Intracellular imaging of Qdots-labeled DNA in cyanobacteria.
In this contribution, they have attempted to develop a labeling technique for in vivo imaging of functionally active plasmid DNA in cyanobacterial cells through its decoration with semiconductor quantum dots (Qdots) as fluorescent nanoprobes. For that purpose biotinylated plasmid slr2060 DNA was conjugated with Qdots-streptavidine. The intact DNA was visualized in a single green color by light microscopy. These Qdots-DNA conjugates were capable of expressing the acyltransferase enzyme. Qdots-DNA conjugates and confocal microscope imaging technique were adopted to visualize the gene transport across the membrane of the live cyanobacteria cell in real time. Long-term kinetic study enabled to reveal the steps of extracellular and intracellular microenvironment for plasmid transportation into the live cell. To confirm these processes a confocal microscope and indicator plate assay test were applied in tandem. In this contribution, Qdots-labeled plasmid DNA was utilized for the first time for long-term intracellular imaging studies in cyanobacteria species PCC6803. The results showed that the Qdots-labeled plasmid DNA detection could be used as a powerful labeling technique for visualization of exogenous DNA entry and tracking into living cells by confocal microscopy.


Finite element simulation of Goldmann tonometry after refractive surgery.
The problem of accuracy of intraocular pressure (IOP) measurement using Goldmann Applanation Tonometry (GAT) after a refractive surgery is still unresolved. In this study a numerical simulation of refractive surgery and GAT is proposed as a method to evaluate accuracy of the correction formula for GAT reading after changes in corneal curvature and thickness. In the finite element analysis the effect of the corneal shell buckling was taken into account. This effect is responsible for the nonlinear relation of Goldmann applanation tonometer measurement and intraocular pressure. Goldmann applanation tonometry was simulated for different ablation depths and values of intraocular pressure levels. The results of the simulation indicate a strong relation between the Goldmann applanation reading and the intraocular pressure level for values greater than nominal (about 16 mmHg). The estimation error of the intraocular pressure after changes in corneal geometry, is lower than 1 mmHg for IOP = 32 mmHg and lower than 3 mmHg for IOP = 48 mmHg. The proposed correction formula of Goldmann applanation tonometry occurred to be useful in the cases after the corneal refractive surgery regardless of the intraocular pressure values and ablation depth.


Frequency and localization of congenital anomalies of the middle and inner ears: a human temporal bone histopathological study.
This study investigated congenital anomalies occurring in the middle and the inner ears, with particular attention to their features, localizations, and frequencies. One hundred human temporal bones obtained from 73 individuals, aged 31 gestational weeks to 39 years, each of whom had anomalies of the middle ear and/or inner ear, were used for this study. The temporal bones had been removed at autopsy, fixed, dehydrated, embedded in celloidin, and sectioned horizontally or vertically at 20 microns. Every 10th horizontal section or every 20th vertical section was stained with hematoxylin and eosin, mounted and studied under a light microscope. In the middle ear the structure most often found to be anomalous was the facial nerve; in the inner ear it was the lateral semicircular canal. The implications of the anomalies observed are discussed as they relate to fetal development, dysfunction of the ear, and clinical interpretation of diagnostic radiological studies.


Added value of neurotechnology for forensic psychiatric and psychological assessment.
The attention for neuroscience in relation to criminal behavior is growing rapidly, and research shows that neurobiological factors have added value to the understanding of psychological and social factors in explaining delinquency. There is evidence that neurotechnology can be used in criminal justice and may be of relevance for forensic psychiatric and psychological assessment. However, the question is whether scientific knowledge of neurobiological factors is applicable in daily practice of forensic assessment. Incorporation of basic technologies, e.g., psychophysiology (heart rate, skin conductance, wearables), hormonal measures (cortisol, testosterone), and neuropsychological testing might be evident, since they can be applied relatively easy. Moreover, a body of research shows the additive value of these technologies in this field. In addition, first steps are taken to apply these technologies in individual diagnostics, treatment, and risk assessment. Complex neurotechnologies like functional MRI (e.g., brain reading) and EEG show potential to be applicable in criminal justice, once it is known what additional information these indices offer for individual cases.


Magnetic resonance imaging findings in tubercular arthritis of elbow.
To evaluate magnetic resonance imaging (MRI) features of tubercular involvement of elbow joint. Fourteen patients with tubercular arthritis of elbow were evaluated. The following findings were recorded on MRI (n=12): bones involved; erosions, intraosseous abscesses, synovial thickening, and effusion; hypointensity within the thickened synovium on T2-weighted images; and periarticular soft tissue changes. The common abnormalities on MRI were synovial thickening and bone erosions (n=12), soft tissue (n=9)/intraosseous (n=5) abscesses, and T2 hypointensity within the thickened synovium (n=5). A diagnosis of elbow tuberculosis should be considered if there is a combination of findings involving bone and soft tissue.


A fatal case of inappropriate ADH secretion induced by cyclophosphamide therapy.
Cyclophosphamide is used extensively to treat malignancies. A 5-year-old boy with stage IV neuroblastoma is described who developed a fatal syndrome of inappropriate antidiuretic hormone (ADH) secretion after high dose cyclophosphamide therapy.


Chest trauma: evaluation by two-dimensional echocardiography.
Patients with either blunt or penetrating chest injuries may develop a variety of cardiac complications. The studies of 76 patients with suspected cardiac injury obtained over a 30-month period were reviewed in order to determine how frequently and in what manner two-dimensional echocardiography (2DE) is of value in the assessment of such patients. Thirty-nine patients had blunt trauma (group I), and 37 had penetrating trauma (group II). The 2DE findings in group I were: no visible abnormality in 19, pericardial effusions in six, and wall motion abnormalities in two; the studies were technically inadequate in six. In group II patients, the 2DE findings were: no visible abnormality in 14, pericardial effusions in 12, wall motion abnormalities in three, and unusual abnormalities such as foreign body or intrathoracic air in three; the studies were technically inadequate in four. This study shows that satisfactory 2DE can be performed in up to 87% of unselected patients who sustain chest injuries and does provide clinically valuable information that cannot be easily obtained by other noninvasive tests. In this series, 2DE was of greatest value in the detection of pericardial effusions that were present in 27% and of unusual abnormalities including intrathoracic air and foreign bodies such as a bullet.


ZnO-Templated Selenized and Phosphorized Cobalt-Nickel Oxide Microcubes as Rapid Alkaline Water Oxidation Electrocatalysts.
Oxygen electrocatalysis is of remarkable significance for electrochemical energy storage and conversion technologies, together with fuel cells, metal-air batteries, and water splitting devices. Substituting noble metal-based electrocatalysts by decidedly effective and low-cost metal-based oxygen electrocatalysts is imperative for the commercial application of these technologies. Herein, a novel strategy is presented to fabricate selenized and phosphorized porous cobalt-nickel oxide microcubes by using a sacrificial ZnO spherical template and the resulting microcubes are employed as an oxygen evolution reaction (OER) electrocatalyst. The selenized samples manifest desirable and robust OER performance, with comparable overpotential at 10 mA cm-2 (312 mV) as RuO2 (308 mV) and better activity when the current reaches 13.7 mA cm-2 . The phosphorized samples exhibit core-shell structure with low-crystalline oxides inside amorphous phosphides, which ensures superior activity than RuO2 with the same overpotential (at 10 mA cm-2 ) yet lower Tafel slope. Such a surface doping method possibly will provide inspiration for engineering electrocatalysts applied in water oxidation.


Genetics of the guppy as a model for experiment in aquaculture.
The guppy, Poecilia reticulata, is one of the most famous tropical ornamental fish in the world. There are many varieties and breeds which have been bred by aqua lists for many years. The guppy has frequently been used as model organism for experiments in fish genetics because of its short life cycle, ease of breeding and reproductive capacity. The laboratory strains which were created from local (Japanese) strains and varieties were used as an experimental genetic model for aquaculture. These laboratory strains were maintained as closed colonies for five to 20 years in our laboratory. One of the roles of model experiments in fish genetics to perform experiments which take a long time in which are commercially important, such as genetic drift, as the effect of inbreeding during the growth and maintenance of population. In this review, we mainly considered the results obtained in our laboratory relating to genetic drift, and the effects of inbreeding, heterosis and inheritance of quantitative traits.


Modified hypoglossal-facial nerve anastomosis for peripheral-type facial palsy caused by pontine infarction: A case report and literature review.
Peripheral-type facial palsy could be caused by a lesion in the tegmentum of the pons, such as infarction, with a rare occurrence. We herein described a case of unilateral peripheral-type facial palsy induced by dorsolateral pontine infarction and treated this patient using modified hypoglossal-facial nerve anastomosis. A 60-year-old female presented with dizziness, hearing drop, diplopia, and peripheral-type facial palsy. Brain Magnetic Resonance Imaging showed a dorsolateral pontine infarction on the right side which exactly refers to the location of the ipsilateral facial nucleus or facial nerve fascicles at the pons. Subsequent electrophysiological examinations confirmed poor facial nerve function of this patient and modified hypoglossal-facial nerve anastomosis was then performed. This case reminded medical practitioners not to ignore the possibility of involvement of a central cause in peripheral-type facial palsy patients. In addition, modified hypoglossal-facial nerve anastomosis served as a useful skill improvement that may help reduce hemiglossal dysfunction while restoring facial muscle function.


Homocysteine and atherothrombosis.
Atherosclerosis with or without thrombosis superimposed is the most frequent cause of ischemic heart disease (IHD), peripheral arterial disease, and a main cause of stroke. Conflicting results have been reported in genetic, observational, and experimental studies on the relationship between homocysteine and these atherothrombotic diseases. Although cardiovascular complications are common in homocystinuric patients (severe hyperhomocysteinemia), IHD, the most frequent manifestation of atherothrombosis in the general population, appears to be rare. On the basis of findings in individuals with hyperhomocysteinemia of genetic origin, there is in fact no clear evidence for a causal role of homocysteine in the pathogenesis of atherothrombotic disease, and the positive association between plasma homocysteine and IHD observed in many, but not all epidemiologic studies does not prove causality. To infer causality from observational studies, there should be a temporal, consistent, strong, independent, graded (dose-response effect), and duration-dependent relationship between exposure and outcomes, and a biologically plausible mechanism should exist. The relationship between plasma homocysteine levels and IHD does not fulfill these criteria beyond reasonable doubt. In the general population, plasma homocysteine levels are to a great extent determined by dietary habits, and plasma homocysteine could be a marker, or a consequence, of atherothrombosis and/or risk-associated behavior (e.g., a diet low in fruits and vegetables) rather than a cause of atherothrombosis. Experimentally, hyperhomocysteinemia is not in itself atherogenic in normal animals with relatively low plasma cholesterol levels. The homocysteine theory of atherosclerosis should be tested more thoroughly in hypercholesterolemic animals that develop atherosclerosis spontaneously to determine whether elevated plasma homocysteine levels are harmful under atherogenic conditions. A causal role of homocysteine in atherothrombotic disease remains to be established.


In vivo measurement of calcium by the 37Ar method: a study of the effect of recirculating breath collection systems on the exhalation rate.
A study has been made of the effect that different methods of breath collection have on the measurement of calcium in vivo by the 40Ca(n,alpha) 37Ar method. The effect of open and rebreathing breath collection methods has been examined by using intravenous injections of 133Xe. This study has indicated that comparison of calcium measurements between individuals and between centres is likely to be accurate only if breath is collected on 'open circuit'.


Understanding proximal humerus fractures: image analysis, classification, and treatment.
Proximal humerus fractures are difficult to define because of their extreme variability and potential for complexity. We designed a study to evaluate further why this is true. Radiographs of 113 proximal humeral fractures were assessed by 3 knowledgeable observers. The observers were asked to answer independently 9 questions about the fracture, to classify the fracture according to the Neer classification, and to recommend treatment. Two months later, a learning session was held to discuss discrepancies among the observers and to develop learning points to improve analysis of the images. Two months later, the radiographs were reassessed. Developing 10 learning points enhanced the ability to interpret images at the second review and provide more consistent fracture classification with statistically significant improvements. The problem is understanding the images of complex fractures-not the classification system. To enhance consistency in understanding these fractures, imaging of complex fractures must be enhanced.


Evidence-based and tailored medication in type 2 diabetes: a pathway learned from clinical trials.
In Japan, the choice of anti-diabetic medication is officially recommended according to the patient's glycemic condition and disease phenotype, unlike most other regions where metformin is recommended as the first-line medication. There has been an increase in the number of available glucose-lowering agents, making it necessary to select these agents based on ever-improving evidence obtained from clinical trials. For the dipeptidyl peptidase-4 inhibitor class of drugs, nine drugs are currently available on the market in Japan. Although previous cardiovascular outcome trials (CVOTs) demonstrated non-inferiority for both major adverse cardiovascular events (MACEs) and safety for some drugs of the class, the design and results of the CARMELINA trial seemed to be slightly different from earlier trials in that it showed the drugs were safe and partially effective even in patients with renal impairment. Thus, recent CVOTs on newer glucose-lowering agents have mainly focused on the major impacts of individual classes and drugs on clinical outcomes behind their glucose-lowering action. The diverse features of the classes and individual drugs may have also highlighted not only the class-effects, but also the drug-effects of glucose-lowering agents. This will lead to clinical-based evidence and assist with optimum selection of the class and/or drug for tailored medication in patients with type 2 diabetes.


Contribution of Axial Motor Impairment to Physical Inactivity in Parkinson Disease.
The objective of this study was to investigate the relationships between motor symptoms of Parkinson disease (PD) and activity limitations in persons with PD. This is a cross-sectional study of persons with mild to moderate PD (N = 90). Associations among axial motor features, limb motor signs, the Physical Activity Scale for the Elderly, the ability to perform Activities of Daily Living (ADLs), and level of ADL dependency were studied. A composite score of axial motor features included the following Unified Parkinson Disease Rating Scale items: speech, rigidity of the neck, arising from chair, posture, gait, and postural stability. A composite score of limb motor signs included the following Unified Parkinson Disease Rating Scale items: tremor at rest of all extremities, action tremor, rigidity of all extremities, finger taps, hand movement, rapid alternating hand movements, and foot tapping. Axial motor features of PD were significantly correlated with physical inactivity (P < 0.001), decreased ADL (P < 0.001), and increase in ADL dependency (P < 0.001). Limb motor signs significantly correlated with decreased ADL (P < 0.001) and level of ADL dependency (P = 0.035) but did not correlate with physical inactivity. After controlling for age, sex, disease duration, and comorbidity, axial motor features contributed significantly to physical inactivity, decreased ADL, and increase in ADL dependency, whereas the limb motor signs did not. Axial motor impairment contributed to physical inactivity and decreased ability to perform ADLs in persons with PD.


Exosomes carry IL-10 and antigen/MHC II complexes to induce antigen-specific oral tolerance.
It is known that the immune tolerance can be naturally established in the intestine, while the mechanism by which the immune tolerance development in the intestine is not fully understood yet. Vasoactive intestinal peptides (VIP) has the immune regulatory functions. This study aims to investigate the role of VIP in the immune tolerance development in the intestine. Intestinal epithelial cell (IEC)-derived exosomes were prepared. The exosomes carried IL-10 and antigen/MHC II complexes. VIP-deficient (VIPd) mice and wild type mice were employed to test the role of VIP in the development of immune tolerance in the intestine. VIPd mice failed to induce type 1 regulatory T cells (Tr1 cells) in the intestine and retarded the establishment of antigen (Ag)-specific immune tolerance. Exposure to VIP in the culture induced IL-10 expression in intestinal epithelial cells (IECs). Exosomes derived from ovalbumin (OVA, used as a specific Ag)/VIP-primed IECs carried IL-10 and OVA/MHC II complexes; these exosomes were designated IL10CARs (IL-10/chimeric antigen receptor-carrying exosomes). IL10CARs could recognize OVA-specific CD4+ T cells and converted OVA-specific CD4± T cells to OVA-specific Tr1 cells. Administration of IL10CARs suppressed experimental food allergy. The data show that IL10CARs are capable of suppressing experimental FA by inducing antigen-specific Tr1 cells, which has the translation potential for FA treatment.


[Synopsis of the results of some studies of the pathogenesis and clinical aspects of chronic gastritis in relation to stomach ulcer].
A review is given of our own results concerning gastric mucosa biopsy and gastritis classification. Moreover, results regarding the gastritis-induced influence upon the gastric mucosa barrier in the form of histotopochemical investigations of gastric mucus substances are briefly presented. By means of measurements of gastric motility (own method of evaluation), the results of the influence upon gastric motility in atrophic antrum gastritis are discussed.


"I can guess the month … but beyond that, I can't tell" an exploratory qualitative study of health care provider perspectives on gestational age estimation in Rajasthan, India.
Accurately estimating gestational age is essential to the provision of time-sensitive maternal and neonatal interventions, including lifesaving measures for imminent preterm birth and trimester-specific health messaging. We explored healthcare provider perspectives on gestational age estimation in the state of Rajasthan, India, including the methods they use (last menstrual period [LMP] dating, ultrasound, or fundal height measurement); barriers to making accurate estimates; how gestational age estimates are documented and used for clinical decision-making; and what could help improve the accuracy and use of these estimates. We interviewed 20 frontline healthcare providers and 10 key informants. Thematic network analysis guided our coding and synthesis of findings. Health care providers reported that they determined gestational age using some combination of LMP, fundal height, and ultrasound. Their description of their practices showed a lack of standard protocol, varying levels of confidence in their capacity to make accurate estimates, and differing strategies for managing inconsistencies between estimates derived from different methods. Many frontline healthcare providers valued gestational age estimation more to help women prepare for childbirth than as a tool for clinical decision making. Feedback on accuracy was rare. The providers sampled could not offer ultrasound directly, and instead could only refer women to ultrasound at higher level facilities, and usually only in the second or third trimesters because of late antenatal care-seeking. Low recall among pregnant women limited the accuracy of LMP. Fundal height was heavily relied upon, despite its lack of precision. The accuracy of gestational age estimates is influenced by factors at four levels: 1. health system (protocols to guide frontline workers, interventions that make use of gestational age, work environment, and equipment); 2. healthcare provider (technical understanding of and capacity to apply the gestational age estimation methods, communication and rapport with clients, and value assessment of gestational age); 3. client (time of first antenatal care, migration status, language, education, cognitive approach to recalling dates, and experience with biomedical services); and, 4. the inherent limitations and ease of application of the methods themselves.


Porcine ileal polypeptide causes an increase in cytoplasmic Ca2+ in both parietal and chief cells resulting in acid and pepsinogen secretion.
Porcine ileal polypeptide, an enterooxyntin isolated from distal small intestinal mucosal epithelium, has been observed to stimulate gastric acid secretion in vivo as well as in vitro (Wider, M.D. et al. (1984) Endocrinology 115, 1484-1491, Wider M.D. et al. (1986) Endocrinology 118, 1546-1550). We report here that porcine ileal polypeptide stimulates both acid (aminopyrine accumulation) and pepsinogen secretion in isolated, enriched populations of guinea pig parietal and chief cells in a dose-dependent manner. Further, 10(-9) M porcine ileal polypeptide caused an increase in cytoplasmic Ca2+ concentration in both parietal and chief cells similar in magnitude to that observed with gastrin-17 (10(-8) M) (as measured by both fura-2 and aequorin) and cholecystokinin octapeptide (CCK-OP) (10(-8) M), respectively. Porcine ileal polypeptide has been observed to cause no stimulation of cAMP production in gastric glands from guinea pigs (Gespach, C., personal communication) nor is there any effect of medium Ca2+ depletion on acid production observed with guinea pig gastric mucosal sections. It is concluded that porcine ileal polypeptide, at concentrations similar to circulating levels observed in plasma of normal pigs (5 x 10(-9) M), acts directly on the parietal and chief cells to cause the mobilization of intracellular Ca2+ from the stores resulting in acid and pepsinogen secretion. These experiments demonstrate that this peptide is a potent enterooxyntin and chief cell secretagogue which acts via the same signal transduction mechanisms as gastrin and cholecystokinin.


Strategies of protein selection by weanling and adult rats.
Weanling and adult male rats were offered pairs of diets containing either 0 and 20%, 0 and 40%, 0 and 60%, or 10 and 40% casein. Initially they preferred the lower protein diets, and then after one to ten days abruptly switched to adequate levels of protein choice. After 14 days, the diets were changed so that the first group received 10 and 40%, the second 20 and 60%, the third 10 and 40%, and the fourth 0 and 60% casein. Following the change, all weanling rats showed significant and systematic shifts in percentage of total energy chosen as protein (%P-E); most adults did not. Within each group, the variability in %P-E selected between different rats was higher than the day-to-day variability of individuals. In the adults no significant correlations were observed between protein selection and brain serotonin metabolism. We conclude that protein intake in rats is regulated in the sense that all animals learnt to eat sufficient protein to maintain growth, and most animals ate a constant amount of protein each day. On the other hand, the range of protein intake between individuals, and the shifts in selection among the weanlings when diet choices were changed seem to preclude the existence of a mechanism which precisely regulates protein intake.


A new in vivo method for measuring caries activity with a colorimeter.
The aim of this in vivo study was to assess the association between caries prevalence and changes in mineralization measured with a colorimeter (Color Compare CC 400, JENOPTIK, Jena, Germany). After a clinical examination (defs/DMFS, initial caries lesions), an area of a deciduous tooth was etched in each of the 35 children (psi = 8.11+/-2.41 years) with 37% phosphoric acid gel for 1 min. Immediately after, this demineralization was stained with 2% aqueous methylene blue and the red/green/blue spectrum measured with a colorimeter. Twenty-four hours later, the remineralization of this area was measured following the same staining procedure. Color measurements were clearly reduced after 24 h, indicating remineralization, and they correlated highly with the age of the children (Spearman correlation coefficient r = -0.48, p = 0.004). Correlations between the number of initial caries lesions in the deciduous and permanent dentition and color measurements after demineralization were statistically significant (r = 0.41 and 0.37, p = 0.02 and 0.045, respectively). The difference between the first and second measurements correlated significantly with the number of initial caries lesions in the permanent dentition (r = 0.42, p = 0.02). The values after artificial demineralization correlated with the number of initial lesions for the permanent (r = 0.368, p = 0.045) and deciduous (r = 0.408, p = 0.015) dentition. This resistance to artificial demineralization had stronger correlation coefficients with the caries incidence than the caries experience and initial lesions, which are considered to be the most valid caries predictors. In conclusion, these data suggest that the degree of demineralization after etching and its changes with time could be associated with caries parameters. Its use in prospective clinical trials on caries activity could be a successful approach.


The relative frequency of paediatric oral and maxillofacial pathology in New Zealand: A 10-year review of a national specialist centre.
There has been no previous report of the prevalence of paediatric oral and maxillofacial pathology in a New Zealand oral pathology diagnostic service. The aim of this study was to review cases of paediatric oral pathology to determine relative frequencies of oral lesions in this age group. Paediatric oral pathology cases (≤15 years of age) received between 2007 and 2016 were retrieved from the electronic database of the Oral Pathology Centre, University of Otago. Data collected included diagnoses (categorised into 12 groups), age at diagnosis, and gender. The prevalence of each diagnosis was calculated in terms of percentage of all diagnoses made. Male-to-female ratio and mean age at diagnosis were also determined. A total of 1139 paediatric cases were identified representing 5.2% of all cases. The most common diagnostic group was salivary gland pathology (25.4%), followed by dental (24.8%) pathology. The most prevalent lesion was mucocoele (23%), followed by dental follicle (14.1%). Malignancies were rare with only two cases identified. The findings provide an insight into the prevalence of paediatric oral pathology for clinicians. Mucocoele was the most common diagnosis made, suggesting a high prevalence of soft tissue injury as a main presenting concern warranting diagnosis and management through biopsy.


A systematic review of the effectiveness of alcohol brief interventions for the UK military personnel moving back to civilian life.
Higher levels of alcohol consumption have been observed in the UK armed forces compared with the general population. For some, this may increase the risk of using alcohol as a coping strategy when adjusting to multiple life events occurring when moving back into civilian life. A systematic review was conducted to determine the effectiveness of alcohol brief interventions for military personnel during transition. Electronic databases including Medline, Central, Healthcare Management Information Consortium (HMIC) and Embase, and grey literature, were searched. Two reviewers independently assessed potential studies for inclusion, extracted data and assessed quality of selected articles using an established instrument. Ten studies met criteria for inclusion. Studies were synthesised narratively. Interventions were heterogeneous, and bias within studies may have acted to increase or decrease their reported effectiveness. The findings suggest some evidence for effectiveness of self-administered web-based interventions, involving personalised feedback over a number of sessions, and system-level electronic clinical reminders. All studies were from the USA. Delivery of interventions by a clinician during motivational interviews was most effective for those with post-traumatic stress disorder symptoms. A UK trial of web-based interventions with personalised feedback is recommended.


Progress over the first decade of CASP experiments.
CASP has now completed a decade of monitoring the state of the art in protein structure prediction. The quality of structure models produced in the latest experiment, CASP6, has been compared with that in earlier CASPs. Significant although modest progress has again been made in the fold recognition regime, and cumulatively, progress in this area is impressive. Models of previously unknown folds again appear to have modestly improved, and several mixed alpha/beta structures have been modeled in a topologically correct manner. Progress remains hard to detect in high sequence identity comparative modeling, but server performance in this area has moved forward.


[Age-related changes of albumin and actin of human myocardium].
In the human myocardium tissue, proteomic technologies revealed the products of 2 genes (alpha-actin and albumin), existing as fragments; their appearance and increased contents correlated with age. The age-related variants differ from the mature forms by the absence of N-terminal fragments of the amino acid sequences. In the chronic ischemic heart disease (CIHD), these age-dependent proteins were found in 50% of cases (in the age group 31-40 years), while in the control group such combination was detected only in 10% of the examined individuals. Subsequent studies in this field would probably reveal molecular mechanisms responsible for impairment and/or ageing of the cardiac muscle and also of the adaptation-dysadaptations mechanisms in the CIHD.


Unexpected source of Fukushima-derived radiocesium to the coastal ocean of Japan.
There are 440 operational nuclear reactors in the world, with approximately one-half situated along the coastline. This includes the Fukushima Dai-ichi Nuclear Power Plant (FDNPP), which experienced multiple reactor meltdowns in March 2011 followed by the release of radioactivity to the marine environment. While surface inputs to the ocean via atmospheric deposition and rivers are usually well monitored after a nuclear accident, no study has focused on subterranean pathways. During our study period, we found the highest cesium-137 (137Cs) levels (up to 23,000 Bq⋅m-3) outside of the FDNPP site not in the ocean, rivers, or potable groundwater, but in groundwater beneath sand beaches over tens of kilometers away from the FDNPP. Here, we present evidence of a previously unknown, ongoing source of Fukushima-derived 137Cs to the coastal ocean. We postulate that these beach sands were contaminated in 2011 through wave- and tide-driven exchange and sorption of highly radioactive Cs from seawater. Subsequent desorption of 137Cs and fluid exchange from the beach sands was quantified using naturally occurring radium isotopes. This estimated ocean 137Cs source (0.6 TBq⋅y-1) is of similar magnitude as the ongoing releases of 137Cs from the FDNPP site for 2013-2016, as well as the input of Fukushima-derived dissolved 137Cs via rivers. Although this ongoing source is not at present a public health issue for Japan, the release of Cs of this type and scale needs to be considered in nuclear power plant monitoring and scenarios involving future accidents.


PATRI-paternity inference using genetic data.
PATRI is a new application for paternity analysis using genetic data that accounts for the sampling fraction of potential fathers.


How do Ontario family medicine residents perform on global health competencies? A multi-institutional survey.
There is an increased interest in global health among medical students, family medicine residents, and medical educators. This paper is based on research to assess confidence in knowledge and skills in global health in family medicine residents in five universities across Ontario. A web-based survey was sent to 166 first-year family medicine residents from five universities within Ontario. Descriptive statistics were used to analyze residents' confidence in their knowledge and skills in global health. The strength of association between each of the self-perceived knowledge and skills variables was assessed by the Spearman correlation coefficient. The response rate ranged from 29% to 66% across the five universities. Self-perceived knowledge scores revealed that 34.3% of the respondents were very confident, 51.9% were somewhat confident, and 13.8% were not at all confident about their global health knowledge. Participants' confidence scores were lower in relation to knowledge of access to health care for low income nations (44.3%), and were better on their global health skills related to working in a team (70.9%) and listening actively to patients' concerns (64.6%). The global health competency scale has identified key areas of strengths and weaknesses of family medicine programs in global health education. This can be used to evaluate and analyze progress over time.


Pentosan polysulfate induces low-level persistent prion infection keeping measurable seeding activity without PrP-res detection in Fukuoka-1 infected cell cultures.
Each prion strain has its own characteristics and the efficacy of anti-prion drugs varies. Screening of prion disease therapeutics is typically evaluated by measuring amounts of protease-resistant prion protein (PrP-res). However, it remains unclear whether such measurements correlate with seeding activity, which is evaluated by real-time quaking-induced conversion (RT-QuIC). In this study, the effects of anti-prion compounds pentosan polysulfate (PPS), Congo red, and alprenolol were measured in N2a58 cells infected with Fukuoka-1 (FK1) or 22L strain. The compounds abolished PrP-res and seeding activity, except for N2a58/FK1 treated with PPS. Interestingly, the seeding activity of N2a58/FK1, which was reduced in the presence of PPS, was not lost and remained at low levels. However, upon removal of PPS, both were gradually restored to their original levels. These results indicate that low-level persistent prion infection keeping measurable seeding activity is induced by PPS in a strain-dependent manner. Furthermore, for protein misfolding cyclic amplification (PMCA), the anti-prion effect of PPS decreased in FK1 compared to 22L, suggesting that the differences occur at the level of the direct conversion. Our findings demonstrate that the advantages of RT-QuIC and PMCA can be exploited for more accurate assessment of therapeutic drug screening, reflecting strain differences.


Murine interleukin-12 prevents the development of cancer cachexia in a murine model.
Murine colon 26 carcinoma causes cachexia even when the tumor burden is small. In this tumor model, murine IL-12 suppressed the induction of cancer cachexia and also inhibited tumor growth. IL-12 reduced the serum levels of IL-6, a cachexia mediator in this model, and alleviated the body weight loss and other abnormalities associated with cachexia, such as adipose tissue wasting and hypoglycemia. The anticachectic activity was observed even at low doses of IL-12, insufficient to inhibit tumor growth. IL-12 greatly increased levels of IFN-gamma in the tumor tissue and, to a lesser extent, in the circulation. IFN-gamma given intraperitoneally also prevented cancer cachexia, although it did not reduce IL-6 levels either in the tumor or in the circulation. In athymic mice bearing the same colon 26 tumor, IL-12 was no longer anticachectic and did not induce IFN-gamma. These results indicate that the anticachectic activity of IL-12 is T-cell-dependent and results from at least 2 mechanisms, the down-regulation of IL-6 and the up-regulation of IFN-gamma.


Fed-batch process for the psychrotolerant marine bacterium Pseudoalteromonas haloplanktis.
Pseudoalteromonas haloplanktis is a cold-adapted γ-proteobacterium isolated from Antarctic sea ice. It is characterized by remarkably high growth rates at low temperatures. P. haloplanktis is one of the model organisms of cold-adapted bacteria and has been suggested as an alternative host for the soluble overproduction of heterologous proteins which tend to form inclusion bodies in established expression hosts. Despite the progress in establishing P. haloplanktis as an alternative expression host the cell densities obtained with this organism, which is unable to use glucose as a carbon source, are still low. Here we present the first fed-batch cultivation strategy for this auspicious alternative expression host. The key for the fed-batch cultivation of P. haloplanktis was the replacement of peptone by casamino acids, which have a much higher solubility and allow a better growth control. In contrast to the peptone medium, on which P. haloplanktis showed different growth phases, on a casamino acids-containing, phosphate-buffered medium P. haloplanktis grew exponentially with a constant growth rate until the stationary phase. A fed-batch process was established by feeding of casamino acids with a constant rate resulting in a cell dry weight of about 11 g l⁻¹ (OD540 = 28) which is a twofold increase of the highest densities which have been obtained with P. haloplanktis so far and an eightfold increase of the density obtained in standard shake flask cultures. The cell density was limited in the fed-batch cultivation by the relatively low solubility of casamino acids (about 100 g l⁻¹), which was proven by pulse addition of casamino acid powder which increased the cell density to about 20 g l⁻¹ (OD540 = 55). The growth of P. haloplanktis to higher cell densities on complex medium is possible. A first fed-batch fermentation strategy could be established which is feasible to be used in lab-scale or for industrial purposes. The substrate concentration of the feeding solution was found to influence the maximal biomass yield considerably. The bottleneck for growing P. haloplanktis to high cell densities still remains the availability of a highly concentrated substrate and the reduction of the substrate complexity. However, our results indicate glutamic acid as a major carbon source, which provides a good basis for further improvement of the fed-batch process.


Outcomes of 23- and 24-weeks gestation infants in Wellington, New Zealand: A single centre experience.
Optimal perinatal care of infants born less than 24 weeks gestation remains contentious due to uncertainty about the long-term neurodevelopment of resuscitated infants. Our aim was to determine the short-term mortality and major morbidity outcomes from a cohort of inborn infants born at 23 and 24 weeks gestation and to assess if these parameters differed significantly between infants born at 23 vs. 24 weeks gestation. We report survival rates at 2-year follow-up of 22/38 (58%) at 23 weeks gestation and 36/60 (60%) at 24 weeks gestation. Neuroanatomical injury at the time of discharge (IVH ≥ Grade 3 and/or PVL) occurred in in 3/23 (13%) and 1/40 (3%) of surviving 23 and 24 weeks gestation infants respectively. Rates of disability at 2 years corrected postnatal age were not different between infants born at 23 and 24 weeks gestation. We show evidence that with maximal perinatal care in a tertiary setting it is possible to achieve comparable rates of survival free of significant neuroanatomical injury or severe disability at age 2 in infants born at 23-week and 24-weeks gestation.


The Relationship of MRI-Derived Alzheimer's and Cerebrovascular-Related Signatures With Level of and Change in Health and Financial Literacy.
The cortical thickness "signature" of Alzheimer's disease (AD-CT) and white matter hyperintensity (WMH) burden have each been associated with cognitive aging and incident AD and related dementias. Less is known about how these structural neuroimaging markers associate with other critical behaviors. We investigated associations of AD-CT and WMH volumes with a composite index of health and financial literacy given that the ability to access, understand, and utilize health and financial information significantly influences older adults' health outcomes. Participants were 303 adults without dementia (age∼80 years; 74% women) from the Rush Memory and Aging Project. Baseline 3T MRI T1-weighted structural and T2-weighted FLAIR data were used to assess AD-CT and WMH volumes, respectively. Literacy was measured using questions designed to assess comprehension of health and financial information and concepts, yielding a total literacy score. Multivariable linear mixed effects regression models determined the relationship of each neuroimaging marker, first separately and then combined, with the level of and change in literacy. Reduced AD-CT and higher WMH at baseline were each associated with lower levels of literacy; only AD-CT was associated with the rate of decline in literacy over time. The association of AD-CT with change in literacy persisted when both neuroimaging markers were included in the same model. The cortical thickness signature of AD predicts changes in health and financial literacy in nondemented older adults suggesting that the multidimensional construct of health and financial literacy relies on specific brain networks implicated in AD.


[Rheumatological Diseases and Sleep: Somnological Aspects of Diagnostics and Therapy].
This PubMed-based review discusses primary and secondary sleep disorders associated with rheumatological diseases. It presents the pathophysiological interaction of sleep-related diseases and rheumatological disorders and summarises clinical symptoms, diagnostic investigation and therapies from a somnological perspective. 70 % of patients suffering from rheumatological diseases report poor sleep quality, numerous awakenings at night and non-restorative sleep. More than 20 % of these patients are found to have primary sleep disorders such as obstructive sleep apnoea (OSA) and the restless legs syndrome (RLS). Primary and secondary sleep disorders may increase symptoms associated with rheumatological diseases, e. g. excessive daytime sleepiness, fatigue, depression, pain intensity, and disease activity. Vice versa, pain intensity and inflammatory markers worsen sleep quality. In patients with rheumatic diseases, obesity as well as disease-related skeletal characteristics may be predisposing factors for obstructive sleep apnoea. The restless legs syndrome, which frequently occurs in rheumatological diseases, lowers sleep quality due to a sensory stimulus and periodic leg movements causing sleep fragmentation. Somnological diagnostic investigation consists of sleep-related questionnaires and scales. Objective tests are used to measure reaction time and vigilance. Sleep-related breathing and movement disorders can be identified with screening devices and polygrafic monitoring. A final polysomnografic sleep study is necessary to make the diagnosis and to initiate a specific treatment and follow-up examinations. Sleep disorders associated with rheumatological diseases may be treated with behavioural and drug therapies. Drug therapy is commonly used in the management of insomnia and RLS. Most cases of OSAS can be treated with CPAP or UPS devices. Interdisciplinary cooperation in the fields of somnology and rheumatology may improve treatment in RA patients.


4,4'-Dichlorodiphenyltrichloroethane (DDT) and 4,4'-dichlorodiphenyldichloroethylene (DDE) promote adipogenesis in 3T3-L1 adipocyte cell culture.
4,4'-Dichlorodiphenyltrichloroethane (DDT), a chlorinated hydrocarbon insecticide, was extensively used in the 1940s and 1950s. DDT is mainly metabolically converted into 4,4'-dichlorodiphenyldichloroethylene (DDE). Even though most countries banned DDT in the 1970s, due to the highly lipophilic nature and very stable characteristics, DDT and its metabolites are present ubiquitously in the environment, including food. Recently, there are publications on relationships between exposure to insecticides, including DDT and DDE, and weight gain and altered glucose homeostasis. However, there are limited reports regarding DDT or DDE and adipogenesis, thus we investigated effects of DDT and DDE on adipogenesis using 3T3-L1 adipocytes. Treatment of DDT or DDE resulted in increased lipid accumulation accompanied by increased expression of CCAAT/enhancer-binding protein α (C/EBPα), peroxisome-proliferator activated receptor-γ (PPARγ), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), adipose triglyceride lipase, and leptin. Moreover, treatment of DDT or DDE increased protein levels of C/EBPα, PPARγ, AMP-activated protein kinase-α (AMPKα), and ACC, while significant decrease of phosphorylated forms of AMPKα and ACC were observed. These finding suggest that increased lipid accumulation caused by DDT and DDE may mediate AMPKα pathway in 3T3-L1 adipocytes.


Historical approach to the surgical treatment of erectile dysfunction.
Throughout human history, erectile dysfunction has represented one of the most omnipresent health problems. This has resulted in a search for solutions that, one after the other, have been shown to be fruitless. In this context, the emergence of possible surgical solutions at the start of the 20th century represented a revolution that, even then, would take several decades to demonstrate their effectiveness. We performed a literature review that shows the process in the development of potential surgical treatments for hormonal restoration for erectile dysfunction, followed by the sudden emergence of vascular surgery, with new anastomosis techniques, and in the future, the development of penile prosthetic implants as alternative treatments. The publication of results from erectile dysfunction surgery has been lagging for decades due to a lack of objectivity, given that sexual function is a topic restricted by patients' privacy. This situation has led to a reliance on results reported by various authors whose actual credibility could not be verified, with subsequent demonstrations showing that some of these results were not reproducible. This article reviews some of the most important milestones in the progress of surgeries designed to treat erectile dysfunction. The achievements and apparent failures provide a reason for reflection on how we far we have come and how far we can go in the near future.


Risk Factors and Clinical Outcomes of Recurrent Laryngeal Nerve Paralysis After Esophagectomy for Thoracic Esophageal Carcinoma.
The objectives of this study were to assess the incidence of recurrent laryngeal nerve paralysis (RLNP) using laryngoscopy after esophagectomy for thoracic esophageal carcinoma and to clarify the risk factors influencing postoperative RLNP. A total of 299 patients who underwent laryngoscopic examination after esophagectomy were retrospectively reviewed. Patients who were found to have postoperative RLNP were followed up every 1–3 months, with a median follow-up period of 3 months. Recovery from paralysis was also evaluated on the basis of each affected nerve. Multivariate analyses using logistic regression were used to identify independent risk factors for RLNP. Cumulative recovery rate was calculated using Kaplan–Meier method. A total of 178 (59.5%) patients were diagnosed with RLNP by first laryngoscopy [bilateral in 59 (33.1%) patients, right in 15 (8.4%), and left in 104 (58.4%)]. In 206 patients who underwent transthoracic and thoracoscopic esophagectomy, independent risk factors for RLNP were lymph node dissection along the right RLN (odds ratio [OR] 3.01, 95% confidence interval [CI] 1.06–8.54, P = 0.04) and cervical anastomosis (OR 5.94, 95% CI 1.78–19.80, P < 0.01). Cumulative recovery rate from RLNP was 61.7% at 12 months after esophagectomy with 91 nerves eventually recovering from paralysis. Median recovery time was 6 months. RLNP developed in 60 % of patients after esophagectomy and may be associated with lymphadenectomy around the right RLN and cervical esophageal mobilization. Although 62% of affected nerves recovered within 12 months, great attention should be given when performing these procedures.


Plasma angiopoietin 2 concentrations are related to impaired lung function and organ failure in a clinical cohort receiving high-dose interleukin 2 therapy.
The pathophysiology and therapeutic options in sepsis-induced lung injury remain elusive. High-dose interleukin 2 therapy (HDIL-2) is an important protocol for advanced malignancies but is limited by systemic inflammation and pulmonary edema that is indistinguishable from sepsis. In preclinical models, IL-2 stimulates angiopoietin 2 (AngP-2) secretion, which increases endothelial permeability and causes pulmonary edema. However, these relationships have not been fully elucidated in humans. Furthermore, the relevance of plasma AngP-2 to organ function is not clear. We hypothesized that plasma AngP-2 concentrations increase during HDIL-2 and are relevant to clinical pathophysiology. We enrolled 13 subjects with metastatic melanoma or renal cell carcinoma admitted to receive HDIL-2 and collected blood and spirometry data daily. The plasma concentrations of AngP-2 and IL-6 were measured with enzyme-linked immunosorbent assay. At baseline, the mean AngP-2 concentration was 2.5 (SD, 1.0) ng/mL. Angiopoietin 2 concentrations increased during treatment: the mean concentration on the penultimate day was 16.0 (SD, 4.5) ng/mL and increased further to 18.6 (SD, 4.9) ng/mL (P < 0.05 vs. penultimate) during the last day of therapy. The forced expiratory volume in 1 s decreased during treatment. Interestingly, plasma AngP-2 concentrations correlated negatively with forced expiratory volume in 1 s (Spearman r = -0.78, P < 0.0001). Plasma AngP-2 concentrations also correlated with plasma IL-6 concentrations (r = 0.61, P < 0.0001) and Sequential Organ Failure Assessment scores (r = 0.68, P < 0.0001). Plasma AngP-2 concentrations increase during HDIL-2 administration and correlate with pulmonary dysfunction. High-dose IL-2 may serve as a clinical model of sepsis and acute lung injury. Further investigation is warranted.


Molecular cloning, characterization, and expression analysis of two different types of lectins from the oriental river prawn, Macrobrachium nipponense.
Lectins, which are widely expressed in invertebrates, play important roles in many biological processes, including protein trafficking, cell signaling, pathogen recognition, as effector molecules, and so on (Wang and Wang, 2013). This study identified one novel M-type lectin and one L-Type lectin, designated as MnMTL1 and MnLTL1, from the oriental river prawn Macrobrachium nipponense. The full-length cDNA of MnMTL1 was 2064 bp with a 1761 bp ORF encoding a putative protein of 586 deduced amino acids. The full-length cDNA of MnLTL1 was 1744 bp with a 972 bp ORF encoding a 323-amino acid peptide. The deduced MnMTL1 protein contained a putative type II transmembrane region and a 440-aa Glycoside hydrolase family 47 (GH47) domain. One luminal carbohydrate recognition domain and a 23-aa type I transmembrane region were identified from the MnLTL1. MnMTL1 shared 78% identity with Marsupenaeus japonicus M-type lectin and MnLTL1 shared 83% similarity with M. japonicus L-type lectin. RT-PCR analysis showed that MnMTL1 and MnLTL1 were expressed in all tested tissues. Quantitative real-time PCR analysis revealed that MnMTL1 and MnLTL1 are substantially fluctuant during Aeromonas hydrophila and Aeromonas veronii infections. Based on immune responses and previous literature, we assumed that MnMTL1 and MnLTL1 might be functioned as pattern recognition receptors and play important roles in the immune response of M. nipponense.


A semi-interpenetrating network ionic composite hydrogel with low modulus, fast self-recoverability and high conductivity as flexible sensor.
There is a growing demand for hydrogel-based sensors due to their biomimetic structures and properties, as well as biocompatibility. However, it is still a challenge to fabricate hydrogel sensor with integration of good mechanical properties and high conductivity. Herein, a tough and conductive hydrogel is developed with semi-interpenetrating network formed by incorporating carboxymethyl chitosan and sodium chloride into polyacrylamide network. The hydrogels have high tensile strength, elongation and toughness, but low modulus comparable to human skin. In addition, the hydrogels exhibit fast self-recovery and satisfactory self-healing capabilities. Owing to the existence of sodium chloride, the hydrogel also has high conductivity, good water retention property and anti-freezing ability. When used as a strain sensor, it demonstrates a broad strain window and shows a high sensitivity in monitoring human motions. This work provides a facile method in fabricating multifunctional ionic conductive hydrogel for applications in wearable electronics and soft robotics.


The development of the imagination and imaginary worlds.
Evidence from developmental psychology on children's imagination is currently too limited to support Dubourg and Baumard's proposal and, in several respects, it is inconsistent with their proposal. Although children have impressive imaginative powers, we highlight the complexity of the developmental trajectory as well as the close connections between children's imagination and reality.


Fluid resuscitation after severe trauma injury : U-shaped associations between tetrastarch dose and survival time or frequency of acute kidney failure.
Using tetrastarch for fluid resuscitation after a severe trauma injury may increase risks of death and acute kidney injury. The importance of tetrastarch dose, however, is unknown. A retrospective observational study was performed in two trauma centres using data on type and amount of fluids (balanced crystalloids or tetrastarch) used for pre- and acute in-hospital shock management. We evaluate independent associations between the relative and absolute volumes of tetrastarch and 90-day survival time or the frequency of severe acute kidney failure (AKF). We studied 271 patients who had sustained a severe blunt trauma injury (average predicted mortality according to the Revised Injury Severity Classification Score (RISC) 15.1 ± 1.4% [mean, standard deviation]), and who had required more than 2 days of intensive care therapy. In all, 75.3% of patients had received tetrastarch with a crystalloid/colloid ratio of 2.93 ± 2.60. The 90-day mortality was 11.1%, and 7.8% of the patients developed severe AKF. After adjusting for confounders, we found a U-shaped, nonlinear association between absolute or relative volumes of tetrastarch and survival time (p = 0.003 and 0.025, respectively). Optimal relative volumes of tetrastarch approximately ranged from 20 to 30% of total fluids. Giving less than about 1000 ml, or more than about 2000 ml tetrastarch was significantly associated with an increased risk of developing severe AKF (p = 0.023). There was a complex U‑shaped association between the tetrastarch dose and morbidity/mortality of patients after a severe trauma injury. The optimal crystalloid/tetrastarch ratio for acute shock management appears to range from about 2.5 to 4.0.


Four year follow-up of black schoolchildren with non-ejection systolic clicks and mitral systolic murmurs.
In 1972 we conducted a survey of 12,050 urban Black schoolchildren and detected 168 (prevalence rate of 14 per 1,000) with a non-ejection systolic click (NESC), a late systolic murmur, or both. The etiology of the mitral valve abnormality was unknown but we considered that a significant proportion might have early rheumatic heart disease. The auscultatory features four years later of 139 of the original 168 subjects as well as those of 139 age- and sex-matched controls are presented in this study. No cardiac abnormality was detected in as many as 55 of the subjects. Five children now had pansystolic murmurs but the mitral regurgitation was assessed as mild in four. Twenty-five (17.9 per cent) of the controls, 23 of whom had NESCs, had auscultatory features compatible with mitral valve prolapse. These findings do not support our earlier suggestion that a large number of the 1972 subjects have mild rheumatic heart disease. The results are in accord with other studies which have indicated that auscultatory features compatible with mitral valve prolapse are common in "normals" and also that the prognosis of the specific "billowing mitral leaflet syndrome" is generally benign.


Synergistic Strategies to Accelerate the Development of Function-Promoting Therapies: Lessons From Operation Warp Speed and Oncology Drug Development.
Functional limitations and physical disabilities associated with aging and chronic disease are major concerns for human societies and expeditious development of function-promoting therapies is a public health priority. Expert panel discussion. The remarkable success of Operation Warp Speed for the rapid development of COVID-19 vaccines, COVID-19 therapeutics, and of oncology drug development programs over the past decade have taught us that complex public health problems such as the development of function-promoting therapies will require collaboration among many stakeholders, including academic investigators, the National Institutes of Health, professional societies, patients and patient advocacy organizations, the pharmaceutical and biotechnology industry, and the U.S. Food and Drug Administration. There was agreement that the success of well designed, adequately powered clinical trials will require careful definitions of indication/s, study population, and patient-important endpoints that can be reliably measured using validated instruments, commensurate resource allocation, and versatile organizational structures such as those used in Operation Warp Speed.


The impact of genetic aberrations on response to radium-223 treatment for castration-resistant prostate cancer with bone metastases.
Radium (Ra)-223 is an established treatment option for patients with metastatic castrate-resistant prostate cancer (mCRPC) who have symptomatic bone metastases without soft tissue disease. Studies have indicated genetic aberrations that regulate DNA damage response (DDR) in prostate cancer can increase susceptibility to treatments such as poly ADP-ribose polymerase inhibitors and platinum-based therapies. This study aims to evaluate mCRPC response to Ra-223 stratified by tumor genomics. This is a retrospective study of mCRPC patients who received Ra-223 and genetic testing within the Mayo Clinic database (Arizona, Florida, and Minnesota) and Tulane Cancer Center. Patient demographics, genetic aberrations, treatment responses in terms of alkaline phosphatase (ALP) and prostate-specific antigen (PSA), and survival were assessed. Primary end points were ALP and PSA response. Secondary end points were progression-free survival (PFS) and overall survival (OS) from time of first radium treatment. One hundred and twenty-seven mCRPC patients treated with Ra-223 had germline and/or somatic genetic sequencing. The median age at time of diagnosis and Ra-223 treatment was 61.0 and 68.6 years, respectively. Seventy-nine (62.2%) had Gleason score ≥ 8 at time of diagnosis. 50.4% received prior docetaxel, and 12.6% received prior cabazitaxel. Notable alterations include TP53 (51.7%), BRCA 1/2 (15.0%), PTEN (13.4%), ATM (11.7%), TMPRSS2-ERG (8.2%), RB deletion (3.4%), and CDK12 (1.9%). There was no significant difference in ALP or PSA response among the different genetic aberrations. Patients with a TMPRSS2-ERG mutation exhibited a trend toward lower OS 15.4 months (95% confidence interval [CI] 10.0-NR) versus 26.8 months (95% CI 20.9-35.1). Patients with an RB deletion had a lower PFS 6.0 months (95% CI 1.28-NR) versus 9.0 months (95% CI 7.3-11.1) and a lower OS 13.9 months (95% CI 5.2-NR) versus 26.5 months (95% CI 19.8-33.8). Among mCRPC patients treated with Ra-223 at Mayo Clinic and Tulane Cancer Center, we did not find any clear negative predictors of biochemical response or survival to treatment. TMPRSS2-ERG and RB mutations were associated with a worse OS. Prospective studies and larger sample sizes are needed to determine the impact of genetic aberrations in response to Ra-223.


Thermal injury to the tongue from an operative laryngoscope.
To understand risk and possible mechanisms of thermal injury to the tongue during suspension laryngoscopy. Tongue injury was noted following suspension laryngoscopy in a cluster of cases; the findings raised suspicion for thermal injury. To characterize the potential for thermal injury, a lighted laryngoscope was placed in contact with samples of tongue. Tissue heating was recorded over time at fixed distances from the light carrier within a laryngoscope. Comparisons were made between two light sources and carriers. Maximal tissue heating using a newer-model light source and new carrier was 16.7 degrees F immediately beneath the light carrier tip and 19.8 degrees F at 1 cm distal to the carrier tip. Other combinations of an older source and carriers failed to raise temperatures. Heating up to 10.7 degrees F occurred with the new source and an older carrier. Tissue heating may occur from contact with operative laryngoscopes. This is an important patient safety issue in laryngology.


Corneal endothelial specular microscopy following deep lamellar keratoplasty with lyophilised tissue.
To assess the corneal endothelial cell density following deep lamellar keratoplasty (DLK) carried out by air dissection and with the transplantation of lyophilised tissue. Contact endothelial specular microscopy was carried out on a series of patients who had undergone DLK with a minimum of 1 year post-operative follow-up. Twenty eyes of 18 patients were examined at follow-up times ranging from 1 to 8 years post-operatively (mean 3 years). Indications for surgery were: keratoconus (n = 12), herpes simplex virus (HSV) keratitis (n = 1), herpes zoster ophthalmicus (HZO) keratitis (n = 1), lipid keratopathy (n = 2), lattice dystrophy (n = 1) and corneal scarring (n = 3). Overall, mean post-operative cell density was 2417 cells/mm2 (range 928-3656 cells/mm2). In eyes with pathological conditions not likely to have affected the endothelial cell density, such as keratoconus or lattice degeneration, the mean cell density was 2837 cells/mm2 (range 1030-3656 cells/mm2). In patients undergoing DLK for conditions such as keratoconus the post-operative cell density was at a normal level in the majority of cases. Cell loss through this surgical intervention thus appears generally to be small. The prospect for long-term survival of these grafts is good.


Ultraviolet light-induced chromosomal aberrations in cultured cells from Cockayne syndrome and complementation group C xeroderma pigmentosum patients: lack of correlation with cancer susceptibility.
Both Cockayne syndrome (CS) and xeroderma pigmentosum (XP) are inherited diseases with defective repair of damage induced in DNA by UV. Patients with XP, but not those with CS, have an increased susceptibility to formation of sunlight-induced skin tumors. We determined the frequency of UV-induced chromosomal aberrations in cultured lymphoblastoid cell lines from five CS patients and three complementation-group-C XP patients to determine whether such aberrations were abnormally increased only in the XP cells. We found that CS cells had the same abnormally increased number of induced aberrations as the XP cells, indicating that the number of UV-induced aberrations in XP group C cells does not account for the susceptibility of these XP patients to sunlight-induced skin cancer.


NiII and CoII binary and ternary complexes of 3-formylchromone: spectroscopic characterization, antimicrobial activities, docking and modeling studies.
Reactions of 3-formylchromone (L) with Ni(ii) and Co(ii) ions having different anions (acetate, perchlorate, nitrate, and chloride) yielded a series of binary and ternary octahedral complexes with the general formula [ML n L' m X y (S) a ]Z y ·bS, where M = Ni or Co, n = 1-3, L' = auxiliary ligand = 8-hydroxyquinoline or 1,10-phenanthroline, m = 1 or 2, X = acetate or chloride, y = 0 or 2, S = H2O or MeOH, a = 0-2, Z = nitrate or perchlorate and b = 0-1.5. Elemental and thermal analyses and infra-red, electronic, mass, magnetic susceptibility and molar conductivity measurements were successfully utilized to characterize the structures of the chromone complexes. The chromone ligand acts as a neutral bidentate ligand through its formyl and γ-pyrone oxygen atoms. The obtained complexes were formed with molar ratios 1 : 2 and 1 : 3 M : L for the binary and 1 : 2 : 1 and 1 : 1 : 1 M : L : L' for the ternary complexes. The kinetic parameters of the thermal degradation steps were estimated and explained using the Coats-Redfern equations. The synthesized complexes showed antimicrobial activity with higher activity toward Candida albicans and Bacillus subtilis. Docking studies showed good agreement with the antimicrobial activity. Molecular modeling of the synthesized complexes was performed using Hyperchem at the PM3 level and the calculated structures correlate with the experimental data.


Early neurological worsening in acute ischaemic stroke patients.
Neurological worsening in acute ischaemic stroke patients is common with significant morbidity and mortality. To determine the factors associated with early neurological worsening within the first 9 h after onset of acute ischaemic stroke. The National Institute of Health Stroke Scale (NIHSS) was used to assess stroke severity. Early neurological worsening was defined as NIHSS score increase ≥4 NIHSS points within 9 h of symptom onset compared to NIHSS score within 3 h of symptom onset. Patients with early neurological worsening were compared to patients with unchanged or improved NIHSS scores. Of the 2484 patients admitted with ischaemic stroke, 552 patients had NIHSS score within 3 h of symptom onset, and 44 (8.0%) experienced early neurological worsening. The median NIHSS on admission was 8.4 in both groups. Early neurological worsening was associated with low body temperature on admission (P = 0.01), proximal compared to distal MCA occlusion (P = 0.007) and with ipsilateral internal carotid artery stenosis >50% or occlusion (P = 0.04). Early neurological worsening was associated with higher NIHSS day 7 (P < 0.001) and higher mortality within 7 days of stroke onset (P = 0.005). Early neurological worsening has serious consequences for the short-term outcome for patients with acute ischaemic stroke and is associated with low body temperature on admission, and with extracranially and intracranially large-vessel stenosis or occlusion.


Skewed fate and hematopoiesis of CD34+ HSPCs in umbilical cord blood amid the COVID-19 pandemic.
Umbilical cord blood (UCB) is an irreplaceable source for hematopoietic stem progenitor cells (HSPCs). However, the effects of SARS-CoV-2 infection and COVID-19 vaccination on UCB phenotype, specifically the HSPCs therein, are currently unknown. We thus evaluated any effects of SARS-CoV-2 infection and/or COVID-19 vaccination from the mother on the fate and functionalities of HSPCs in the UCB. The numbers and frequencies of HSPCs in the UCB decreased significantly in donors with previous SARS-CoV-2 infection and more so with COVID-19 vaccination via the induction of apoptosis, likely mediated by IFN-γ-dependent pathways. Two independent hematopoiesis assays, a colony forming unit assay and a mouse humanization assay, revealed skewed hematopoiesis of HSPCs obtained from donors delivered from mothers with SARS-CoV-2 infection history. These results indicate that SARS-CoV-2 infection and COVID-19 vaccination impair the functionalities and survivability of HSPCs in the UCB, which would make unprecedented concerns on the future of HSPC-based therapies.


Whole Genome Amplification from Blood Spot Samples.
Whole genome amplification is an invaluable technique when working with DNA extracted from blood spots, as the DNA obtained from this source often is too limited for extensive genetic analysis. Two techniques that amplify the entire genome are common. Here, both are described with focus on the benefits and drawbacks of each system. However, in order to obtain the best possible WGA result the quality of input DNA extracted from the blood spot is essential, but also time consumption, flexibility in format and elution volume and price of the technology are factors influencing system choice. Here, three DNA extraction techniques are described and the above aspects are compared between the systems.


Genetic Diversity of Listeria Detected in the Production Environment of Meat Processing.
The safety of food production as concerns Listeria is the key to the sanitary wellbeing of manufactured products. Molecular-genetic methods for the analysis of Listeria, including whole-genome sequencing, are effective in monitoring persistent contaminants and in the epidemic investigation of cases of foodborne infections. They have been adopted in the European Union, United States, and Canada. In Russia, multilocus and whole-genome sequencing has proven itself in the analysis of clinical food isolates and Listeria from the environment. The objective of the study was molecular-genetic characterization of Listeria detected in the industrial environment of meat processing. To characterize the Listeria isolates, microbiological methods were used according to GOST (State Standard) 32031-2012, as well as multilocus sequencing, including the analysis of seven housekeeping genes and four virulence genes, as well as whole-genome sequencing. In swabs that were positive for the presence of Listeria spp. taken at two meat-processing plants in Moscow, Listeria monocytogenes constituted 81% and L. welshimeri 19%. The predominant genotype (Sequence Type, ST) of L. monocytogenes was ST8. The variety was supplemented with ST321, ST121, and ST2330 (CC9 (Clonal Complex 9)). L. welshimeri, which prevailed in the second production, was represented by ST1050 and ST2331. The genomic characteristics of L. welshimeri isolates confirmed that they have high adaptive capabilities both as concerns production conditions (including resistance to disinfectants) and the metabolic peculiarities of the gastrointestinal tract of animals. L. monocytogenes CC9 and CC121 are also correlated with food production in other countries. However, L. monocytogenes CC8 and CC321 can cause invasive listeriosis. The concordance in the internalin profile of the ST8 isolates from the industrial environment with the clinical isolates ST8 and ST2096 (CC8) is a cause for concern. The study showed the effectiveness of molecular-genetic methods in determining the diversity of Listeria detected in the production environment of meat processing, and laid the foundation for monitoring of persistent contaminants.


Fabry-Pérot resonances and a crossover to the quantum Hall regime in ballistic graphene quantum point contacts.
We report on the observation of quantum transport and interference in a graphene device that is attached with a pair of split gates to form an electrostatically-defined quantum point contact (QPC). In the low magnetic field regime, the resistance exhibited Fabry-Pérot (FP) resonances due to np'n(pn'p) cavities formed by the top gate. In the quantum Hall (QH) regime with a high magnetic field, the edge states governed the phenomena, presenting a unique condition where the edge channels of electrons and holes along a p-n junction acted as a solid-state analogue of a monochromatic light beam. We observed a crossover from the FP to QH regimes in ballistic graphene QPC under a magnetic field with varying temperatures. In particular, the collapse of the QH effect was elucidated as the magnetic field was decreased. Our high-mobility graphene device enabled observation of such quantum coherence effects up to several tens of kelvins. The presented device could serve as one of the key elements in future electronic quantum optic devices.


Homeostasis of plasma electrolytes, water and sodium pools in the Estuarine Crocodile, Crocodylus porosus, from fresh, saline and hypersaline waters.
1. Total body water and exchangeable Na pools have been measured in hatchling and juvenile Estuarine Crocodiles captured from a wide range of salinity (0-64‰). Plasma electrolyte concentrations are presented for hatchlings over the same range of salinity. 2. Plasma electrolyte concentrations in hatchlings are constant across the entire salinity range studied. Hatchlings and juveniles, up to 5 kg body weight, maintain constant weight-corrected total body water pools but show a decline in exchangeable sodium pools with increasing salinity, suggesting a shift in the distribution of electrolytes or water between extra- and intra-cellular fluid compartments. 3. Both water and Na pools scale allometrically with body weight (allometric coefficients of 0.984 and 0.944 respectively). Expression of weight-specific pool sizes in units of ml/100 g or mmol/kg is, therefore, potentially misleading. Demonstration of homeostasis with respect to pool size depends upon the expression of pool size in units of ml or mmol per unit length and upon detailed consideration of weight/length and volume/length scaling relationships. The implications of these findings for future studies of the ecology of C. porosus in saline habitats are discussed.


Relationship between cranio-cervical flexion range of motion and pressure change during the cranio-cervical flexion test.
The purpose of this study was to quantify the sagittal angular displacement of the head (cranio-cervical flexion) for the five incremental stages of the cranio-cervical flexion test (CCFT). Range of cranio-cervical flexion during the CCFT was measured using a digital imaging method in 20 healthy volunteer subjects. The intra-and inter-rater reliability of the digital imaging technique for the assessment of this movement were also examined. The results of this study demonstrated a linear relationship between the incremental pressure targets of the CCFT and the percentages of full range cranio-cervical flexion range of motion (ROM) measured in the supine lying position of the test using a digital imaging technique. A mean of 22.9% full range cranio-cervical flexion was used to reach the first pressure target of the CCFT followed by linear increments up to 76.6% for the last stage of the test. An increasing amount of cranio-cervical flexion ROM was used to achieve the five successive stages of the CCFT reflecting an increasing contractile demand on the deep cervical flexor muscles. Excellent inter-rater (ICC=0.994) and intra-rater reliability (ICC=0.988-0.998) were demonstrated for the angular measurements using this digital imaging technique.


Contribution of three-dimensional volume contrast imaging to the sonographic assessment of the fetal uterus.
To investigate the contribution of volume contrast imaging (VCI) in assessing the fetal uterus in normally developed female fetuses. The pelvis of 38 normal female fetuses was examined at 20-22 and 32-34 weeks' gestation using both conventional two-dimensional (2D) ultrasound and VCI on the same transverse or oblique longitudinal view of the fetal pelvis. Two experienced sonographers evaluated the ability of both techniques to image the fetal uterus. Results were compared by kappa index to evaluate the interobserver variability. A clear picture of the fetal uterus was obtained in 50% and 82-87% of the cases at 20-22 weeks' gestation and in 80-85% and 95-100% of the cases at 32-34 weeks' gestation using conventional 2D ultrasound and VCI, respectively. There was moderate to good agreement of uterus visualization between the two observers, with kappa values ranging from 0.43 to 0.65. The lower level of agreement was obtained for conventional 2D ultrasound during the second trimester. Our results suggest that VCI may be successfully applied to prenatal ultrasonography of the fetal pelvis anatomy. By enhancing the contrast between the intrapelvic organs, VCI provides a clearer picture of the fetal uterus.


Revisiting the melanomagenic pathways and current therapeutic approaches.
Melanoma is one of the most aggressive forms of skin cancer with a steady increase in global incidence and mortality rate over the past five decades. Paradoxically, both reduced and excessive sun exposure has been linked to increased risk of melanoma incidence and death. Although the histological classification of melanoma is useful in diagnosis, its molecular subtypes are often determined by somatic mutations, which could be UV-dependent or -independent. Multiple genes involved in cancer development are often mutated dysregulating molecular pathways with concomitant phenotypic heterogeneity. Hence, treating melanoma has been a challenge, with patients experiencing poor clinical outcomes to current therapeutic options. This presents an unmet need to understand the interaction of molecular networks underpinning melanogenesis. This review describes the crosstalk of signaling cascades in melanoma development and the putative druggable targets, with the view of elucidating newer and better therapeutic strategies for the disease.


Influence of process variables on essential oil microcapsule properties by carbohydrate polymer-protein blends.
Carbohydrate polymer-protein blends Zanthoxylum limonella oil (ZLO) loaded microcapsules were prepared by multiple emulsion solvent evaporation technology and the influence of various processing variables on the properties of ZLO loaded microcapsules were examined systematically. It was found that the internal aqueous alginate phase volume, external aqueous gelatin phase volume and concentration of surfactant in external aqueous gelatin phase have a significant influence on microcapsules properties. The essential oil-loaded microcapsules were smooth and spherical in shape as revealed by scanning electron micrograph. Results of Fourier transform infrared (FTIR) spectroscopy indicated stable character and showed the absence of chemical interaction between the microencapsulated oil and carbohydrate polymer-protein blends. Differential scanning calorimetry (DSC) study revealed the antioxidant nature of ZLO in the microcapsules. The release rate of ZLO loaded microcapsules was analyzed by UV-vis spectrophotometer. 83.80% of oil encapsulation efficiency was obtained depending upon the processing variables. Thus, proper control of the processing variables involved in this technology could allow effective incorporation of essential oil into the core of the carbohydrate polymer-protein blends matrix.


Characterisation of Pseudomonas rhamnolipids.
The Gram negative organism, Pseudomonas aeruginosa, is often found in the lungs of patients with cystic fibrosis and other forms of severe bronchiectasis, where it secretes a number of extracellular toxins including the mono- and dirhamnolipids. The principal monorhamnolipid from P. aeruginosa has previously been identified as rhamnosyl-3-hydroxydecanoyl-3-hydroxydecanoate (Rh-C10.C10). A number of related mono- and dirhamnolipids have been purified from cultures of a clinical isolate of P. aeruginosa and identified by fast atom bombardment and electron impact mass spectrometry: these contain the 3-hydroxyoctanoyl-3-hydroxydecanoate (C8.C10) and 3-hydroxydecanoyl-3-hydroxydodecanoate (C10.C12) homologues. Structural isomers were also present where the order of the lipid linkage was transposed (Rh-C10.C8 and Rh-C12.C10). Unsaturated mono- and dirhamnolipids containing the 3-hydroxydecanoyl-3-hydroxydodec-5-enoate (C10.C12:1) lipid were also present.


Dental adhesives in contemporary restorative dentistry.
Significant progress has been made in the area of adhesives in restorative dentistry. With respect to composite restoratives, bond strengths greater than the targeted 17 MPa are now routinely achieved by modern dentin bonding systems in laboratory tests. Each adhesive system must be handled according to the manufacturer's instructions and with careful attention to the details of application for maximal success. Clinical documentation of the success of the modern systems is limited. This especially true for the multipurpose applications often advocated by the product instructions or clinicians lecturing from personal anecdotal experience. The confirmation of laboratory results with controlled clinical trials often occurs late or not at all. A thorough understanding of the in vivo performance is needed to gain the knowledge necessary to further the technologic advances in this area.


[Chronic experimental testing of a new formulated fish product--an analog of salmon based on isolated krill protein].
White non-inbred rats received rations with varying content of the test fish product. Animals given the ration with casein served as controls. The changes in the animals' body mass, the relative mass of the internal organs, as well as their morphology and parameters of protein and lipid metabolism were studied. The analysis of the results obtained has shown that the fish product investigated in the amounts comprising 1.8 and 4.5% of the total calorific value of the ration produces no changes in the animal's body.


Transcriptomic analysis of the fat body of resistant and susceptible silkworm strains, Bombyx mori (Lepidoptera), after oral treatment with fenpropathrin.
The widespread use of pyrethroid pesticides has brought serious economic losses in sericulture, but there is still no viable solution. The key to solving the problem is to improve silkworm resistance to pesticides, which depends on understanding the resistance mechanism of silkworms to pesticides. This study aimed to use transcriptomes to understand the underlying mechanism of silkworm resistance to fenpropathrin, which will provide a theoretical molecular reference for breeding pesticide-resistant silkworm varieties. In this study, the fat bodies of two strains with differential resistance after 12 h of fenpropathrin feeding were analyzed using RNA-Seq. After feeding fenpropathrin, 760 differentially expressed genes (DEGs) were obtained in the p50(r) strain and 671 DEGs in the 8y strain. The DEGs involved in resistance to fenpropathrin were further identified by comparing the two strains, including 207 upregulated DEGs in p50(r) and 175 downregulated DEGs in 8y. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that these fenpropathrin-related DEGs are mainly enriched in the metabolism and transporter pathways. Moreover, 28 DEGs involved in the metabolic pathway and 18 in the transporter pathway were identified. Furthermore, organic cation transporter protein 6 (BmOCT6), a transporter pathway member, was crucial in enhancing the tolerance of BmN cells to fenpropathrin. Finally, the knockdown of the expression of the homologs of BmOCT6 in Glyphodes pyloalis (G. pyloalis) significantly decreased the resistant level of larvae to fenpropathrin. The findings showed that the metabolism and transporter pathways are associated with resistance to fenpropathrin in silkworm, and OCT6 is an effective and potential target not only for silkworm breeding but also for pest biocontrol.


Determinants of food allergy.
Food allergy is an emerging epidemic in the United States and the Western world. The determination of factors that make certain foods allergenic is still not clearly understood. Only a tiny fraction of thousands of proteins and other molecules is responsible for inducing food allergy. In this review, the authors present 3 examples of food allergies with disparate clinical presentations: peanut, soy, and mammalian meat. The potential relationships between allergen structure and function, emphasizing the importance of cross-reactive determinants, immunoglobulin E antibodies to the oligosaccharides, and the immune responses induced in humans are discussed.


Robotic liver resection as a bridge to liver transplantation.
The surgical robotic system is superior to traditional laparoscopy in regards to 3-dimensional images and better instrumentation. Robotic surgery for hepatic resection has not yet been extensively reported. The aim of this article is to report the first known case of liver resection with the use of a robot in France. A 61-year-old male with hepatitis C liver cirrhosis and hepatocellular carcinoma was referred for surgical treatment. Preoperative clinical evaluation and laboratory data disclosed a Child-Pugh class A5 patient. Magnetic resonance imaging showed a 3.4-cm tumor in segment III. Liver size was normal, and there were not signs of portal hypertension. Five trocars were used. Liver transection was achieved with Harmonic scalpel and bipolar forceps without pedicle clamping. Hemostasis of raw surface areas was accomplished with interrupted stitches. Operative time was 180 minutes. Blood loss was minimal, and the patient did not receive transfusion. The recovery was uneventful, and the patient was discharged on the fifth postoperative day without ascites formation. The robotic approach may enable liver resection in patients with cirrhosis. The da Vinci robotic system allowed for technical refinements of laparoscopic liver resection due to 3-dimensional visualization of the operative field and instruments with wrist-type end-effectors.


Strategies for improving performance in long duration events: Olympic distance triathlon.
This review focuses on strategic aspects that may affect performance in a long-duration Olympic event, the Olympic distance triathlon. Given the variety of races during the Olympic Games triathlon, strategic aspects include improving technological features as well as energetics factors affecting overall triathlon performance. During the last decade, many studies have attempted to identify factors reducing the metabolic load associated (or not) with the development of fatigue process by analysing the relationship between metabolic and biomechanical factors with exercise duration. To date, a consensus exists about the benefit of adopting a drafting position during the swimming or the cycling part of the triathlon. Other potential strategic factors, such as the production of power output or the selection of cadence during the cycling or the running leg, are likely to affect the overall triathlon performance. Within this approach, pacing strategies are observed by elite athletes who swim or cycle in a sheltered position, inducing several changes of pace, intensity or stochastic shifts in the amplitude of the physiological responses. The analysis of these parameters appears to arouse some experimental and practical interest from researchers and coachers, especially for long-distance Olympic events.


Prognostic value of SPECT myocardial perfusion entropy in high-risk type 2 diabetic patients.
Risk stratification of patients with type 2 diabetes mellitus (T2D) remains suboptimal. We hypothesized that myocardial perfusion entropy (MPE) quantified from SPECT myocardial perfusion images may provide incremental prognostic value in T2D patients independently from myocardial ischemia. T2D patients with very high and high cardiovascular risk were prospectively included (n = 166, 65 ± 12 years). Stress perfusion defect was quantified by visual evaluation of SPECT MPI. SPECT MPI was also used for the quantification of rest and stress MPE. The primary end point was major adverse cardiac events (MACEs) defined as cardiac death, myocardial infarction (MI), and myocardial revascularization > 3 months after SPECT. Forty-four MACEs were observed during a 4.6-year median follow-up. Significant differences in stress MPE were observed between patients with and without MACEs (4.19 ± 0.46 vs. 3.93 ± 0.40; P ≤ .01). By Kaplan-Meier analysis, the risk of MACEs was significantly higher in patients with higher stress MPE (log-rank P ≤ 01). Stress MPE and stress perfusion defect (SSS ≥ 4) were significantly associated with the risk of MACEs (hazard ratio 2.77 and 2.06, respectively, P < .05 for both) after adjustment for clinical and imaging risk predictors as identified from preliminary univariate analysis. MPE demonstrated incremental prognostic value over clinical risk factors, stress test EKG and SSS as evidenced by nested models showing improved Akaike information criterion (AIC), reclassification (global continuous net reclassification improvement [NRI]: 63), global integrated discrimination improvement (IDI: 6%), and discrimination (change in c-statistic: 0.66 vs 0.74). Stress MPE provided independent and incremental prognostic information for the prediction of MACEs in diabetic patients. NCT02316054 (12/12/2014).


The intracellular calcium antagonist, TMB-8, inhibits prolactin gene expression in GH3 cells.
We examined the effects of the drug, TMB-8, which promotes sequestration of intracellular Ca2+, on the ability of extracellular Ca2+ to stimulate prolactin gene expression in GH3 cells. TMB-8 inhibited prolactin mRNA levels in a dose-dependent manner in the concentration range of 2.5-10 microM. Prolactin mRNA levels were increased about 18-fold by the addition of 0.1 mM CaCl2, and about 25-fold by the addition of 0.4 mM CaCl2. Addition of 10 microM TMB-8 reduced these levels to about 4-fold and 7-fold, respectively. At 10 microM TMB-8 did not effect total protein synthesis or the Ca2+-induced aggregation of the cells, indicating a selective inhibition by the drug of prolactin gene expression. Both TMB-8 and the calmodulin inhibitor, calmidazolium, reversed the effects of Ca2+ on prolactin mRNA levels in cells that had been pretreated for 2 days with 0.4 mM CaCl2.


Predictors of success following endovascular aneurysm repair: mid-term results.
Australian cases of endovascular aneurysm repair (EVAR) performed between 1999 and 2001 have been evaluated to determine the mid-term (6 months to 5 years) safety and efficacy of the procedure. This study looks at predictors of success, based on mid-term follow-up data. This study uses results obtained from a prospective semi-voluntary register (audit) of Australian data obtained from surgeons in the private and public sector. Peri-operative mortality for patients enrolled in the audit was 1.8%. Ninety-three percent of procedures were technically successful (890/961). Nearly 13% of patients have had re-interventions (mostly endoluminal) at follow-up. Analysis of audit data shows that the likelihood of experiencing post-operative complications or requiring additional procedures increases with ASA rating, increasing age, large pre-operative aneurysm size, aneurysm angle >45 degrees and number of co-morbid conditions diagnosed. This study confirms satisfactory mid-term results in a, national rather than unit specific, setting. Predictors of clinical failure or need for re-intervention include large aneurysm size, neck angulation >or=45 degrees and short infrarenal neck.


Arsenic-induced histopathology and synthesis of stress proteins in liver and kidney of Channa punctatus.
As3+, considered effective for aquatic weed control, has been found to be harmful to several species of freshwater teleosts. Channa punctatus (Bloch) exposed for 14 days to nonlethal concentrations (1/20 LC50 and 1/10 LC50) of As2O3 were sampled on days 0, 1, 2, 7, and 14. Tissue disorientation, peliosis, and vacuolization accompanied by karyolysis, apoptosis, and necrosis of hepatocytes were significant on days 1, 2, and 7. In the kidney shrinkage of the glomerulus and increase in the Bowman's space were observed on days 1, 2, and 7. Irregularities in the renal tubule including apoptotic and necrotic cells were also common. Decreased intertubular space and enlargement of the height of the brush border cells were noteworthy. Corresponding with the histopathological lesions, dose-dependent disturbances in liver and renal functions and induction of heat shock protein 70 were significant at the early phase of arsenic treatment while metallothionein was induced at a later phase of treatment.


Surgical Treatment Protocol for Peripheral Nerve Dysfunction of the Lower Extremity: A Systematic Approach.
To date, more than 150 surgical techniques have been described for the treatment of intractable nerve pain. However, owing to their technical complexity, as well as the lack of comparative studies in the literature, there is currently no consensus on the appropriate management of this often debilitating condition. Therefore, we present our surgical algorithm, based on Seddon's classification to differentiate the degree of nerve injury, and subsequent treatment course for the management of lower extremity neurogenic pain.


Complexes With Biologically Active Ligands. Part 2. Preparation of Copper(II) Complexes of Positively-Charged Derivatives of Aminoglutethimide.
Cu(II) complexes of 1-[4-(3-ethyl-piperidine-2,6-dione)-3-yl]-phenyl-2,4,6-trisubstituted pyridinium perchlorates, containing alkyl, aryl and combinations of these two types of moieties in their molecule were synthesized and characterized by elemental analysis, spectroscopy, magnetic, thermogravimetric and conductimetric measurements. In these complexes, Cu(II) ions are in octahedral geometry with four water molecules occupying the equatorial coordination sites and the two organic ligands in deprotonated state the remaining axial ones. The donor atom of these ligands is constituted by the ionized nitrogen of the glutarimide moiety. The new derivatives possess weak inhibitory activity towards the zinc enzyme carbonic anhydrase.


Stereoelectroencephalography-guided laser ablation in neocortical epilepsy: Electrophysiological correlations and outcome.
We aimed to study the correlation between seizure outcomes in patients with drug-resistant epilepsy (DRE) who underwent laser interstitial thermal therapy (LITT) and stereoelectroencephalographic electrophysiologic patterns with respect to the extent of laser ablation. We retrospectively analyzed 16 consecutive DRE patients who underwent LITT. A seizure onset zone (SOZ) was obtained from multidisciplinary patient management conferences and again was confirmed independently by two epileptologists based on conventional analysis. SOZs were retrospectively divided into localized, lobar and multilobar, and nonlocalized onset types. A posteriori-predicted epileptogenic zone (PEZ) was identified using the previously developed "EZ fingerprint" pipeline. The completeness of the SOZ and PEZ ablation was compared and correlated with the duration of seizure freedom (SF). Of 16 patients, 11 had an a posteriori-identified PEZ. Three patients underwent complete ablation of SOZ with curative intent, and the other 13 with palliative intent. Of three patients with complete ablation of the SOZ, two had concordant PEZ and SOZ and achieved 40- and 46-month SF without seizure recurrence. The remaining patient, without any PEZ identified, had seizure recurrence within 1 month. Six of 13 patients with partial ablation of the SOZ and PEZ achieved mean seizure freedom of 19.8 months (range = 1-44) with subsequent seizure recurrence. The remaining seven patients had partial ablation of the SOZ without the PEZ identified or ablation outside the PEZ with seizure recurrence within 1-2 months, except one patient who had 40-month seizure freedom after ablation of periventricular heterotopia. Only complete ablation of the well-restricted SOZ concordant with the PEZ was associated with long-term SF, whereas partial ablation of the PEZ might lead to SF with eventual seizure recurrence. Failure to identify PEZ and ablation limited to the SOZ often led to 1-2 months of SF.


Highlights of the basic components of evidence-based practice.
This editorial provides a brief review of the basic components of evidence-based practice.