. Secondary immunological complications (25%) are arthritis and Erythema nodosum. Diagnosis is made by culture, serology, of which demonstration of specific antibodies against released proteins is more reliable than demonstration of agglutinins and antigen detection by indirect immunofluorescence in biopsies. Antibiotic treatment of mild enteric forms is questionable, extra-mesenteric forms should be treated. Appropriate antibiotics are trimethoprim, chloramphenicol, tetracycline and the new fluoroquinolones. Studies are in progress (Leeuwarden and Hanover, MHH) to elucidate the indication of antibiotic treatment of Yersinia-arthritis patients.


Hydrothermal formation of N/Ti3+ codoped multiphasic (brookite-anatase-rutile) TiO2 heterojunctions with enhanced visible light driven photocatalytic performance.
Mixed phased TiO2 catalysts codoped with N and Ti3+ have been successfully synthesized using a low-temperature, one step hydrothermal method using TiN as the precursor. The as prepared samples were studied for their crystalline structure, morphology, composition, and optical properties using various analytical techniques such as X-ray diffraction (XRD), field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), ultraviolet-visible diffuse reflectance spectroscopy (UV-vis DRS), and X-ray photoelectron spectroscopy (XPS). It was observed that N and Ti3+ codoped TiO2 samples having mixed phases of brookite, anatase and rutile could be obtained at a wide range of hydrothermal time durations ranging from 24 h to 72 h. The as-prepared samples exhibit a distinct red shift, suggesting that N and Ti3+ codoping significantly enhances the optical absorption characteristics of TiO2. The photocatalytic activity of the prepared samples was studied using methylene blue and colorless resorcinol dyes. The prepared samples demonstrated good photocatalytic activity because of their excellent mixed phase crystalline structures and an increase in the threshold wavelength response. The mechanism of the photocatalytic degradation reaction was also studied. This work provides a novel strategy to fabricate and extend the visible light response of TiO2, which facilitates their application in the environment remediation and energy conversion.


[An epidemiological analysis of bronchiolitis in the health region of Tarragona].
The purpose of this study was to analyze the epidemiology of bronchiolitis in our area and to determine if changes in our medical installations have affected the course of this disease. Infants less than 12 months of age with bronchiolitis that had been hospitalized between October, 1992 and January 1996 were studied retrospectively. The patients were divided into two groups; those attended in the old Pediatric Department and those seen in the new installations. In the first group, the majority of the thorax X-rays were normal and in the second air trapping was more frequently seen. The infants in the first group were admitted with a shorter evolution time and the mean hospitalization time was significantly higher (p < 0.05. IC = 95%: 1.68-3.62) than in the second group (7.7 +/- 3.75 vs. 5 +/- 3.36 days, respectively). In addition, this difference was even more significant (p < 0.05. IC = 95%: 1.22-4.38) if syncytial respiratory virus had been isolated (8.93 +/- 2.94 vs. 6 +/- 4.41 days, respectively). We did not find any epidemiological differences in our area in relationship to bronchiolitis during the past four years. We believe that the shorter hospitalization period in the second group could be attributed to working in the new facilities.


Directed evolution for improved secretion of cancer-testis antigen NY-ESO-1 from yeast.
NY-ESO-1 is a highly immunogenic tumor antigen and a promising vaccine candidate in cancer immunotherapy. Access to purified protein both for vaccine formulations and for monitoring antigen-specific immune responses is vital to vaccine development. Currently available recombinant Escherichia coli-derived NY-ESO-1 is isolated from inclusion bodies as a complex protein mixture and efforts to improve the purity of this antigen are required, especially for later-stage clinical trials. Using yeast cell surface display and fluorescence activated cell sorting techniques, we have engineered an NY-ESO-1 variant (NY-ESO-L5; C(75)A C(76)A C(78)A L(153)H) with a 100x improved display level on yeast compared to the wild-type protein. This mutant can be effectively produced as an Aga2p-fusion and purified in soluble form directly from the yeast cell wall. In the process, we have identified the epitope recognized by anti-NY-ESO-1 mAb E978 (79-87, GARGPESRL). The availability of an alternative expression host for this important antigen will help avoid artifactual false positive tests of patient immune response due to reaction against expression-host-specific contaminants.


Tetraphenylethylene-Based Hydrogen-Bonded Organic Frameworks (HOFs) with Brilliant Fluorescence.
By synergistically employing four key strategies: (I) introducing tetraphenylethylene groups as the central core unit with aggregation-induced emission (AIE) properties, (II) optimizing the π-conjugated length by extending the building block branches, (III) incorporating flexible groups containing ethylenic bonds, and (IV) applying crystal engineering to attain dense stacking mode and highly twisty conformation, we successfully synthesized a series of hydrogen-bonded organic frameworks (HOFs) exhibiting exceptional one/two-photon excited fluorescence. Notably, when utilizing the fluorescently superior building block L2, HOF-LIFM-7 and HOF-LIFM-8 exhibiting high quantum yields (QY) of 82.1 % and 77.1 %, and ultrahigh two-photon absorption (TPA) cross-sections of 148959.5 GM and 123901.1 GM were achieved. These materials were successfully employed in one and two-photon excited lysosome-targeting cellular imaging. It is believed that this strategy, combining building block optimization and crystal engineering, holds significant potential for guiding the development of outstanding fluorescent HOF materials.


Immunotherapy of prolactinoma with a T helper 1 activator adjuvant and autoantigens: a case report.
To date, efforts to reliably manipulate the immune system to promote tumor regression in the brain have been disappointing. We report a unique experience of successful immunotherapy to treat a pituitary macroprolactinoma. A 31-year-old woman with an established history of pituitary macroprolactinoma who had undergone tumor resection followed by radiation was admitted to our clinic. The diagnosis had been made due to the patient's symptoms, a serum prolactin (PRL) level of 29,600 mIU/l, a brain MRI revealing a 23 x 19 x 18 mm pituitary mass and a positive PRL immunohistochemistry of the mass. Six months following surgery, she reexperienced headache, excessive sweating and a serum PRL concentration of 2,960 mIU/l despite receiving 30 mg/day bromocriptine. Brain MRI revealed a pituitary mass (3 x 6 x 8 mm) compatible with a pituitary adenoma. Twenty micrograms per milliliter of G2 (as a T helper 1 activator adjuvant) was inoculated intradermally once per week for 24 consecutive weeks (each injection contained 10 mug of G2). The autoantigens were inoculated at the same time with G2. After immunotherapy, serum PRL concentration decreased to 82 mIU/l, the patient's symptoms disappeared, skin thickness increased to normal and bromocriptine dosage was tapered to 20 mg per week. A follow-up brain MRI revealed almost complete disappearance of the tumor. The patient does not complain of any problems at 1-year follow-up. Activation of both nonspecific (natural killer cells) and specific (cytotoxic T lymphocytes) immunity in relation to the T helper 1 cytokine network is a promising strategy for the treatment of tumors of the central nervous system in humans, especially pituitary macroprolactinomas.


Photochromic bisthienylethene as multi-function switches.
Bisthienylethenes (BTEs) are one of the most promising families of photochromic compounds because of their fatigue resistance and thermally irreversible properties for use in optoelectronic devices such as ultrahigh-density optical data storage, molecular switches, logic gates, molecular wires, sensors, and so on. This article describes recent development of switchable photochromic bisthienylethene materials, especially multi-switchable bisthienylethene materials including multi-color photochromic materials, multi-switchable organogelators and liquid crystals. We also highlight our recent contributions in this field.


Determination of total antioxidant capacity of milk by CUPRAC and ABTS methods with separate characterisation of milk protein fractions.
Most milk-applied antioxidant assays in literature are based on the isolation and quantification of individual antioxidative compounds, whereas total antioxidant capacity (TAC) gives a more holistic picture due to cooperative action of antioxidants. Recently, the cupric reducing antioxidant capacity (CUPRAC) method has been modified to measure the antioxidant capacities of thiol-containing proteins, where the classical ammonium acetate buffer - that may otherwise precipitate proteins- was replaced with concentrated urea buffer (able to expose embedded thiol groups of proteins to oxidative attack) adjusted to pH 7.0. Thus, antioxidant capacity of milk was investigated with two competing TAC assays, namely CUPRAC and ABTS (2,2'-azinobis(3-ethylbenzothiazoline-6-sulphonic acid))/persulphate, because only these assays were capable of evaluating protein contribution to the observed TAC value. As milk fat caused turbidity, experiments were carried out with skim milk or defatted milk samples. To determine TAC, modified CUPRAC method was applied to whole milk, separated and redissolved protein fractions, and the remaining liquid phase after necessary operations. Both TAC methods were investigated for their dilution sensitivity and antioxidant power assessment of separate milk fractions such as casein and whey. Proteins like β-lactoglobulin and casein (but not simple thiols) exhibited enhanced CUPRAC reactivity with surfactant (SDS) addition. Addition of milk protein fractions to whole skim milk produced significant 'negative-biased' deviations (up to -26% relative standard error) from TAC absorbance additivity in the application of the ABTS method, as opposed to that of the CUPRAC method less affected by chemical deviations from Beer's law thereby producing much smaller deviations from additivity (i.e. the property of additivity is valid when the measured TAC of a mixture is equal to the sum of individual antioxidant capacities of its constituents).


Confirmation of germ-line transmission in the red fluorescence protein (RFP) transgenic cloned male cat.
The production of transgenic animals is highly desirable for biotechnology and basic research. We investigated the reproductive ability of a red fluorescence protein (RFP) transgenic cloned male cat (RFP TG cat) by natural mating with a domestic female cat. The RFP expression levels were examined in early embryogenesis, tissues from 45-day-old two fetuses, and four RFP TG cat offspring. The RFP gene was detected in tissue samples from one dead kitten, including several organs and the skin. Also, under a fluorescent light source, we were able to directly detect the RFP expression of in in vitro-produced blastocysts derived with sperm from the RFP TG cat. These results indicate that the RFP TG cat exhibits normal reproductive fertility, stable germ-line transmission of the RFP transgene, and characteristic RFP expression in its offspring. We isolated feline neural progenitor cells from a 45-day-old fetus derived from the natural mating of the RFP TG cat with a domestic female cat. Isolated brain and retinal progenitor cells were successfully passaged at least four times post isolation (day 23), and showed a high RFP expression level. This method of producing genetically modified cloned cats will be important for generating biomedical models of human diseases.


Evidence of Interruption of the comM Gene in a Large Series of Clinical Isolates of Multidrug-Resistant Acinetobacter baumannii.
Recent studies have recognized the ATPase-encoding comM gene as a hot spot for the integration of Acinetobacter baumannii resistance islands (RIs). Despite the circulation of high numbers of multidrug-resistant A. baumannii (MDR-AB) isolates in Middle East countries, no information is available about the interruption of comM and subsequent transposition into comM in isolates belonging to the global clones (GC) GC1, GC2, or GC3. In this study 401 A. baumannii isolates from hospitals in Tehran, Iran, were included. The resistance profile was determined by disc diffusion against 22 antibiotics. PCR was used to assess the GC type, presence of the comM gene, and the boundary junctions (J1 and J2) of RIs. Most of the MDR-AB isolates (384 of 388; 98%) and more than half of the susceptible A. baumannii isolates (9 of 13; 69%) had interrupted comM gene-carrying integrative elements. Among the isolates tested, 57 belonged to GC1, 86 to GC2, and 8 to GC3. A set of 250 isolates showed distinct patterns of allele-specific PCR for ompA, csuE, and blaOXA-51-like genes. All but 2 of the GC1 isolates and 2 of the GC2 isolates contained interrupted comM genes. Four A. baumannii isolates harbored intact comM, but were multiply resistant to antibiotics. This study demonstrated that the comM gene is targeted by transposons in Iranian MDR-AB isolates belonging to different GCs. The data also showed that the carriage of interrupted comM is not exclusive to MDR isolates of A. baumannii.


Explicit and implicit attitudes of occupational therapy workshops' staff towards people with intellectual disabilities.
The aim of this article is to present explicit and implicit attitudes of occupational therapy (OT) staff towards people with intellectual disabilities. The study was conducted on a group of 77 OT employees. To explore the explicit attitude, the Conditional Respect for Persons with Disabilities Questionnaire (Kurtek, Roczniki Psychologiczne, 2018, 4, 327-344) was used, while to estimate the implicit attitude, the Intellectual Disability Attitudes Implicit Association Test was applied (Kurtek, Roczniki Psychologiczne, 2021, 1, 43-64). At the explicit level, OT staff tended to tolerate negative and overrate positive behaviours of people with intellectual disabilities, which indicates a tendency to favour the individuals. However, the opposite devalorizing tendency was observed at the implicit dimension, which indicates aversive ableism. Although the study confirmed the independence of the two dimensions of the personnel's attitude, relationships were observed between the disclosure of negativity towards antagonistic behaviours of the people with intellectual disabilities and a decrease in the level of their implicit devaluation.


Identification of cGMP-dependent protein kinase anchoring proteins (GKAPs).
To promote both efficiency and selectivity, many protein kinases and phosphatases are maintained in specific subcellular microenvironments through their association with anchoring proteins. In this study, we describe a new class of proteins, called GKAPS, that specifically bind the Type II cGMP-dependent protein kinase (PKG). GKAPs were detected in rat aorta, brain, and intestine using a protein overlay technique. The PKG binding proteins were distinct from AKAPs, proteins known to bind the cAMP-dependent protein kinase (PKA). Furthermore, a synthetic peptide that blocks association of PKA with AKAPs did not affect the PKG-GKAP interaction. Deletion mutagenesis was used to map the GKAP binding determinants within PKG to the N-terminal regulatory region. While most GKAPs were tissue-specific, a ubiquitous PKG-binding protein was detected and identified as myosin. Analysis of myosin fragments revealed that PKG binds within Subfragment 2. The results define a novel class of anchoring proteins that may target PKG for specific functional roles.


Biogenic crust dynamics on sand dunes.
Sand dunes are often covered by vegetation and biogenic crusts. Despite their significant role in dune stabilization, biogenic crusts have rarely been considered in model studies of dune dynamics. Using a simple model, we study the existence and stability ranges of different dune-cover states along gradients of rainfall and wind power. Two ranges of alternative stable states are identified: fixed crusted dunes and fixed vegetated dunes at low wind power; and fixed vegetated dunes and active dunes at high wind power. These results suggest a crossover between two different forms of desertification.


Evaluation of trimethoprim-sulphamethoxazole compound in treatment of salmonella infections.
Fifty patients suffering from infections caused by various salmonella species were treated with trimethoprim-sulphamethoxazole compound. Twenty-three had enteric fever and two were biliary carriers of Salmonella typhi. The other 25 suffered from infections caused by salmonella species other than S. typhi or S. paratyphi B. Twenty-one of the patients with enteric fever responded clinically to the drug, one failed treatment, and one died. Two patients suffering from typhoid fever relapsed and three temporarily excreted S. typhi in stools following treatment. One of the typhoid carriers was successfully treated. All patients with infections caused by salmonella species other than S. typhi or S. paratyphi B responded to treatment but 17 continued to excrete the organism in their stools after the course of trimethoprim-sulphamethoxazole compound. Four patients developed rashes during therapy and two became anaemic.


Inflammation stimulates remyelination in areas of chronic demyelination.
A major challenge in multiple sclerosis research is to understand the cause or causes of remyelination failure and to devise ways of ameliorating its consequences. This requires appropriate experimental models. Although there are many models of acute demyelination, at present there are few suitable models of chronic demyelination. The taiep rat is a myelin mutant that shows progressive myelin loss and, by 1 year of age, its CNS tissue has many features of chronic areas of demyelination in multiple sclerosis: chronically demyelinated axons present in an astrocytic environment in the absence of acute inflammation. Using the taiep rat and a combination of X-irradiation and cell transplantation, it has been possible to address a number of questions concerning remyelination failure in chronic multiple sclerosis lesions, such as whether chronically demyelinated axons have undergone changes that render them refractory to remyelination and why remyelination is absent when oligodendrocyte progenitor cells (OPCs) are present. Our experiments show that (i) transplanted OPCs will not populate OPC-containing areas of chronic demyelination; (ii) myelination competent OPCs can repopulate OPC-depleted chronically demyelinated astrocytosed tissue, but this repopulation does not result in remyelination--closely resembling the situation found in some multiple sclerosis plaques; and (iii) the induction of acute inflammation in this non-remyelinating situation results in remyelination. Thus, we can conclude that axonal changes induced by chronic demyelination are unlikely to contribute to remyelination failure in multiple sclerosis. Rather, remyelination fails either because OPCs fail to repopulate areas of demyelination or because if OPCs are present they are unable to generate remyelinating oligodendrocytes owing to the presence of inhibitory factors and/or a lack of the stimuli required to activate these cells to generate remyelinating oligodendrocytes. This non-remyelinating situation can be transformed to a remyelinating one by the induction of acute inflammation.


Influence of sextant prostate needle biopsy or surgery on the detection and harvest of intact circulating prostate cancer cells.
The feasibility of harvesting intact, circulating prostate cancer cells from the blood of men with advanced prostate cancer has previously been demonstrated. We studied the influence of sextant prostate needle biopsy and radical prostatectomy on harvesting intact circulating prostate cancer cells. Via standard venipuncture 20 c.c. blood were obtained preoperatively, and 30 minutes and 3 days postoperatively from 23 men with clinically localized prostate cancer undergoing surgery. Similarly, blood was obtained before and after routine prostate biopsy from 13 men for an elevated prostate specific antigen level and/or abnormal digital rectal examination. The blood cells were removed via density centrifugation and magnetic cell sorting. The remaining prostate epithelial cells were characterized by indirect fluorescent immunocytochemical staining and fluorescent in situ hybridization using deoxyribonucleic acid probes. Sextant biopsy of the prostate induced circulating cells in 3 of 13 men (23%), only 1 of whom demonstrated cells with aneuploidy (Gleason score 3+4 = 7). Circulating cells were detected preoperatively, 30 minutes or 3 days postoperatively in 35% of radical prostatectomy cases. Of the patients 13% had detectable circulating cells 30 minutes postoperatively only and 9% had cells harvested on postoperative day 3. Persistence of circulating prostate cancer cells was noted in 13% of men on postoperative day 3. Serum prostate specific antigen level and pathological stage did not appear to be related to harvested cell number. Prostate cancer cells can be harvested from men with clinically localized disease undergoing sextant needle biopsy or radical prostatectomy. Routine prostate biopsy and surgery may influence the number of measurable circulating cells in the short term but the clinical significance and long-term prevalence of detectable circulating cells are unknown. Further studies are needed to evaluate the clinical usefulness of this assay for detecting, staging and monitoring prostate cancer.


Quantitative trait loci controlling allergen-induced airway hyperresponsiveness in inbred mice.
Identification of the genetic loci underlying asthma in humans has been hampered by variability in clinical phenotype, uncontrolled environmental influences, and genetic heterogeneity. To circumvent these complications, the genetic regulation of asthma-associated phenotypes was studied in a murine model. We characterized the strain distribution patterns for the asthma-related phenotypes airway hyperresponsiveness (AHR), lung eosinophils, and ovalbumin (OVA)-specific serum immunoglobulin (Ig) E induced by allergen exposure protocols in A/J, AKR/J, BALB/cJ, C3H/HeJ, and C57BL/6J inbred strains and in (C3H/HeJ x A/J)F1 mice. Expression of AHR differed between strains and was sometimes discordant with lung eosinophils or serum IgE. Furthermore, we identified two distinct quantitative trait loci (QTL) for susceptibility to allergen-induced AHR, Abhr1 (allergen-induced bronchial hyperresponsiveness) (lod = 4. 2) and Abhr2 (lod = 3.7), on chromosome 2 in backcross progeny from A/J and C3H/HeJ mice. In addition, a QTL on chromosome 7 was suggestive of linkage to this trait. These QTL differ from those we have previously found to control noninflammatory AHR in the same crosses. Elucidation of the genes underlying these QTL will facilitate the identification of biochemical pathways regulating AHR in animal models of asthma and may provide insights into the pathogenesis of human disease.


Flexible, Low-Cost Sensor Based on Electrolyte Gated Carbon Nanotube Field Effect Transistor for Organo-Phosphate Detection.
A flexible enzymatic acetylcholinesterase biosensor based on an electrolyte-gated carbon nanotube field effect transistor is demonstrated. The enzyme immobilization is done on a planar gold gate electrode using 3-mercapto propionic acid as the linker molecule. The sensor showed good sensing capability as a sensor for the neurotransmitter acetylcholine, with a sensitivity of 5.7 μA/decade, and demonstrated excellent specificity when tested against interfering analytes present in the body. As the flexible sensor is supposed to suffer mechanical deformations, the endurance of the sensor was measured by putting it under extensive mechanical stress. The enzymatic activity was inhibited by more than 70% when the phosphate-buffered saline (PBS) buffer was spiked with 5 mg/mL malathion (an organophosphate) solution. The biosensor was successfully challenged with tap water and strawberry juice, demonstrating its usefulness as an analytical tool for organophosphate detection.


Functional electrical stimulation on chronic and acute hemiplegic shoulder subluxation.
The present study investigated and assessed the effectiveness of a functional electrical stimulation (FES) program in the management of acute and chronic shoulder subluxation. By their postonset duration, hemiplegic subjects with subluxation participating in the study were placed into a short-duration group and a long-duration group. Subjects in each group were further assigned randomly to either a control subgroup or an experimental subgroup. The experimental subgroups of both short and long duration received FES therapy in which supraspinatus and posterior deltoid were induced to contract repetitively up to 6 hr/day for 6 wk. The duration of the FES session and muscle contraction/relaxation ratio were progressively increased as performance improved. The experimental subgroup of short duration showed significant improvements in reducing subluxation as indicated by x-ray compared with the control subgroup of short duration after the first FES treatment. The same effect was not shown for the experimental subgroup of long duration. The second FES treatment program only resulted in an insignificant change of shoulder subluxation for both the short- and long-duration subgroups. The present study suggests that hemiplegic subjects with short postonset duration are effectively trained for shoulder subluxation by the first FES treatment program. The same FES showed not to be effective when applied to the subjects with subluxation of > 1 yr.


Surveying the landscape of Huntington's disease mechanisms, measurements, and medicines.
Though 20 years have now passed since the cloning of the huntingtin gene (HTT), there remains no treatment for Huntington's Disease (HD) that alters the course of disease or lifespan of patients. The reasons for this are manifold, and likely have to do with the diverse cellular pathways disrupted by mutant HTT (mHTT) protein expression. Furthermore, the evaluation of efficacy using a putative intervention is complex, largely due to the slow course of disease and variability in the classic techniques for evaluating patient symptoms and quality of life, which make the patient populations and duration of trials particularly imposing. However, there are signs for hope both in the clinic and at the bench. This review serves three purposes. It discusses the known cellular pathologies in HD, the current and upcoming methods for clinical evaluation of disease progress, and the tested and untested interventions proposed to counter the progression in animal models and patients. With the vast knowledge of pathology accumulated over two decades of modeling HD in animals and following it in patients, as well as the advances in intervention techniques both pharmaceutical and genetic, there is reason for optimism in the field. Such optimism can only be tempered by the lack of success in the clinic to this point, though patients, scientists, and clinicians all remain enthusiastic about each new trial, and progress can only continue until an effective treatment is found.


Safety of hepatitis B virus core antibody-positive grafts in liver transplantation: A single-center experience in China.
Given the shortage of suitable liver grafts for liver transplantation, proper use of hepatitis B core antibody-positive livers might be a possible way to enlarge the donor pool and to save patients with end-stage liver diseases. However, the safety of hepatitis B virus core antibody positive (HBcAb+) donors has been controversial. Initial studies were mainly conducted overseas with relatively small numbers of HBcAb+ liver recipients, and there are few relevant reports in the population of mainland China. We hypothesized that the safety of HBcAb+ liver grafts is not suboptimal. To evaluate the safety of using hepatitis B virus (HBV) core antibody-positive donors for liver transplantation in Chinese patients. We conducted a retrospective study enrolling 1071 patients who underwent liver transplantation consecutively from 2005 to 2016 at West China Hospital Liver Transplantation Center. Given the imbalance in several baseline variables, propensity score matching was used, and the outcomes of all recipients were reviewed in this study. In the whole population, 230 patients received HBcAb+ and 841 patients received HBcAb negative (HBcAb-) liver grafts. The 1-, 3- and 5-year survival rates in patients and grafts between the two groups were similar (patient survival: 85.8% vs 87.2%, 77.4% vs 81.1%, 72.4% vs 76.7%, log-rank test, P = 0.16; graft survival: 83.2% vs 83.6%, 73.8% vs 75.9%, 70.8% vs 74.4%, log-rank test, P = 0.19). After propensity score matching, 210 pairs of patients were generated. The corresponding 1-, 3- and 5-year patient and graft survival rates showed no significant differences. Further studies illustrated that the post-transplant major complication rates and liver function recovery after surgery were also similar. In addition, multivariate regression analysis in the original cohort and propensity score-matched Cox analysis demonstrated that receiving HBcAb+ liver grafts was not a significant risk factor for long-term survival. These findings were consistent in both HBV surface antigen-positive (HBsAg+) and HBsAg negative (HBsAg-) patients.Newly diagnosed HBV infection had a relatively higher incidence in HBsAg- patients with HBcAb+ liver grafts (13.23%), in which HBV naive recipients suffered most (31.82%), although this difference did not affect patient and graft survival (P = 0.50 and P = 0.49, respectively). Recipients with a high HBV surface antibody (anti-HBs) titer (more than 100 IU/L) before transplantation and antiviral prophylaxis with nucleos(t)ide antiviral agents post-operation, such as nucleos(t)ide antiviral agents, had lower de novo HBV infection risks. HBcAb+ liver grafts do not affect the long-term outcome of the recipients. Combined with proper postoperative antiviral prophylaxis, utilization of HBcAb+ grafts is rational and feasible.


Association of Utilization Management Policy With Uptake of Hypofractionated Radiotherapy Among Patients With Early-Stage Breast Cancer.
Breast cancer accounts for the largest portion of cancer-related spending in the United States. Although hypofractionated radiotherapy after breast-conserving surgery is a cost-effective and convenient treatment strategy for patients with early-stage breast cancer, less than 40% of eligible women received hypofractionated radiotherapy in 2013. To assess the association of a large commercial payer's utilization management policy with the use of hypofractionated radiotherapy among women with early-stage breast cancer and its associated cost. A retrospective, adjusted difference-in-differences economic analysis was conducted using administrative claims data from January 1, 2012, to June 1, 2018, of women 18 years or older with early-stage breast cancer who were eligible for hypofractionated radiotherapy according to 2011 guidelines from the American Society for Radiation Oncology and were continuously enrolled in 14 geographically diverse commercial health plans covering 6.9% of US adult women. Women who received mastectomy, brachytherapy, or less than 11 or more than 40 external beam fractions of radiotherapy were excluded. A utilization management policy was used to encourage the use of hypofractionated radiotherapy among women in fully insured and Medicare Advantage (fully insured) plans. Under the new policy, claims for extended-course radiotherapy were not reimbursed for fully insured women who were eligible for hypofractionated radiotherapy. This policy did not apply to women in self-insured or Medicare supplemental insurance (self-insured) plans, allowing these groups to serve as a comparison group. The primary outcome was use of hypofractionated radiotherapy, and the secondary outcome was the cost of this type of radiotherapy. Of 10 540 eligible women, 3619 (34.3%) were in fully insured plans and thus subject to the policy. There were no meaningful differences between the fully insured and self-insured groups in mean (SD) age at the start of radiotherapy (63.8 [8.6] vs 65.0 [8.9] years), mean (SD) Charlson Comorbidity Index score (3.0 [1.5] vs 3.2 [1.6]), or practice setting (outpatient hospital setting, 2982 of 3619 [82.4%] vs 5600 of 6921 [80.9%]). The policy was associated with an increase in use of hypofractionated radiotherapy among fully insured patients subject to the policy (adjusted percentage point difference-in-difference, 4.2%; 95% CI, 0.0%-8.4%; P = .05) and a nonsignificant decrease in radiotherapy-associated expenditures (-$2275 relative to self-insured patients; P = .09). Spillover analyses revealed a significantly higher uptake of hypofractionated radiotherapy among self-insured patients who were indirectly exposed to the policy (adjusted percentage point difference-in-difference, 8.5%; 95% CI, 3.6%-13.5%; P < .001) compared with those who were not exposed. This study suggests that a payer's utilization management policy was associated with direct and spillover increases in the use of hypofractionated radiotherapy, even after accounting for a long-term secular trend in the uptake of hypofractionated radiotherapy in the control groups. Utilization management may promote evidence-based cancer care.


Aii20J, a wide-spectrum thermostable N-acylhomoserine lactonase from the marine bacterium Tenacibaculum sp. 20J, can quench AHL-mediated acid resistance in Escherichia coli.
Acyl homoserine lactones (AHLs) are produced by many Gram-negative bacteria to coordinate gene expression in cellular density dependent mechanisms known as quorum sensing (QS). Since the disruption of the communication systems significantly reduces virulence, the inhibition of quorumsensing processes or quorum quenching (QQ) represents an interesting anti-pathogenic strategy to control bacterial infections. Escherichia coli does not produce AHLs but possesses an orphan AHL receptor, SdiA, which is thought to be able to sense the QS signals produced by other bacteria and controls important traits as the expression of glutamate-dependent acid resistance mechanism, therefore constituting a putative target for QQ. A novel AHL-lactonase, named Aii20J, has been identified, cloned and over expressed from the marine bacterium Tenacibaculum sp. strain 20 J presenting a wide-spectrum QQ activity. The enzyme, belonging to the metallo-β-lactamase family, shares less than 31 % identity with the lactonase AiiA from Bacillus spp. Aii20J presents a much higher specific activity than the Bacillus enzyme, maintains its activity after incubation at 100 ºC for 10 minutes, is resistant to protease K and α-chymotrypsin, and is unaffected by wide ranges of pH. The addition of Aii20J (20 μg/mL) to cultures of E. coli K-12 to which OC6-HSL was added resulted in a significant reduction in cell viability in comparison with the acidresistant cultures derived from the presence of the signal. Results confirm the interaction between AHLs and SdiA in E. coli for the expression of virulence-related genes and reveal the potential use of Aii20J as anti-virulence strategy against important bacterial pathogens and in other biotechnological applications.


Novel phenotype of RNA synthesis expressed by vesicular stomatitis virus isolated from persistent infection.
Vesicular stomatitis virus (VSV) stocks isolated from two persistently infected mouse L-cell lines (designated VSV-PI stocks) express an altered phenotype of RNA synthesis. This phenotype is different from the RNA synthesis phenotype expressed by the viruses used to initiate the persistently infected lines, wild-type VSV and VSV ts-0-23 (a group III, ts-, RNA+ mutant). At 34 and 37 degrees C in L cells productively infected with VSV-PI stocks derived from the two cell lines, transcription of virus mRNA was significantly reduced, whereas replication of the 40S genomic RNA species was enhanced compared with wild-type VSV or ts-0-23. At 34 and 37 degrees C, both VSV-PI stocks replicated with equal or greater efficiency than wild-type VSV; 37 degrees C was the temperature at which the persistently infected cultures were maintained. At 40 degrees C, both VSV-PI stocks were temperature sensitive, and clonal VSV-PI isolates from both cell lines belong to complementation group I (RNA-). Standard ts- mutants (derived by mutagenesis of wild-type VSV) belonging to RNA- complementation groups I, II, and IV do not express the VSV-PI RNA synthesis phenotype at the permissive temperature, making this phenotype distinctive to persistent infection. Since the two VSV-PI populations from persistently infected cell lines initiated with different viruses both evolved this unique phenotype of RNA synthesis, the expression of this phenotype may play an important role in the maintenance of persistence.


Synthesis, structure, and H2O2-dependent catalytic functions of disulfide-bridged dicopper(I) and related thioether-copper(I) and thioether-copper(II) complexes.
A disulfide-bridged dicopper(I) complex, [Cu2(Py2SSPy2)](ClO4)2 (1) (Py2SSPy2 = bis(2-[N,N-bis(2-pyridylethyl)-amino]-1,1- dimethylethyl)disulfide), a thioether-copper(I) complex, [Cu(iPrSPy2)](ClO4) (2) (iPrSPy2 = N-(2-isopropylthio-2-methyl)propyl-N,N-bis-2-(2-pyridyl)ethylamine, and a thioether-copper(II) complex, [Cu-(PheSPy2)(H2O)](ClO4)2 (3) (PheSPy2 = N-(2-methyl-2-phenethylthio)propyl-N,N-bis-2-(2- pyridyl)ethylamine), were newly synthesized by the reactions of Cu(ClO4)2.6H2O with a thiol ligand of Py2SH (N,N-bis[2-(2-pyridyl)-ethyl]-1,1-dimethyl-2- mercaptoethylamine) and thioether ligands of iPrSPy2 and PheSPy2, respectively. For complexes 1 and 2, X-ray analyses were performed. Complex 1 crystallizes in the triclinic space group P1, and complex 2 crystallizes in the orthorhombic space group Pbca with the following unit cell parameters: for 1, a = 15.165 (3) A, b = 22.185 (4) A, c = 14.989 (3) A, alpha = 105.76 (1) degrees, beta = 90.82 (2) degrees, gamma = 75.23 (1) degrees, and Z = 2; for 2, a = 17.78 (2) A, b = 17.70 (1) A, c = 15.75 (1) A, and Z = 8. Complex 1 is the first structurally characterized example obtained by the redox reaction Cu(II) + RSH-->Cu(I) + RSSR and has two independent structures (1a, 1b) which mainly differ in S-S bond distances, Cu(I)...Cu(I) separations, and C-S-S-C dihedral angles of the disulfide units. The S-S bond distances of 2.088(7) A in 1a and 2.070(7) A in 1b are indicative of significant activation of the S-S bonds by the dicopper centers. Fragment molecular orbital (FMO) analyses and molecular orbital overlap population (MOOP) analyses based on the extended Hückel method clarify the preferable formation of the disulfide S-S bond in 1 rather than the formation of a thiolate-copper(II) complex within the Py2S- ligand framework. Catalytic functions of complexes 1-3 were investigated with peroxides (H2O2 and tBuOOH) as oxidants. Complex 1 catalyzed the selective oxidation of cyclohexane to cyclohexanol and mediated the cyclohexene epoxidation in the presence of H2O2. A transient dark green intermediate observed in the reaction of 1 with H2O2 is characterized by UV-vis, EPR, and resonance Raman spectroscopies, identifying it as a Cu(II)-OOH species, 1(OOH). The resonance Raman features of the nu(O-O) bands at 822 and 836 cm-1, which are red-shifted to 781 and 791 cm-1, respectively, upon introduction of H2(18)O2, are indicative of formation of two kinds of Cu-OOH species rather than the Fermi doublet and the significant weakening of the O-O bonds. These mechanistic studies demonstrate that by virtue of the electron-donating ability of the disulfide unit the Cu-OOH species can be actually activated for one-electron oxidation, which has been reported so far unfavorable for other vibrationally characterized Cu-OOH species.


Cerebral blood oxygenation measurement based on oxygen-dependent quenching of phosphorescence.
Monitoring of the spatiotemporal characteristics of cerebral blood and tissue oxygenation is crucial for better understanding of the neuro-metabolic-vascular relationship. Development of new pO2 measurement modalities with simultaneous monitoring of pO2 in larger fields of view with higher spatial and/or temporal resolution will enable greater insight into the functioning of the normal brain and will also have significant impact on diagnosis and treatment of neurovascular diseases such as stroke, Alzheimer's disease, and head injury. Optical imaging modalities have shown a great potential to provide high spatiotemporal resolution and quantitative imaging of pO2 based on hemoglobin absorption in visible and near infrared range of optical spectrum. However, multispectral measurement of cerebral blood oxygenation relies on photon migration through the highly scattering brain tissue. Estimation and modeling of tissue optical parameters, which may undergo dynamic changes during the experiment, is typically required for accurate estimation of blood oxygenation. On the other hand, estimation of the partial pressure of oxygen (pO2) based on oxygen-dependent quenching of phosphorescence should not be significantly affected by the changes in the optical parameters of the tissue and provides an absolute measure of pO2. Experimental systems that utilize oxygen-sensitive dyes have been demonstrated in in vivo studies of the perfused tissue as well as for monitoring the oxygen content in tissue cultures, showing that phosphorescence quenching is a potent technology capable of accurate oxygen imaging in the physiological pO2 range. Here we demonstrate with two different imaging modalities how to perform measurement of pO2 in cortical vasculature based on phosphorescence lifetime imaging. In first demonstration we present wide field of view imaging of pO2 at the cortical surface of a rat. This imaging modality has relatively simple experimental setup based on a CCD camera and a pulsed green laser. An example of monitoring the cortical spreading depression based on phosphorescence lifetime of Oxyphor R3 dye was presented. In second demonstration we present a high resolution two-photon pO2 imaging in cortical micro vasculature of a mouse. The experimental setup includes a custom built 2-photon microscope with femtosecond laser, electro-optic modulator, and photon-counting photo multiplier tube. We present an example of imaging the pO2 heterogeneity in the cortical microvasculature including capillaries, using a novel PtP-C343 dye with enhanced 2-photon excitation cross section.


Myogenic waves and myogenic programs during Xenopus embryonic myogenesis.
Although Xenopus is a key model organism in developmental biology, little is known about the myotome formation in this species. Here, we assessed the expression of myogenic regulatory factors of the Myod family (MRFs) during embryonic development and revealed distinct MRF programs. The expression pattern of each MRF during embryonic development highlights three successive myogenic waves. We showed that a first median and lateral myogenesis initiates before dermomyotome formation: the median cell population expresses Myf5, Myod, and Mrf4, whereas the lateral one expresses Myod, moderate levels of Myogenin and Mrf4. The second wave of myoblasts arising from the dermomyotome is characterized by the full MRF program expression, with high levels of Myogenin. The third wave is revealed by Myf5 expression in the myotome and could contribute to the formation of plurinucleated fibers at larval stages. Furthermore, Myf5- or Myod-expressing anlagen are identified in craniofacial myogenesis. The first median and lateral myogenesis and their associated MRF programs have probably disappeared in mammals. However, some aspects of Xenopus myogenesis have been conserved such as the development of somitic muscles by successive myogenic waves and the existence of Myf5-dependent and -independent lineages.


The disease burden attributable to 18 occupational risks in China: an analysis for the global burden of disease study 2017.
China has more than 18% of the global population and over 770 million workers. However, the burden of disease attributable to occupational risks is unavailable in China. We aimed to estimate the burden of disease attributable to occupational exposures at provincial levels from 1990 to 2017. We estimated the summary exposure values (SEVs), deaths and disability-adjusted life years (DALYs) attributable to occupational risk factors in China from 1990 to 2017, based on Global Burden of Disease Study (GBD) 2017. There were 18 occupational risks, 22 related causes, and 35 risk-outcome pairs included in this study. Meanwhile, we compared age-standardized death rates attributable to occupational risk factors in provinces of China by socio-demographic index (SDI). The SEVs of most occupational risks increased from 1990 to 2017. There were 323,833 (95% UI 283,780 - 369,061) deaths and 14,060,210 (12,022,974 - 16,125,763) DALYs attributable to total occupational risks in China, which were 27.9 and 22.1% of corresponding global levels, respectively. For attributable deaths, major risks came from occupational particulate matter, gases, and fumes (PGFs), and for the attributable DALYs, from occupational injuries. The attributable burden was higher in males than in females. Compared with high SDI provinces, low SDI provinces, especially Western China, had higher death rates attributable to total occupational risks, occupational PGFs, and occupational injuries. Occupational risks contribute to a huge disease burden in China. The attributable burden is higher in males, and in less developed provinces of Western China, reflecting differences in risk exposure, socioeconomic conditions, and type of jobs. Our study highlights the need for further research and focused policy interventions on the health of workers especially for less developed provinces in China to reduce occupational health losses effectively.


Correlation of jugular venous oxygen saturation to spontaneous fluctuations of cerebral perfusion pressure in patients with severe head injury.
Continuous measurements of mean arterial pressure (MAP), ICP, and jugular venous oxygen saturation (SjO2) were performed in 11 patients with severe head injury (GCS 3-7) to assess the dependence of SjO2 from the cerebral perfusion pressure (CPP), trying to establish an indirect measure of cerebrovascular autoregulation. Changes in CPP resulting from spontaneous fluctuations in MAP or ICP induced highly significant alterations in SjO2 in the range of 0.14-0.56% SjO2 mmHg-1 CPP in all patients and all periods after trauma. The analysis of the distribution of the SjO2:CPP-ratios showed the highest frequency of values in the range of 0.0-0.25% SjO2 mmHg-1 CPP in 9 of the 11 patients. Within the first 2 days after trauma, a more pronounced dependency of SjO2 from changes in CPP was found, but this was not statistically significant. No predictable relationship of the SjO2:CPP-ratio to the level of ICP could be demonstrated in the patients. Because changes in SjO2 induced by alterations in CPP were found in all patients and throughout the acute phase of severe head injury, these changes more probably reflect physiological alterations in CBF with varying perfusion pressure rather than impaired autoregulation after head trauma. Although assessment of cerebral autoregulation by estimation of the SjO2:CPP-ratio offers new possibilities for monitoring of these patients, the high frequency of erroneous readings or irregular fluctuations of the SjO2-signal from the fibreoptic catheter limits the usefulness of the SjO2-dependency from CPP for practical use in the intensive care unit.


[The determination of the intensity of premolar and molar maximal forces during the isometric contraction of the masticatory muscles due to forced mandibular closure].
The purpose of this study to quantify the activity of the masticatory muscles. For this we recorded the maximum bite force of opposing teeth during voluntary clenching. The study was carried out on 31 students aged 21 to 28 with a satisfactory dental arch. The measurements were obtained on one side only. Nine thickness of the traducers were used for the premolar zone and two for the molar zone. We determined an optimal thickness enabling the highest measurement: 6.5 mm for the premolars and 5.2 for the molars. The highest measurements were averaged and the following results were obtained: premolars-35 kgf for females and 50 kgf for males; molars 100 kgf for females and 130 kgf for males.


The interpretation of hepatitis B virus vaccine immunogenicity tests on mice.
The "Proposed requirements for Hepatitis B vaccine" published by the W.H.O. does not contain distinct immunogenicity tests for the quality control of the HBV vaccine. In this study we focus on a number of alternatives of conducting immunogenicity tests on mice and on questions as: should the mice necessarily be of H-2q haplotype? Is it necessary to screen the mice for the presence of anti-HBs prior to injection? How should the radioimmunological anti-HBs determination be interpreted? What is the cut-off value (2.1 X N or 10 m IU/ml) that will be used in this determination. There can be concluded that ED50 rates depends upon the used alternatives. The results of the immunogenicity tests on mice are compared with in vitro activity assays of the vaccine.


Development and Evaluation of a Duo Chikungunya Virus Real-Time RT-PCR Assay Targeting Two Regions within the Genome.
Chikungunya virus (CHIKV) re-emerged as a globalized health threat fifteen years ago. There are dozens of RT-PCR assays published. An inventory of the latter was made, and after in silico analysis, two assays were selected for their ability to detect strains belonging to the five CHIKV genetic lineages. They were combined in order to provide a robust assay not affected by genetic point mutations and the resulting Duo CHIKV real-time RT-PCR assay was compared to the two parental single-plex tests against five strains belonging to the five genetic lineages. The Duo CHIKV assay performed equally, or better, in terms of sensitivity, specificity, linearity and signal intensity. Dual-target assays are better suited for viruses having the propensity to evolve into new variants via point mutations or major sequence deletions/insertions. Here, we demonstrated that combining two single systems into a dual-target assay did not impair sensitivity and specificity, and proved a potent diagnostic tool to face a potential emergence of CHIKV variants by newly evolving mutations.


No difference in small bowel microbiota between patients with irritable bowel syndrome and healthy controls.
Several studies have indicated that colonic microbiota may exhibit important differences between patients with irritable bowel syndrome (IBS) and healthy controls. Less is known about the microbiota of the small bowel. We used massive parallel sequencing to explore the composition of small bowel mucosa-associated microbiota in patients with IBS and healthy controls. We analysed capsule biopsies from the jejunum of 35 patients (26 females) with IBS aged 18-(36)-57 years and 16 healthy volunteers (11 females) aged 20-(32)-48 years. Sequences were analysed based on taxonomic classification. The phyla with the highest total abundance across all samples were: Firmicutes (43%), Proteobacteria (23%), Bacteroidetes (15%), Actinobacteria (9.3%) and Fusobacteria (7.0%). The most abundant genera were: Streptococcus (19%), Veillonella (13%), Prevotella (12%), Rothia (6.4%), Haemophilus (5.7%), Actinobacillus (5.5%), Escherichia (4.6%) and Fusobacterium (4.3%). We found no difference among major phyla or genera between patients with IBS and controls. We identified a cluster of samples in the small bowel microbiota dominated by Prevotella, which may represent a common enterotype of the upper small intestine. The remaining samples formed a gradient, dominated by Streptococcus at one end and Escherichia at the other.


Estimating the economic incentives necessary for eliminating child labor in Ghanaian cocoa production.
Concerns about the use of child labor in West African cocoa production became widespread in the early 2000s in many high-income countries. In 2015 in Ghana, 91.8% (or a total of 878,595) of the children working in the cocoa sector were involved in a form of hazardous work. Child labor in cocoa production is not just a symptom of poverty but also a contributing factor, as children often forgo a formal education to work in cocoa orchards. Current Ghanaian law prohibits child labor, but, with many cocoa households living in poverty, child labor becomes a necessity for survival, and as such, current child labor laws are rarely enforced. Therefore, an effective policy that eliminates child labor could compensate farmers by providing an economic incentive. In this paper, we develop and calibrate a farm household model to estimate the cocoa price premium necessary to eliminate child labor from cocoa production while leaving the farm household welfare unchanged. This welfare-neutral price premium removes the negative effects of eliminating child labor for the farm household. Varying degrees of child labor exists, with certain forms posing a greater risk to children's wellbeing. The results show that eliminating the worst forms of child labor would require a cocoa price premium of 2.81% and eliminating regular work (non-hazardous work but over the maximum hours allowed for a child) and the worst forms would require an 11.81% premium, which could be paid for by the well-established Ghanaian Cocoa Marketing Board. An incentive for the Cocoa Marketing Board to pay the price premium and monitor and enforce this policy would be the ability to differentiate their cocoa as child-labor free and not lose market share to countries who cannot currently certify this practice.


Predictive Modeling of Huntington's Disease Unfolds Thalamic and Caudate Atrophy Dissociation.
Atrophy in the striatum is a hallmark of Huntington's disease (HD), including the period before clinical motor diagnosis (before-CMD), but it extends to other subcortical structures. The study of the covariation of these structures could improve the detection of disease-related longitudinal progression before-CMD, provide mechanistic insights of the disease, and potentially be used to obtain accurate prospective estimates of atrophy before-CMD and early after-CMD. We analyzed data from 337 before-CMD individuals, 236 healthy control subjects, and 95 early after-CMD individuals from three studies, and we used nine subcortical regions volumes in two analyses. First, we discriminated before-CMD from healthy control trajectories by integrating volume changes from these regions. Second, we estimated prospective atrophy before-CMD and early after-CMD by considering the influence of a region's present volume over the future volume of another one. Before-CMD progression was robustly detected across studies. Indeed, detection of before-CMD progression improved when multiple structures were integrated, as opposed to analyzing the striatum alone, likely because of the reduced partial correlation between caudate and thalamic volume change before-CMD. Our multivariate atrophy prediction model found a thalamus-caudate association that is consistent with this pattern, which yields an improved caudate atrophy prediction in early after-CMD. This study is the first attempt to validate before-CMD multivariate subcortical change detection across studies and to do multivariate prospective atrophy prediction in HD. These models achieve improved performance by detecting a dissociation between caudate and thalamic atrophy trajectories, and they provide a possible mechanistic understanding of the dynamics of HD. © 2022 International Parkinson and Movement Disorder Society.


Functional loss of ubiquitin-specific protease 14 may lead to a novel distal arthrogryposis phenotype.
Multiple congenital contractures (MCC) comprise a number of rare, non-progressive conditions displaying marked phenotypic and etiologic heterogeneity. A genetic cause can be established in approximately half of the affected individuals, attributed to genetic defects in the formation and functioning of the central and peripheral nervous system, neuromuscular junctions, skeletal muscles, and connective tissue. Ubiquitin-specific protease 14 (USP14) encodes a major proteasome-associated deubiquitinating enzyme with an established dual role as an inhibitor and an activator of proteolysis, maintaining protein homeostasis. Usp14-deficient mice show a phenotype similar to lethal human MCC phenotypes, with callosal anomalies, muscle wasting, and early lethality, attributed to neuromuscular junction defects due to decreased monomeric ubiquitin pool. We describe a new, autosomal recessive MCC phenotype in three fetuses from two different branches of a consanguineous family, presenting with distal arthrogryposis, underdevelopment of the corpus callosum, and dysmorphic facial features. Exome sequencing identified a biallelic 4-bp deletion (c.233_236delTTCC; p.Leu78Glnfs*11, SCV002028347) in USP14, and sequencing of family members showed segregation with the phenotype. RT-qPCR experiment in an unaffected heterozygote revealed that mutant USP14 was expressed, indicating that abnormal transcript escapes nonsense-mediated mRNA decay. We propose that herein described fetuses represent the first human phenotype of USP14 loss, with callosal anomalies and/or cortical malformations, multiple contractures, and recognizable dysmorphic facial features.


Evaluation of the effect of interexaminer reliability in clinical trials of dental caries prevention.
Data from a 3-yr clinical trial were used to assess reliability of two dentists who, without standardizing techniques, independently examined 286 continuous participants. Only 13.1 of 128 tooth surfaces (third molars excluded) showed a change in caries status during the trial by one or both examiners' findings. Although there was poor agreement between the examiners (46.5%) on these changes, they agreed very closely on measuring the cariostatic effects in the various treatment groups because the disagreements were random and were similar among groups.


Linkage Analysis and Association Mapping QTL Detection Models for Hybrids Between Multiparental Populations from Two Heterotic Groups: Application to Biomass Production in Maize (Zea mays L.).
Identification of quantitative trait loci (QTL) involved in the variation of hybrid value is of key importance for cross-pollinated species such as maize (Zea mays L.). In a companion paper, we illustrated a new QTL mapping population design involving a factorial mating between two multiparental segregating populations. Six biparental line populations were developed from four founder lines in the Dent and Flint heterotic groups. They were crossed to produce 951 hybrids and evaluated for silage performances. Previously, a linkage analysis (LA) model that assumes each founder line carries a different allele was used to detect QTL involved in General and Specific Combining Abilities (GCA and SCA, respectively) of hybrid value. This previously introduced model requires the estimation of numerous effects per locus, potentially affecting QTL detection power. Using the same design, we compared this "Founder alleles" model to two more parsimonious models, which assume that (i) identity in state at SNP alleles from the same heterotic group implies identity by descent (IBD) at linked QTL ("SNP within-group" model) or (ii) identity in state implies IBD, regardless of population origin of the alleles ("Hybrid genotype" model). This last model assumes biallelic QTL with equal effects in each group. It detected more QTL on average than the two other models but explained lower percentages of variance. The "SNP within-group" model appeared to be a good compromise between the two other models. These results confirm the divergence between the Dent and Flint groups. They also illustrate the need to adapt the QTL detection model to the complexity of the allelic variation, which depends on the trait, the QTL, and the divergence between the heterotic groups.


[Acute urinary retention in a child with acute disseminated encephalomyelitis].
Acute disseminated encephalomyelitis (ADEM) is an immune-mediated inflammatory demyelinating encephalomyelitis with often monosymptomatic abrupt onset, followed by multifocal neurologic symptomatology depending on lesion-site. Diagnosis is made on the basis of characteristic magnetic resonance imaging (MRI) signal alterations. ADEM is sensitive to steroid therapy, immunoglobulins and plasmapheresis, presents usually a monophasic course and disappears completely after 2 or 3 weeks. Resolution of MRI lesions appears usually within 6 months of presentation. We report on a 14-year-old male, admitted to our Emergency Unit because of fever and acute urinary retention with a normal neurological examination. Urinary tract ultrasonography and mictional cystography were normal; electrophysiology showed a mild involvement of the peripheral nervous system and brain and spine MRI revealed disseminated areas of increased signal on T2-weighted sequences suggestive of ADEM. Steroid therapy brought about clinical recovery in a few days. Resolution of lesions on MRI after 4 months and absence of relapses during four-year clinical follow-up confirmed definitive diagnosis. Our case is interesting because, to our knowledge, this is the first literature report with acute urinary retention as predominant symptom in monosymptomatic forms. Another peculiar feature is the absence of associated neurologic symptomatology despite MRI evidence of important brain and spine alterations.


Plastic bullet injuries of the face and jaws.
The plastic bullet or plastic baton round was introduced as an anti-riot weapon in 1976. It has evolved from the rubber bullet and wooden baton round. During the recent unrest in South Africa the plastic bullet was used in riot control. Five cases of facial injury are reported. One involved the middle third of the face and 4 the lower third. In all cases skin lacerations compounded facial fractures. Mandibular fractures ranged from a single displaced body fracture to severe comminuted fractures. The middle-third injury was sufficiently severe to result in blindness of one eye.


Open science practices need substantial improvement in prognostic model studies in oncology using machine learning.
To describe the frequency of open science practices in a contemporary sample of studies developing prognostic models using machine learning methods in the field of oncology. We conducted a systematic review, searching the MEDLINE database between December 1, 2022, and December 31, 2022, for studies developing a multivariable prognostic model using machine learning methods (as defined by the authors) in oncology. Two authors independently screened records and extracted open science practices. We identified 46 publications describing the development of a multivariable prognostic model. The adoption of open science principles was poor. Only one study reported availability of a study protocol, and only one study was registered. Funding statements and conflicts of interest statements were common. Thirty-five studies (76%) provided data sharing statements, with 21 (46%) indicating data were available on request to the authors and seven declaring data sharing was not applicable. Two studies (4%) shared data. Only 12 studies (26%) provided code sharing statements, including 2 (4%) that indicated the code was available on request to the authors. Only 11 studies (24%) provided sufficient information to allow their model to be used in practice. The use of reporting guidelines was rare: eight studies (18%) mentioning using a reporting guideline, with 4 (10%) using the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis Or Diagnosis statement, 1 (2%) using Minimum Information About Clinical Artificial Intelligence Modeling and Consolidated Standards Of Reporting Trials-Artificial Intelligence, 1 (2%) using Strengthening The Reporting Of Observational Studies In Epidemiology, 1 (2%) using Standards for Reporting Diagnostic Accuracy Studies, and 1 (2%) using Transparent Reporting of Evaluations with Nonrandomized Designs. The adoption of open science principles in oncology studies developing prognostic models using machine learning methods is poor. Guidance and an increased awareness of benefits and best practices of open science are needed for prediction research in oncology.


Pathways of mucin O-glycosylation in normal and malignant rat colonic epithelial cells reveal a mechanism for cancer-associated Sialyl-Tn antigen expression.
The Sialyl-Tn antigen (Sialyl alpha-Ser/Thr) is expressed as a cancer-associated antigen on the surface of cancer cells. Its presence is associated with a poor prognosis in patients with colorectal and other cancers. We previously reported that Sialyl-Tn expression in LSC human colon cancer cells could be explained by a specific lack of the activity of core 1 beta3-Gal-transferase (Brockhausen et al., Glycoconjugate J. 15, 595-603, 1998) and an inability to synthesize the common O-glycan core structures. To support this mechanism, or find other mechanisms to explain Sialyl-Tn antigen expression, we investigated the O-glycosylation pathways in clonal rat colon cancer cell lines that were selected for positive or negative expression of Sialyl-Tn antigen, and compared these pathways to those in normal rat colonic mucosa. Normal rat colonic mucosa had very active glycosyltransferases synthesizing O-glycan core structures 1 to 4. Several sialyl-, sulfo- and fucosyltransferases were also active. An M type core 2 beta6-GlcNAc-transferase was found to be present in rat colon mucosa and all of the rat colon cancer cells. O-glycosylation pathways in rat colon cancer cells were significantly different from normal rat colonic mucosa; for example, rat colon cancer cells lost the ability to synthesize O-glycan core 3. All rat colon cancer cell lines, regardless of the Sialyl-Tn phenotype, expressed glycosyltransferases assembling complex O-glycans of core 1 and core 2 structures (unlike human LSC colon cancer cells which lack core 1 beta3-Gal-transferase activity). It was the activity of CMP-sialic acid:GalNAc-mucin alpha6-sialyltransferase that coincided with Sialyl-Tn expression. Sialyl-Tn negative cells had a several fold higher activity of core 2 beta6-GlcNAc-transferase which synthesizes complex O-glycans that may mask adjacent Sialyl-Tn epitopes. The results suggest a new mechanism controlling Sialyl-Tn expression in cancer cells.


Expression of D-myo-inositol-3-phosphate synthase in soybean. Implications for phytic acid biosynthesis.
Phytic acid, a phosphorylated derivative of myo-inositol, functions as the major storage form of phosphorus in plant seeds. Myo-inositol phosphates, including phytic acid, play diverse roles in plants as signal transduction molecules, osmoprotectants, and cell wall constituents. D-myo-inositol-3-phosphate synthase (MIPS EC 18.104.22.168) catalyzes the first step in de novo synthesis of myo-inositol. A soybean (Glycine max) MIPS cDNA (GmMIPS1) was isolated by reverse transcriptase-PCR using consensus primers designed from highly conserved regions in other plant MIPS sequences. Southern-blot analysis and database searches indicated the presence of at least four MIPS genes in the soybean genome. Northern-blot and immunoblot analyses indicated higher MIPS expression and accumulation in immature seeds than in other soybean tissues. MIPS was expressed early in the cotyledonary stage of seed development. The GmMIPS1 expression pattern suggested that it encodes a MIPS isoform that functions in seeds to generate D-myo-inositol-3-phosphate as a substrate for phytic acid biosynthesis.