Transgender in Africa: invisible, inaccessible, or ignored?
Transgender people are an important key population for HIV risk globally, and several studies have found HIV prevalence rates in transgender populations that are significantly higher than those among other key populations such as men who have sex with men (MSM). There is a lack of research on transgender populations in Africa, and at present, there is almost no data available on HIV prevalence and risk among transgender people on the continent. It is possible that the invisibility of transgender people in epidemiological data from Africa is related to the criminalisation of same-sex behaviour in many countries and the subsequent fear of negative repercussions from participation in research. Alternatively, transgender people may be being overlooked in research due to confusion among researchers about how to ask questions about gender identity. It is also possible that transgender populations have simply been ignored in research to date. Without research on transgender-specific HIV prevalence and risk, it is very difficult to know what interventions and services are needed for this risk population. Therefore, it is important that researchers, governments, Non Governmental Organisations (NGOs) and donor organisations begin to pay explicit attention to transgender people in their HIV-related research and programmes in Africa.


Psychology/Counseling: a universal competency in athletic training.
To present the rationale that certified athletic trainers (ATCs) may require structured educational training in the psychological aspects of athletic injury. We searched MEDLINE, Psych Lit, Psyc- INFO, First Search, and SPORT Discus databases for the years 1990 through 1999 under the search terms "psychological distress," "depression," "athletic injury," and "rehabilitation adherence." Psychological factors are significant predictors of athletic injury. Athletic injury is accompanied by significant psychological distress, which has been shown to impair rehabilitation compliance and possibly physical recovery. Although "counseling" and knowledge of psychological aspects of injury are required National Athletic Trainers' Association competencies, extant data suggest that athletic trainers may lack training in this competency. Evidence suggests that (1) psychological distress is prospectively associated with the incidence of athletic injury, and prolonged psychological distress, specifically depression, may occur after athletic injury; (2) psychological factors may also either hinder or facilitate rehabilitation adherence, compliance, and recovery; (3) psychological distress may persist even after physical recovery has been completed; (4) psychosocial factors related to injury occurrence and injury recovery may be overlooked by ATCs, but knowledge of these factors and appropriate use of referral sources may enhance the effectiveness of ATCs; and (5) ATCs may benefit from structured educational experiences specific to the National Athletic Trainers' Association psychology/counseling competency. With 75% of a national survey of ATCs indicating that they do not have access to a sport psychologist, it would be advantageous for ATCs to gain adequate training in the recognition, evaluation, and treatment of psychological factors associated with athletic injury. The literature also suggests that structured educational training with respect to psychological aspects of athletic injury would be well received by ATCs.


Presentation of Original Research at the European Congress of Radiology 2010: Frequency of Publication in Medline-Indexed Journals Within 5 Years After Presentation.
To determine the rate at which original studies presented orally at the European Congress of Radiology (ECR) 2010 were published in Medline-indexed journals and to identify factors predictive of publication. A total of 869 abstracts were included in the study. A Medline search of articles published between March 2010 and February 2015 was conducted to identify articles written by the first, second, and/or last authors of all abstracts published in the Scientific Program of ECR 2010. The publication year, journal, country of origin, subspecialty and nature of the research (i. e., human, animal or technical) were recorded. Between March 2010 and February 2015 a total of 450 abstracts (publication rate, 51.8 %) were subsequently published in 125 Medline-indexed journals, chiefly in European Radiology (11.1 %). 443/450 (98.4 %) articles were published in English language. The subspecialties of molecular imaging and cardiac imaging had the highest publication rates (75.0 % and 62.0 %, respectively), while computer application studies had the lowest (27.6 %). The nature of research, origin of the abstract and subspecialty significantly influenced the subsequent publication rate. More than half of the original studies presented orally at ECR 2010 were subsequently published in Medline-indexed journals. More articles were published in the journal European Radiology than in any other identified journal. · ECR 2010 had a high subsequent publication rate. · Most subsequently published articles were published in radiology journals. · Nearly all articles were published in the English language. · Dollinger M, Zeman F, Müller-Wille R et al. Presentation of Original Research at the European Congress of Radiology 2010: Frequency of Publication in Medline-Indexed Journals Within 5 Years After Presentation. Fortschr Röntgenstr 2017; 190: 327 - 333.


Intentional deep overfit learning (IDOL): A novel deep learning strategy for adaptive radiation therapy.
Applications of deep learning (DL) are essential to realizing an effective adaptive radiotherapy (ART) workflow. Despite the promise demonstrated by DL approaches in several critical ART tasks, there remain unsolved challenges to achieve satisfactory generalizability of a trained model in a clinical setting. Foremost among these is the difficulty of collecting a task-specific training dataset with high-quality, consistent annotations for supervised learning applications. In this study, we propose a tailored DL framework for patient-specific performance that leverages the behavior of a model intentionally overfitted to a patient-specific training dataset augmented from the prior information available in an ART workflow-an approach we term Intentional Deep Overfit Learning (IDOL). Implementing the IDOL framework in any task in radiotherapy consists of two training stages: (1) training a generalized model with a diverse training dataset of N patients, just as in the conventional DL approach, and (2) intentionally overfitting this general model to a small training dataset-specific the patient of interest ( N + 1 ) generated through perturbations and augmentations of the available task- and patient-specific prior information to establish a personalized IDOL model. The IDOL framework itself is task-agnostic and is, thus, widely applicable to many components of the ART workflow, three of which we use as a proof of concept here: the autocontouring task on replanning CTs for traditional ART, the MRI super-resolution (SR) task for MRI-guided ART, and the synthetic CT (sCT) reconstruction task for MRI-only ART. In the replanning CT autocontouring task, the accuracy measured by the Dice similarity coefficient improves from 0.847 with the general model to 0.935 by adopting the IDOL model. In the case of MRI SR, the mean absolute error (MAE) is improved by 40% using the IDOL framework over the conventional model. Finally, in the sCT reconstruction task, the MAE is reduced from 68 to 22 HU by utilizing the IDOL framework. In this study, we propose a novel IDOL framework for ART and demonstrate its feasibility using three ART tasks. We expect the IDOL framework to be especially useful in creating personally tailored models in situations with limited availability of training data but existing prior information, which is usually true in the medical setting in general and is especially true in ART.


Isolation of cDNAs for trypsinogen from the winter flounder, Pleuronectes americanus.
Knowledge of the timing of digestive enzyme expression in developing larvae is essential for evaluating the appropriateness of formulated larval diets. Since little is known at the molecular biological level about the ontogeny of digestive enzyme function in flatfish, we have isolated cDNA clones for key digestive enzymes such as trypsinogen. Portions of trypsinogen genes have been amplified from winter flounder cDNA libraries by PCR using primers based on sequence motifs conserved among trypsinogen genes from other organisms. The PCR products were sequenced, cloned, and used as radioactively labeled probes to screen the libraries. Three distinct trypsinogen cDNAs have been isolated, representing the first cDNAs for winter flounder digestive enzymes. The first type (Flounder 1) is very similar to a trypsinogen sequence reported from a related flounder, Pleuronectes platessa. The second type (Flounder 2) is related to sequences reported from Atlantic salmon, cod, and the Antarctic fish, Paranotothenia magellanica. The third type (Flounder 3) shows limited similarity to the Antarctic fish trypsinogen sequence. All three cDNAs encode a cleavable signal sequence at the amino-terminal end, and Flounder 1 and 2 contain the characteristic acidic sequence for activation of the trypsinogen proenzyme to trypsin. Southern hybridization experiments indicate that Flounder 1 and 3 are single-copy genes, whereas Flounder 2 may be present in more than one copy. In addition, Flounder 2 detects homologs in a wide variety of other fish species. The sequence information will be used to establish RT-PCR assays for larval winter flounder (Pleuronectes americanus) digestive enzyme expression.


Immunologic investigation of Chinese hemophiliacs with and without human immunodeficiency virus infection.
Cellular and humoral immune functions in Chinese hemophiliacs with and without human immunodeficiency virus (HIV) infection were compared with those of healthy controls. There was a significant increase in peripheral T8 cells and a significant decrease of peripheral T4 cells as well as the T4/T8 ratio in 3 hemophiliacs with HIV infection when compared with 26 hemophiliacs without HIV infection and 18 healthy controls (P less than 0.005, P less than 0.05 and P less than 0.002, respectively). In contrast, there were no statistical differences in the above mentioned parameters between hemophiliacs without HIV infection and healthy controls. All the three HIV seropositive hemophiliacs had anergy for 1:2000 OT test whereas among the 15 HIV seronegative hemophiliacs, only two had anergy for 1:2000 OT test. These results demonstrate that the immunological abnormalities of the 3 HIV seropositive hemophiliacs were attributed to HIV infection, and that even though hemophiliacs without HIV infection had been treated with blood products, their immune functions are generally normal. These findings are somewhat different from those reported abroad. This difference may be due to the fact that Chinese hemophiliacs are often treated with much smaller dose of blood products as a part of the treatment of their coagulative defects.


A built-in strategy to mitigate transgene spreading from genetically modified corn.
Transgene spreading is a major concern in cultivating genetically modified (GM) corn. Cross-pollination may cause the spread of transgenes from GM cornfields to conventional fields. Occasionally, seed lot contamination, volunteers, mixing during sowing, harvest, and trade can also lead to transgene escape. Obviously, new biological confinement technologies are highly desired to mitigate transgene spreading in addition to physical separation and isolation methods. In this study, we report the development of a built-in containment method to mitigate transgene spreading in corn. In this method, an RNAi cassette for suppressing the expression of the nicosulfuron detoxifying enzyme CYP81A9 and an expression cassette for the glyphosate tolerant 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene G10 were constructed and transformed into corn via Agrobacterium-mediated transformation. The GM corn plants that were generated were found to be sensitive to nicosulfuron but resistant to glyphosate, which is exactly the opposite of conventional corn. Field tests demonstrated that GM corn plants with silenced CYP81A9 could be killed by applying nicosulfuron at 40 g/ha, which is the recommended dose for weed control in cornfields. This study suggests that this built-in containment method for controlling the spread of corn transgenes is effective and easy to implement.


Manufacture of acid gels from skim milk using high-pressure homogenization.
The effect of high-pressure homogenization (HPH) alone or in combination with a thermal treatment (TT) was investigated for the manufacture of acid gels from skim milk. Raw skim milk was subjected to HPH (0 to 350 MPa) or a TT (90 degrees C, 5 min), or both, in the following processing combinations: 1) HPH, 2) HPH followed by TT, 3) TT followed by HPH, 4) TT, and 5) raw milk (control). After treatments, L* (lightness) values were measured, and then skim milk was acidified with 3% glucono-delta-lactone and rheological properties (G' and gelation time), and whey holding capacity was evaluated. Treatments in which HPH and TT were combined showed greater L* values than those in which just HPH was applied. In all treatments, the L* values decreased as the pressure was increased up to 300 MPa with little change afterward. Gelation times were lower when HPH was combined with TT compared with the acid skim milk gels that were just pressure treated. The final G' in gels obtained from skim milk subjected to the combined process (HPH and TT) was greater and pressure-dependent compared with all other gels. A maximum G' (~320 Pa) was observed with skim milk subjected to a combination of thermal processing before or after HPH at 350 MPa. Acid gels obtained from HPH milk at 350 MPa showed a linear decrease in whey holding capacity over time, retaining 20% more whey after centrifugation for 25 min compared with samples treated at lower pressures and all other treatments. Our results suggest that HPH in combination with TT can be used to improve the rheological properties and stability of yogurt, thus decreasing the need for additives.


Comparison of polymyxin B, tigecycline, cefepime, and meropenem MICs for KPC-producing Klebsiella pneumoniae by broth microdilution, Vitek 2, and Etest.
We report MIC agreement and error rates between broth microdilution (BMD), Vitek 2, and Etest against 48 clinical KPC-producing Klebsiella pneumoniae isolates for polymyxin B, tigecycline, cefepime, and meropenem. Both commercial testing methods were useful for tigecycline testing; Etest provided a conservative estimate of polymyxin B susceptibility. We suggest that laboratories consider the supplemental use of reference BMD or Etest for cefepime and meropenem for susceptibility testing of KPC-producing K. pneumoniae, as Vitek 2 did not provide reliable results.


Population pharmacokinetics of teicoplanin administered by subcutaneous or intravenous route and simulation of optimal loading dose regimen.
To investigate the population pharmacokinetics of teicoplanin in patients treated by the subcutaneous (sc) and/or intravenous (iv) route. Non-linear mixed-effects modelling described teicoplanin concentrations from 98 patients with infection caused by Gram-positive cocci. Monte Carlo simulations were performed to evaluate the probability of target attainment (PTA) of various dosage regimens. Teicoplanin concentrations were best described by a two-compartment model with clearance predicted by estimated glomerular filtration rate. Estimated absorption rate constant (between-subject variability) was 0.039 h-1 (77%), clearance was 0.305 L/h (28%), central volume was 10.3 L (49%), inter-compartmental clearance was 4.42 L/h (66%) and peripheral volume was 97.4 L (51%). The sc route was associated with lower initial Cmin and AUC (day 3: loading phase) compared with the iv route. This difference appeared to vanish after 14 days, with comparable simulated PTAs based on the Cmin and AUC for all tested dosages (400, 600, 800 and 1000 mg every 12 h). However, a loading dose regimen with five administrations of either 400 or 600 mg was not sufficient to achieve the target Cmin (≥15 mg/L) for both routes. Also, PTAs for higher MIC (≥1.0 mg/L) were poor with all regimens for both routes. This is the first study examining the pharmacokinetic/pharmacodynamic implications of using the sc route for teicoplanin. Subcutaneous administration is associated with lower Cmin and AUC values after the loading phase compared with iv administration. Therefore, iv administration should be preferred in the first few days of therapy. This study also shows that loading doses of teicoplanin higher than currently recommended should be used to improve PTA.


Prediction of drinking water quality with machine learning models: A public health nursing approach.
The aim of this study is to use machine learning models to predict drinking water quality from a public health nursing approach. Machine learning study. "Water Quality Dataset" was used in the study. The dataset contains physical and chemical measurements of water quality for 2400 different water bodies. The process consists of four stages: Data processing with Synthetic Minority Oversampling Technique, hyperparameter tuning with 10-fold cross-validation, modeling and comparative analysis. 80% of the dataset is allocated as training data and 20% as test data. ML models logistic regression, K-nearest neighbor, support vector machine, random forest, XGBoost, AdaBoost Classifier, Decision Tree algorithms were used for water quality prediction. Accuracy, precision, recall, F1 score and AUC performance metrics of ML models were compared. To evaluate the performance of the models, 10-fold cross-validation was used and a comparative analysis was performed. The p-values of the models were also compared. N this study, where drinking water quality was predicted with seven different ML algorithms, it can be said that XGBoost and Random Forest are the best classification models in all performance metrics. There is a significant difference in all ML algorithms according to the p-value. The H0 hypothesis is accepted for these algorithms. According to the H0 hypothesis, there is no difference between actual values and predicted values. In conclusion, the use of ML models in the prediction of drinking water quality can help nurses greatly improve access to clean water, a human right, be more knowledgeable about water quality, and protect the health of individuals.


Erythropoietin reduces the development of experimental inflammatory bowel disease.
Inflammatory bowel disease is characterized by oxidative and nitrosative stress, leukocyte infiltration, and up-regulation of the expression of intercellular adhesion molecule-1 (ICAM-1) in the colon. Erythropoietin (EPO) is a potent stimulator of erythroid progenitor cells, and its expression is enhanced by hypoxia. Here we investigate the effects EPO has on the development of experimental colitis. To address this question, we used an experimental model of colitis induced by dinitrobenzene sulfonic acid (DNBS). When compared with DNBS-treated mice, EPO (1000 IU/kg day s.c.)-treated mice subjected to DNBS-induced colitis experienced significantly lower rates in the extent and severity of the histological signs of colon injury. DNBS-treated mice experienced diarrhea and weight loss. At 4 days after administration of DNBS, the mucosa of the colon exhibited large areas of necrosis. Neutrophil infiltration (determined by histology as well as an increase in myeloperoxidase activity in the mucosa) was associated with up-regulation of ICAM-1. Immunohistochemistry for nitrotyrosine and poly(ADP-ribose) showed an intense staining in the inflamed colon. On the contrary, the treatment of DNBS-treated mice with EPO significantly reduced the degree of diarrhea and weight loss caused by administration of DNBS. EPO also caused a substantial reduction of the degree of colon injury, the rise in myeloperoxidase activity (mucosa), and the increase in staining (immunohistochemistry) for nitrotyrosine as well as the up-regulation of ICAM-1 caused by DNBS in the colon. Thus, treatment of rat with EPO reduces the degree of colitis caused by DNBS. We propose that EPO may be useful in the treatment of inflammatory bowel disease.


[Influence of habitual chocolate consumption over the Mini-Mental State Examination in Spanish older adults].
There are associations described between dementia, mild cognitive impairment (MCI) and foods with a high content of polyphenols. To assess the infl uence of habitual chocolate consumption over the MMSE in Spanish older adults. Cross-sectional study, using data of the follow-up of the Seniors-Study on Nutrition and Cardiovascular Risk in Spain (ENRICA) cohort. Habitual chocolate consumption in the last year was assessed with a computerized dietary history; differences between dark chocolate and milk chocolate were recorded. Chocolate intake was classified into the following categories: no consumption, < 10 g/day, and ≥ 10 g/day. Validated MMSE scores for Spain were obtained during an interview and different cutoff points were used to define ≤ 25, ≤ 24 and ≤ 23. Linear and logistic regression models were used to calculate adjusted beta coefficients and odds ratios (OR). Compared to non-consumers, participants with a habitual chocolate consumption of ≥ 10 g/d had a better MMSE score (adjusted beta coefficient and 95% confidence interval: 0.26 (0.02-0.50; p trend = 0.05); for dark chocolate, the results were also statistically significant (0.48 [0.18-0.78]; p trend < 0.001). Total chocolate consumption was not associated with higher likelihood of having MCI. However, dark chocolate consumption was associated with less likelihood of MCI (OR and 95%CI for MMSE ≤ 25: 0.39 [0.20-0.77]; for MMSE ≤ 24: 0.26 [0.10-0.67]; and for MMSE ≤ 23: 0.25 [0.07-0.82]). Our results suggest that habitual dark chocolate consumption might improve cognitive function among the older population.


Bovine gamma globulin-specific CD4+ T cells are retained by bovine gamma-globulin-tolerant mice.
Immunological tolerance is an acquired state of antigen-specific nonresponsiveness which is generally attributed to either the deletion or suppression of tolerogen-specific T helper cell clones. Unresponsiveness to xenogeneic immunoglobulins can be readily induced and has been extensively studied in order to ascertain the means by which tolerance is established and maintained. As an absence of reactivity to foreign immunoglobulin has been noted in situations where suppressor cell activity was minimized, this tolerant state has often been ascribed to clonal deletion. The present study demonstrates that bovine gamma-globulin (BGG)-tolerant mice are unable to generate humoral responses to BGG in vivo and yet harbor BGG-specific CD4+CD8- T cells which can divide and secrete interleukin 2 when stimulated in vitro. Indeed, the in vitro reactivity to BGG of these cells exceeded that of a similar population of non-immune cells. This is in direct opposition to the loss of response that would be expected if clonal deletion were operative. The presence of BGG-specific CD4+ T cells, which appear to be at least partly primed, in mice unresponsive to BGG, indicates that tolerance to BGG is likely to be dependent on unidentified immunoregulatory processes rather than clonal deletion.


Navigating the Chemical Space and Chemical Multiverse of a Unified Latin American Natural Product Database: LANaPDB.
The number of databases of natural products (NPs) has increased substantially. Latin America is extraordinarily rich in biodiversity, enabling the identification of novel NPs, which has encouraged both the development of databases and the implementation of those that are being created or are under development. In a collective effort from several Latin American countries, herein we introduce the first version of the Latin American Natural Products Database (LANaPDB), a public compound collection that gathers the chemical information of NPs contained in diverse databases from this geographical region. The current version of LANaPDB unifies the information from six countries and contains 12,959 chemical structures. The structural classification showed that the most abundant compounds are the terpenoids (63.2%), phenylpropanoids (18%) and alkaloids (11.8%). From the analysis of the distribution of properties of pharmaceutical interest, it was observed that many LANaPDB compounds satisfy some drug-like rules of thumb for physicochemical properties. The concept of the chemical multiverse was employed to generate multiple chemical spaces from two different fingerprints and two dimensionality reduction techniques. Comparing LANaPDB with FDA-approved drugs and the major open-access repository of NPs, COCONUT, it was concluded that the chemical space covered by LANaPDB completely overlaps with COCONUT and, in some regions, with FDA-approved drugs. LANaPDB will be updated, adding more compounds from each database, plus the addition of databases from other Latin American countries.


Ibuprofen agglomerates preparation by phase separation.
The compression ability and dissolution rate of ibuprofen are poor. There are many processes to optimize these properties through adapted formulations. However, it would be more satisfactory to obtain directly during the crystallization step crystalline particles that can be directly compressed and quickly dissolved. This was the aim of this work. Ibuprofen spherical agglomerates were obtained using a very simple method based on the difference of solubility of ibuprofen in ethanol and in water. By cooling down an ibuprofen-saturated solution in an ethanol/water 50/50 mixture from 60 degrees C to room temperature under stirring, a phase separation occurs. Ibuprofen crystallizes in separated water droplets. After separation by sieving and drying, spherical agglomerates were obtained. A study of the physical properties of ibuprofen agglomerates was carried out using electron scanning microscopy and X-ray powder diffraction. The compression ability was tested using an instrumented tablet machine, and the dissolution rate was measured using continuous flow cells. An improvement in compression and dissolution properties of the spherical agglomerates produced was observed. The process of crystallization in a separated dispersed phase could be envisaged each time a drug exhibits opposite solubilities in two miscible solvents.


Cost-effectiveness of adjunctive eptifibatide in patients undergoing coronary stenting in Germany.
To determine the cost-effectiveness of adding eptifibatide to the standard treatment for selected high-risk patients undergoing coronary stenting in Germany. Furthermore, to investigate the impact of several extrapolation methods on the results. A Markov model was developed to reflect the clinical events in this specific patient population, including target vessel revascularization, myocardial infarction, and death. To extrapolate clinical data beyond 1 year, a linear, an exponential, and a Weibull survival curves were estimated. Patient characteristics and transition probabilities were derived from a high-risk subgroup of the ESPRIT trial; patient-level utility data came from a published Dutch study. Costs were calculated from a hospital and from a third-party payer perspective. For both perspectives, the additional treatment with eptifibatide is the considered dominant alternative. The incremental net benefit of its use exceeds €10,000 for both perspectives. Results proved stable in probabilistic sensitivity analysis as well as under the different extrapolation scenarios. Eptifibatide is likely to be dominant strategy with 77.7 and 96.7% of the simulations leading to QALYs gained and generating cost savings from both the hospital and the third-party payer perspective. Eptifibatide offsets its additional treatment costs by avoiding costly repeat procedures and leads to positive QALY gains by preventing cardiovascular events lending themselves to transient or permanent lower quality of life. The method used to extrapolate the short-term risks did not impact on results, mainly due to similar clinical risk profiles between the two treatment groups in the long term.


Patient Identification of Diagnostic Safety Blindspots and Participation in "Good Catches" Through Shared Visit Notes.
Policy Points Patients and families can identify clinically relevant errors, including "blindspots"-safety hazards that are difficult for clinicians or organizations to see. Health information transparency, including patient access to electronic visit notes, now federally mandated in the US and the subject of policy debate worldwide, creates a new opportunity to engage patients in diagnostic safety. However, not all patients access notes. Patient identification of blindspots in their notes underscores the need to systematically and equitably engage willing patients in safety, promote patient "good catches," and establish routine systems for patient feedback to help avoid preventable diagnostic errors and delays. Policy shifts toward health information transparency provide a new opportunity for patients to contribute to diagnostic safety. We investigated whether sharing clinical notes with patients can support identification of "diagnostic safety blindspots"-potentially consequential breakdowns in the diagnostic process that may be difficult for clinical staff to observe. We used mixed methods to analyze patient-reported ambulatory documentation errors among 22,889 patients at three US health care centers who read ≥ 1 visit note(s). We identified blindspots by tailoring a previously established taxonomy. We used multiple regression analysis to identify factors associated with blindspot identification. 774 patients reported a total of 962 blindspots in 4 categories: (1) diagnostic misalignments (n = 421, 43.8%), including inaccurate symptoms or histories and failures or delay in diagnosis; (2) errors of omission (38.1%) including missed main concerns or next steps, and failure to listen to patients; (3) problems occurring outside visits (14.3%) such as tests, referrals, or appointment access; and (4) multiple low-level problems (3.7%) cascading into diagnostic breakdowns. Many patients acted on the blindspots they identified, resulting in "good catches" that may prevent potential negative consequences. Older, female, sicker, unemployed or disabled patients, or those who work in health care were more likely to identify a blindspot. Individuals reporting less formal education; those self-identifying as Black, Asian, other, or multiple races; and participants who deferred decision-making to providers were less likely to report a blindspot. Patients who read notes have unique insight about potential errors in their medical records that could impact diagnostic reasoning but may not be known to clinicians-underscoring a critical role for patients in diagnostic safety and organizational learning. From a policy standpoint, organizations should encourage patient review of visit notes, build systems to track patient-reported blindspots, and promote equity in note access and blindspot reporting.


Antibacterial and Inhibitory Activities against Nitric Oxide Production of Coumaronochromones and Prenylated Isoflavones from Millettia extensa.
A chemical investigation of leaf and root extracts of Millettia extensa led to the isolation and structural elucidation of four new prenylated isoflavones, millexatins G-J (1-4), and three new coumaronochromones, millexatins K-M (5-7), along with 16 known compounds. The structures of the new compounds were determined on the basis of NMR and MS data. Compound 4 is a rare isoflavone having a 2-hydroxyethyl moiety at C-8, whereas the structures of compounds 5-7 formally arise from a ring closure through HO-2' and C-2. The absolute configurations at the C-2 and C-3 positions of 5 and 6 were determined from their ECD spectra through comparison with those of previously reported compounds. Most of compounds were evaluated for their inhibitory effects against nitric oxide (NO) production on RAW264.7 macrophages and their antibacterial activities. Compounds 18 and 19 inhibited NO production with IC50 values of 8.5 and 14.3 μM, respectively. Compounds 13 and 14 showed antibacterial activity against various Gram-positive bacteria with MIC values ranging from 2 to 8 μg/mL.


Impairment of muscle stretch reflexes in tick paralysis.
Experiments with tick-paralyzed dogs and woodchucks have shown impairment of stretch reflexes in addition to partial paralysis at the neuromuscular junction. Stretch reflexes disappear very early during paralysis, whereas nociceptive reflexes do not appear to be directly affected. The early incoordination and the ascending nature of the paralysis may be related to impairment of stretch reflex pathways.


Ultrasonic guided percutaneous ethanol injection with or without combined radiofrequency ablation for hepatocellular carcinomas.
The aim of this retrospective study was to evaluate whether radiofrequency ablation (RFA) combined percutaneous ethanol injection (PEI) in the management of hepatocellular carcinoma (HCC) improves treatment outcomes. We retrospectively included 66 HCC patients who received RFA or RFA plus PEI from February 2011 to January 2014 in Jingmen No. 1 People's Hospital. Moreover, 31 cases received RFA plus PEI as the experiment group and 35 subjects treated with RFA aloe as the control group. The overall survival and treatment related complications were compared between the two groups. For RFA group, the 1-year, 2-year, and 3-year survival rate were 82.0%, 69.3%, and 30.7%, respectively, with the median survival time of 27.1 months. For RFA plus PEI group, the 1-year, 2-year, and 3-year survival rate were 97.1%, 73.9%, and 37.5%, respectively, with the median survival time of 33.6 months. The overall survival of the two groups was not statistical different with the hazard ratio of 1.48 (P > 0.05); three cases of treatment associated complications were found in RFA group with 1 abscess, 1 pleural effusion, and 1 portal vein thrombosis. Moreover, 2 cases of complication were recorded in RFA plus PEI group with 1 pleural effusion and 1 portal vein thrombosis. The complicated incidence rate was not statistical different between the two groups (P < 0.05). The combination treatment of HCC was safe and had a slightly higher primary effectiveness rate than RFA alone.


Plasminogen activators of the pituitary gland: enzyme characterization and hormonal modulation.
We studied plasminogen activator (PA) of the rat pituitary gland in organ and cell monolayer culture. Both anterior and intermediate lobes contain, synthesize and secrete a mixture consisting of the two known types of PA: urokinase and so-called tissue PA. Both enzymes were formed essentially by all PA secreting cells, and PA was identified specifically in mammotrophs, corticotrophs, and luteinizing hormone containing gonadotrophs. Pituitary PA production was modulated on exposure to a variety of biological effectors: anterior lobe PA secretion was stimulated by agents that raised intracellular cAMP concentration; his process depended on de novo enzyme synthesis. Enzyme production was repressed by androgens and glucocorticoids. When anterior lobe cultures were maintained in plasminogen-free media, the extracellular, secreted forms of ACTH consisted almost exclusively of the high molecular weight forms (31,000 and 23,000); the smaller forms (13,000 and 4,500) were also found in the extracellular medium of cultures supplemented with plasminogen. In contrast, the size distribution of intracellular ACTH species was unaffected by the presence of plasminogen. These results resemble those previously obtained with pancreatic islets and are consistent with the possibility that plasmin, generated by PA secretion, participates in prohormone processing. PA synthesis in intermediate lobe explants was stimulated by exposure to dibutyryl cAMP, and repressed by hydrocortisone. In accordance with the dopaminergic control of intermediate lobe function in some vertebrates, apomorphine strongly repressed PA synthesis in intermediate, but not anterior lobe cultures.


Novel peptide with a specific calcium-binding capacity from whey protein hydrolysate and the possible chelating mode.
A novel peptide with a specific calcium-binding capacity was isolated from whey protein hydrolysates. The isolation procedures included diethylaminoethyl (DEAE) anion-exchange chromatography, Sephadex G-25 gel filtration, and reversed-phase high-performance liquid chromatography (HPLC). A peptide with a molecular mass of 237.99 Da was identified by liquid chromatography-electrospray ionization/mass spectrometry (LC-ESI/MS), and its amino acid sequence was confirmed to be Gly-Tyr. The calcium-binding capacity of Gly-Tyr reached 75.38 μg/mg, increasing by 122% when compared to the hydrolysate complex. The chelating interaction mode between the Gly-Tyr and calcium ion was investigated, indicating that the major binding sites included the oxygen atom of the carbonyl group and nitrogen of the amino or imino group. The folding and structural modification of the peptide arose along with the addition of the calcium ion. The profile of (1)H nuclear magnetic resonance (NMR) spectroscopy demonstrated that the electron cloud density around the hydrogen nucleus in the peptide changed was caused by the calcium ion. The results of ζ potential showed that the Gly-Tyr-Ca chelate was a neutral molecule in which the calcium ion was surrounded by the specific binding sites of the peptide. Moreover, thermogravimetry-differential scanning calorimetry (TG-DSC) and calcium-releasing assay revealed that the Gly-Tyr-Ca chelate exerted excellent thermal stability and solubility in both acidic and basic conditions, which were beneficial to calcium absorption in the gastrointestinal tract of the human body and, therefore, improved its bioavailability. These findings further the progress in the research of whey protein, suggesting the potential in making peptide-calcium chelate as a dietary supplement.


N-H...F hydrogen bonds in fluorinated benzanilides: NMR and DFT study.
Using (19)F and (1)H-NMR (with (14)N decoupling) spectroscopic techniques together with density functional theoretical (DFT) calculations, we have investigated weak molecular interactions in isomeric fluorinated benzanilides. Simultaneous presence of through space nuclear spin-spin couplings ((1h)J(N-HF)) of diverse strengths and feeble structural fluctuations are detected as a function of site specific substitution of fluorine atoms within the basic identical molecular framework. The transfer of hydrogen bonding interaction energies through space is established by perturbing their strengths and monitoring the effect on NMR parameters. Multiple quantum (MQ) excitation, up to the highest possible MQ orders of coupled protons, is utilized as a tool for accurate (1)H assignments. Results of NMR studies and DFT calculations are compared with the relevant structural parameters taken from single crystal X-ray diffraction studies.


Machine learning early prediction of respiratory syncytial virus in pediatric hospitalized patients.
Respiratory syncytial virus (RSV) causes millions of infections among children in the US each year and can cause severe disease or death. Infections that are not promptly detected can cause outbreaks that put other hospitalized patients at risk. No tools besides diagnostic testing are available to rapidly and reliably predict RSV infections among hospitalized patients. We conducted a retrospective study from pediatric electronic health record (EHR) data and built a machine learning model to predict whether a patient will test positive to RSV by nucleic acid amplification test during their stay. Our model demonstrated excellent discrimination with an area under the receiver-operating curve of 0.919, a sensitivity of 0.802, and specificity of 0.876. Our model can help clinicians identify patients who may have RSV infections rapidly and cost-effectively. Successfully integrating this model into routine pediatric inpatient care may assist efforts in patient care and infection control.


[Biochemical and anatomic changes in the muscles after leg bone lengthening by the Ilizarov method].
In process of crus lengthening, following the method, given by Ilizarov G. A., with 22 adult patients have been studied the peculiarities of metabolic processes of muscle tissue of the lengthened segment as well as the muscle tissue structural changes. As the tests were used; determination of lactate dehydrogenase content and its isoenzymatic spectrum in the blood serum, the residual products of lactic and pyruvic acids glycolysis, relating to the higher indications of the internal medium of an organism; carboxylase activity detection. Energy provision of an organism was estimated according to the ATP content; anatomical state of muscles of the lengthened extremity segment and muscle tissue structure were estimated by means of contrast myography. Dynamics of biochemical indexes suggests that the sparing character of an operation, patient mobility from the first days, preservation of locomotive and supporting function contribute to prevention of metabolic disease and ensure earlier transformation of catabolic reaction to anabolic one. Carboxylase and lactate-dehydrogenase activity increase indicates the biochemical adaptation of an organism. Metabolic changes well correlate with the detected structural changes in the lengthened crus muscles.


Platelet glycoproteins IIb and IIIa: evidence for a family of immunologically and structurally related glycoproteins in mammalian cells.
Human and bovine cultured cell lines and circulating leukocytes were examined for the presence of surface proteins similar to platelet glycoproteins IIb (GPIIb) and IIIa (GPIIIa). Human endothelial cells, smooth muscle cells, and MG-63 fibroblast-like cells were found to have surface proteins that cross-reacted with platelet GPIIb and GPIIIa antibodies, existed as complexes, and had molecular weights similar to those of the corresponding platelet glycoproteins. Bovine endothelial cells and smooth muscle cells also expressed GPIIb- and GPIIIa-like surface proteins. Metabolic labeling studies with [35S]methionine demonstrated that the cultured cells synthesized these glycoproteins. The GPIIIa-like protein in human endothelial and smooth muscle cells had the same isoelectric point as platelet GPIIIa, whereas their GPIIb alpha-like protein was slightly more acidic than platelet GPIIb alpha (pI = 5.2-5.3 versus 5.5). Platelet and endothelial cell GPIIb alpha (but not GPIIIa) showed an increased electrophoretic mobility in Ca2+ -containing versus EDTA-containing gels, implying a Ca2+ -GPIIb alpha interaction. The amino acid sequence of the amino termini of platelet GPIIb alpha and GPIIb beta and of the alpha chains of the leukocyte LFA-1 and Mac-1 glycoprotein complexes had significant sequence homology. These data indicate that glycoproteins that have either immunological cross-reactivity or amino-terminal sequence homology with the platelet GPIIb-IIIa complex are widely distributed in human and non-human adherent cells and circulating leukocytes and suggest that these proteins may be the products of a large gene family whose expression is cell specific.


Desiccation tolerance in the vegetative tissues of the fern Mohria caffrorum is seasonally regulated.
As there is limited information on the mechanisms of vegetative desiccation tolerance in pteridophytes, we undertook a comprehensive anatomical, ultrastructural, physiological and biochemical study on the fern Mohria caffrorum. Our data show that this species is desiccation-tolerant during the dry season, and desiccation-sensitive in the rainy season. This system allows the verification of protection mechanisms by comparison of tolerant and sensitive tissues of the same species at the same developmental age. Tolerant fronds acquire protection mechanisms during drying that are mostly similar to those reported for angiosperms. These include: (i) chlorophyll masking by abaxial scales and frond curling; (ii) increased antioxidant capacity that is maintained in dry tissues; (iii) mechanical stabilization of vacuoles in the dry state; (iv) de novo production of heat stable proteins (at least one identified as a putative chaperonin); (v) accumulation of protective carbohydrates (sucrose, raffinose family oligosaccharides and cyclitols). This study has implications for the biotechnological production of drought-tolerant crops, and allows speculation on the evolution of vegetative desiccation tolerance.


Macroepidemiological aspects of porcine reproductive and respiratory syndrome virus detection by major United States veterinary diagnostic laboratories over time, age group, and specimen.
This project investigates the macroepidemiological aspects of porcine reproductive and respiratory syndrome virus (PRRSV) RNA detection by veterinary diagnostic laboratories (VDLs) for the period 2007 through 2018. Standardized submission data and PRRSV real-time reverse-transcriptase polymerase chain reaction (RT-qPCR) test results from porcine samples were retrieved from four VDLs representing 95% of all swine samples tested in NAHLN laboratories in the US. Anonymized data were retrieved and organized at the case level using SAS (SAS® Version 9.4, SAS® Institute, Inc., Cary, NC) with the use of PROC DATA, PROC MERGE, and PROC SQL scripts. The final aggregated and anonymized dataset comprised of 547,873 unique cases was uploaded to Power Business Intelligence-Power BI® (Microsoft Corporation, Redmond, Washington) to construct dynamic charts. The number of cases tested for PRRSV doubled from 2010 to 2018, with that increase mainly driven by samples typically used for monitoring purposes rather than diagnosis of disease. Apparent seasonal trends for the frequency of PRRSV detection were consistently observed with a higher percentage of positive cases occurring during fall or winter months and lower during summer months, perhaps due to increased testing associated with well-known seasonal occurrence of swine respiratory disease. PRRSV type 2, also known as North American genotype, accounted for 94.76% of all positive cases and was distributed across the US. PRRSV type 1, also known as European genotype, was geographically restricted and accounted for 2.15% of all positive cases. Co-detection of both strains accounted for 3.09% of the positive cases. Both oral fluid and processing fluid samples, had a rapid increase in the number of submissions soon after they were described in 2008 and 2017, respectively, suggesting rapid adoption of these specimens by the US swine industry for PRRSV monitoring in swine populations. As part of this project, a bio-informatics tool defined as Swine Disease Reporting System (SDRS) was developed. This tool has real-time capability to inform the US swine industry on the macroepidemiological aspects of PRRSV detection, and is easily adaptable for other analytes relevant to the swine industry.


The effect of type and level of protein, fibre and starch on nitrogen excretion patterns in rats.
1. Three series of nitrogen balance experiments were performed with growing rats to test the effect of type and level of protein, fibre and starch on N excretion patterns. The design involved eighteen treatments in a 3 X 3 X 2 factorial experiment with five rats per dietary treatment. The eighteen treatments resulted from a combination of three protein treatments, three fibre treatments and two starch treatments. Protein treatments consisted of one level (15 g N/kg DM) of casein fortified with methionine, a protein of high digestibility, and two levels (15 and 20 g N/kg DM) of autoclaved brown beans (Phaseolus vulgaris), a protein source of low digestibility. The fibre treatments were two levels of cellulose powder and one level of barley hulls. The two starch treatments were autoclaved potato starch and autoclaved and raw potato starch (1:1, w/w). 2. The inclusion of raw potato starch reduced true protein digestibility markedly when the protein source was casein, but the corresponding biological values were increased significantly with this treatment. This strongly indicated a movement of urea from the blood to the intestines. This assumption was also supported by significantly lower blood urea concentrations in animals given raw starch. The influence of raw starch on true protein digestibility was, however, significantly less when cellulose and barley hulls were included. This is probably due to reduced transit time from fibre inclusion. The nature of the gut contents also supported this hypothesis. 3. The inclusion of raw potato starch when brown beans were the source of protein had much less effect on true protein digestibility and biological value than when casein was the protein source. This was probably due to the low digestibility of DM and protein in this food leaving sufficient energy and protein for maximum microbial growth. The inclusion of fibre also had little effect on N excretion patterns with the brown-bean diets. 4. An increase in the level of brown bean inclusion reduced true protein digestibility only on the diets containing raw starch whereas the biological value was consistently reduced regardless of starch treatment. The lower biological values were associated with significantly higher blood urea concentrations. Increasing the level of brown bean inclusion also resulted in higher fresh weights of caecum, colon and contents. 5. The present work proves that, through dietary manipulation, it is possible to affect nitrogen excretion patterns in rats.


Separation of oligonucleotides in N-methyl-formamide-based polymer matrices by capillary electrophoresis.
N-Methylformamide (NMF)-based matrices for capillary electrophoretic separation of nucleic acids have been developed. The use of an organic solvent as liquid base for the separation matrices allowed a hydrophobic polymer, C16-derivatized 2-hydroxyethyl cellulose (HEC), to be employed as structural element in the sieving medium. With a matrix consisting of 5% w/v of this polymer dissolved in NMF containing 50 mM ammonium acetate, p(dA)12-18 and p(dA)40-60 oligonucleotides were baseline separated. The addition of ammonium acetate to the buffer and separation matrix resulted in enhanced separation efficiency. Furthermore, it was possible to tailor the sieving performance of the separation medium by the use of a binary mixture of C16-derivatized HEC and PVP. Differences in sieving behavior of the various matrices evaluated are discussed.


Governance change and institutional adaptation: a case study from Harenna forest, ethiopia.
Many common pool resources have traditionally been managed through intricate local governance arrangements. Over time, such arrangements are confronted with manifold political, social, economic and ecological changes. However, the ways in which local governance arrangements react to such changes are poorly understood. Using the theoretical concept of institutional adaptation, we analyse the history of Harenna forest, Ethiopia, to examine processes of institutional change over the last 150 years. We find that the traditional institutions that governed Harenna's resources persisted, in essence, over time. However, these institutions were modified repeatedly to address changes caused by varying formal, supra-regional governance regimes, the development of markets for forest products, increasing population pressure and changes in formal property rights. A key mechanism for adaptation was combining elements from both informal and formal institutions, which allowed traditional rules to persist in the guise of more formal arrangements. Our findings also highlight several constraints of institutional adaptation. For example, by abolishing fora for collective decision-making, regime changes limited adaptive capacity. To conclude, we argue that such insights into traditional resource governance and its adaptability and dynamics over time are essential to develop sustainable approaches to participatory forest management for the future, both in Harenna and more generally.


Detection and characterization of Wolbachia infections in natural populations of aphids: is the hidden diversity fully unraveled?
Aphids are a serious threat to agriculture, despite being a rather small group of insects. The about 4,000 species worldwide engage in highly interesting and complex relationships with their microbial fauna. One of the key symbionts in arthropods is Wolbachia, an α-Proteobacterium implicated in many important biological processes and believed to be a potential tool for biological control. Aphids were thought not to harbour Wolbachia; however, current data suggest that its presence in aphids has been missed, probably due to the low titre of the infection and/or to the high divergence of the Wolbachia strains of aphids. The goal of the present study is to map the Wolbachia infection status of natural aphids populations, along with the characterization of the detected Wolbachia strains. Out of 425 samples from Spain, Portugal, Greece, Israel and Iran, 37 were found to be infected. Our results, based mainly on 16S rRNA gene sequencing, indicate the presence of two new Wolbachia supergroups prevailing in aphids, along with some strains belonging either to supergroup B or to supergroup A.


Neurological accidents caused by repetitive breath-hold dives: two case reports.
We report two Japanese male professional breath-hold divers (33 and 39 years of age) who experienced neurological disorders during repetitive dives to over 20 m of seawater. One patient had right homonymous hemianopsia, and the other presented with right hemiparesis with facial involvement and sensory deficit. In addition, they each had a history of neurological problems following such dives. Magnetic resonance images of their brains disclosed multiple T2-weighted hyperintensities corresponding to their neurological symptoms. Their brain lesions suggest a multiple cerebral infarction caused by occlusion of the cerebral arteries. We conclude that the repetitive deep breath-hold dives induced the brain involvement.


[Cardiometric data as indications to surgical treatment of elderly and senile patients suffering from thyrotoxicosis].
On the basis of studying clinical symptoms of thyrotoxicosis in elderly patients and an analysis of results of investigation of the heart the authors marked out additional indications to surgical treatment of this category of patients. Results of surgical treatment of elderly and senile patients suffering from thyrotoxicosis are also described.


Shared decision-making and the orthopaedic workforce.
Studies of physician workforce need a standard of an appropriately sized workforce to compare projections. Although many studies use average rates of healthcare use as a standard, regional benchmarks provide a pragmatic alternative approach to estimating a reasonably sized physician workforce and avoid many of the problems of needs- and demand-based planning. Wide geographic variations in the rates of many procedures, unexplained by differences in population characteristics, suggest that supply-induced demand or physician practice style or both may be the major determinates of the rates for these procedures. In the current study, the authors explore some of these differences in orthopaedic procedure rates and their implications for workforce planning. For example, the rates of hip fracture are fairly uniform across geographic regions, whereas the rates of spine surgery vary sixfold and the rates of spinal fusion vary 10-fold. Shared decision-making is the process of giving patients informed choices about their treatment options based on current best evidence. Careful studies of treatment effectiveness and shared decision-making hold the promise of allowing patients' preferences and values to determine the right rate of healthcare use. These rates could allow workforce projections to be compared with optimal benchmarks for future planning.


Ionic conductivity and structure of M1-xPbxF2 (M = Ca, Sr, Ba) solid solutions prepared by ball milling.
Nanocrystalline M1-xPbxF2 (M = Ca, Sr, Ba) solid solutions were prepared by ball milling mixtures of binary parent materials. The structure of the obtained materials was investigated by 19F MAS NMR spectroscopy and XRPD, and their ionic conductivity by impedance spectroscopy. It was found that fluorite-structured solid solutions over the whole range of compositions can be prepared by ball milling for all three systems, closing the broad miscibility gap of the CaF2-PbF2 system. The fluoride ion conductivity increased with increasing Pb content of the solid solutions, with Ba0.10Pb0.90F2 showing the highest conductivity of all samples prepared, being 1.5 orders of magnitude smaller than the one of PbSnF4. Ca1-xPbxF2 showed a fluoride ion conductivity increase which can be assigned to geometric frustration induced disorder. Ball milling of pure PbF2 revealed an increase of the fluoride ion conductivity by 2.5 orders of magnitude in the case of PbF2 containing a large amount of β-PbF2 compared to microcrystalline β-PbF2. Its fluoride ion conductivity is also 2.5 orders of magnitude larger than the fluoride ion conductivity of ball milled PbF2 consisting of a small amount of β-PbF2 but a large amount of α-PbF2 pointing to differently conducting and structured grain boundaries of α-PbF2 and β-PbF2.


Low-molecular-weight solutes released during mild acid hydrolysis of the lipopolysaccharide of Pseudomonas aeruginosa.
A careful examination of the low-molecular-weight solutes released during mild acid hydrolysis of the lipopolysaccharide of Pseudomonas aeruginosa (N.C.T.C. 1999) revealed the presence of ethanolamine triphosphate. During storage, the compound decomposed to give ethanolamine pyrophosphate, identified in a previous study (Drewry et al., 1971); PP(i) may be a further decomposition product. Evidence for the attachment of ethanolamine triphosphate to a polysaccharide fraction was obtained, but the possibility that some was attached to the lipid A moiety was not excluded. Basic compounds released during the hydrolysis of lipopolysaccharide included amino acids, polyamines and oligopeptides.


A clustering algorithm using DNA marker information for sub-pedigree reconstruction.
In a mass disaster scenario in which many people are dead, it may be that small family groups are among the dead, and investigators may need to identify such groups, e.g., to return bodies to living relatives for burial. We consider the problem of identifying small groups of closely related people within a large group of people through the use of DNA marker information. We propose a likelihood-ratio-based distance measure of the relatedness between pairs of individuals and use an estimate of this measure as a means of clustering related people into groups. We show the effectiveness of our approach on real examples and through simulations, which suggest that the method is quite reliable for identifying very close relationships. We discuss the use of our clustering algorithm in a two-stage pedigree reconstruction procedure and suggest directions in which the analysis could be extended. Applications include the identification of family groups among bodies found in mass graves and identification of family groups in animal populations.


Design and validation of 2 objective structured clinical examination stations to assess core undergraduate examination skills of the hand and knee.
To evaluate the development, validity, and reliability of 2 undergraduate Objective Structured Clinical Examination (OSCE) stations for core hand and knee examination skills. Two OSCE stations for hand and knee based on core skills were developed, and qualitatively assessed for face and content validity by an expert consensus panel. Construct validity was evaluated by comparing the performance of third- (n = 21) and fifth-year (n = 50) medical students with 6 specialist registrars (SpR) in rheumatology. Concurrent validity was evaluated by correlating the scores of the fifth-year students with their eventual final examination scores. The fifth-year data were used to calculate the interrater and intrarater reliabilities of 2 examiners. Intrarater reliability analyzed repeat scores using videotapes of the examinations. Both stations were deemed to fulfil face and content validity criteria by the expert consensus panel. There was no significant difference in the mean scores of the third- and fifth-years. There were significant differences in the mean scores between both student groups and the SpR in both stations consistent with a valid construct theory. The fifth-year hand OSCE results correlated moderately with other indices of clinical skills, but not knowledge, and satisfied concurrent validity. Inter- and intrarater reliability for both stations was high. These OSCE stations are valid and reliable tools for testing competency in core hand and knee examination skills. They can be used in educational research as outcome measures of specific teaching interventions and can also be used as an early feedback tool when teaching joint examination.


Reversible Aggregation of Molecular-Like Fluorophores Driven by Extreme pH in Carbon Dots.
The origin of carbon-dots (C-dots) fluorescence and its correlation with the dots structure still lack a comprehensive model. In particular, the core-shell model does not always fit with the experimental results, which, in some cases, suggest a molecular origin of the fluorescence. To gain a better insight, we have studied the response of molecular-like fluorophores contained in the C-dots at extreme pH conditions. Citric acid and urea have been employed to synthesize blue and green-emitting C-dots. They show a different emission as a function of the pH of the dispersing media. The photoluminescence has been attributed to molecular-like fluorophores: citrazinic acid and 4-hydroxy-1H-pyrrolo[3,4-c]-pyridine-1,3,6-(2H,5H)-trione. 3D and time-resolved photoluminescence, ultraviolet-visible (UV-vis) spectroscopy, and dynamic light scattering have been used to determine the aggregation state, quantum yield and emission properties of the C-dots. The dependence of the C-dots blue and green components on the chemical environment indicates that the origin of fluorescence is due to molecular-like fluorophores.


360 Degrees of Facial Perception: Congruence in Perception of Frontal Portrait, Profile, and Rotation Photographs.
Studies in social perception traditionally use as stimuli frontal portrait photographs. It turns out, however, that 2D frontal depiction may not fully capture the entire morphological diversity of facial features. Recently, 3D images started to become increasingly popular, but whether their perception differs from the perception of 2D has not been systematically studied as yet. Here we investigated congruence in the perception of portrait, left profile, and 360° rotation photographs. The photographs were obtained from 45 male athletes under standardized conditions. In two separate studies, each set of images was rated for formidability (portraits by 62, profiles by 60, and 360° rotations by 94 raters) and attractiveness (portraits by 195, profiles by 176, and 360° rotations by 150 raters) on a 7-point scale. The ratings of the stimuli types were highly intercorrelated (for formidability all rs > 0.8, for attractiveness all rs > 0.7). Moreover, we found no differences in the mean ratings between the three types of stimuli, neither in formidability, nor in attractiveness. Overall, our results clearly suggest that different facial views convey highly overlapping information about structural facial elements of an individual. They lead to congruent assessments of formidability and attractiveness, and a single angle view seems sufficient for face perception research.


The circle of Willis predicts the antihypertensive effects of carotid artery stenting.
OBJECTIVE Carotid artery stenting (CAS) has antihypertensive effects, but the durability and degree of this response remain variable. The authors propose that this clinical variability is a function of the presence or absence of a complete circle of Willis (COW). Incomplete COWs perfuse through a higher-resistance pial collateral pathway, and therefore patients may require a higher mean arterial pressure (MAP). Carotid artery revascularization in these patients would reduce the end-organ collateral demand that has been hypothesized to drive the MAP response. METHODS Using a retrospective, nonrandomized within-subject case-control design, the authors compared the postoperative effects of CAS in patients with and without a complete COW by using changes in MAP and antihypertensive medication as end points. They recorded MAP and antihypertensive medications 3 months prior to surgery, preoperatively, immediately postoperatively, and at the 3-month follow-up. RESULTS Data were collected from 64 consecutive patients undergoing CAS. Patients without a complete COW (25%) were more likely to demonstrate a decrease in BP response to stenting (i.e., a drop in MAP of 10 mm Hg and/or a reduction or cessation of BP medications at 3 months postoperatively). Of the patients in the incomplete COW cohort, 75% had this outcome, whereas of those in the complete COW cohort, only 41% had it (p < 0.041). These findings remained statistically significant in a logistic regression analysis for possible confounders (p < 0.024). A receiver operating curve analysis of preoperative data indicated that a MAP > 96.3 mm Hg was 55.5% sensitive and 57.4% specific for predicting a complete COW and that patients with a MAP > 96.3 mm Hg were more likely to demonstrate a good MAP decrease following CAS (p < 0.0092). CONCLUSIONS CAS is associated with a significant decrease in MAP and/or a reduction/cessation in BP medications in patients in whom a complete COW is absent.


Implication of type 4 NADPH oxidase (NOX4) in tauopathy.
Aggregates of the microtubule-associated protein tau are a common marker of neurodegenerative diseases collectively termed as tauopathies, such as Alzheimer's disease (AD) and frontotemporal dementia. Therapeutic strategies based on tau have failed in late stage clinical trials, suggesting that tauopathy may be the consequence of upstream causal mechanisms. As increasing levels of reactive oxygen species (ROS) may trigger protein aggregation or modulate protein degradation and, we had previously shown that the ROS producing enzyme NADPH oxidase 4 (NOX4) is a major contributor to cellular autotoxicity, this study was designed to evaluate if NOX4 is implicated in tauopathy. Our results show that NOX4 is upregulated in patients with frontotemporal lobar degeneration and AD patients and, in a humanized mouse model of tauopathy induced by AVV-TauP301L brain delivery. Both, global knockout and neuronal knockdown of the Nox4 gene in mice, diminished the accumulation of pathological tau and positively modified established tauopathy by a mechanism that implicates modulation of the autophagy-lysosomal pathway (ALP) and, consequently, improving the macroautophagy flux. Moreover, neuronal-targeted NOX4 knockdown was sufficient to reduce neurotoxicity and prevent cognitive decline, even after induction of tauopathy, suggesting a direct and causal role for neuronal NOX4 in tauopathy. Thus, NOX4 is a previously unrecognized causative, mechanism-based target in tauopathies and blood-brain barrier permeable specific NOX4 inhibitors could have therapeutic potential even in established disease.


Sinirhodobacter hankyongi sp. nov., a novel denitrifying bacterium isolated from sludge.
A novel Gram-reaction-negative, facultative-aerobic, motile, non-spore-forming, oval-shaped and denitrifying bacterium, designated BO-81T, was isolated from sludge sampled in the Republic of Korea. This bacterium was investigated via a polyphasic approach to reveal its taxonomic position. The results of phylogenetic analysis based on 16S rRNA gene sequencing indicated that strain BO-81T belonged to the family Rhodobacteraceae and was related to the closest species Sinirhodobacter ferrireducens (98.8 % sequence similarity), 'Sinorhodobacter hungdaonensis' (98.4 %), Rhodobacter lacus (97.8 %), Sinorhodobacter populi (96.8 %) and Rhodobacter maris (96.2 %). The average nucleotide identity and DNA-DNA hybridization values between strain BO-81T and its closely related strains were 77.7-94.2 % and 20.1-55.9 %, respectively, indicating that BO-81T represents a novel species of the genus Sinirhodobacter. Growth occurred at 18-40 °C on Reasoner's 2A medium in the presence of 0-7 % NaCl (w/v) and at pH 6.0-9.0. Strain BO-81T was characterized chemotaxonomically as having ubiquinone 10 as its predominant respiratory quinone, summed feature 8 (C18 : 1 ω6c and/or C18 : 1 ω7c) as its major fatty acid and phosphatidylglycerol and phosphatidylethanolamine as its predominant polar lipids. The G+C content of the genomic DNA was 68.3 mol%. The results of physiological and biochemical tests allowed phenotypic differentiation of strain BO-81T from other Sinirhodobacter species with validly published names. Therefore, the isolate represented a novel species, for which the name Sinirhodobacter hankyongi sp. nov. (type strain BO-81T=KACC 19677T=LMG 30808T) is proposed.


Demonstration that Australian Pasteurella multocida isolates from sporadic outbreaks of porcine pneumonia are non-toxigenic (toxA-) and display heterogeneous DNA restriction endonuclease profiles compared with toxigenic isolates from herds with progressive atrophic rhinitis.
Capsular types A and D of Pasteurella multocida cause economic losses in swine because of their association with progressive atrophic rhinitis (PAR) and enzootic pneumonia. There have been no studies comparing whole-cell DNA profiles of isolates associated with these two porcine respiratory diseases. Twenty-two isolates of P. multocida from diseased pigs in different geographic localities within Australia were characterised genotypically by restriction endonuclease analysis (REA) with the enzyme CfoI. Seven of 12 P. multocida isolates from nasal swabs from pigs in herds where PAR was either present or suspected displayed a capsular type D phenotype. These were shown to possess the toxA gene by polymerase chain reaction (PCR) and Southern hybridisation, and further substantiated by production of cytotoxin in vitro. The CfoI profile of one of these seven isolates, which was from the initial outbreak of PAR in Australia (in Western Australia, WA), was identical with profiles of all six other toxigenic isolates from sporadic episodes in New South Wales (NSW). The evidence suggests that the strain involved in the initial outbreak was responsible for the spread of PAR to the eastern states of Australia. Another 10 isolates, representing both capsular types A and D, were isolated exclusively from porcine lung lesions after sporadic outbreaks of enzootic pneumonia in NSW and WA. CfoI restriction endonuclease profiles of these isolates revealed considerable genomic heterogeneity. Furthermore, none of these possessed the toxA gene. This suggests that P. multocida strains with the toxA gene do not have a competitive survival advantage in the lower respiratory tract or that toxin production does not play a role in the pathology of pneumonic lesions, or both. REA with polyacrylamide gel electrophoresis and silver staining was found to be a practical and discriminatory tool for epidemiological tracing of P. multocida outbreaks associated with PAR or pneumonia in pigs.


Autism at a glance: A pilot study optimizing thin-slice observations.
Borrowing from a clinical psychology observational methodology, thin-slice observations were used to assess autism characteristics in toddlers. Thin-slices are short observations taken from a longer behavior stream which are assigned ratings by multiple raters using a 5-point scale. The raters' observations are averaged together to assign a "thin-slice" value for each observation. In this study, a total of 60 toddlers were selected from a video archive: 20 children with typical development, 20 children with developmental language disorder, and 20 children with autism. In the first part of this study, 20 raters observed small play segments between toddlers and an assessor. Raters assigned scores to each of the 60 toddlers on items related to autism symptomatology. Item analysis and generalizability and decision studies were conducted to determine the factor structure and optimal number of raters to achieve a stable estimate of autism characteristics. In the second part of the study, generalizability and decision studies were conducted to determine the most efficient and optimal combination of raters and naturalistic contexts. This pilot study provides recommendations for optimizing the utility of thin-slice observations for measuring autism symptomatology in young children.


Aneurysms of the abdominal aorta. Incidence in blacks and whites in North Carolina.
We examined race and sex relative to the unexpected finding of an abdominal aortic aneurysm (AAA) at 1,665 autopsies plus 545 abdominal computed tomographic scans in subjects over the age of 50 years. We compared our demographic data with those of North Carolina and our hospital to determine if the data base was representative. White males had a higher incidence (4.2%) of AAA than any other group of race and sex (1.2% to 1.6%) or combination of groups. Although whites (2.9%) had a higher incidence than blacks (1.5%) and males (3.4%) had a higher incidence than females (1.3%), this can be attributed to the influence of the white male. The demographic data of the group studied were similar to those of our institution's admissions and to the North Carolina population. We conclude that (1) there is an increased incidence of AAA in the white male compared with the white female, black male, and black female in North Carolina; (2) there is no difference in the incidence of AAA in the white female, black male, and black female; (3) race alone may not influence the incidence of AAA as there was no difference between white and black females.


Capsella bursa-pastoris (L.) Medic. as a biomonitor of heavy metals.
Capsella bursa-pastoris (L.) Medic. (shepherd's purse) has been tested as a possible biomonitor of heavy metals in the city of Bradford, UK and compared with Poa annua L. (annual meadow-grass), a species with a similar ecology that had previously been studied for biomonitoring potential. Forty-two sites (urban roadside, urban, urban park, suburban and rural) in and around Bradford were investigated. Concentrations of Pb, Cd, Zn and Cu have been determined in soils and in washed and unwashed plant leaves. Differences between the washed and unwashed samples, reflecting airborne and soil entry routes, respectively, varied according to the metal pollutant. There were significant relationships between the heavy metal concentration in samples of surface soil (depth 0-10 cm) and washed leaves, the concentrations being greater with progressively increased urbanisation of the sites. Capsella bursa-pastoris has been found to be a useful biomonitor of the four heavy metals studied, and it may be a particularly useful species since it could monitor short-term changes in pollution in urban areas.


Protective effects of total flavonoids of Bidens bipinnata L. against carbon tetrachloride-induced liver fibrosis in rats.
Bidens bipinnata L. is well known in China as a traditional Chinese medicine and has been used to treat hepatitis in clinics for many years. In a previous study we found that total flavonoids of Bidens bipinnata L. (TFB) had a protective effect against carbon tetrachloride (CCl4)-induced acute liver injury in mice. Now this study was designed to investigate its therapeutic effect against CCl4-induced liver fibrosis in rats and to determine, in part, its mechanism of action. The liver fibrosis model was established by subcutaneous injection of 50% CCl4 twice a week for 18 weeks. TFB (40, 80 and 160 mg kg(-1)) was administered by gastrogavage daily from the 9th week. The results showed that TFB (80 and 160 mg kg(-1)) treatment for 10 weeks significantly reduced the elevated liver index (liver weight/body weight) and spleen index (spleen weight/body weight), elevated levels of serum transaminases (alanine aminotransferase and aspartate aminotransferase), hyaluronic acid, type III procollagen and hepatic hydroxyproline. In addition, TFB markedly inhibited CCl4-induced lipid peroxidation and enhanced the activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase. Moreover, TFB (80 and 160 mg kg(-1)) treatment improved the morphologic changes of hepatic fibrosis induced by CCl4 and suppressed nuclear factor (NF)-kappaB, alpha-smooth muscle actin (SMA) protein expression and transforming growth factor (TGF)-beta1 gene expression in the liver of liver fibrosis of rats. In conclusion, TFB was able to ameliorate liver injury and protect rats from CCl4-induced liver fibrosis by suppressing oxidative stress. This process may be related to inhibiting the induction of NF-kappaB on hepatic stellate cell activation and the expression of TGF-beta1.


Modulation of alloimmunity to major histocompatibility complex class I by cotransfer of cytokine genes in vivo.
Major histocompatibility complex (MHC) class I antigen is a potent stimulus for alloimmune responses and is the principal immunologic target mediating acute cellular rejection of allografts. Using a method of direct in vivo gene transfer of cDNA encoding donor type MHC class I, we showed in a rat model that recipient muscle could express the transferred MHC class I cDNA, resulting in alloimmunization of the recipient. This was most graphically demonstrated by accelerated rejection of cardiac allografts expressing the same MHC class I as encoded by the immunizing cDNA. We now report the use of the particle-mediated gene transfer via a gene gun (Geneva, Middleton, WI, USA) to transfer MHC class I, as well as cytokine gene expression vectors, into rat skin. Compared to intramuscular injection, gene gun transfer to skin resulted in more efficient immunization. Donor-specific cytotoxic T lymphocyte (CTL) responsiveness and antibody levels increased. Furthermore, coexpression of certain cytokine genes with the MHC class I cDNA modulated the immune response. Specifically, coimmunization with IL-10 cDNA abrogated immunity to allo-MHC class I, while coimmunization with GM-CSF cDNA enhanced it. The influence of expression of these genes in skin was demonstrated by alteration of donor cardiac allograft survival. This model is useful for induction and modulation of alloimmune responses and may be used to develop gene therapy strategies to modify them.


Advances in Parameter Estimation and Learning from Data for Mathematical Models of Hepatitis C Viral Kinetics.
Mathematical models, some of which incorporate both intracellular and extracellular hepatitis C viral kinetics, have been advanced in recent years for studying HCV-host dynamics, antivirals mode of action, and their efficacy. The standard ordinary differential equation (ODE) hepatitis C virus (HCV) kinetic model keeps track of uninfected cells, infected cells, and free virus. In multiscale models, a fourth partial differential equation (PDE) accounts for the intracellular viral RNA (vRNA) kinetics in an infected cell. The PDE multiscale model is substantially more difficult to solve compared to the standard ODE model, with governing differential equations that are stiff. In previous contributions, we developed and implemented stable and efficient numerical methods for the multiscale model for both the solution of the model equations and parameter estimation. In this contribution, we perform sensitivity analysis on model parameters to gain insight into important properties and to ensure our numerical methods can be safely used for HCV viral dynamic simulations. Furthermore, we generate in-silico patients using the multiscale models to perform machine learning from the data, which enables us to remove HCV measurements on certain days and still be able to estimate meaningful observations with a sufficiently small error.


Spatiotemporal airy light bullets in the linear and nonlinear regimes.
We demonstrate the realization of intense Airy-Airy-Airy (Airy(3)) light bullets by combining a spatial Airy beam with an Airy pulse in time. The Airy(3) light bullets belong to a family of linear spatiotemporal wave packets that do not require any specific tuning of the material optical properties for their formation and withstand both diffraction and dispersion during their propagation. We show that the Airy(3) light bullets are robust up to the high intensity regime, since they are capable of healing the nonlinearly induced distortions of their spatiotemporal profile.


Hereditary spastic paraplegias: time for an objective case definition and a new nosology for neurogenetic disorders to facilitate biomarker/therapeutic studies.
Hereditary spastic paraplegias (HSPs) are heterogeneous neurodegenerative disorders characterized by progressive lower limb weakness and spasticity as core symptoms of the degeneration of the corticospinal motor neurons. Even after exclusion of infectious and toxic mimickers of these disorders, the definitive diagnosis remains tricky, mainly in sporadic forms, as there is significant overlap with other disorders. Since their first description, various attempts failed to reach an appropriate classification. This was due to the constant expansion of the clinical spectrum of these diseases and the discovery of new genes, a significant number of them was involved in overlapping diseases. Areas covered: In this perspective review, an extensive literature study was conducted on the historical progress of HSP research. We also revised the previous and the current classifications of HSP and the closely related neurogenetic disorders and analyzed the areas of overlap. Expert opinion: There is undeniable need for objective case definition and reclassification of all neurogenetic disorders including HSPs, a prerequisite to improve patient follow-up, biomarker identification and develop therapeutics. The challenge is to understand why mutations can give rise to multiple phenotypic presentations along this spectrum of diseases in which the corticospinal tract is affected.


Analysis of sequences regulating larval expression of the Adh gene of Drosophila melanogaster.
The effects of a series of eight, 50 base pair internal deletions in the 5' region upstream of the proximal transcription start site of the Adh gene of Drosophila melanogaster were examined in a quantitative assay. Mixtures of two plasmids, one bearing a deleted gene, the other with an intact reference gene, were injected into alcohol dehydrogenase-negative embryos. Third instar larvae of the injected generation were assayed for relative alcohol dehydrogenase enzyme activity. Quantitative analysis of the eight deletions indicated that two regions were required for any detectable enzyme activity and one region was required for appropriate tissue specificity. The remaining five deletions significantly decreased, but did not eliminate activity. When the deleted genes were placed on a plasmid with an intact reference gene, activities of all but one deletion were restored to levels equivalent to that of the intact reference gene (regardless of orientation). This restoration of activity did not occur when the regulatory region of the intact gene was replaced with the Hsp70 heat shock promoter nor when the 50-base pair deletion encompassed the region that includes the TATA sequence. The fact that seven of the eight deleted genes express activity in the presence of a reference gene on the same plasmid suggests that the deleted gene is controlled by regulatory elements in the reference gene. Further, these regulatory elements exhibit no preference for their own, more proximate, promoter.


Suicide risk communication and intervention preferences for veterans and service members.
Despite the investment of public resources to fight staggering suicide rates among veterans, we know little about how veterans and service members in crisis communicate suicidal ideations, and what interventions they are willing to receive. We aim to identify communication and suicide intervention preferences of veterans and service members in times of crisis. Descriptive statistics were used to explore veterans communication of suicidal ideations. While 89.9% of participants indicated they were willing to speak to someone when having thoughts of suicide, less than 26% of participants indicated they were willing to bring up their thoughts with a crisis line or veterans organization. Rather, they indicate that family members (62.2%) and military friends (51.1%) would be their primary outreach. Logistic regression was used to determine whether or not preferred interventions varied by participant demographic characteristics. While the majority of participants indicated they were willing to allow intervention (88.6%), no one method was accepted by the majority of the population. The most accepted means of communication was to proactively contact a friend or family member about general life struggles (32.6%) or suicide-specific concerns (27.5%). Many participants were open to receiving resources (42.0%), suicide-specific mental health treatment (36.3%), and some sort of lethal means safety intervention (19.1%-26.4%). The age, marital status, and veterans status of participants significantly impacted what interventions they were willing to allow. We discuss the implications of these findings and the need for evidence-based, multimodal interventions in order to assist veterans in need.


Adaptive goal setting and financial incentives: a 2 × 2 factorial randomized controlled trial to increase adults' physical activity.
Emerging interventions that rely on and harness variability in behavior to adapt to individual performance over time may outperform interventions that prescribe static goals (e.g., 10,000 steps/day). The purpose of this factorial trial was to compare adaptive vs. static goal setting and immediate vs. delayed, non-contingent financial rewards for increasing free-living physical activity (PA). A 4-month 2 × 2 factorial randomized controlled trial tested main effects for goal setting (adaptive vs. static goals) and rewards (immediate vs. delayed) and interactions between factors to increase steps/day as measured by a Fitbit Zip. Moderate-to-vigorous PA (MVPA) minutes/day was examined as a secondary outcome. Participants (N = 96) were mainly female (77%), aged 41 ± 9.5 years, and all were insufficiently active and overweight/obese (mean BMI = 34.1 ± 6.2). Participants across all groups increased by 2389 steps/day on average from baseline to intervention phase (p < .001). Participants receiving static goals showed a stronger increase in steps per day from baseline phase to intervention phase (2630 steps/day) than those receiving adaptive goals (2149 steps/day; difference = 482 steps/day, p = .095). Participants receiving immediate rewards showed stronger improvement (2762 step/day increase) from baseline to intervention phase than those receiving delayed rewards (2016 steps/day increase; difference = 746 steps/day, p = .009). However, the adaptive goals group showed a slower decrease in steps/day from the beginning of the intervention phase to the end of the intervention phase (i.e. less than half the rate) compared to the static goals group (-7.7 steps vs. -18.3 steps each day; difference = 10.7 steps/day, p < .001) resulting in better improvements for the adaptive goals group by study end. Rate of change over the intervention phase did not differ between reward groups. Significant goal phase x goal setting x reward interactions were observed. Adaptive goals outperformed static goals (i.e., 10,000 steps) over a 4-month period. Small immediate rewards outperformed larger, delayed rewards. Adaptive goals with either immediate or delayed rewards should be preferred for promoting PA. ClinicalTrials.gov ID: NCT02053259 registered prospectively on January 31, 2014.


Experiences in intracranial surgery for aneurysms.
This is a report of 54 cases of saccular aneurysms operated upon intracranially with a total operative mortality of 7.4%, poor results in four cases (7.4%) and excellent results in 46 cases (85.1%). For 53 supratentorial aneurysms, the operative mortality was 5.6%, with two operative deaths (4.8%) in the last 41 cases. Intermittent vascular occlusion with a newly developed special forceps and the use of moderate arterial hypotension were of value in dealing with these aneurysms.


Two new Brazilian patients with Gómez-López-Hernández syndrome: reviewing the expanded phenotype with molecular insights.
Gómez-López-Hernández (GLH) syndrome or cerebello-trigeminal dysplasia is a neurocutaneous syndrome whose etiology is unknown at the present time. We report two additional Brazilian patients, including the oldest one known to date (age 29). Here, we review the expanded phenotype in four patients with new clinical, psychiatric, radiological, and molecular investigations. One patient may have hypomania within the bipolar spectrum disorder with onset in childhood and adolescence. Primary growth hormone (GH) deficiency was ruled out in all patients, although one of them might have developed secondary GH deficiency due to partial hypopituitarism following severe hydrocephalus. Brain magnetic resonance angiography disclosed no azygous anterior cerebral artery (ACA) but only normal variants. Molecular analysis of the lysosomal acid phosphatase gene (ACP2) was performed, but no pathogenic mutations were identified. We present an overview of the phenotypic features of all patients described to date. There are currently 12 unrelated patients reported in the literature, 5 of whom are Brazilian. We discuss new molecular insights and speculate about the pathogenesis of GLH syndrome.


Sequential Customized Therapeutic Keratectomy in Patients With a History of Radial Keratotomy.
To evaluate the outcome of sequential customized therapeutic keratectomy (SCTK) in reducing higher order aberrations (HOAs) and improving quality of vision in highly aberrated corneas consequent to previous radial keratotomy (RK). A retrospective review of patients undergoing SCTK treatment from January 2012 to October 2020 was conducted in the Eye Center, Humanitas Clinical and Research Center (Rozzano, Italy). Indications for treatment in patients who had RK were significantly and/or progressively reduced corrected distance visual acuity (CDVA) combined with visual symptoms critically affecting quality of life. Preoperative and postoperative CDVA, corneal topography and aberrometry, Scheimpflug tomography, and anterior segment optical coherence tomography were registered. Thirty-four patients who underwent RK a mean of 26.62 ± 7.10 years before SCTK treatment were included. SCTK induced a significant improvement of CDVA from 0.44 ± 0.82 logMAR preoperatively to 0.15 ± 0.64 logMAR postoperatively (P < .001). No patient experienced worsening of CDVA, whereas 8 patients (23,50%) gained one line and 23 patients (67.65%) gained two lines or more. A significant decrease in corneal coma, trefoil, and spherical aberrations was also noted (P = .003, .003, and .004, respectively). SCTK proved to be a safe and effective option to treat highly aberrated eyes following RK. The authors suggest the use of SCTK as a first-line approach for the treatment of HOAs after RK and avoiding more invasive procedures such as corneal transplantation or intraocular lens implantation. [J Refract Surg. 2023;39(12):808-816.].


Drinking water source and chlorination byproducts. I. Risk of bladder cancer.
We conducted a population-based case-control study of bladder cancer in Iowa in 1986-1989 to evaluate the risk posed by tapwater containing chlorination byproducts. We combined information about residential history, drinking water source, beverage intake, and other factors with historical data from water utilities and measured contaminant levels to create indices of past exposure to chlorination byproducts. The study comprised 1,123 cases and 1,983 controls who had data relating to at least 70% of their lifetime drinking water source. After we adjusted for potential confounders, we calculated odds ratios for duration of chlorinated surface water of 1.0 (referent), 1.0, 1.1, 1.2, and 1.5 for 0, 1-19, 20-39, 40-59, and > or =60 years of use. We also found associations with total and average lifetime byproduct intake, as represented by trihalomethane estimates. Positive findings were restricted to men and to ever-smokers. Among men, odds ratios were 1.0 (referent), 1.1, 1.3, 1.5, and 1.9, and among ever-smokers, 1.0, 1.1, 1.3, 1.8, and 2.2, after adjustment for intensity and timing of smoking. Among nonsmoking men and women, regardless of smoking habit, there was no association. Among men, smoking and exposure to chlorinated surface water mutually enhanced the risk of bladder cancer. The overall association of bladder cancer risk with duration of chlorinated surface water use that we found is consistent with the findings of other investigations, but the differences in risk between men and women, and between smokers and nonsmokers, have not been widely observed.


[The comparative benchmark analysis of the methods used to verify etiology of myocarditis associated with alcoholic cardiomyopathy].
Immunohistochemical (IHC) methods and polymerase chain reaction (PCR) were employed to study the cases of death from alcoholic cardiomyopathy (ACMP) among the patients presenting with interstitial myocarditis who did not have this condition in their medical histories. IHC studies revealed the expression of anti-parvovirus B19 antibodies in cardiomyocytes (CMC) and inflammatory infiltrate cells of 40% of the patients. These antibodies were expressed in vascular smooth cells and inflammatory infiltrate cells from 70% of the patients. Cardiomyocytes expressed VP1 antigen of enteroviruses. The expression of V 19 parvovirus antigen occurred in 67% of the patients who died from alcoholic cardiomyopathy. The parvovirus V 19 was expressed in a smaller number of cardiomyocytes than enterovirus V1. PCR revealed the presence of parvovirus in 35% of the patients with ACMP compared with 15% of the control subjects. Type 6 herpes simplex virus was identified with the help of PCR in 30% of the patients with alcoholic cardiomyopathy, butonly in 8% of the patients in the control group. It is concluded that the use of immunohistochemical methods and polymerase chain reaction extends the diagnostic potential of histiological studies carried out to elucidate etiology of myocarditis in the patients who died from alcoholic cardiomyopathy.


Optimal timing for the resection of pulmonary metastases in patients with colorectal cancer.
This study aims to clarify the surgical treatment time of pulmonary metastasis in patients with colorectal cancer.Early relapse after resection of pulmonary metastasis is often encountered when the interval from the detection of pulmonary metastasis to pulmonary metastasectomy was short.In this retrospective analysis, data of patients with colorectal cancer who underwent surgical treatment of pulmonary metastasis at the Gunma Prefectural Cancer Center, Gunma, from April 2001 through September 2018 were evaluated. The patients were divided into 2 groups. We examined the interval period from the diagnosis of pulmonary metastasis to pulmonary metastasectomy. This period was divided into every 3 months, and the prognosis of each group was compared with clarify the appropriate timing of pulmonary metastasectomy.The primary endpoints were 5-year overall survival and recurrence-free survival rates.The most significant difference was observed when the cutoff value was 9 months (5-year recurrence-free survival 45.8% vs 85.6%, P < .01). No significant difference was found in any background factors between the 2 groups. Twenty-five patients (34.7%) experienced recurrence after pulmonary metastasectomy. The most common site of recurrence was the lung (48%). Among the 12 cases of recurrence of pulmonary metastasis, 11 cases belonged to the <9 months group. A multivariable survival analysis found that the interval period of <9 months was a significant predictor of recurrence.Our study suggests that clinical follow-up for 9 months prior pulmonary metastasectomy in colorectal patients would improve the prognosis.


The standing heel-rise test: relation to chronic venous disorders and balance, gait, and walk time in injection drug users.
Injection drug use can impair mobility. When mobility is impaired in combination with other potential pathologic changes to the veins, muscles, and joints of the lower legs, chronic venous disorders can develop. The heel-rise test, an assessment of eccentric-concentric muscle action of calf muscle function with regard to plantar flexion, can be used to measure ankle mobility. To examine the test-retest reliability and construct validity of the heel-rise test in relation to chronic venous disorders in persons with a history of injection drug use (N = 104), a test-retest study (M = 45.9+/-12.9 days from first to second test) was conducted. Participants were assessed for chronic venous disorders of the legs and walk time; they also completed the heel-rise and Tinetti Balance and Gait tests. Test-retest reliability was found to be good for full heel rise of right and left legs (ICC = .66 and .67, respectively). Heel-rise performance was positively correlated with balance (r = .38 to .47) and gait (r = .38 to .45) and negatively related to walk time (r = -.30 to -.35) (P <0.01). Participants who injected in the groin, legs, or feet performed fewer heel rises than those who injected in the arms and upper body only or those who did not inject drugs. Chronic venous disorders accounted for 7% to 17% of the variance in heel rise. The heel-rise test as a measure of calf muscle function is supported by these results, implicating the role of mobility restriction in the etiology of venous disease. Although more research is needed regarding its performance, the heel-rise test may be a low-cost, noninvasive screening or assessment tool in a variety of outpatient settings.