Quantitative PCR in epidemiology for early detection of visceral leishmaniasis cases in India.
Studies employing serological, DTH or conventional PCR techniques suggest a vast proportion of Leishmania infected individuals living in regions endemic for Visceral Leishmaniasis (VL) remain asymptomatic. This study was designed to assess whether quantitative PCR (qPCR) can be used for detection of asymptomatic or early Leishmania donovani infection and as a predictor of progression to symptomatic disease. The study included 1469 healthy individuals living in endemic region (EHC) including both serology-positive and -negative subjects. TaqMan based qPCR assay was done on peripheral blood of each subject using kDNA specific primers and probes. A large proportion of EHC 511/1469 (34.78%) showed qPCR positivity and 56 (3.81% of 1469 subjects) had more than 1 calculated parasite genome/ml of blood. However, the number of individuals with parasite load above 5 genomes/ml was only 20 (1.36% of 1469). There was poor agreement between serological testing and qPCR (k = 0.1303), and 42.89% and 31.83% EHC were qPCR positive in seropositive and seronegative groups, respectively. Ten subjects had developed to symptomatic VL after 12 month of their follow up examination, of which eight were initially positive according to qPCR and among these, five had high parasite load. Thus, qPCR can help us to detect significant early parasitaemia, thereby assisting us in recognition of potential progressors to clinical disease. This test could facilitate early intervention, decreased morbidity and mortality, and possibly interruption of disease transmission.


Ocular angiogenesis in disease states.
Other contributors to this symposium will concern themselves with the stimulus to angiogenesis. My role is to review the character and topography of neovascularization with the eye. It would be redundant, however, if I were merely to recount the morphology of ocular new vessels and their location and not, in the process, draw attention to facets which may provide a clue to their pathogenesis and to attempt some sort of clinico-pathological correlation. This synopsis is confined to pathological angiogenesis involving the retina, iris, and cornea. Preretinal neovascularization alone will be discussed, since other papers will examine the intra-and subretinal locations.


Homeostatic Left Heart integration and disintegration links atrio-ventricular covariation's dyshomeostasis in Hypertrophic Cardiomyopathy.
Left ventricle and left atrium are and have been practically always analyzed separately in common clinically and non-clinically oriented cardiovascular investigations. Both classic and speckle tracking echocardiographic data contributed to the knowledge about deformational impairments occurring in systo-diastolic differences. Recently new trajectory based approaches allowed a greater awareness about the entire left ventricle or left atrium revolution and on their deficiencies that take place in presence of hypertrophic cardiomyopathy. However, surprisingly, the concomitant function of the two left heart chambers has not been analyzed for their geometrical/mechanical relationship. For the first time we study here, by acquiring left ventricle and left atrial geometries on the same heartbeat, the trajectory attributes of the entire left heart treated as a whole shape and the shape covariation of its two subunits. We contrasted healthy subjects with patients affected by hypertrophic cardiomyopathy. We found impaired left heart trajectory mainly in terms of orientation and size. More importantly, we found profound differences in the direction of morphological covariation of left ventricle and left atrium. These findings open to new perspectives in pathophysiological evaluation of different diseases by allowing the appreciation of concomitant functioning of both left heart whole geometry and of its two chambers.


The global research and emerging trends in autophagy of pancreatic cancer: A bibliometric and visualized study.
To present the global research features and hotspots, and forecast the emerging trends by conducting a bibliometric analysis based on literature related to autophagy of pancreatic cancer from 2011 to 2022. The literature data regarding autophagy of pancreatic cancer were retrieved and downloaded from the Web of Science Core Collection (WOSCC) from Clarivate Analytics on June 10th, 2022. VOSviewer (version 1.6.18) was used to perform the bibliometric analysis. A total of 616 studies written by 3993 authors, covered 45 countries and 871 organizations, published in 263 journals and co-cited 28152 references from 2719 journals. China (n=260, 42.2%) and the United States (n=211, 34.3%) were the most frequent publishers and collaborated closely. However, publications from China had a low average number of citations (25.35 times per paper). The output of University of Texas MD Anderson Cancer Center ranked the first with 26 papers (accounting for 4.2% of the total publications). Cancers (n=23, 3.7%; Impact Factor = 6.639) published most papers in this field and was very pleasure to accept related researches. Daolin Tang and Rui Kang published the most papers (n=18, respectively). The research hotspots mainly focused on the mechanisms of autophagy in tumor onset and progression, the role of autophagy in tumor apoptosis, and autophagy-related drugs in treating pancreatic cancer (especially combined therapy). The emerging topics were chemotherapy resistance mediated by autophagy, tumor microenvironment related to autophagy, autophagy-depended epithelial-mesenchymal transition (EMT), mitophagy, and the role of autophagy in tumor invasion. Attention has been increasing in autophagy of pancreatic cancer over the past 12 years. Our results undoubtedly provide scholars with new clues and ideas in this field.


Group B streptococcal toxic shock-like syndrome: report of a case and purification of an associated pyrogenic toxin.
A patient with streptococcal toxic shock-like syndrome (TSLS) caused by Streptococcus agalactiae (group B Streptococcus) is described. The patient had all of the defining criteria for toxic shock syndrome (TSS), including fever, hypotension, erythematous rash, desquamation, and involvement of multiple organs. Neither Staphylococcus aureus nor group A streptococci were recovered, but vaginal and urine cultures yielded group B streptococci. The group B streptococcal isolate gave negative results in antibody tests for the production of TSS toxin 1, staphylococcal enterotoxins, and streptococcal scarlet fever toxins. However, the strain produced a novel pyrogenic toxin. This toxin, purified from culture fluids by ethanol precipitation, isoelectric focusing, and reverse-phase high-pressure liquid chromatography, had a molecular weight of 12,000 and an isoelectric point of approximately 7.0. The purified toxin was pyrogenic in rabbits, enhanced the susceptibility of the animals to lethal endotoxin shock, and caused the proliferation of rabbit splenocytes; these properties define pyrogenic toxins. When given to three rabbits via a subcutaneous miniosmotic pump, the toxin caused TSS-like symptoms ending in death. Three additional group B streptococcal strains from patients with TSLS were tested and were found to produce a toxin with similar properties.


Predictors of Postthrombolysis Outcome and Symptomatic Postthrombolysis Hemorrhage following Intravenous Thrombolysis with Alteplase for Acute Ischemic Stroke.
Background Thrombolysis improves the outcome in acute ischemic stroke (AIS), albeit with an increased risk of symptomatic intracranial hemorrhage (sICH). Biomarkers to find patients at risk of sICH, and guide treatment and prognosis would be valuable. Methods Consecutive patients of AIS thrombolysed between February 2017 and September 2019 at Calcutta National Medical College were studied prospectively for sICH and outcome at 6-month follow-up. We identified the independent risk factors for unfavorable outcomes, mortality, and sICH using multivariate analysis. Prethrombolysis and 24-hour postthrombolysis fibrinogen levels were estimated to evaluate its biomarker role. Results Out of 180 AIS patients admitted during the study period, 60 patients were thrombolysed. Door to needle time was <3 hours among 24 patients and 3 to 4.5 hours among 36 patients. Favorable outcomes occurred among 76.67% and sICH occurred among 13.33% patients. Upper tertile of National Institute of Health Stroke Scale (NIHSS) had the highest adjusted odds for sICH (17.5 [95% confidence intervals=1.7-178.44]). Total anterior circulation stroke had the highest adjusted odds for unfavorable outcome (19.11 [3.9-92.6]). Following thrombolysis, the mean (standard deviation) fibrinogen level of 449.27 (32.87) decreased 7% to postthrombolysis level of 420 (20.5; p< 0.0001). Higher tertiles of fibrinogen levels had progressively increasing odds for morbidity and sICH. Conclusion Congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke (double weight), i.e., CHADS2 score >2, low ejection fraction, the occurrence of total anterior circulation stroke and higher mean arterial blood pressure, blood glucose level, NIHSS score, and fibrinogen at admission were the common risk factors significantly predicting postthrombolysis sICH and morbidity. Antiplatelet and anticoagulant therapy, lower ASPECT (Alberta Stroke Program Early CT Score), and higher SEDAN scores also predicted sICH . Fibrinogen levels were significantly higher among those developing sICH and having unfavorable outcome. The performance of thrombolysis within 3 hours or between 3 and 4.5 hours after symptom onset did not affect morbidity, mortality, or the occurrence of sICH.


An improved assay for the detection of Toxoplasma gondii antibodies in human serum by flow cytometry.
The diagnosis of toxoplasmosis relies primarily on the demonstration of specific antibodies to Toxoplasma gondii. We describe a flow cytometry method for the determination of antibodies to whole fixed tachyzoites by indirect immunofluorescence. Fixed tachyzoites in suspension have characteristic light scattering properties. The amount of IgM, IgG, and IgA antibodies from patients' sera bound to the tachyzoites can be estimated from the mean fluorescence intensities observed using class-specific conjugates for different Ig heavy chains. Appropriate serum dilutions for the estimation of specific IgG titres and for the discrimination between sera positive and negative for IgA and IgM antibodies were established using 40 random sera from pregnant women. The method proved to be quantitative and highly sensitive as compared with currently used assays. Coefficients of variation between series ranged from 6.4% to 12.2% and could be controlled by the inclusion of positive and negative standard sera in the test series. The method might represent a major improvement in cost effectiveness as compared with routine immunofluorescence assay by fluorescent microscopy when the volume of testing is sufficient. It can be fully automated, and its large scale application is currently under investigation.


[Assessment of gait disorders in older people].
Gait disorders are frequent and important to assess in older people because they provide unique diagnostic and prognostic information. Gait disorders can be regarded as a marker of frailty because they are associated with several adverse consequences, including falls, cognitive disorders, functional decline, institutionalization, hospitalization, and death. Using structured instruments, gait assessment could be performed in primary care practice to classify the level of sensorimotor deficit and provide the necessary information to decide how to best intervene to improve gait performances, prevent falls as well as functional decline.


Clinical features associated with seroconversion to Anaplasma marginale, Babesia bigemina and Theileria parva infections in African cattle under natural tick challenge.
A longitudinal study was conducted in Southeast Uganda for 14 months on 640 Zebu cattle kept under natural tick challenge, with a view to identifying clinical features for prediction of seroconversion to Anaplasma marginale, Babesia bigemina and Theileria parva infections. Physical examination, condition scoring and tick counts were undertaken on all cattle every 4 weeks. In addition, 5300 sera were collected and analysed for antibodies against A. marginale, B. bigemina and T. parva infections using the enzyme-linked immunosorbent assay (ELISA). The major clinical features compiled included weight loss, fever (rectal temperature), anaemia (packed cell volume), pallor of mucous membranes, lymph node enlargement, staring coat, diarrhoea and lacrymation. The risk factors included tick challenge at village level, sex, age, Rhipicephalus spp. density and Boophilus spp. density on individual animals. Using a binary logistic regression model, the clinical features and risk factors were analysed. The results suggest that increasing rectal temperature was associated with increased probability for seroconversion to A. marginale, while high level of Rhipicephalus spp. density and increasing packed cell volume (PCV) were significantly associated with reduced probability of seroconversion. Although statistically significant, none of the factors had large effects, with odds ratios (OR) of 0.87, 1.15 and 0.98 for Rhipicephalus spp. density, rectal temperature and PCV, respectively. For B. bigemina infection, a high level of Boophilus spp. density, anaemia and staring coat were significantly associated with increased probability of seroconversion (OR 1.50, 1.78, 1.37, respectively). Presence of lacrymation and old age were associated with reduced probability of seroconversion (OR 0.52, 0.86 respectively). For T. parva infection, lymph node enlargement (OR 1.30) was associated with increased probability of seroconversion, while high Rhipicephalus spp. density and increasing packed cell volume (PCV) were associated with reduced probability of seroconversion (OR 0.68 and 0.98, respectively). In conclusion, presence and intensity of the respective tick vectors for tick-borne diseases, age and clinical features such as anaemia, fever, staring coat, lymph node enlargement and lacrymation are indicators for seroconversion to A. marginale, B. bigemina and T. parva infections in cattle. These indicators for seroconversion could be exploited in the development of decision support tools for clinical diagnosis of tick-borne diseases.


Quantum mechanical spin dynamics of a molecular magnetoreceptor.
Radical pair recombination reactions are known to be sensitive to extremely weak magnetic fields and can therefore be said to function as molecular magnetoreceptors. The classic example is a carotenoid-porphyrin-fullerene (C•+PF•-) radical pair that has been shown to provide a "proof-of-principle" for the operation of a chemical compass [K. Maeda et al., Nature 453, 387 (2008)]. Previous simulations of this radical pair have employed semiclassical approximations, which are routinely applicable to its 47 coupled electronic and nuclear spins. However, calculating the exact quantum mechanical spin dynamics presents a significant challenge and has not been possible until now. Here, we use a recently developed method to perform numerically converged simulations of the C•+PF•- quantum mechanical spin dynamics, including all coupled spins. A comparison of these quantum mechanical simulations with various semiclassical approximations reveals that, while it is not perfect, the best semiclassical approximation does capture essentially all of the relevant physics in this problem.


Micro-vibration-based slip detection in tactile force sensors.
Tactile sensing provides critical information, such as force, texture, shape or temperature, in manipulation tasks. In particular, tactile sensors traditionally used in robotics are emphasized in contact force determination for grasping control and object recognition. Nevertheless, slip detection is also crucial to successfully manipulate an object. Several approaches have appeared to detect slipping, the majority being a combination of complex sensors with complex algorithms. In this paper, we deal with simplicity, analyzing how a novel, but simple, algorithm, based on micro-vibration detection, can be used in a simple, but low-cost and durable, force sensor. We also analyze the results of using the same principle to detect slipping in other force sensors based on flexible parts. In particular, we show and compare the slip detection with: (i) a flexible finger, designed by the authors, acting as a force sensor; (ii) the finger torque sensor of a commercial robotic hand; (iii) a commercial six-axis force sensor mounted on the wrist of a robot; and (iv) a fingertip piezoresistive matrix sensor.


It's about time--directing our attention toward modifying the course of COPD.
The course of COPD has traditionally been equated with an accelerated decline in the forced expiratory volume in one second (FEVi) over time in patients with COPD, compared to healthy individuals. However, other important clinical outcomes associated with COPD also worsen over time and should also be considered in conceptualizing the course of COPD. These include health status, breathlessness related to activities of daily living, exercise capacity, the frequency of exacerbations, and peripheral muscle weakness. These outcomes are often quite responsive to therapy of COPD. Presently there is no evidence that any treatment other than smoking cessation can normalise the rate of decline of FEVi, and therefore be considered as modifying the physiologic course of the disease. Thus, smoking cessation reigns as the primary disease modifying strategy in COPD. Even though there are a number of smoking cessation products on the market and smoking prevalence continues to decrease marginally each year, more needs to be done to provide comprehensive programmes to help people quit smoking. In the US in 2004, 37.5% of preventable deaths were found to be tobacco-related. The FEVi does not reflect the clinical manifestations or the total burden of this multidimensional illness. As novel therapeutic agents become available that may alter the underlying pathology of COPD, additional markers and outcomes of disease progression will be needed to provide a more comprehensive assessment. There has been increasing interest in predicting and assessing mortality as it is the final outcome of disease progression. In this review we have considered three approaches toward modifying the course of COPD: smoking cessation, reduction in lung hyperinflation through medical and surgical approaches, and long-term pharmacotherapy.


The role of nutritional assessment and early enteral nutrition for combined pancreas and kidney transplant candidates.
Early post-operative enteral nutrition is an important part of perioperative management and is strongly supported by ESPEN Guidelines. However, there is limited evidence into the use of Early Enteral Nutrition (EEN) after combined Pancreas and Kidney Transplantation (PKT). We know malnutrition in type-1 diabetics with end stage renal failure (ESRF) is a common problem and a significant risk factor. Therefore, we introduced EEN in our patients. We monitored and recorded nutritional data on 29 PKT recipients who underwent transplantation between Oct 2007 and Jan 2010 without a nutritional assessment or EEN [Monitored Group (MG)] and on 30 PKT recipients between Feb 2010 and Dec 2013 who received a nutritional assessment and EEN (Naso-jejunal feed or oral intake with supplementation, according to their nutritional status) [Fed Group (FG)]. The end-point was to assess patients' daily post-transplant nutritional intake. This was calculated as a percentage of estimated nutritional requirements using the Schofield equation with a 25% added stress factor and relevant activity factor. Following a literature search and realistic targets our aim was to reach >60% requirements: achievement of ≥60% energy requirements by day-7 (7d-60%) and at the time of discharge (total-60%) [13,14]. There was no significant difference between MG and FG patients in cold ischemic time (CIT), recipient-age and donor-age, Length of Stay and donor-creatinine. In contrast, FG patients were less frequently in predialysis status 41.4% vs. 26.7%, p = 0.001; and had higher incidence of BMI <22.5 kg/m2 63.3% vs. 48.3%, p = <0.005. In outcomes, FG patients more frequently achieved a higher average % of nutritional requirements in the first week 39.69% vs. 22.37%, p = <0.005; as well as during whole in-patient stay 57.24% vs. 44.43%, p = <0.005 (Table 3, Figs. 1 and 2). The FG spent a greater proportion during the first week 66.7% vs. 31%, p = <0.005; and of whole their admission 93.3% vs. 75.9%, p = <0.005; meeting more than 60% of nutritional requirements. Most important, the need for parenteral nutrition within the FG was significantly lower, 7.1% vs. 20.7%, p < 0.005 (Table 3). Our results show that these patients benefit from planned EEN and receive better nutritional support when compared to the patients managed with the historic, reactive approach to nutritional care. Nutritional intake in the first week as well as during the whole admission was superior in patients receiving active EEN despite a more difficult post-operative course due to higher incidence of re-operations compared to the control group. Also the need for parenteral nutrition was significantly lower in this group. In addition, pre-transplant nutritional assessment is beneficial and accurately highlights those who may be at risk of malnutrition pre and post-operatively.


Health consequences of electric lighting practices in the modern world: A report on the National Toxicology Program's workshop on shift work at night, artificial light at night, and circadian disruption.
The invention of electric light has facilitated a society in which people work, sleep, eat, and play at all hours of the 24-hour day. Although electric light clearly has benefited humankind, exposures to electric light, especially light at night (LAN), may disrupt sleep and biological processes controlled by endogenous circadian clocks, potentially resulting in adverse health outcomes. Many of the studies evaluating adverse health effects have been conducted among night- and rotating-shift workers, because this scenario gives rise to significant exposure to LAN. Because of the complexity of this topic, the National Toxicology Program convened an expert panel at a public workshop entitled "Shift Work at Night, Artificial Light at Night, and Circadian Disruption" to obtain input on conducting literature-based health hazard assessments and to identify data gaps and research needs. The Panel suggested describing light both as a direct effector of endogenous circadian clocks and rhythms and as an enabler of additional activities or behaviors that may lead to circadian disruption, such as night-shift work and atypical and inconsistent sleep-wake patterns that can lead to social jet lag. Future studies should more comprehensively characterize and measure the relevant light-related exposures and link these exposures to both time-independent biomarkers of circadian disruption and biomarkers of adverse health outcomes. This information should lead to improvements in human epidemiological and animal or in vitro models, more rigorous health hazard assessments, and intervention strategies to minimize the occurrence of adverse health outcomes due to these exposures.


Transcriptome sequencing of two wild barley (Hordeum spontaneum L.) ecotypes differentially adapted to drought stress reveals ecotype-specific transcripts.
Wild barley is adapted to highly diverse environments throughout its geographical distribution range. Transcriptome sequencing of differentially adapted wild barley ecotypes from contrasting environments contributes to the identification of genes and genetic variation involved in abiotic stress tolerance and adaptation. Two differentially adapted wild barley ecotypes from desert (B1K2) and Mediterranean (B1K30) environments were analyzed for drought stress response under controlled conditions. The desert ecotype lost more water under both irrigation and drought, but exhibited higher relative water content (RWC) and better water use efficiency (WUE) than the coastal ecotype. We sequenced normalized cDNA libraries from drought-stressed leaves of both ecotypes with the 454 platform to identify drought-related transcripts. Over half million reads per ecotype were de novo assembled into 20,439 putative unique transcripts (PUTs) for B1K2, 21,494 for B1K30 and 28,720 for the joint assembly. Over 50% of PUTs of each ecotype were not shared with the other ecotype. Furthermore, 16% (3,245) of B1K2 and 17% (3,674) of B1K30 transcripts did not show orthologous sequence hits in the other wild barley ecotype and cultivated barley, and are candidates of ecotype-specific transcripts. Over 800 unique transcripts from each ecotype homologous to over 30 different stress-related genes were identified. We extracted 1,017 high quality SNPs that differentiated the two ecotypes. The genetic distance between the desert ecotype and cultivated barley was 1.9-fold higher than between the Mediterranean ecotype and cultivated barley. Moreover, the desert ecotype harbored a larger proportion of non-synonymous SNPs than the Mediterranean ecotype suggesting different demographic histories of these ecotypes. The results indicate a strong physiological and genomic differentiation between the desert and Mediterranean wild barley ecotypes and a closer relationship of the Mediterranean to cultivated barley. A significant number of novel transcripts specific to wild barley were identified. The higher SNP density and larger proportion of SNPs with functional effects in the desert ecotype suggest different demographic histories and effects of natural selection in Mediterranean and desert wild barley. The data are a valuable genomic resource for an improved genome annotation, transcriptome studies of drought adaptation and a source of new genetic markers for future barley improvement.


Biosynthesis of human von Willebrand factor.
Endothelium forms the inner lining of all blood vessels and, as a consequence, is in direct contact with the blood. Because of this and the synthesis and secretion of hemostatic components, the endothelium is able to modulate coagulation and fibrinolysis. An important hemostatic factor synthesized by endothelial cells is the von Willebrand factor (vWF). vWF is a large plasma glycoprotein which promotes the adhesion of platelets to the vessel wall after a vascular injury. vWF is initially synthesized as a pre-pro-polypeptide. During its transport to the outside of the cell, the single-chain polypeptides are assembled into multimers. The pro-polypeptide can be cleaved and also be secreted. Free pro-polypeptide is identified as von Willebrand antigen II, a plasma glycoprotein of unknown function. Plasma vWF consists of a heterogenous series of multimers, composed of an apparently single-type glycoprotein subunit, linked together by disulfide bonds. The hemostatic potency of vWF was shown to increase with increasing multimer size. Therefore, the multimeric assembly of vWF is a crucial aspect in vWF biosynthesis. Furthermore, vWF synthesized by endothelial cells can either be secreted constitutively or stored and released upon stimulation of the endothelial cell. In this review, data are presented which contribute to the understanding of the biosynthetic pathway and complex processing which vWF has to undergo before it is secreted by the endothelial cell. These data have allowed a prediction of the sequential events underlying vWF biosynthesis, processing, multimer assembly, and secretion.


Does the Angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism modify the response to ACE inhibitor therapy?--A systematic review.
Pharmacogenetic testing to individualize ACE inhibitor therapy remains controversial. We conducted a systematic review to assess the effect modification of the insertion/deletion (I/D) polymorphism of the ACE gene on any outcome in patients treated with ACE inhibitors for cardiovascular and/or renal disease. Our systematic review involved searching six electronic databases, then contacting the investigators (and pharmaceutical industry representatives) responsible for the creation of these databases. Two reviewers independently selected relevant randomized, placebo-controlled trials and abstracted from each study details on characteristics and quality. Eleven studies met our inclusion criteria. Despite repeated efforts to contact authors, only four of the eleven studies provided sufficient data to quantify the effect modification by genotypes. We observed a trend towards better response to ACE inhibitors in Caucasian DD carriers compared to II carriers, in terms of blood pressure, proteinuria, glomerular filtration rate, ACE activity and progression to end-stage renal failure. Pooling of the results was inappropriate, due to heterogeneity in ethnicity, clinical domains and outcomes. Lack of sufficient genetic data from the reviewed studies precluded drawing any convincing conclusions. Better reporting of genetic data are needed to confirm our preliminary observations concerning better response to ACE inhibitors among Caucasian DD carriers as compared to II carriers.


[Multiple ischemic foci of the brain in female patient with cardiac myxoma and numerous vascular anomalies].
The ischemic stroke is the most frequent neurological pathology. It's etiology is quite complex. Around 20% of the ischemic stroke cases are caused by arteriosclerosis, 25% by lacunar stroke, remaining 30% are strokes with unclear etiology, around 20%--emboli, and 5% include other causes. The ischemic stroke, especially in younger patients suggests that a detailed and multidimensional diagnostic should be carried out. Presented the case of a female patient with multiple ischemic foci of the brain, whom cardiac myxoma and numerous vascular anomalies were detected. Ischemic foci of the brain might be caused by myxoma, but one cannot excluded other mechanism of their occurrence.


[RNA interference in functional genomics and medical research].
RNA interference (RNAi) is a post-transcriptional gene silencing process by targeting mRNA for degradation in a sequence-specific manner. This powerful platform has enormous potential in functional genomics and medical research. As a tool to knock out expression of specific genes in a variety of organisms, RNAi was used to investigate gene function in a high throughput fashion. Highly conserved in evolution RNAi appears to have evolved as a cellular defense mechanism in plants and animals to suppress viral infection, transposon jumping and endogenous aberrant genes. Exploiting the natural mechanism, the researchers can shut down disease-causing genes and develop novel therapeutics against infection, tumor and other disease.


Development of a Quantitative Diagnostic Criterion for Gastric Linitis Plastica: Findings From a Large Single-Institutional Study.
Gastric linitis plastica (GLP) is a descriptive term but lacks a quantitative definition. Several relatively quantitative criteria had been proposed, such as tumor involving a limit of one-third or two-thirds of the gastric surface. However, these criteria needed doctors to subjectively judge tumor infiltration area, which made diagnosis difficult to be objective and reproducible. This study aimed to propose a quantitative diagnostic criterion for distinguishing GLP. We performed a retrospective cohort study of 2,907 patients with Borrmann III and IV gastric cancer (GC) who underwent gastrectomy between 2011 and 2018 in our center. The Kaplan-Meier curves showed that patients with an observed tumor size more than 8 cm had obviously lower overall survival (OS) and disease-free survival (DFS) rates than those with a size less than 8 cm(p < 0.001; p < 0.001). However, there was no significantly different prognosis of patients with tumor sizes between more than 8 cm and more than 10 cm (p = 0.248; p = 0.534). Moreover, patients with tumor sizes greater than 8 cm more presented with advanced stage and had extremely poor 3-year OS and DFS (31.4%; 29.3%), with a stronger propensity toward peritoneal metastasis. Therefore, we considered patients' observed tumor size more than 8 cm as a critical value for distinguishing the prognosis of Borrmann III and IV GC. Furthermore, we proposed an observed tumor size more than 8 cm as a quantitative diagnostic criterion for GLP on the premise of satisfying the originally descriptive and pathological definition regardless of Borrmann type.


Aryl morpholino triazenes inhibit cytochrome P450 1A1 and 1B1.
Many cytochrome P450 1A1 and 1B1 (CYP1A1 and CYP1B1) inhibitors, such as resveratrol, have planar, hydrophobic, aromatic rings in their structure and exhibit anti-cancer activity. Aryl morpholino triazenes have similar structural features and in addition contain a triazene unit consisting of three consecutive, conjugated nitrogen atoms. Several aryl morpholino triazenes, including 4-[(E)-2-(3,4,5-trimethoxyphenyl)diazenyl]-morpholine (2), were prepared from a reaction involving morpholine and a diazonium ion produced from different aniline derivatives, such as 3,4,5-trimethoxyaniline. The aryl morpholino triazenes were then screened at 100μM for their ability to inhibit CYP1A1 and CYP1B1 using ethoxyresorufin as the substrate. Triazenes that inhibited the enzymes to less than 80% of the uninhibited enzyme activity were assayed to determine their IC50 value. Compound 2 was the only triazene to inhibit both CYP1A1 and CYP1B1 to the same degree as resveratrol with IC50 values of 10μM and 18μM, respectively. Compounds 3 and 6 selectively inhibited CYP1B1 over CYP1A1 with IC values of 2μM and 7μM, respectively. Thus, aryl morpholino triazenes are a new class of compounds that can inhibit CYP1A1 and CYP1B1 and potentially prevent cancer.


Bilateral granulomatous mastitis with a different etiology.
Idiopathic granulomatous mastitis (IGM) and Tuberculosis mastitis (TM) are rare inflammatory diseases of the breast that can clinically mimic malignancy causing misdiagnosis as breast cancer. We present a rare case of bilateral granulomatous mastitis with a different etiology. An initial lesion developed in the right breast was diagnosed as IGM, which was treated with antibiotics and surgery. A subsequent lesion developed in the contralateral breast 5 months later and was diagnosed as TM, which also completely responded to antituberculosis medication without surgical excision. Differential diagnosis was made using the results of the polymerase chain reaction for tuberculosis (TBC-PCR) of both of the breast lesions in addition to typical pathologic findings of IGM in the right breast and an antituberculosis medication response in the left breast. To the best of our knowledge, this is the first case of bilateral granulomatous mastitis with a different etiology.


Don't Blame the System; They've Chosen the Wrong One.
While trying to represent patients in the design of integrated care, I have heard the words system, systemic and holism used frequently. Few of those using the words seem to be aware of the history of systems thinking, or its principles. Health interventions are instead designed using logic modelling, which is aholistic and disintegrative. This concern is illustrated in relation to the UK's Better Care Fund, which was an attempt to reduce hospital admissions by co-ordinating care. Systems thinking is then used to provide a possible distinction between three operating systems for the UK's National Health Service (NHS). The first, an ideal market operating system, is inherently fantastic, and doubly so when it is impossible to determine who has contributed what to which outcomes. The accountable professional operating system may re-emerge as the rational option. However, weak analysis can lead to the emergence of a quasi-market operating system, which lacks the capacity to integrate the essential elements of a viable system. The fault lies not with systems thinking, but with the failure to study how viable systems are constructed.


Improving combination cancer therapy: the CombiPlex® development platform.
Current combination therapy approaches assume that better outcomes are achieved by combining drugs at their maximally tolerated doses. However, administration of individual agents cannot consistently deliver synergistic drug ratios to tumor cells due to differences in pharmacokinetics of the individual drugs. Further, the toxicity of combination regimens often necessitates administration of suboptimal dosages. Delivery technologies, such as the CombiPlex® platform, can enable efficient and sustained delivery of combination treatments at a synergistic ratio. The CombiPlex platform determines synergistic drug ratios in vitro and identifies an appropriate nanoscale carrier to maintain that ratio in vivo and enhance its delivery to tumor cells. CPX-351, a dual-drug liposomal encapsulation of cytarabine and daunorubicin, is the first clinical proof-of-concept example of the CombiPlex platform.


Efficacy and safety of intraoperative mitomycin C as adjunct therapy for pterygium surgery.
The primary objective of this study was to determine if intraoperative application of mitomycin C (MMC) is safe as an adjunct for pterygium surgery. The secondary objectives of the study were to determine if MMC reduces pterygium recurrence rate and to evaluate the effect of MMC on intraocular pressure. We conducted a nonconcurrent prospective study of 68 patients with primary or recurrent pterygium. Patients underwent a comprehensive eye examination preoperatively and postoperatively to evaluate for possible complications associated with the use of MMC. The recurrence rate of pterygia was also included in the data. We examined a total of 68 patients (68 eyes). The follow-up time ranged from 12 to 98 months (mean = 27.7 +/- 28.8 months). Only 2 postoperative complications were reported: a scleral dellen and a conjunctival cyst. Eight patients (12.0%) with primary pterygium had a recurrence of pterygia after surgery. However, no recurrences occurred in patients with previous recurrent pterygia. Findings in our study suggest that MMC is efficacious in preventing recurrences and a safe adjunct therapy during pterygium surgery. Findings in our study suggest that intraoperative MMC application leads to few complications while providing a significant reduction in the recurrence rate.


A Case of Pediatric Abdominal Wall Reconstruction: Components Separation within the Austere War Environment.
Reconstructive surgeons supporting military operations are required to definitively treat severe pediatric abdominal injuries in austere environments. The safety and efficacy of using a components separation technique to treat large ventral hernias in pediatric patients in this setting remains understudied. Components separation technique was required to achieve definitive closure in a 12-month-old pediatric patient in Kandahar, Afghanistan. Her course was complicated by an anastomotic leak after small bowel resection. Her abdominal was successfully reopened, the leak repaired, and closed primarily without incident on postinjury day 9. Abdominal trauma with a large ventral hernia requiring components separation is extremely rare. A pediatric patient treated with components separation demonstrated minimal complications, avoidance of abdominal compartment syndrome, and no mortality.


Juvenile hormone acid: evidence for a hormonal function in induction of vitellogenin in larvae of Manduca sexta.
In the tobacco hornworm (Manduca sexta), vitellogenin (Vg), the major yolk protein precursor, and its mRNA are first detectable in the prepupal stage; and production of both can be enhanced by methoprene, a juvenile hormone (JH) analog. Competence to respond to methoprene is acquired after ecdysteroid-initiated commitment for metamorphosis. Here we show that acquisition of competence requires prior exposure to JH-II acid in addition to ecdysteroid. Application of 20-hydroxyecdysone or RH5992, an ecdysteroid analog, to isolated abdomens from feeding larvae (precommitment) results in exposure of the dorsal vessel (EDV), a sign of metamorphic commitment--but such abdomens do not make Vg in response to methoprene. However, injection of JH-II acid along with 20-hydroxyecdysone into isolated abdomens causes Vg production in response to methoprene. Methoprene acid similarly induces competence to respond to methoprene. Northern blot analysis confirmed that Vg transcripts are present in fat body only if isolated abdomens were pretreated with both ecdysteroid, and JH-II acid or methoprene acid. The latter two can induce competence even in precocious prepupae resulting from removal of the corpora allata (the glands that produce JH) from early penultimate larvae. JH-III acid and related metabolites such as farnesol, farnesoic acid, and methyl farnesoate do not induce competence. Hitherto, JH acids have been regarded as precursors or catabolites of JHs. Here we show for the first time that JH acid has a hormonal function that cannot be performed by JH itself.


Intrapulmonary arteriovenous malformation causing recurrent strokes.
This case reveals a left pulmonary arteriovenous malformation (PAVM) as a cause of recurrent cerebral and cerebellar emboli. Extensive workup excluded other etiologies of emboli formation, and the patient was transferred to a tertiary care center for percutaneous embolotherapy. In the absence of a clear etiology, PAVM should be considered as a potential cause of recurrent cerebral emboli, especially in the absence of carotid disease, intracardiac thrombus, atrial septal defect, and patent foramen ovale. Diagnostic work-up for the PAVM can be cost effective and expedited by utilization of agitated saline contrast echocardiography, as noted in our case.


Recent advances in understanding of meiosis initiation and the apomictic pathway in plants.
Meiosis, a specialized cell division to produce haploid cells, marks the transition from a sporophytic to a gametophytic generation in the life cycle of plants. In angiosperms, meiosis takes place in sporogenous cells that develop de novo from somatic cells in anthers or ovules. A successful transition from the mitotic cycle to the meiotic program in sporogenous cells is crucial for sexual reproduction. By contrast, when meiosis is bypassed or a mitosis-like division occurs to produce unreduced cells, followed by the development of an embryo sac, clonal seeds can be produced by apomixis, an asexual reproduction pathway found in 400 species of flowering plants. An understanding of the regulation of entry into meiosis and molecular mechanisms of apomictic pathway will provide vital insight into reproduction for plant breeding. Recent findings suggest that AM1/SWI1 may be the key gene for entry into meiosis, and increasing evidence has shown that the apomictic pathway is epigenetically controlled. However, the mechanism for the initiation of meiosis during sexual reproduction or for its omission in the apomictic pathway still remains largely unknown. Here we review the current understanding of meiosis initiation and the apomictic pathway and raised several questions that are awaiting further investigation.


Oocyte spontaneous activation in different rat strains.
Oocyte spontaneous activation (OSA) has been reported to occur during in vitro culture of ovulated rat oocytes. The objective of this study was to compare the rate of oocyte spontaneous activation and the level of maturation promoting factor (MPF) activity in oocytes from different strains. Twelve strains were selected from two commercial sources. Females were superovulated and oocytes collected 17 h after hCG injection. Denuded oocytes were cultured in M16 medium under oil at 37 degrees C and 5% CO(2) in air. The proportion of activated oocytes was determined after 6 h of in vitro culture. Data were compared by analysis of variance (ANOVA), considering each animal as an experimental unit. MPF activity was determined in oocytes from the different strains at 0, 1.5, and 3 h after oocyte collection. The log ratio of the MPF activity at 1.5 and 3 h relative to 0 hours for each animal was analyzed by ANOVA. While significant (p < 0.01) differences were observed between strains in the rate of OSA, there were no differences between strains in the level of MPF during the time points measured (p > 0.3).


Dentists' attitudes toward continuing dental education: nontopic factors of demand for courses.
This article reports the results of a survey of dentists' attitudes that influence their demand for continuing education. Unlike the bulk of previous studies, which identified course topics of interest to dentists, this survey investigated attributes of courses unrelated to content. The 1,472 respondents from seven western and mid-western states indicated their attitudes toward mandatory attendance, tuition charges, associated costs, length of course, cancellation policies, reputation of instructor, offerings for auxiliaries, and other attributes of continuing education programs. The findings suggest the need for changes in program management and for further research into factors unrelated to course content that influence demand for dental continuing education courses.


Impact of prognostic nutritional index on outcomes in patients with Mycobacterium avium complex pulmonary disease.
Onodera's prognostic nutritional index (PNI) is useful in predicting prognosis of various diseases. But the usefulness of PNI in non-surgical patients has not been sufficiently proven yet. In patients with mycobacterium avium complex pulmonary disease (MAC-PD), malnutrition is an important factor that affects the quality of life and morbidity. Here, we aimed to evaluate whether PNI is related with clinical outcomes in MAC-PD patients. We examined 663 patients diagnosed with MAC-PD between May 2005 and November 2017. PNI score was calculated at the time of diagnosis and treatment initiation, and patients were divided into malnutrition and non-malnutrition groups according to a cut-off PNI score of 45. As the recommended duration of treatment for MAC-PD is 12 months following sputum conversion, treatment duration less than 12 months was defined as treatment intolerance. Survivals were compared with the log-rank test. Multivariate logistic regression and multivariate Cox proportional hazards models were used to estimate the odds ratio (OR) and hazards ratio (HR) for treatment intolerance and mortality, respectively. Of the 306 patients that received treatment, 193 received treatment longer than 12 months. In the multivariable logistic regression model, malnutrition at the time of treatment initiation was related with treatment intolerance (OR: 2.559, 95% confidence interval [CI]: 1.414-4.634, P = 0.002). Patients in the malnutrition group at the time of diagnosis exhibited lower survival (P<0.001) and malnutrition at the time of diagnosis was a significant risk for all-cause mortality (HR: 2.755, 95% CI: 1.610-4.475, P<0.001). Malnutrition, as defined by PNI, is an independent predictor for treatment intolerance and all-cause mortality in patients with MAC-PD.


Syd/JIP3 and JNK signaling are required for myonuclear positioning and muscle function.
Highlighting the importance of proper intracellular organization, many muscle diseases are characterized by mispositioned myonuclei. Proper positioning of myonuclei is dependent upon the microtubule motor proteins, Kinesin-1 and cytoplasmic Dynein, and there are at least two distinct mechanisms by which Kinesin and Dynein move myonuclei. The motors exert forces both directly on the nuclear surface and from the cell cortex via microtubules. How these activities are spatially segregated yet coordinated to position myonuclei is unknown. Using Drosophila melanogaster, we identified that Sunday Driver (Syd), a homolog of mammalian JNK-interacting protein 3 (JIP3), specifically regulates Kinesin- and Dynein-dependent cortical pulling of myonuclei without affecting motor activity near the nucleus. Specifically, Syd mediates Kinesin-dependent localization of Dynein to the muscle ends, where cortically anchored Dynein then pulls microtubules and the attached myonuclei into place. Proper localization of Dynein also requires activation of the JNK signaling cascade. Furthermore, Syd functions downstream of JNK signaling because without Syd, JNK signaling is insufficient to promote Kinesin-dependent localization of Dynein to the muscle ends. The significance of Syd-dependent myonuclear positioning is illustrated by muscle-specific depletion of Syd, which impairs muscle function. Moreover, both myonuclear spacing and locomotive defects in syd mutants can be rescued by expression of mammalian JIP3 in Drosophila muscle tissue, indicating an evolutionarily conserved role for JIP3 in myonuclear movement and highlighting the utility of Drosophila as a model for studying mammalian development. Collectively, we implicate Syd/JIP3 as a novel regulator of myogenesis that is required for proper intracellular organization and tissue function.


Liposome transport of hydrophobic drugs: gel phase lipid bilayer permeability and partitioning of the lactone form of a hydrophobic camptothecin, DB-67.
The design of liposomal delivery systems for hydrophobic drug molecules having improved encapsulation efficiency and enhanced drug retention would be highly desirable. Unfortunately, the poor aqueous solubility and high membrane binding affinity of hydrophobic drugs necessitates extensive validation of experimental methods to determine both liposome loading and permeability and thus the development of a quantitative understanding of the factors governing the encapsulation and retention/release of such compounds has been slow. This report describes an efflux transport method using dynamic dialysis to study the liposomal membrane permeability of hydrophobic compounds. A mathematical model has been developed to calculate liposomal membrane permeability coefficients of hydrophobic compounds from dynamic dialysis experiments and partitioning experiments using equilibrium dialysis. Also reported is a simple method to study the release kinetics of liposome encapsulated camptothecin lactone in plasma by comparing the hydrolysis kinetics of liposome entrapped versus free drug. DB-67, a novel hydrophobic camptothecin analogue has been used as a model permeant to validate these methods. Theoretical estimates of DB-67 permeability obtained from the bulk solubility diffusion model and the "barrier-domain" solubility diffusion model are compared to the experimentally observed value. The use of dynamic dialysis in drug release studies of liposome and other nanoparticle formulations is further discussed and experimental artifacts that can arise without adequate validation are illustrated through simulations.


Circulatory miR-223-3p Discriminates Between Parkinson's and Alzheimer's Patients.
MiR-223-3p is involved in the regulation of a broad range of cellular processes and in many types of pathological processes as cancer, autoimmune and inflammatory diseases. MiR-223-3p has been indicated as negative regulator of NLRP3 protein, a key protein of inflammasome. The chronic inflammasome activation, an underlying feature of neurodegenerative disorders, is induced by misfolded protein aggregates, including amyloid-beta and alpha-synuclein, resulting in pro-inflammatory cytokines secretion and propagating of neuroinflammation. The aim of the study was to analyze whether circulatory miR-223-3p could be used as biomarker in neurodegeneration and to clarify its possible relationship with inflammasome activation. miR-223-3p concentration was evaluated in serum of Alzheimer's (AD) and Parkinson's disease (PD) or mild cognitive impairment (MCI) patients and healthy controls (HC). Compared to HC, miR-223-3p serum concentration was reduced in MCI and AD, but up-regulated in PD (p < 0.0001), and it decreased progressively from MCI to moderate (p < 0.0001) to severe AD (p = 0.0016). Receiver operating characteristic analysis showed that miR-223-3p concentration discriminates between AD, PD and MCI vs. HC, as well as between AD and PD. miR-223-3p serum concentration discriminates between AD/MCI and PD, suggesting that this molecule could be a potential non-invasive biomarker for differential diagnosis and prognosis of these neurodegenerative conditions.


Synthesis and formulation studies of griseofulvin analogues with improved solubility and metabolic stability.
Griseofulvin (1) is an important antifungal agent that has recently received attention due to its antiproliferative activity in mammalian cancer cells. Comprehensive SAR studies have led to the identification of 2'-benzyloxy griseofulvin 2, a more potent analogue with low micromolar anticancer potency in vitro. Analogue 2 was also shown to retard tumor growth through inhibition of centrosomal clustering in murine xenograft models of colon cancer and multiple myeloma. However, similar to griseofulvin, compound 2 exhibited poor metabolic stability and aqueous solubility. In order to improve the poor pharmacokinetic properties, 11 griseofulvin analogues were synthesized and evaluated for biological activity and physiological stabilities including SGF, plasma, and metabolic stability. Finally, the most promising compounds were investigated in respect to thermodynamic solubility and formulation studies. The 2'-benzylamine analogue 10 proved to be the most promising compound with low μM in vitro anticancer potency, a 200-fold increase in PBS solubility over compound 2, and with improved metabolic stability. Furthermore, this analogue proved compatible with formulations suitable for both oral and intravenous administration. Finally, 2'-benzylamine analogue 10 was confirmed to induce G2/M cell cycle arrest in vitro.


Oak genotype and phenolic compounds differently affect the performance of two insect herbivores with contrasting diet breadth.
Research on plant-herbivore interactions has long recognized that plant genetic variation plays a central role in driving insect abundance and herbivory, as well as in determining plant defense. However, how plant genes influence herbivore feeding performances, and which plant defensive traits mediate these effects, remain poorly understood. Here we investigated the feeding performances of two insect leaf chewers with contrasting diet breadth (the generalist Lymantria dispar L. and the specialist Thaumetopoea processionea L.) on different genotypes of pedunculate oak (Quercus robur L.) and tested the role of leaf phenolics. We used leaves from four clones of 30 Q. robur full-sibs grown in a common garden to estimate the performance of both herbivores in laboratory feeding trials and to quantify the concentration of constitutive chemical defences (phenolic compounds). We found that tree genetics influenced leaf consumption by T. processionea but not by L. dispar. However genetic variation among trees did not explain growth rate variation in either herbivore nor in leaf phenolics. Interestingly, all phenolic compounds displayed a positive relationship with L. dispar growth rate, and leaf consumption by both herbivores displayed a positive relationship with the concentrations of condensed tannins, suggesting that highly defended leaves could induce a compensatory feeding response. While genetic variation in oaks did not explain herbivore growth rate, we found positive genetic correlations between the two herbivores for leaf consumption and digestion. Overall, we found that oak genotype and phenolic compounds partly and independently contribute to variability in herbivore performance. We challenged the current view of plant-insect interaction and provided little support to the idea that the effect of plant genotype on associated organisms is driven by plant defences. Together, our results point to the existence of genetically determined resistance traits in oaks whose effects differ between herbivores and motivate further research on mechanisms governing oak-herbivore interactions.


Frequency comb with a spectral range of 0.4-5.2 µm based on a compact all-fiber laser and LiNbO3 waveguide.
This Letter presents a 0.4-5.2-µm frequency comb from a compact laser. We designed an integrated fiber device for a figure-9 laser and constructed an all-fiber laser system. The spectrum of the fiber laser was scaled to the broadband region using a chirped periodically poled lithium niobate waveguide. To use this system for gas sensing, a mid-infrared comb with a spectral range of 2.5-5.2 µm and average power of 2.1 mW was divided using an optical filter. The optical part was packaged in a 305 mm × 225 mm × 62 mm box. The comb was stabilized by locking the repetition rate and carrier-envelope offset frequency of the seed source. The system provided an ultrabroadband spectral range from 0.4 to 5.2 µm, which could be applied to spectroscopy, frequency metrology, and optical synthesizers.


The in situ study of surface species and structures of oxide-derived copper catalysts for electrochemical CO2 reduction.
Oxide-derived copper (OD-Cu) has been discovered to be an effective catalyst for the electroreduction of CO2 to C2+ products. The structure of OD-Cu and its surface species during the reaction process are interesting topics, which have not yet been clearly discussed. Herein, in situ surface-enhanced Raman spectroscopy (SERS), operando X-ray absorption spectroscopy (XAS), and 18O isotope labeling experiments were employed to investigate the surface species and structures of OD-Cu catalysts during CO2 electroreduction. It was found that the OD-Cu catalysts were reduced to metallic Cu(0) in the reaction. CuO x species existed on the catalyst surfaces during the CO2RR, which resulted from the adsorption of preliminary intermediates (such as *CO2 and *OCO-) on Cu instead of on the active sites of the catalyst. It was also found that abundant interfaces can be produced on OD-Cu, which can provide heterogeneous CO adsorption sites (strong binding sites and weak binding sites), leading to outstanding performance for obtaining C2+ products. The Faradaic efficiency (FE) for C2+ products reached as high as 83.8% with a current density of 341.5 mA cm-2 at -0.9 V vs. RHE.


Activation of Pax7-positive cells in a non-contractile tissue contributes to regeneration of myogenic tissues in the electric fish S. macrurus.
The ability to regenerate tissues is shared across many metazoan taxa, yet the type and extent to which multiple cellular mechanisms come into play can differ across species. For example, urodele amphibians can completely regenerate all lost tissues, including skeletal muscles after limb amputation. This remarkable ability of urodeles to restore entire limbs has been largely linked to a dedifferentiation-dependent mechanism of regeneration. However, whether cell dedifferentiation is the fundamental factor that triggers a robust regeneration capacity, and whether the loss or inhibition of this process explains the limited regeneration potential in other vertebrates is not known. Here, we studied the cellular mechanisms underlying the repetitive regeneration of myogenic tissues in the electric fish S. macrurus. Our in vivo microinjection studies of high molecular weight cell lineage tracers into single identified adult myogenic cells (muscle or noncontractile muscle-derived electrocytes) revealed no fragmentation or cellularization proximal to the amputation plane. In contrast, ultrastructural and immunolabeling studies verified the presence of myogenic stem cells that express the satellite cell marker Pax7 in mature muscle fibers and electrocytes of S. macrurus. These data provide the first example of Pax-7 positive muscle stem cells localized within a non-contractile electrogenic tissue. Moreover, upon amputation, Pax-7 positive cells underwent a robust replication and were detected exclusively in regions that give rise to myogenic cells and dorsal spinal cord components revealing a regeneration process in S. macrurus that is dependent on the activation of myogenic stem cells for the renewal of both skeletal muscle and the muscle-derived electric organ. These data are consistent with the emergent concept in vertebrate regeneration that different tissues provide a distinct progenitor cell population to the regeneration blastema, and these progenitor cells subsequently restore the original tissue.


[The dependence of the marginal adaptation of composite fillings in caries cavities of class ii by black, on the state of oral hygiene and intensity of caries].
The problem of treatment of dental caries by fillings in dentistry is the key point in dentistry. Thus the main issue is the long-term functioning of the restorations. Particularly acute, this problem in the reduction of cavities class II according to Black, where the pressure on the filling is sufficiently high. It was examined and treated 87 patients with different levels of oral hygiene of oral cavity and caries of varying intensity and whom 186 defects of hard tissues of teeth class II Black were fitted. All patients were divided into 3 groups depending on the type of filling material selected. Each group was in turn divided into two groups depending on the type of the prepared cavity. In a subgroup (1) the preparation was carried out without additional primary cavity retention elements. In a subgroup (2) the preparation was carried out with the main cavity in the form of retention elements as extra place on the chewing surface. Analyzing the quality of edge adjacent of fillings and restorations in the long-term period (24 months) depending on the intensity of caries and oral hygiene, we found that the best results were obtained in patients with low intensity of caries, and in patients with a high level of oral hygiene of patients in all study groups. The best results in the short and long-term periods were obtained in II and IІІ groups. It should be noted that these groups the particularity of preparation has no influence on the quality of the restoration. According to restorations of group I where the restorative material was composite material as chemical hardening"Charisma PPF" ( "Heraeus Kulser"), this relation takes place. The best results in the short and long-term periods shown those restorations, under which created at preparing retention elements in the form of extra place.


Interactions of inorganic phosphate and sulfate anions with collagen.
We use direct infrared measurements to determine the number of binding sites, their dissociation constants, and preferential interaction parameters for inorganic phosphate and sulfate anions in collagen fibrils from rat tail tendons. In contrast to previous reports of up to 150 bound phosphates per collagen molecule, we find only 1-2 binding sites for sulfate and divalent phosphate under physiological conditions and approximately 10 binding sites at low ionic strength. The corresponding dissociation constants depend on NaCl concentration and pH and vary from approximately 50 microM to approximately 1-5 mM in the physiological range of pH. In fibrils, bound anions appear to form salt bridges between positively charged amino acid residues within regions of high excess positive charge. In solution, we found no evidence of appreciable sulfate or phosphate binding to isolated collagen molecules. Although sulfate and divalent phosphate bind to fibrillar collagen at physiological concentrations, our X-ray diffraction and in vitro fibrillogenesis experiments suggest that this binding plays little role in the formation, stability and structure of fibrils. In particular, we demonstrate that the previously reported increase in the critical fibrillogenesis concentration of collagen is caused by preferential exclusion of "free" (not bound to specific sites) sulfate and divalent phosphate from interstitial water in fibrils rather than by anion binding. Contrary to divalent phosphate, monovalent phosphate does not bind to collagen. It is preferentially excluded from interstitial water in fibrils, but it has no apparent effect on critical fibrillogenesis concentration at physiological NaCl and pH.


Classification techniques with minimal labelling effort and application to medical reports.
There are a number of approaches to classify text documents. Here, we use Partially Supervised Classification (PSC) and argue that it is an effective and efficient approach for real-world problems. PSC uses a two-step strategy to cut down on the labelling effort. There are a number of methods that have been proposed for each step. An evaluation of various methods is conducted using real-world medical documents. The results show that using EM to build the classifier yields better results than SVM. We also experimentally show that careful selection of a subset of features to represent the documents can improve performance.


Tasimelteon for non-24-hour sleep-wake disorder in totally blind people (SET and RESET): two multicentre, randomised, double-masked, placebo-controlled phase 3 trials.
Most totally blind people have non-24-hour sleep-wake disorder (non-24), a rare circadian rhythm disorder caused by an inability of light to reset their circadian pacemaker. In two consecutive placebo-controlled trials (SET and RESET), we assessed safety and efficacy (in terms of circadian entrainment and maintenance) of once-daily tasimelteon, a novel dual-melatonin receptor agonist. We undertook the placebo-controlled, randomised, double-masked trials in 27 US and six German clinical research centres and sleep centres. We screened totally blind adults (18-75 years of age), who were eligible for the randomisation phase of SET if they had a non-24-hour circadian period (τ) of 24·25 h or longer (95% CI greater than 24·0 and up to 24·9 h), as calculated from measurements of urinary 6-sulphatoxymelatonin rhythms. For SET, we used block randomisation to assign patients (1:1) to receive tasimelteon (20 mg) or placebo every 24 h at a fixed clock time 1 h before target bedtime for 26 weeks. Patients who entered the open-label group receiving tasimelteon in SET or who did not meet the SET inclusion criteria but did meet the RESET inclusion criteria were screened for RESET. A subset of the patients who entered the open-label group before the RESET study and who had eligible τ values were screened for RESET after completing the open-label treatment. In RESET, we withdrew tasimelteon in a randomised manner (1:1) in patients who responded (ie, entrained) after a tasimelteon run-in period. Entrainment was defined as having τ of 24·1 h or less and a 95% CI that included 24·0 h. In SET, the primary endpoint was the proportion of entrained patients, assessed in the intention-to-treat population. The planned step-down primary endpoint assessed the proportion of patients who had a clinical response (entrainment at month 1 or month 7 plus clinical improvement, measured by the Non-24 Clinical Response Scale). In RESET, the primary endpoint was the proportion of non-entrained patients, assessed in the intention-to-treat population. Safety assessments included adverse events and clinical laboratory measures, assessed in all treated patients. These trials are registered with ClinicalTrials.gov, numbers NCT01163032 and NCT01430754. Between Aug 25, 2010, and July 5, 2012, we screened 391 totally blind patients for SET, of whom 84 (22%) were assigned to receive tasimelteon (n=42) or placebo (n=42). Two patients in the tasimelteon group and four in the placebo group discontinued the study before τ was measured, due to adverse events, withdrawal of consent, and a protocol deviation. Circadian entrainment occurred in eight (20%) of 40 patients in the tasimelteon group compared with one (3%) of 38 patients in the placebo group at month 1 (difference 17%, 95% CI 3·2-31·6; p=0·0171). Nine (24%) of 38 patients showed a clinical response, compared with none of 34 in the placebo group (difference 24%, 95% CI 8·4-39·0; p=0·0028). Between Sept 15, 2011, and Oct 4, 2012, we screened 58 patients for eligibility in RESET, 48 (83%) of whom had τ assessed and entered the open-label tasimelteon run-in phase. 24 (50%) patients entrained, and 20 (34%) were enrolled in the randomisation phase. Two (20%) of ten patients who were withdrawn to placebo remained entrained compared with nine (90%) of ten who continued to receive tasimelteon (difference 70%, 95% CI 26·4-100·0; p=0·0026). No deaths were reported in either study, and discontinuation rates due to adverse events were comparable between the tasimelteon (3 [6%] of 52 patients) and placebo (2 [4%] of 52 patients) treatment courses. The most common side-effects associated with tasimelteon in SET were headache (7 [17%] of 42 patients given tasimelteon vs 3 [7%] of 42 patients given placebo), elevated liver enzymes (4 [10%] vs 2 [5%]), nightmares or abnormal dreams (4 [10%] vs none), upper respiratory tract infection (3 [7%] vs none], and urinary tract infections (3 [7%] vs 1 [2%]). Once-daily tasimelteon can entrain totally blind people with non-24; however, continued tasimelteon treatment is necessary to maintain these improvements. Vanda Pharmaceuticals.


Measurement invariance of language brokering extent and attitudes in linguistic minority adolescents: Item response theory analyses.
Using item response theory, we sought to evaluate measurement invariance of language brokering extent and attitudes in 3 linguistic minority groups of adolescents. The sample included 765 (302 Chinese American, 327 Korean American, and 136 Mexican American; 57% females) ninth graders from immigrant families. Differential item functioning was detected for several items, and we retained items with equivalent parameters across 3 groups. The final items showed adequate internal consistency reliability and criterion validity. The refined scale is cross-ethnically invariant and appropriate for use with Chinese-American, Korean-American, and Mexican-American adolescents to compare their language brokering experiences. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Age-related changes in glucocorticoid fast feedback inhibition of adrenocorticotropin in man.
A decrease in hypothalamic-pituitary-adrenal axis sensitivity to glucocorticoid feedback suppression seems to occur with aging. To investigate possible abnormalities in the inhibitory effect of glucocorticoids on ACTH secretion in the elderly, we evaluated the endogenous ACTH response to hydrocortisone (25 mg as an i.v. bolus) in 15 healthy aged (65-88 yr) and 15 healthy young (18-26 yr) men. Blood samples for ACTH and cortisol determinations were collected at -15, 0, 2, 5, 10, 15, 30, 45, 60, 90, 120, and 180 min. Hydrocortisone injection produced a rapid increase in plasma cortisol levels within the first 2 min in both groups. In old men, in concomitance with the cortisol increase, ACTH levels showed only a slight and nonsignificant decrease within the first 15 min, followed by a pronounced and significant decline thereafter. In young subjects, in concomitance with the plasma cortisol increase, a marked decrease in ACTH levels was observed within the first 15 min, followed by a less pronounced decline thereafter. The response curve of ACTH inhibition could be arbitrarily divided in two parts. The first part (from 0-60 min) showed a significant difference between old and young men, whereas the remaining part of the curve (from 60-180 min) showed no differences between the two groups. The slower response in glucocorticoid feedback inhibition of ACTH in old men supports the concept of some alteration in the central regulation by steroids in aging. Age-related vascular factors affecting cortisol penetration through the blood-brain barrier more than hippocampus-hypothalamus receptor abnormalities could be involved in the fast component of hypothalamic-pituitary-adrenal axis feedback regulation.


Combination chemotherapy with 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride and bleomycin in meningeal carcinomatosis in rats.
Combination chemotherapy with 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and bleomycin (BLM) was evaluated using an experimental model of meningeal carcinomatosis induced in Sprague-Dawley rats by intracisternal inoculation of 1 X 10(4) Walker 256 tumor cells. Tumor-bearing animals were treated by i.v. administration of cyclophosphamide, BLM, ACNU, or a combination thereof, starting on Day 5 after tumor inoculation. BLM, 5 mg/kg on Day 5 as well as 5 mg/kg/day on Days 5, 7, 9, 11, and 13, was ineffective. Cyclophosphamide, 30 mg/kg, or ACNU, 15 or 30 mg/kg, on Day 5 increased the median survival time by 52, 70, and 82%, respectively. The combination of ACNU, 15 mg/kg, and cyclophosphamide, 15 mg/kg, increased median survival time by 73%, while the combination of ACNU, 15 mg/kg, and BLM, 5 mg/kg, resulted in a maximal increase of median survival time of 200% when the agents were given on Day 5. The combination of ACNU, 15 mg/kg on Day 5, and BLM, 5 mg/kg/day on Days 5, 7, 9, 11, and 13, increased median survival time by over 360% and cured 60% of the animals. These results point to the therapeutic advantage inherent in ACNU and BLM combination therapy.


New treatment of subglottic stenosis due to Wegener's granulomatosis.
The presented new endoscopic surgical technique offers a safe and successful approach for treatment of subglottic stenosis due to Wegener's granulomatosis. Subglottic stenosis is a potentially limiting and complex condition among patients with Wegener's granulomatosis. It causes various symptoms and often requires interventional therapy. The purpose of this study was to evaluate a new endoscopic submucosal technique. Altogether 13 consecutive patients with subglottic stenosis due to Wegener's granulomatosis were treated with a new endoscopic technique. The procedure was carried out endoscopically, removing the stenotic part submucosally, sealing back the raised mucosal flap, and the bare areas were soaked with mitomycin-C. Follow-up telephone interviews were carried out and hospital records were reviewed. Patients included 3 males and 10 females, with an average age of 37.5 years. A total of 37 procedures were performed, with an average of 2.8 procedures per patient. There was a statistically significant reduction in the all symptoms related to the stenoses (p < 0.05). Mean follow-up period was 3.5 years (range 1.5-6.5 years). Overall success rate was 85%. Only one patient relapsed following adequate medical and surgical treatment. No perioperative mortality was recorded.


Diabetes prevention, weight loss, and social support: program participants' perceived influence on the health behaviors of their social support system.
This study examined participants' perceptions of how their involvement in a well-established weight loss and diabetes prevention program influenced their social support persons (SSPs). Utilizing a mixed-methods approach, participants were surveyed to determine their perceived influence on SSPs. Compared to controls, intervention participants reported that SSPs' lifestyle changes were more positively influenced by their study participation, and their amount of weight loss was related to favorability of perceived changes in SSPs' eating habits. Themes of lifestyle changes, knowledge dissemination, and motivation emerged from responses. Future lifestyle change interventions could potentially capitalize on program participants' influence on their social support networks.


In Vitro Toxicity Assessment of Stilbene Extract for Its Potential Use as Antioxidant in the Wine Industry.
The reduction of sulfur dioxide in wine is a consumer's demand, considering the allergic effects that may occur in people who are sensitive to it. Stilbenes are candidates of great interest for this purpose because of their antioxidant/antimicrobial activities and health properties, and also because they are naturally found in the grapevine. In the present study, the in vitro toxicity of an extract from grapevine shoots (with a stilbene richness of 45.4%) was assessed in two human cell lines. Significant damage was observed from 30 μg/mL after 24 h, and 40 µg/mL after 48 h of exposure. Similarly, the ultrastructural study revealed a significant impairment of cell growing. The extract was able to protect cells against an induced oxidative stress at all concentrations studied. In view of the promising results, a more exhaustive toxicological assessment of the extract is needed to confirm the safety of its further use as additive in wine.


Stomach gas analyses in canine acute gastric dilatation with volvulus.
The origin of the gas in the stomachs of dogs with acute gastric dilatation or gastric dilatation with volvulus (GDV) often is disputed. We tested the hypothesis that gaseous distention resulted from aerophagia. Ten cases of GDV that were submitted to an emergency clinic were sampled intraoperatively. With the abdomen open, the needle of a vacutainer blood collection set was inserted into the distended stomach, and gas was collected into 10 mL glass vacutainer vials with rubber stoppers. These were stored at room temperature for 1-7 days and then analyzed by gas chromatography and mass spectroscopy. CO2 composition ranged from 13 to 20%. One dog had an H2 concentration of 29%. Because the CO2 content of atmospheric air is less than 1%, these findings suggest that the gaseous gastric distention in GDV is not the result of aerophagia.


Concepts and folk theories.
Human cognition is characterized by enormous variability and structured by universal psychological constraints. The focus of this chapter is on the development of knowledge acquisition because it provides important insight into how the mind interprets new information and constructs new ways of understanding. We propose that mental content can be productively approached by examining the intuitive causal explanatory "theories" that people construct to explain, interpret, and intervene on the world around them, including theories of mind, of biology, or of physics. A substantial amount of research in cognitive developmental psychology supports the integral role of intuitive theories in human learning and provides evidence that they structure, constrain, and guide the development of human cognition.


Cutting edge: thymic crosstalk regulates delta-like 4 expression on cortical epithelial cells.
Interactions between Notch1 receptors on lymphoid progenitors and Delta-like 4 (DL4) ligands on cortical thymic epithelial cells (cTEC) are essential for T cell lineage commitment, expansion, and maturation in the thymus. Using a novel mAb against DL4, we show that DL4 levels on cTEC are very high in the fetal and neonatal thymus when thymocyte expansion is maximal but decrease dramatically in the adult when steady-state homeostasis is attained. Analysis of mutant mouse strains where thymocyte development is blocked at different stages indicates that lymphostromal interactions ("thymus crosstalk") are required for DL4 down-regulation on cTEC. Reconstitution of thymocyte development in these mutant mice further suggests that maturation of thymocytes to the CD4(+)CD8(+) stage and concomitant expansion are needed to promote DL4 down-regulation on cTEC. Collectively, our data support a model where thymic crosstalk quantitatively regulates the rate of Notch1-dependent thymopoiesis by controlling DL4 expression levels on cTEC.


In vitro and in silico methods for the biomechanical assessment of osseointegrated transfemoral prostheses: a systematic review.
The amputee population according to the World-Health-Organization is about 40 million. However, there is a high abandon rate of socket prostheses for the lower limb (25%-57%). The direct connection between the external prosthesis and the patient's bone makes osseointegrated prostheses for transfemoral amputees advantageous (e.g., improvement of the motor control) compared to socket prostheses, which are currently the gold standard. However, similarly to other uncemented prostheses, the osseointegrated ones are at risk of aseptic loosening and adverse bone remodelling caused by stress-shielding. The preclinical assessment of these prostheses has already been evaluated using different methods which did not provide unanimous and comparable evidence. To compare data from different investigations, a clear and detailed overview of the methods used to assess the performance is necessary. In this review 17 studies investigating the primary stability, stress shielding and stress concentration of osseointegrated transfemoral prostheses are examined. Primary stability consists in the biomechanical stability upon implant insertion. Primary stability is assessed measuring extraction force (either with a pull-out or a push-out test) and micromotion at the interface between the implant and the host bone with LVDT (in vitro test) or numerical models. Stress-shielding causes adaptive changes in the bone density around metal implants, and thus in the bone strength and stiffness. Stress-shielding is assessed with strain gauges or numerical models measuring the load transfer and the strain distribution on the surface of the femur, and between the implant and the bone respectively. Stress concentration can lead to the formation of cracks inside the bone, resulting in fractures. The stress concentration is assessed measuring the load transfer and the strain energy density at the interface between the implant and the bone, using numerical models. As a result, a global view and consensus about the methods are missing from all these tests. Indeed, different setup and loading scenario were used in the in vitro test, while different model parameters (e.g., bone properties) were used in the numerical models. Once the preclinical assessment method is established, it would be important to define thresholds and acceptance criteria for each of the possible failure scenarios investigated.


Determinants of multidrug-resistant tuberculosis in Addis Ababa, Ethiopia.
Multidrug-resistant tuberculosis (MDR-TB) has been jeopardizing the global effort to prevent and control tuberculosis (TB). However, data on MDR-TB in Ethiopia in general, and in our study area in particular, are very scarce. The aim of this study was to identify determinants of MDR-TB in a cohort of patients managed in two referral hospitals of Addis Ababa, Ethiopia, between April 1, 2013 and June 30, 2013. A health facility-based case-control study was conducted. A total of 710 TB patients (229 confirmed MDR-TB and 481 drug susceptible TB patients) were enrolled in this study. Identified independent determinants for MDR-TB were contact history with a known TB patient (adjusted odds ratio [AOR]: 1.9, 95% CI: 1.1-3.3), previous history of TB treatment (AOR: 11.9, 95% CI: 6.8-21), history of hospitalization (AOR: 4.4 95% CI: 2.2-7.8), sputum-smear positivity (AOR: 1.9, 95% CI: 1.1-3.4), and social stigma (AOR: 5.1, 95% CI: 1.8-14.4). These identified factors should be considered for use in MDR-TB screening tool development if universal drug susceptibility testing is not possible. Moreover, TB infection control practices in health care settings should be further strengthened. As factors may vary from region to region, further broader studies need to be conducted in other parts of Ethiopia.


[Research progress on biocomposites based on bioactive glass].
Bioactive glass (BG) has been widely used in the preparation of artificial bone scaffolds due to its excellent biological properties and non-cytotoxicity, which can promote bone and soft tissue regeneration. However, due to the brittleness, poor mechanical strength, easy agglomeration and uncontrollable structure of glass material, its application in various fields is limited. In this regard, most current researches mainly focus on mixing BG with organic or inorganic materials by freeze-drying method, sol-gel method, etc., to improve its mechanical properties and brittleness, so as to increase its clinical application and expand its application field. This review introduces the combination of BG with natural organic materials, metallic materials and non-metallic materials, and demonstrates the latest technology and future prospects of BG composite materials through the development of scaffolds, injectable fillers, membranes, hydrogels and coatings. The previous studies show that the addition of BG improves the mechanical properties, biological activity and regeneration potential of the composites, and broadens the application of BG in the field of bone tissue engineering. By reviewing the recent BG researches on bone regeneration, the research potential of new materials is demonstrated, in order to provide a reference for future related research.


Identification of osteopenic women at high risk of fracture: the OFELY study.
About one-half of women with incident fractures have BMD above the WHO diagnostic threshold of osteoporosis. In the OFELY study, low BMD, increased markers of bone turnover, and prior fracture could be used to identify, within osteopenic women, those at high risk of fracture. Recent data suggest that about one-half of women with incident fractures have BMD above the World Health Organization (WHO) diagnostic threshold of osteoporosis (T score<or=-2.5). We aimed to identify, within osteopenic women, those at high risk of fracture. In the 671 postmenopausal women (mean age: 62 years) belonging to the Os des Femmes de Lyon (OFELY) population-based prospective cohort, we measured at baseline BMD by DXA at the spine and total hip, bone turnover markers (BTM) and clinical risk factors for osteoporosis. All fragility vertebral or nonvertebral fractures, confirmed by radiographs, were assessed during a median follow-up of 9.1 years (IQ: 2.3). 158 incident fractures were recorded in 116 women: 8% in normal, 48% in osteopenic, and 44% in osteoporotic women. Among osteopenic women, low BMD (-2.5<T score<or=-2.0) was associated with an increased fracture risk with an age-adjusted hazard ratio (HR) of 2.5 (1.3-4.6). In addition, age, prior fracture, and high BTM-but not other risk factors-were independently associated with an increased fracture risk with an age-adjusted HR of 2.2 (1.2-4.3) for prior fractures and 2.2 (1.4-3.8) for bone alkaline phosphatase (BALP) in the highest quartile. In the whole group of osteopenic women, a large majority of incident fractures occurred in those with a low BMD, prior fractures, or BALP in the highest quartile, with an age-adjusted HR of 5.3 (2.3-11.8). The 10-year probability of fracture in osteopenic women was 26% if at least one predictor was present, contrasting with 6% in those without any of the three risk factors. In postmenopausal women with osteopenia, low BMD, increased BTM, and prior fracture are associated with an increased risk of fracture in the subsequent 10 years. Their assessment may play an important role in identifying women at high risk of fracture who could not be adequately detected by BMD measurement alone and who may benefit from a therapeutic intervention.


Ultrafast excited-state dynamics in the green fluorescent protein variant S65T/H148D. 2. Unusual photophysical properties.
In the preceding accompanying paper [Shu, X., et al. (2007) Biochemistry 46, 12005-12013], the 1.5 A resolution crystal structure of green fluorescent protein (GFP) variant S65T/H148D is presented, and the possible consequences of an unusual short hydrogen bond (<or=2.4 A) between the carboxyl oxygen of Asp148 and the phenol oxygen of the chromophore are discussed. This work reports the femtosecond time-resolved emission of this variant at pH 5.6 by ultrafast fluorescence upconversion spectroscopy. Following excitation at 400 nm, green fluorescence is observed at 510 nm with a rise on a time scale that is faster than the 170 fs instrument response. Time-resolved emission spectra at 140 K also exhibit the immediate appearance of green fluorescence, and this extremely fast process is hardly affected by deuteration of exchangeable protons. These results appear to be dramatically different from those of wild-type GFP, in which the green fluorescence at 508 nm is produced on the picosecond time scale as a result of excited-state proton transfer from the state that is excited at 400 nm. The unique features observed in S65T/H148D and apparent ultrafast excited-state proton transfer are discussed in light of evidence for multiple states underlying the band at around 415 nm, as suggested by steady-state fluorescence spectra. The behavior of these different states may explain the novel photophysical properties observed for this GFP variant, including the ultrafast green fluorescence and the absence of completely matched decay in blue fluorescence. It is speculated that two different orientations of the Asp introduced at position 148, not distinguishable by chromatography, mass spectrometry, or X-ray crystallography, give rise to the two functionally distinct populations.


Damage control or definitive repair? A retrospective review of abdominal trauma at a major trauma center in South Africa.
This study set out to review a large series of trauma laparotomies from a single center and to compare those requiring damage control surgery (DCS) with those who did not, and then to interrogate a number of anatomic and physiologic scoring systems to see which best predicted the need for DCS. All patients over the age of 15 years undergoing a laparotomy for trauma during the period from December 2012 to December 2017 were retrieved from the Hybrid Electronic Medical Registry (HEMR) at the Pietermaritzburg Metropolitan Trauma Service (PMTS), South Africa. They were divided into two cohorts, namely the DCS and non-DCS cohort, based on what was recorded in the operative note. These groups were then compared in terms of demographics and spectrum of injury, as well as clinical outcome. The following scores were worked out for each patient: Penetrating Abdominal Trauma Index (PATI), Injury Severity Score, Abbreviated Injury Scale-abdomen, and Abbreviated Injury Scale-chest. A total of 562 patients were included, and 99 of these (18%) had a DCS procedure versus 463 (82%) non-DCS. The mechanism was penetrating trauma in 81% of cases (453 of 562). A large proportion of trauma victims were male (503 of 562, 90%), with a mean age of 29.5±10.8. An overall mortality rate of 32% was recorded for DCS versus 4% for non-DCS (p<0.001). In general patients requiring DCS had higher lactate, and were more acidotic, hypotensive, tachycardic, and tachypneic, with a lower base excess and lower bicarbonate, than patients not requiring DCS. The most significant organ injuries associated with DCS were liver and intra-abdominal vascular injury. The only organ injury consistently predictive across all models of the need for DCS was liver injury. Regression analysis showed that only the PATI score is significantly predictive of the need for DCS (p=0.044). A final multiple logistic regression model demonstrated a pH <7.2 to be the most predictive (p=0.001) of the need for DCS. DCS is indicated in a subset of severely injured trauma patients. A pH <7.2 is the best indicator of the need for DCS. Anatomic injuries in themselves are not predictive of the need for DCS. Level III.


Aetiology and outcome of non-traumatic altered states of consciousness in north western Ethiopia.
Awareness of the relative prevalence of diseases causing altered states of consciousness (ASC) in a particular geographic locality could greatly facilitate the approach to patient management. This prospective study has, therefore, evaluated 202 patients with ASC admitted to the medical wards of GCMS teaching hospital in a two year period, between January 1994 and December 1995. ASC was defined as a clinical state manifested by conditions ranging from confusion and disorientation in person, place and time to stupor and deep coma. History, physical examination, limited laboratory tests and course of the patient in the hospital were used to identify the aetiology. There were 122 (60.4%) males and 80 (39.6%) females with male to female ratio of 3:2. Most of the patients, 122 (60.4%), belong to the age group below 40 years and the median age was 33 years (range = 15.84). The median duration of hospital stay was six days (range = 1-90). The commonest cause was infections, 111 (55%) followed by metabolic disorders, 45 (22.3%), structural lesions, 30 (14.9%) and poisoning, seven (3.5%). The aetiology was not identified in nine (4.5%) of the patients. Cerebral malaria was the commonest infectious cause followed by chronic meningitis and/or encephalitis. In hospital mortality rate was 60.4%. Unknown diagnosis, structural neurologic and metabolic causes were associated with increased mortality rate, with p values of 0.002, 0.009 and 0.015, respectively. The same was true for presence of HIV infection, P = 0.02. Since infectious causes are the commonest causes in our series, of which most are treatable with a relatively favourable outcome, critical evaluation for infections and early intervention is recommended. In addition, diagnostic facilities, especially for structural central nervous system lesions has to be improved because successful treatment and prognosis depends on the identification of a specific aetiology.


Applying Blockchain Technology in Network Public Opinion Risk Management System in Big Data Environment.
Network public opinion represents public social opinion to a certain extent and has an important impact on formulating national policies and judgment. Therefore, China and other countries attach great importance to the study of online public opinion. However, the current researches lack the combination of theory and practical cases and lack the intersection of social and natural sciences. This work aims to overcome the technical defects of traditional management systems, break through the difficulties and pain points of existing network public opinion risk management, and improve the efficiency of network public opinion risk management. Firstly, a network public opinion isolation strategy based on the infectious disease propagation model is proposed, and the optimal control theory is used to realize a functional control model to maximize social utility. Secondly, blockchain technology is used to build a network public opinion risk management system. The system is used to conduct a detailed study on identifying and perceiving online public opinion risk. Finally, a Chinese word segmentation scheme based on Long Short-Term Memory (LSTM) network model and a text emotion recognition scheme based on a convolutional neural network are proposed. Both schemes are validated on a typical corpus. The results show that when the system has a control strategy, the number of susceptible drops significantly. Two days after the public opinion is generated, the number of susceptible people decreased from 1,000 to 250; 3 days after the public opinion is generated, the number of susceptible people stabilized. 2 days after the public opinion is generated, the number of lurkers increased from 100 to 620; 3 days after the public opinion is generated, the number of lurkers stabilized. The data demonstrate that the designed isolation control strategy is effective. Changes in public opinion among infected people show that quarantine control strategies played a significant role in the early days of Corona Virus Disease 2019. The rate of change in the number of infections is more affected when quarantine controls are increased, especially in the days leading up to the outbreak. When the system adopts the optimal control strategy, the influence scope of public opinion becomes smaller, and the control becomes easier. When the dimension of the word vector of emergent events is 200, its accuracy may be higher. This method provides certain ideas for blockchain and deep learning technology in network public opinion control.


Phosphate complexation model and its implications for chemical phosphorus removal.
A phosphate complexation model is developed, in an attempt to understand the mechanistic basis of chemically mediated phosphate removal. The model presented here is based on geochemical reaction modeling techniques and uses known surface reactions possible on hydrous ferric oxide (HFO). The types of surface reactions and their reaction stoichiometry and binding energies (logK values) are taken from literature models of phosphate interactions with iron oxides. The most important modeling parameter is the proportionality of converting moles of precipitated HFO to reactive site density. For well-mixed systems and phosphate exposed to ferric chloride during HFO precipitation, there is a phosphate capacity of 1.18 phosphate ions per iron atom. In poorly mixed systems with phosphate exposed to iron after HFO formation, the capacity decreased to 25% of the well-mixed value. The same surface complexation model can describe multiple data sets, by varying only a single parameter proportional to the availability of reactive oxygen functional groups. This reflects the unavailability of reactive oxygen groups to bind phosphate. Electron microscope images and dye adsorption experiments demonstrate changes in reactive surface area with aging of HFO particles. Engineering implications of the model/mechanism are highlighted.